EVIDENCE TABLES by hkksew3563rd

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									Pre-eclampsia Community Guideline




   EVIDENCE TABLES




     Version for publication 2004
Section: Factors that can be measured early in pregnancy which increase the likelihood of pre-eclampsia in a given pregnancy

Study              Population               Intervention           Outcomes           Results                               Comments          Study Type       Evidence
                                            details                                                                                                            Level
Duckitt 04         Cohort and case          Age: cut-off of        Relative risk      Outcome: pre-eclampsia (RR)           Potential risk    Systematic       II
(review)           control studies for      16, 17, 19, 35         (RR) or odds       Age≥40 primips 1.68(1.23-2.29)        factors were      review with
                   the following            and 40                 ratio (OR) of      Age≥40 multips 1.96(1.34-2.87)        initially         meta-analysis
                   potential risk           Parity: nulliparity;   developing         Nulliparity 2.91(1.28-6.61)           selected by       of cohort and
                                                                                      History 7.19(5.85-8.83)
                   factors for pre-         multiparity;           pre-eclampsia      Multiple preg.2.93(2.04-4.21)
                                                                                                                            consensus         case control
                   eclampsia: age;          History: risk of       for all risk       Family history 2.90(1.70-4.93)        from a            studies
                   parity; history of       pre-eclampsia in       factors.           Diabetes 3.56(2.54-4.99)              multidisciplina
                   previous pre-            second                                    Pre-preg BMI≥35, 4.39(3.52-5.49)      ry guideline
                   eclampsia; family        pregnancy in           For all studies    Booking BMI ≥ 35, 1.55(1.28-1.88)     group set up
                   history of pre-          those with pre-        definition of      Antiphospholipid                      to formulate
                   eclampsia;               eclampsia in first     pre-eclampsia      Antibodies, 9.72(4.34-21.75)          evidence-
                   presence of              pregnancy;             required new                                             based
                   multiple pregnancy;      history of pre-        onset              Booking blood pressure (without       guideline on
                                                                                      known hypertension)
                   underlying medical       eclampsia in first     proteinuria and    Systolic ≥ 130 mmHg (before 18
                                                                                                                            pre-
                   conditions (insulin      pregnancy in           hypertension.      weeks) vs. < 110 mmHg, more           eclampsia.
                   dependant                those with pre-                           likely to develop pre-eclampsia (OR
                   diabetes, pre-           eclampsia in           Perinatal          3.6, 95% CI 2.0,6.6)[IIb]             Change of
                   existing                 second                 outcome for        Diastolic ≥ 80 mmHg (before 18        partner,
                   hypertension, renal      pregnancy.             the following      weeks) vs. < 60 mmHg, more likely     length of co-
                   disease, chronic         Family history:        factors (chronic   to develop pre-eclampsia but not      habitation,
                   auto-immune              positive history in    hypertension;      significant (OR 1.8 (0.7-4.6)[IIb]    use of donor
                   disease and              mother, sister,        BP                 Diastolic (from 9-12 weeks)           eggs or donor
                                                                                      significantly higher in women who
                   presence of              mother-in-law.         measurement        developed pre-eclampsia than in
                                                                                                                            insemination,
                   antiphospholipid         Multiple               at booking;        matched controls [IIb]                ethnic origin
                   antibodies; Body         pregnancy:             booking            MAP > 90 mmHg (first visit)           of mother,
                   Mass Index or            number of              proteinuria        associated with significantly more    and migraine
                   weight; booking          fetuses;                                  severe pre-eclampsia (RR 3.7, 95%     were not
                   blood pressure;          association with       Severe pre-        CI 2.1, 6.6)[IIb]                     selected for
                   confirmed                chorionicity;          eclampsia for                                            this
                   proteinuria prior to     zygosity, parity       the following      Early proteinuria without known       systematic
                   20 weeks                 Diabetes: with or      factors (family    renal disease                         review.



Section: factors which increase likelihood of pre-eclampsia                                                                                                   page 2
                   gestation;               without diabetic     history; BP   No controlled studies found.
                   pregnancy interval       nephropathy;         measurement
                                            associated risk      at booking)   Pre-existing hypertension (CH)
                                            factors.                           21.1% of women with CH vs. 2.3%
                                                                               of the general population developed
                                            Pre-existing                       pre-eclampsia (RR 6.5, 95%CI 5.2-
                                            hypertension;                      8.2)[IIa]
                                            development of
                                            superimposed                       12.1% women with pre-eclampsia
                                            pre-eclampsia;                     vs. 0.3% of women without pre-
                                            Renal disease:                     eclampsia had self-reported
                                            recurrent UTI;                     hypertension [IIa/b]
                                            reflux
                                            nephropathy;                       Prenatal morbidity of women with
                                                                               CH vs. general hospital population:
                                            minimum serum                      overall (OR 8.8, 95% CI 2.6, 39.0);
                                            creatinine conc.                   SGA (OR 5.6, 1.8-16), delivery < 32
                                            124 micromol/l                     weeks (OR 15 (5.7, 38.0) admission
                                            with or without                    to SCBU (OR 7.0( 3.1-16.0))
                                            booking
                                            hypertension.                      A diastolic before 20 weeks most
                                            Chronic                            predictive of superimposed pre-
                                            autoimmune                         eclampsia in women with CH:
                                            disease;                           ≥110mmHg (OR 5.2,1.5-17.2) or ≥
                                                                               100mmHg (OR 3.2,1.0-7.8)
                                            connective tissue                  [IIb]
                                            disease and
                                            rheumatic                          Renal disease (RD)
                                            disease.                           Prevalence of renal disease
                                            Body Mass                          increased in women with pre-
                                            Index; cut-offs of                 eclampsia compared to women with
                                            35, 26, below 25v                  no pre-eclampsia (5.3% vs
                                            above 30; pre-                     1.8%)[IIa]
                                            pregnancy BMI;
                                                                               6.7% of women with renal disease
                                            booking BMI.                       vs 2.6% women in control group
                                            Weight v BMI.                      developed pre-eclampsia [IIb]
                                            Booking BP:
                                            diastolic of >
                                            90mmHg, < 85


Section: factors which increase likelihood of pre-eclampsia                                                          page 3
                                            mmHg at 9-12                        Pregnancy interval
                                            weeks; >                            RR 1.83 (1.72, 1.94) comparing
                                            80mmHg; >                           interpregnancy interval of ≥ 59
                                            85mmHg; < 55 v                      months with an interval of 18-23
                                                                                months [IIb]
                                            70-84mmHg:
                                            systolic of                         Pre-eclampsia occurred in 3.9% of
                                            130mmHg,                            first pregnancies, 1.7% of second
                                            135mmHg; 130 v                      and 1.8% of third. Risk in second
                                            < 110mmHg                           and third was directly related to
                                            before 18 weeks.                    time elapsed since previous
                                            Booking                             delivery, independent of woman’s
                                            proteinuria:                        age or partner change [IIa]
                                            women with no
                                            known renal
                                            disease, no
                                            reversible renal
                                            dysfunction.
                                            Pregnancy
                                            interval: 10
                                            years, >59
                                            months v18-23
                                            months;
                                            association with
                                            parity and change
                                            of paternity.

Marcoux 92         N= cases (172            Information on       Incidence of   Migraine was reported by 16%        Case control    IIb
                   women with pre-          migraine attacks     migraine       of pre-eclamptic women, 12% of
                   eclampsia and 254        in the year before                  women with gestational
                   with gestational         pregnancy                           hypertension and 8% of
                   hypertension) and                                            controls. Adjusted odds ratios
                   controls (505) who                                           (95%CI) of pre-eclampsia and
                   were primiparae                                              gestational hypertension were
                   with no history of                                           2.44 (1.42-4.20) and 1.70 (1.02-
                   hypertension                                                 2.85), respectively.



Section: factors which increase likelihood of pre-eclampsia                                                                        page 4
                   before pregnancy
Moore 83           N=24 women with          Cases required:      Mode of             Eight pre-eclamptic women                            Case control    IIb
(UK)               pre-eclampsia            rise of 30 and       delivery,          (33%) v 3 control women (6%)
                   diagnosed before         15mmHg,              perinatal          described headaches
                   34 weeks, with           respectively, of     outcome,           accompanied by nausea,
                   n=48 controls            systolic and         history, patient   vomiting or visual disturbances
                   randomly selected        diastolic (K1 and    characteristics    (p<0.01) – typical characteristics
                   were matched for         IV), max                                of migraine headache.
                   age and parity.          antenatal
                                            readings ≥140
                                            and 90mmHg;
                                            persistent
                                            proteinuria of 2+
                                            or more.
Stettler 92        Chronic proteinuria      65 pregnancies in    Perinatal          48/65 pregnancies (74%) had          The perinatal    Case series     III
(USA)              complicating             53 women with        outcome by         associated renal insufficiency,      morbidity rate
                   pregnancy                proteinuria          proteinuria +/-    26/65 (40%) had chronic              was also five
                   between 1970-            ≥500mg/24 hours      renal              hypertension.                        times greater
                   1990.                    ( quantified after   insufficiency,                                          than in
                                            ≥2+ or persistent    chronic            62% case and 12% of controls         uncomplicate
                                            1+), no known        hypertension.      had pre-eclampsia (p<0.001),         d
                                            renal disease, no                       23 (43%) of case and 17% of          pregnancies.
                                            reversible renal     Preterm            controls had preterm delivery
                                            dysfunction and      delivery           (p<0.001), 23% of case and
                                            no evidence of       defined as         10% of controls had fetal growth
                                            pre-eclampsia at     delivery < 38      restriction (p=0.01).
                                            discovery of         completed
                                            proteinuria. Renal   weeks. Fetal       Excluding 8 abortions, the
                                            insufficiency        growth             following incidence of
                                            defined as serum     restriction as     complications occurred during
                                            creatinine           determined by      57 pregnancies.
                                            concentration of >   Brenner et al.
                                            0.8 mg/dl that                          Preterm birth occurred in 1/14
                                            persisted            Outcome            (7%) women with proteinuria
                                            throughout           compared with      alone, 8/19 (42%) women with



Section: factors which increase likelihood of pre-eclampsia                                                                                              page 5
                                            pregnancy.         general         proteinuria and renal
                                            Chronic            obstetric       insufficiency, ½ (50%) women
                                            hypertension       population      with proteinuria and chronic
                                            defined as bp ≥    from the same   hypertension, and 17/22 (77%)
                                            140/90mmHg         hospital        women with proteinuria and
                                            before 20 weeks    (controls).     both renal insufficiency and
                                            or before                          chronic hypertension.
                                            pregnancy.                         Proteinuria with renal
                                            Superimposed                       insufficiency, and proteinuria
                                            pre-eclampsia                      with both renal insufficiency and
                                            diagnosed                          chronic hypertension were both
                                            clinically as an                   more likely to result in preterm
                                            acute elevations                   birth (p=0.01, OR 3.4 and
                                            in bp, marked                      p<0.001, OR 15.9, respectively),
                                            increases in                       compared with the general
                                            proteinuria,                       obstetric population. Proteinuria
                                            characteristic                     alone, and with chronic
                                            symptoms, and/                     hypertension were not
                                            or lab evidence.                   significantly different from the
                                                                               general population (OR 0.36
                                                                               and 4.68, respectively).

                                                                               Growth restriction occurred in
                                                                               1/14 (7%) women with
                                                                               proteinuria alone4/19 (21%)
                                                                               women with proteinuria and
                                                                               renal insufficiency, no women
                                                                               with proteinuria and chronic
                                                                               hypertension, and 7/22 (32%)
                                                                               women with proteinuria and
                                                                               both renal insufficiency and
                                                                               chronic hypertension.
                                                                               Proteinuria with both renal
                                                                               insufficiency and chronic
                                                                               hypertension was more likely to
                                                                               result in growth restriction


Section: factors which increase likelihood of pre-eclampsia                                                        page 6
                                                                                    (p=0.004, OR 4.2), compared
                                                                                    with the general obstetric
                                                                                    population. The other groups
                                                                                    were not significantly different
                                                                                    from the general population.


Type of previous pre-eclampsia

Study                 Population            Intervention        Outcomes             Results                           Comments            Study Type       Evidence
                                            details                                                                                                         Level
Banias 92             67 women with         Temporising         Delivery in          Women with severe pre-                                Retrospective    IIb
(USA)                 severe pre-           management          women with           eclampsia were significantly                          case control
                      eclampsia in                              severe pre-          more likely to have had
                      preterm                                   eclampsia            previous pre-eclampsia
                      pregnancy                                 defined as           (p<0.001), previous
                      between 26-32                             ≥160/110 on at       hypertension (p<0.0001),
                      weeks compared                            least 2 occasions    previous renal disease
                      with 134 women                            6 hours apart, >     (p<0.05) and previous
                      who delivered at                          3+ dipstick or       preterm delivery (p<0.001).
                      a similar                                 3g/24 hours or
                      gestational age                           HELLP.
                      with preterm
                      rupture of
                      membranes or
                      preterm labour
                      without pre-
                      eclampsia.
Campbell &            279 women with        Pre-eclampsia       Pre-eclampsia        21/279 cases and 51/4846          Both                Cohort           IIa
MacGillivray 85       pre-eclampsia         (termed                                  controls had pre-eclampsia        pregnancies
(Scotland)            and 4846 who          proteinuric or                           in second pregnancy.              were required
                      were                  severe) in second                                                          to be viable i.e.
                      normotensive in       pregnancy                                Of the women with pre-            > 28/40 weeks
                      first pregnancy       defined as                               eclampsia and low-birth
                      between 1967          diastolic bp ≥                           weight baby (<2500g) in



Section: factors which increase likelihood of pre-eclampsia                                                                                                page 7
                      and 1978 who          90mmHg after                         their first pregnancy 5/42
                      had at least a        26/40 on 2                           (11.9%) had pre-eclampsia
                      second                occasions at least                   in their second pregnancy
                      pregnancy             24 hours apart (or                   compared with 15/226
                                            progressive rise                     (6.6%) who had pre-
                                            in labour to ≥ 90                    eclampsia with a baby ≥
                                            mmHg) and >                          2500g in their first
                                            0.25g/l                              pregnancy.
                                            proteinuria.
                                                                                 Women with pre-eclampsia
                                                                                 in their first pregnancy who
                                                                                 delivered pre-term had an
                                                                                 increased risk of pre-
                                                                                 eclampsia in their second
                                                                                 pregnancy compared to
                                                                                 women with pre-eclampsia
                                                                                 who delivered at term in their
                                                                                 first pregnancy (13.0% vs.
                                                                                 6.8%)

                                                                                 Rates of perinatal morbidity
                                                                                 and mortality are about the
                                                                                 same for women with pre-
                                                                                 eclampsia in their first
                                                                                 pregnancy or recurrent pre-
                                                                                 eclampsia in their second
                                                                                 pregnancy.




Ferrazani 90         n-=444               98 women with chronic   Birth weight (BW),                              Case series    III
(Italy)              hypertensive         hypertension (CH) –     birth percentile     Pre-eclampsia primips
                     women with           documented before 20    (BP) gestational     (n=86) v multips (n=61):
                     singleton            weeks or before         age (GA), SGA (<     no sig. dif. in terms of
                                                                                       SGA, birth weight, birth


Section: factors which increase likelihood of pre-eclampsia                                                                     page 8
                     pregnancies     pregnancy; 199 with         10th percentile by     percentile, week of
                     between 1984-   non-proteinuric             national standard      delivery and perinatal
                     88.             hypertension (GH) after criteria), serum uric mortality.
                                     20 weeks and 147 with       acid (mg/dl) – last
                     Hypertension    hypertension and            value before
                     defined as      proteinuria – n=126 with delivery. Higher
                     bp≥90mmHg in hypertension after 20          value of proteinuria
                     2 consecutive   weeks and n=21 with         (g/l in a random
                     measurements chronic hypertension           sample) before
                     6 hours apart   superimposed with           delivery, preterm
                     (4th K).        significant proteinuria     delivery (PD),
                     Proteinuria >   and an exacerbation of      perinatal death
                     0.3gm/l or >1+  hypertension (Pre). The (PND), stillbirth
                     dipstick in a   two groups were             (SB), neonatal
                     random sample combined as they              death (NND)
                     with no urinary showed the same rate
                     infection.      of SGA (52%).
Hnat 02              598 women with    Secondary             Rates of pre-        156 (5.3%) of primiparous      1/7 centres had   Prospective    IIa
(USA)                previous pre-     analysis of data      eclampsia,           and 107 (17.9%) of             a high            cohort
                     eclampsia (see    from women            severe pre-          multiparous women with         incidence of
                     Buchbinder 02)    enrolled in two       eclampsia and        previous pre-eclampsia         pre-eclampsia.
                     compared with     multicentre trials    perinatal            developed pre-eclampsia; 70
                     2934 nulliparous of aspirin for the     outcome              (2.4%) and 45 (7.5%),
                     women.            prevention of pre-                         respectively, were severe.
                                       eclampsia. Half                            The rates were significantly
                                       the women were                             higher for women with
                                       receiving aspirin                          previous pre-eclampsia
                                       (randomised).                              (p<0.0001 for both
                                       Aspirin and non-                           categories).
                                       aspirin groups
                                       were combined
                                       for analysis.                              For women in both groups
                                                                                  with severe pre-eclampsia,
                                                                                  those with recurrent pre-
                                                                                  eclampsia had higher rates



Section: factors which increase likelihood of pre-eclampsia                                                                                      page 9
                                                                                   of preterm delivery both
                                                                                   before 37 weeks (67% vs.
                                                                                   33%, p=0.0004 and before
                                                                                   35 weeks (36% v 19%,
                                                                                   p=0.041) and higher rates of
                                                                                   placental abruption (6.7% vs.
                                                                                   1.5%) and fetal death (6.7%
                                                                                   vs. 1.4%) than did
                                                                                   nulliparous women with
                                                                                   severe pre-eclampsia.
Koike 02              Women                 Preterm delivery   Development of      In second pregnancy, 10          Population    IIa
(Japan)               delivering before                        hypertension        preterm deliveries due to        cohort
                      37 weeks in first                        (≥140 or            pre-eclampsia: 5/19 women
                      (96 women) or                            ≥90mmHg) on 2       with previous preterm birth
                      second (86                               occasions           due to pre-eclampsia and
                      women)                                   recorded 24         5/1034 women with previous
                      pregnancy                                hours apart with    term delivery.
                      compared with                            proteinuria in
                      women                                    women who           This represents a risk of pre-
                      delivering at                            were                eclampsia related pre-term
                      term in their first                      normotensive        delivery that was 54.4 times
                      (1034 women) or                          before 20 weeks     (17.2-172.5) higher in
                      second (1044                             gestation.          women with a previous pre-
                      women)                                   Women who had       eclampsia related preterm
                      pregnancy.                               baseline systolic   delivery than in women with
                                                               ≥140 or diastolic   a previous term delivery.
                                                               ≥90, a rise,
                                                               respectively, of    Time of onset of pre-
                                                               30mmHg or           eclampsia in first pregnancy
                                                               15mmHg.             was 27.4 +/- 2.1 weeks in
                                                               Delivery when bp    the 5 recurrent pre-eclamptic
                                                               of ≥ 180mmHg        women and 30.4 +/- 3.5
                                                               reached,            weeks in the 14 women with
                                                               eclampsia,          pre-eclampsia only in their
                                                               HELLP,              first pregnancies.



Section: factors which increase likelihood of pre-eclampsia                                                                      page 10
                                                                increasing
                                                                oedema or fetal      Times of onset for the 5
                                                                stress.              recurrent pre-eclamptic
                                                                                     women, in first and second
                                                                                     pregnancy were: 26 and 26
                                                                                     weeks, 27 and 28 weeks, 31
                                                                                     and 32 weeks, 27 and 28
                                                                                     weeks, 26 and 30 weeks.
Mostello 02          Women                 Identify risk      Risk factors         A history of pre-eclampsia       Population       IIb
(USA)                delivered of their    factors for pre-   included previous    confers the highest risk for     based case
                     first 2 singleton     eclampsia in       preterm delivery,    pre-eclampsia in the second      control study
                     pregnancies.          second             previous SGA         pregnancy and the risk is
                     2332 cases with       pregnancies        newborn              inversely proportional to
                     pre-eclampsia in                                              gestational age at delivery of
                     the second                                                    the first pregnancy: adjusted
                     pregnancy and                                                 OR 15.0; 95%CI, 6.3-35.4 for
                     2370 control                                                  20 to 33 weeks; adjusted OR
                                                                                   10.2; 95% CI, 6.2-17.0 for 33
                                                                                   to 36 weeks; and adjusted
                                                                                   OR 7.9; 95% CI 6.3-10.0 for
                                                                                   37 to 45 weeks.
Murphy 2000          N=49,812 births       N=71 women         Incidence of         21/23 multiparous women          Case series      III
(UK)                 at a university       with onset of      preterm pre-         had a poor obstetric history
                     teaching hospital     pre-eclampsia      eclampsia (before    (inc. stillbirth, intrauterine
                     between June          at less than 30    30 weeks);           death, neonatal death, or
                     1986 – March          completed          maternal             severe pre-eclampsia).
                     1997.                 weeks              morbidity, fetal
                                           gestation. Pre-    morbidity and
                                           eclampsia          mortality (SAG <
                                           defined as bp ≥    3rd centile, Apgar
                                           140/90 mmHg        score ≤3 at 1 min
                                           on two             or <7 at 5 min);
                                           separate           oligohydramnios
                                           occasions 6        (AFI<8 or
                                           hours apart in     MPD<2cm), FGR



Section: factors which increase likelihood of pre-eclampsia                                                                         page 11
                                           second half of     (AC<2SD below
                                           pregnancy with     expected
                                           ≥ 1+ protein on    gestational age);
                                           urine dipstick.    interval between
                                                              diagnosis and
                                                              delivery
Odegard 2000         323 cases of          Delivery before    Risk factors for     Previous pre-eclampsia                          Population       IIb
(Norway)             pre-eclampsia         (early onset) or   pre-eclampsia        strongly increased the risk                     based nested
                     (115 were             after 32 weeks     (including parity,   for early onset disease (OR                     case-control
                     parous, 51 had        because of         previous pre-        42.4; 95% CI 11.9-151.6)
                     previous pre-         pre-eclampsia.     eclampsia), with     and for moderate (OR 28.3
                     eclampsia) and        Pre-eclampsia      women with pre-      (11.0-72.9) and severe (OR
                     650 women             defined as:        eclampsia            26.1 (8.5-80.3) disease,
                     without pre-          Mild: an           grouped              compared to parous women
                     eclampsia (407        increase in        according to time    with no previous pre-
                     were parous, 13       diastolic bp       of onset and         eclampsia.
                     had previous          (≥25 mmHg to       severity (mild,
                     pre-eclampsia)        ≥ 90 mmHg)         moderate,
                     from register of      and proteinuria    severe).
                     all births            (≥ 1+ on
                     between Jan 93        dipstick);
                     and Dec 95            moderate ≥
                     (n=12,804             25mmHg
                     women)                increase and
                                           2+ dipstick) or
                                           severe as
                                           diastolic ≥
                                           110mmHg,
                                           increase of
                                           25mmHg and
                                           3+ dipstick.
Sibai 86              N=406 women          Follow up for 2      Subsequent          Women who develop severe     Note women        Retrospective    IIb
(USA)                 with severe pre-     year minimum         pregnancy           pre-eclampsia in the first   were young.       case control
                      eclampsia/                                outcome in terms    pregnancy and have pre-      Mean age in
                      eclampsia in                              of perinatal        eclampsia in a subsequent    first pregnancy



Section: factors which increase likelihood of pre-eclampsia                                                                                        page 12
                      their first                                outcome,            pregnancy have an               17.7 +/- 2.5
                      pregnancies                                incidence of pre-   increased incidence of          years (pre-
                      matched with                               eclampsia (mild,    placental abruption (21/815 v   eclamptic
                      409                                        severe,             7/966; p=0.006), premature      group) and
                      normotensive                               eclampsia –         delivery (122/815 v 91/966;     17.6 +/- 2.8
                      primaparas.                                defined in Sibai    p<0.0001), perinatal            years
                                                                 84) and placental   mortality (48/815 v 29/966;     (normotensive
                                                                 abruption.          p=0.003) and fetal growth       women): range
                                                                                     restriction (58/815 v 32/966;   11-25 years.
                                                                                     p=0.0003) as compared to
                                                                                     women who remain
                                                                                     normotensive in their first
                                                                                     pregnancy.

                                                                                     The risk of having pre-
                                                                                     eclampsia in subsequent
                                                                                     pregnancy is related to time
                                                                                     of onset during first
                                                                                     pregnancy.

Sibai 91              N=125 women           17 women had         Recurrence risk     110/169 (65%) subsequent                        Case series    III
(USA)                 with severe pre-      no further                               pregnancies were
                      eclampsia that        pregnancies, 108                         complicated by pre-
                      developed in the      had 169                                  eclampsia of which 32%
                      second trimester      subsequent                               were second trimester, 32%
                      and underwent         pregnancies                              28-36 weeks and 36% 37 to
                      follow-up for an                                               40 weeks. Overall 21% of
                      average of 5.4                                                 subsequent pregnancies
                      years.                                                         were complicated by severe
                                                                                     pre-eclampsia in the second
                                                                                     trimester.
Sibai 92              N=223 women           23 were              Subsequent          Within the nulliparous group                    Case series    III
(USA)                 with eclampsia;       multiparous and      pregnancy           women who had eclampsia
                      long term follow      159 nulliparous in   outcome (pre-       before 37 weeks gestation in
                      up for 7.2 years      index pregnancy.     eclampsia,          the index pregnancy had



Section: factors which increase likelihood of pre-eclampsia                                                                                        page 13
                      on average.                             eclampsia,          significantly higher
                                                              perinatal death,    incidences of pre-eclampsia
                                                              placental           and poor perinatal outcome
                                                              abruption) and      in subsequent pregnancies
                                                              long-term           as compared with those who
                                                              prognosis by        had eclampsia at ≥ 37 weeks
                                                              time of onset in    gestation.
                                                              index pregnancy
                                                              (≤ 30 weeks, less
                                                              than 37 weeks, ≥
                                                              37 weeks).
                                                              Existence of
                                                              chronic
                                                              hypertension on
                                                              follow up.




Section: factors which increase likelihood of pre-eclampsia                                                     page 14
Section: early referral for specialist input

Relevant studies in previous section.

Section: Gestational age at onset of morbidity

Study                 Population            Intervention   Outcomes            Results                           Comments             Study Type        Evidence
                                            details                                                                                                     Level
Banias 92             67 women with         Temporising    Delivery in women   60/67 (90%) women required        The rate of poor     Retrospective     IIb
(USA)                 severe pre-           management     with severe pre-    delivery within 72 hours due      neonatal             case control
                      eclampsia in                         eclampsia defined   to rapid deterioration of         outcomes in
                      preterm                              as ≥160/110 on at   mother or fetus. Mean             severe pre-
                      pregnancy                            least 2 occasions   delivery (in weeks) for           eclampsia
                      between 26-32                        6 hours apart, >    severe pre-eclampsia group        exceeded that
                      weeks compared                       3+ dipstick or      was 29.8 +/- 1.2 weeks.           expected with
                      with 134 women                       3g/24 hours or                                        preterm delivery
                      who delivered at                     HELLP.              Birth weight significantly less   alone and
                      a similar                                                in case group (p<0.0001).         author
                      gestational age                                                                            suggested it
                      with preterm                                             RDS 38/68; 52/138 (p<0.05)        might reflect pre-
                      rupture of                                               Mortality 16/68; 13/138           existing fetal
                      membranes or                                             (p<0.05)                          compromise.
                      preterm labour                                           SGA 24/68; 16/138
                      without pre-                                             (p<0.05).
                      eclampsia.
                                                                               Delivery before 32 weeks
                                                                               because of pre-eclampsia is
                                                                               associated with more RDS
                                                                               RR 1.48; 1.10-2.00), more
                                                                               SGA babies (RR 3.04 95%CI
                                                                               1.74-5.34) and a higher
                                                                               perinatal mortality rate (RR
                                                                               2.5 95% CI 1.28,4.89) than
                                                                               babies delivered before 32
                                                                               weeks because of preterm




Section: gestational age at onset of morbidity                                                                                                page 15
                                                                                       labour.

                                                                                       Women with severe pre-
                                                                                       eclampsia were significantly
                                                                                       more likely to have had
                                                                                       previous pre-eclampsia
                                                                                       (p<0.001), previous
                                                                                       hypertension (p<0.0001),
                                                                                       previous renal disease
                                                                                       (p<0.05) and previous
                                                                                       preterm delivery (p<0.001).
Douglas 94            All episodes of       Information          Incidence of          383 confirmed cases of           Prospective       III
(UK)                  eclampsia in the      collected from       eclampsia in the      eclampsia: 81 (21%)              case series
                      UK in 1992            review of            UK; maternal          presented before 31 weeks,
                                            hospital case        complications;        169 (44%) before 37
                                            notes and            neonatal mortality;   completed weeks, and 214
                                            questionnaires       type of eclampsia     (56%) at term.
                                            to general           (ante, intra and
                                            practitioners.       post partum) and      Preterm eclampsia occurred
                                                                 gestational           more commonly antepartum.
                                            Gestation of         maturity (before
                                            disease was          31 weeks, before      On stratified analyses,
                                            taken as either      37 completed          corrected for type of seizure,
                                            that at the time     weeks, at term.)      preterm eclampsia was
                                            of the fit, or for                         independently associated
                                            post-natal           Eclampsia defined     with SGA fetuses (RR 4.18
                                            eclampsia at         as occurrence of      (2.49-7.03), the presence of
                                            the time of          convulsions           prodromal symptoms (RR
                                            delivery.            during pregnancy      1.42 (1.18-1.71), one or
                                                                 or in the first 10    more major maternal
                                                                 days postpartum       complication (1.38 (1.02-
                                                                 together with at      1.85) and delivery by
                                                                 least 2 of the        caesarean section (1.43
                                                                 following features    (1.22-1.67).
                                                                 within 24 hours




Section: gestational age at onset of morbidity                                                                                  page 16
                                                       after the             Antepartum cases were
                                                       convulsions:          independently associated
                                                       hypertension;         with more prodromal
                                                       proteinuria;          symptoms (RR 1.23 (1.04-
                                                       thrombocytopenia;     1.47) and significantly more
                                                       increased plasma      cases of multiple
                                                       aspartate             convulsions, major maternal
                                                       transaminase          complications, SGA and a
                                                       concentration.        significantly higher neonatal
                                                                             mortality
Koike 02              Women                 Preterm    Development of        Time of onset of pre-           Population        IIa
(Japan)               delivering before     delivery   hypertension          eclampsia in first pregnancy    cohort
                      37 weeks in first                (≥140 or              was 27.4 +/- 2.1 weeks in
                      (96 women) or                    ≥90mmHg) on 2         the 5 recurrent pre-eclamptic
                      second (86                       occasions             women and 30.4 +/- 3.5
                      women)                           recorded 24 hours     weeks in the 14 women with
                      pregnancy                        apart with            pre-eclampsia only in their
                      compared with                    proteinuria in        first pregnancies.
                      women                            women who were
                      delivering at                    normotensive          Times of onset for the 5
                      term in their first              before 20 weeks       recurrent pre-eclamptic
                      (1034 women) or                  gestation. Women      women, in first and second
                      second (1044                     who had baseline      pregnancy were: 26 and 26
                      women)                           systolic ≥140 or      weeks, 27 and 28 weeks, 31
                      pregnancy.                       diastolic ≥90, a      and 32 weeks, 27 and 28
                                                       rise, respectively,   weeks, 26 and 30 weeks.
                                                       of 30mmHg or
                                                       15mmHg. Delivery
                                                       when bp of ≥
                                                       180mmHg
                                                       reached,
                                                       eclampsia,
                                                       HELLP,
                                                       increasing
                                                       oedema or fetal




Section: gestational age at onset of morbidity                                                                       page 17
                                                              stress.
Long 79               11,158 primips        Parity and pre-   Pre-eclampsia         For pre-term and term         PRECOG group         Retrospective     IIa
(Australia)           and 15,051            eclampsia         defined as new        women with pre-eclampsia,     noted that this      cohort
                      multips between                         bp>140/90,            respectively:                 study predates
                      1971-1978. 380                          generalised                                         widespread use
                      women with pre-                         oedema and            Eclampsia 4/380: 14/799       of antenatal
                      eclampsia before                        proteinuria           Abruption: 27/380; 7/799      corticosteroids.
                      37 weeks, 799                           exclusive of UTI/     Low BW 85/380; 65/799
                      control women                           contaminants.         Low AGPAR 104/380;            Study criteria
                      with pre-                               Outcomes were         114/799                       allowed for 2/3
                      eclampsia after                         eclampsia,            Perinatal mortality 55/380;   criteria
                      37 weeks.                               abruption, birth      4/799                         (hypertension,
                                                              weight less than      Maternal mortality 1/380;     proteinuria,
                                                              10th centile,         1/799                         oedema) to
                                                              APGAR less than                                     define pre-
                                                              5, perinatal                                        eclampsia but
                                                              mortality, and                                      only women with
                                                              maternal death.                                     proteinuria are
                                                                                                                  included in
                                                                                                                  these evidence
                                                                                                                  tables.
Mackay 01             All pregnancy                           Pregnancy related     4024 deaths in 14 years of    Underestimate        Population        III
(USA)                 related deaths                          death. Mortality      which 790 (19.6%) due to      due to               study
                      attributable to                         ratio (MR)            pre-eclampsia or eclampsia.   incomplete
                      pre-eclampsia or                        calculated as         MR < 28 weeks: 12.5           recording and/or
                      eclampsia from                          pregnancy-related     MR 29-32 weeks: 11.2          misclassification.
                      1979 to 1992 in                         deaths at 20          MR 33-36 weeks: 3.3
                      the USA.                                weeks or more         MR > 37 weeks: 0.5
                                                              gestation per
                                                              100,000 live births
Mattar 2000           399 consecutive       Eclampsia         Relative risk of      Relative risk RR (95%CIs)                          Retrospective     IIa
(USA).                women with            defined as new    maternal and          before 32 weeks of:                                cohort
                      eclampsia             onset             neonatal              Abruption
                      between 1977-         convulsions       outcomes before       2.09 (1.19-3.69)
                      1998 in USA.          during or         or after 32 weeks     HELLP




Section: gestational age at onset of morbidity                                                                                                 page 18
                      113 women             postpartum        gestation           2.91(1.67-5.09)
                      onset at 32           pregnancy                             Acute renal failure
                      weeks or before,      unrelated to                          3.25 (1.24-8.53)
                      286 women             other cerebral
                      onset at 32           pathological                          63 (16%) of women with
                      weeks or after.       conditions in                         eclampsia had a diastolic
                                            women with                            blood pressure of ≤ 90mmHg
                                            pre-eclampsia.                        and 14% had absent or trace
                                                                                  of proteinuria.

                                                                                  Women with antepartum
                                                                                  eclampsia were more likely
                                                                                  to have diastolic pressures ≥
                                                                                  110mmHg (58% vs. 45%,
                                                                                  p=0.015) and to have
                                                                                  proteinuria ≥3+ on dipstick
                                                                                  (55% vs. 28%, p=0.000002)
                                                                                  compared with postpartum
                                                                                  eclampsia.

                                                                                  Women who develop
                                                                                  eclampsia at 32 weeks or
                                                                                  before were more likely to
                                                                                  have diastolic pressures ≥
                                                                                  110mmHg (71% vs. 48%,
                                                                                  p<0.0001), to have absent or
                                                                                  trace proteinuria (p<0.0001)
                                                                                  and were less likely to have
                                                                                  severe proteinuria (25% vs.
                                                                                  57%, p<0.0001)

Murphy 2000           N=49,812 births       N=71 women        Incidence of        Maternal complications were:    Case series       III
(UK)                  at a university       with onset of     preterm pre-        HELLP/ELLP 15 (21%)
                      teaching hospital     pre-eclampsia     eclampsia (before   Renal failure 9 (13%)
                      between June          at less than 30   30 weeks);          Eclampsia 1 (1.4%)




Section: gestational age at onset of morbidity                                                                            page 19
                      1986 – March          completed          maternal             Abruption 11(15%)
                      1997.                 weeks              morbidity, fetal
                                            gestation. Pre-    morbidity and        Uterine deaths 12 (16%)
                                            eclampsia          mortality (SAG <     Neonatal deaths 9 (12%)
                                            defined as bp ≥    3rd centile, Apgar   Neonatal survivors 52 (72%)
                                            140/90 mmHg        score ≤3 at 1 min
                                            on two             or <7 at 5 min);     Percentage survivors by
                                            separate           oligohydramnios      gestational age at diagnosis:
                                            occasions 6        (AFI<8 or            < 24 weeks: 4 (33%)
                                            hours apart in     MPD<2cm), FGR        24-26 weeks: 14 (70%)
                                            second half of     (AC<2SD below        27-30 weeks: 34 (83%)
                                            pregnancy with     expected
                                            ≥ 1+ protein on    gestational age);    Percentage survivors by
                                            urine dipstick.    interval between     gestational age at delivery:
                                                               diagnosis and        <24 weeks: 0 (0%)
                                                               delivery             24-26 weeks: 5 (31%)
                                                                                    27-30 weeks: 34 (81%)
                                                                                    ≥ 31 weeks: 13 (93%)

Odegard 2000          323 cases of          Delivery before    Risk factors, with   34/323 cases of pre-            Population       IIb
(Norway)              pre-eclampsia         (early onset) or   women with pre-      eclampsia delivered at 32       based nested
                      and 650 women         after 32 weeks     eclampsia            weeks or before, 289/323        case-control
                      without pre-          because of         grouped              delivered after 32 weeks.
                      eclampsia from        pre-eclampsia.     according to time
                      register of all       Pre-eclampsia      of onset and         65% of women with early
                      births between        defined as:        severity (mild,      onset had severe disease,
                      Jan 93 and Dec        Mild: an           moderate,            27% moderate disease and
                      95 (n=12,804          increase in        severe).             9% mild disease.
                      women)                diastolic bp
                                            (≥25 mmHg to                            22% of late onset had severe
                                            ≥ 90 mmHg)                              disease, 42% had moderate
                                            and proteinuria                         and 36% mild disease.
                                            (≥ 1+ on
                                            dipstick);
                                            moderate ≥




Section: gestational age at onset of morbidity                                                                             page 20
                                            25mmHg
                                            increase and
                                            2+ dipstick) or
                                            severe as
                                            diastolic ≥
                                            110mmHg,
                                            increase of
                                            25mmHg and
                                            3+ dipstick.
Sibai 91              N=125 women           17 women had      Recurrence risk   110/169 (65%) subsequent      Case series       III
(USA)                 with severe pre-      no further                          pregnancies were
                      eclampsia that        pregnancies,                        complicated by pre-
                      developed in the      108 had 169                         eclampsia of which 32%
                      second trimester      subsequent                          were second trimester, 32%
                      and underwent         pregnancies                         28-36 weeks and 36% 37 to
                      follow-up for an                                          40 weeks. Overall 21% of
                      average of 5.4                                            subsequent pregnancies
                      years.                                                    were complicated by severe
                                                                                pre-eclampsia in the second
                                                                                trimester.




Section: gestational age at onset of morbidity                                                                        page 21
Section: rate of progression

Study                Population        Intervention          Outcomes              Results                        Comments   Study Type        Evidence
                                       details                                                                                                 Level
Banias 92            Severe pre-       Temporising           Length of             Temporisation for more                    Case control      IIb
(USA)                eclampsia in      management.           temporisation,        than 72 hours was not
                     preterm           Delivery in women     infant outcome.       possible in 60/67 pre-
                     pregnancy         with severe pre-                            eclamptic pregnancies due
                     between 26-32     eclampsia defined                           to maternal (56 cases) or
                     weeks (some       as ≥160/110 on at                           fetal (4 cases) issues.
                     with chronic      least 2 occasions
                     hypertension      6 hours apart, >                            The rate of poor neo-natal
                     and renal         3+ dipstick or                              outcome in severe pre-
                     disease). 67      3g/24 hours or                              eclampsia exceeded that
                     women with        HELLP.                                      expected with preterm
                     severe pre-                                                   delivery alone.
                     eclampsia
                     matched for
                     gestational age
                     with non-pre-
                     eclamptic
                     women
                     delivered after
                     preterm rupture
                     of membranes
                     or preterm
                     labour.
Barton 01            N= 748 women      Women with mild       Progression to pre-   343 (46%) developed                       Case series       III
(USA)                with mild         gestational           eclampsia             proteinuria and 72 (9.6%)
                     gestational       hypertension          (proteinuria ≥ 1+     severe pre-eclampsia.
                     hypertension (≥   participating in an   on at least 2
                     140/90 mmHg)      outpatient            occasions); rate of   The likelihood of having
                     between 24-35     hypertension          progression to        pre-eclampsia increased
                     weeks gestation   monitoring            severe pre-           with earlier gestational age
                     on enrolment,     programme.            eclampsia             at presentation. There was




Section: rate of progression                                                                                                         page 22
                     between Feb                            (160/110mmHg on       a significant difference in
                     1995 – Feb                             at least 2            the rate of progression
                     1998.                                  occasions with        between those enrolled at
                                                            proteinuria or mild   34-35 weeks gestation and
                                                            hypertension with     those a) at less than 30
                                                            ≥ 3+ proteinuria or   weeks (p=0.008) and b) at
                                                            thrombocytopenia),    32-33 weeks (p=0.009).
                                                            obstetric
                                                            complications,        <30 weeks 52.1%
                                                            neonatal              progressed; 30-31 weeks
                                                            outcomes.             50.0% progressed; 32-33
                                                                                  weeks 49.3% progressed
                                                                                  and 34-35 weeks 37.3%
                                                                                  progressed.

Blackwell 02         142 women with   Expectant             Duration between      Median duration 30 hours      Most women        Case series      III
(USA)                severe pre-      management of         admission and         (range <1 hr – 29 days)       delivered
                     eclampsia        severe pre-           delivery                                            within 48 hours
                     diagnosed        eclampsia defined                           < 48 hours: 79(55.6%) of      for maternal
                     between 26 and   as bp ≥160/110                              whom 74.7% for maternal       indications
                     32 weeks         mmHg with                                   indication.
                     between 1991-    proteinuria (2+ or                          48hrs-7 days: 42 (29.6%) of
                     1998.            more) and non-                              whom 83.3% for maternal
                                      dependant                                   indications.
                                      oedema or bp of ≥                           ≥ 7 days: 21 (14.8%) of
                                      140/90 mmHg                                 whom 76.2% for maternal
                                      plus any of: visual                         indications.
                                      disturbances,
                                      persistent severe
                                      headache,
                                      epigastric pain,
                                      thrombocytopenia,
                                      elevated liver
                                      enzymes,
                                      pulmonary




Section: rate of progression                                                                                                             page 23
                                         oedema, > 5 g/24
                                         hr proteinuria or
                                         oliguria.
Chua 92              N= 42 women         Conservative          Prognosis;             Delivery was necessary           Case series      III
(UK)                 with pre-           management in a       prolongation of        within 2 weeks from onset
                     eclampsia with      high-risk unit        pregnancy              of severe proteinuria in
                     5g or more of                                                    37/42 (88.1%) cases.
                     proteinuria in 24                                                14 within 3 days
                     hours in a 4 year                                                12 between 4-7 days
                     period                                                           9 between 8-11 days
                                                                                      2 between 12-14 days.

                                                                                      Gestational age at delivery
                                                                                      was less than 36 weeks for
                                                                                      all cases.
Douglas 94           All episodes of     Information          Incidence of            383 confirmed cases of           Prospective      III
(UK)                 eclampsia in the    collected from       eclampsia in the        eclampsia: 81 (21%)              case series
                     UK in 1992          review of hospital   UK; maternal            presented before 31
                                         case notes and       complications;          weeks, 169 (44%) before
                                         questionnaires to    neonatal mortality;     37 completed weeks, and
                                         general              type of eclampsia       214 (56%) at term.
                                         practitioners.       (ante, intra and post
                                                              partum) and             325 (85%) women had
                                         Hypertension         gestational maturity    been seen by a doctor or
                                         defined as a         (before 31 weeks,       midwife in the week before
                                         booking diastolic    before 37               their first convulsion. At the
                                         blood pressure of    completed weeks,        time of the last antenatal
                                         < 90mmHg, a          at term.); prodromal    visit:
                                         maximum              signs and               36 (11%): no recorded
                                         diastolic ≥          symptoms                hypertension or proteinuria
                                         90mmHg and an                                32 (10%) had proteinuria
                                         increment of ≥       Eclampsia defined       only
                                         25mmHg.              as occurrence of        71 (22%) had hypertension
                                         Proteinuria          convulsions during      alone
                                         defined as ≥ 1+      pregnancy or in the     186 (57%) had proteinuria




Section: rate of progression                                                                                                  page 24
                                         on a random         first 10 days          and hypertension.
                                         sample or ≥         postpartum
                                         0.3g/24 hour        together with at
                                                             least 2 of the
                                                             following features
                                                             within 24 hours
                                                             after the
                                                             convulsions:
                                                             hypertension;
                                                             proteinuria;
                                                             thrombocytopenia;
                                                             increased plasma
                                                             aspartate
                                                             transaminase
                                                             concentration.
Hall 01               340 women with     Expectant             Prolongation of      Pregnancy was prolonged        Case series      III
(S Africa)            early onset (≥24   management            pregnancy,           by a comparable duration
                      weeks and < 34     (frequent             grouped by age of    for each age group (10 (2-
                      weeks              monitoring in high- woman: ≤ 19            25), 9 (1-47) and 12 (3-36))
                      gestation) pre-    care obstetric        years; 20-34 years   days, respectively for ages
                      eclampsia and      ward)                 and ≥ 35 years.      less than 20 years, 20-34
                      singleton                                                     years, more than 35 years.)
                      pregnancy
                      between 1992-
                      1997
Murphy 2000          N=49,812 births     N=71 women with     Incidence of pre-      Incidence 1 in 682 total       Case series      III
(UK)                 at a university     onset of pre-       eclampsia before       births.
                     teaching            eclampsia at less   30 weeks; interval
                     hospital            than 30             between diagnosis      Mean interval between
                     between June        completed weeks     and delivery           diagnosis and delivery 14
                     1986 – March        gestation. Pre-                            days (range 0-49 days). 15
                     1997.               eclampsia defined                          (21%) were delivered
                                         as bp ≥ 140/90                             within 24 h of diagnosis,
                                         mmHg on two                                18(25%) between 2 and 7
                                         separate                                   days, 38 (54%) between 8




Section: rate of progression                                                                                              page 25
                                         occasions 6 hours                       and 42 days.
                                         apart in second
                                         half of pregnancy
                                         with ≥ 1+ protein
                                         on urine dipstick.
Odendaal 90          N=58 women           Elective delivery   Prolongation of    20 women were not             Randomised         Ib
(S Africa)           with severe pre-     48 hours after      gestational age,   randomised as they            controlled trial
                     eclampsia            betamethasone       requirement for    required delivery within 48
                     between 28-34        (aggressive         ventilation,       hours. Of the randomised
                     weeks gestation.     management,         neonatal           group, there was a mean
                     Defined as           n=20) v. later      complications.     prolongation of 7.1 days in
                     either a)            delivery as                            the expectant management
                     bp>180/120 on        indicated by                           group (p<0.05)
                     two occasions at     maternal or fetal
                     least 30 minutes     condition
                     apart with 2+ or     (expectant
                     more on dipstick     management,
                     b) bp of             n=18).
                     150/100-
                     160/110 on two
                     occasions at
                     least 6 hours
                     apart and 2+ or
                     more on dipstick
                     c) 150/100-
                     160/110 on two
                     occasions at
                     least 6 hours
                     apart and 3+ or
                     more dipstick or
                     d) 140/90 or
                     more with
                     proteinuria and
                     clinical signs of
                     imminent




Section: rate of progression                                                                                            page 26
                     eclampsia.
Saudan 98            N= 845 pregnant    661 in a           Likelihood of          62/416 women in                Definition of     Case series      III
(Australia)          women with new     retrospective      progression from       retrospective analysis and     pre-eclampsia
                     hypertension (bp   analysis and 184   gestational            29/112 women in the            did not require
                     ≥ 140/90 mmHg      in a prospective   hypertension to        prospective study              proteinuria.
                     using phase IV)    study.             pre-eclampsia.         progressed to pre-
                     in the second                         Definition did not     eclampsia. Using
                     half of                               require proteinuria    proteinuria and/or HELLP
                     pregnancy                             but one of the         as a definition, rate of
                                                           following as well as   progression was 6%
                                                           hypertension:          (retrospective) and 18%
                                                           proteinuria ≥ 300      (prospective). Early
                                                           mg/day or              gestation at presentation
                                                           persistently ≥ 2+,     was associated with
                                                           renal impairment,      increased likelihood of
                                                           hepatic dysfunction    progression (combined
                                                           , haematological       data OR (95% CI) 0.82
                                                           abnormalities,         (0.77-0.87) with p value of
                                                           cerebral disorder      < 0.0001) with 42%
                                                           or severe              progressing in those
                                                           hypertension. Also     presenting at or before 30
                                                           used hypertension      weeks and 7% at or after
                                                           plus proteinuria       38 weeks . Duration
                                                           and/or HELLP           between presentation with
                                                           syndrome or            gestational hypertension
                                                           eclampsia for          and diagnosis of pre-
                                                           some analysis.         eclampsia was also greater
                                                                                  with earlier presentation as
                                                                                  follows (median and
                                                                                  interquartile range):
                                                                                  33 (17-50 days) at ≤ 32
                                                                                  weeks presentation
                                                                                  12 (7-22 days) at 32-35
                                                                                  weeks
                                                                                  6 (3-12 days) at ≥ 36 weeks




Section: rate of progression                                                                                                              page 27
Sibai 94             N=95 women          Severe pre-         Prolongation of   A statistically significant                   RCT               Ib
(USA)                with gestational    eclampsia defined   pregnancy         prolongation of pregnancy
                     ages at entry of    as bp of                              in women with conservative
                     28-32 weeks         160/110mmHg or                        management (mean =15.4
                     and severe pre-     more, proteinuria                     days), no increase in
                     eclampsia, 46       of 500mg/24 hr of                     maternal complications,
                     randomised to       more, serum uric                      less time in the neonatal
                     aggressive          acid greater than                     intensive care unit (20.2 v
                     management          5mg/dl. Women                         36.6 days), reduced
                     (delivery in 48     with medical                          incidence of respiratory
                     hours) and 49 to    complications,                        distress syndrome (22.4 v
                     conservative        rupture of                            50.0%), significantly higher
                     management          membranes,                            birth weight (1622 v 1233
                     (delivery for       preterm labour,                       g) but also significantly
                     specific            multifetal                            higher incidence of SGA
                     maternal or fetal   gestation, fetal                      (30 v 11%).
                     indications)        compromise or
                                         platelet count
                                         below 100,000/
                                         microl were
                                         excluded.
Visser 95 (a)        254 consecutive     Temporising         Prolongation of   Median prolongation of                        Case series       III
(Holland)            women with          management with     pregnancy         pregnancy was 14 (range
                     severe pre-         haemodynamic                          0-62 days).
                     eclampsia           treatment.
                     between 20 and                                            Perinatal mortality was
                     32 weeks                                                  20.5%
                     gestation
                     between 1985-
                     93.
Visser 95 (b)        Women with          128 women with      Prolongation of   Median prolongation was        Complete       Case control      IIb
(Holland)            severe pre-         HELLP matched       pregnancy         similar between groups: 10     reversal of
                     eclampsia,          with 128 women                        days (range 0-62) in           HELLP in 43%
                     gestational age     without HELLP                         women with HELLP and 14        women
                     less than 34        and matched for                       days (0-60) in women




Section: rate of progression                                                                                                         page 28
                     weeks              maternal and                              without HELLP.
                                        gestational age.                          Termination within 48 hours
                                                                                  occurred in 22 and 17
                                                                                  women, respectively.
                                                                                   Perinatal mortality was
                                                                                  14.1% in study group,
                                                                                  14.8% in control group.
Withagen 01          222 live born      Temporising        Mortality, morbidity   Median prolongation in        Retrospective     IIb
(Holland)            infants from       treatment.                                study group from 29.3-31.3    case control
                     women with                                                   weeks.
                     early onset pre-
                     eclampsia (24-
                     31 weeks).
                     Defined as bp
                     ≥110mmHh
                     diastolic with
                     proteinuria ≥
                     0.3g/l/24 hr, or
                     persistent
                     diastolic ≥
                     90mmHg with
                     proteinuria plus
                     either eclampsia
                     or HELLP.
                     Control (non
                     pre-eclamptic
                     women)
                     matched for a)
                     gestational age
                     on admission
                     and b)
                     gestational age
                     at birth, with
                     spontaneous
                     idiopathic




Section: rate of progression                                                                                            page 29
                     preterm labour.




Section: rate of progression           page 30
Section: benefit of intervention (delivery)

Study                  Population         Intervention     Outcomes       Results                           Comments   Study Type        Evidence
                                          details                                                                                        Level
Jenkins 2002           39 women with      Retrospective    Maternal and   None of the women required                   Case series       III
(US)                   severe             analysis of      perinatal      dialysis or intensive care unit
                       preeclampsia       database of      outcomes       admission. None of the
                       delivered before   3800 women                      women died. All maternal
                       25 weeks of        with pre-                       morbidities reversed after
                       gestation          eclampsia                       delivery.
                                          delivered
                                          between 1991                    22 (55%) of babies were live-
                                          to 1997. 33/39                  born of whom 4 (10%)
                                          women had                       survived, al with severe
                                          severe-range                    handicaps.
                                          hypertension.
                                          21 (54%) had
                                          morbidities
                                          including
                                          placental
                                          abruption
                                          (n=5), HELLP
                                          (n=9), renal
                                          insufficiency
                                          (n=5),
                                          eclampsia
                                          (n=3).




Section: benefit of intervention                                                                                               page 31
Section: impact of antenatal care on poor outcome related to pre-eclampsia

Study               Population            Intervention      Outcomes                Results                        Comments            Study Type         Evidence
                                          details                                                                                                         Level
Abi-Said 95         66 women with         Eclampsia         Risk factors            Risk factors for eclampsia                         Case control       IIb
(USA)               eclampsia and         defined by                                included: two or fewer
                    264 matched           ACOG 1972                                 prenatal care visits (OR =
                    controls without                                                6.10, 95%CI 2.26-16.41).
                    pre-eclampsia in                                                This was the strongest risk
                    two hospitals                                                   factor for eclampsia.
                    between 1977
                    and 1992
Ansari 95           All singleton         395 cases and     Risk factors included   Marked increase in risk for                        Cohort             IIa
(USA)               births from birth     1962 controls.    no prenatal care,       developing eclampsia
                    certificates                            high weight gain,       comparing women with no
                    between 1984-                           nulliparous women,      ante-natal care with women
                    1990, where                             chronic                 who started their care in
                    eclampsia is                            hypertension,           the first trimester (OR=5.2;
                    listed under                            tobacco smoking,        95%CI 1.7-15.5)
                    maternal                                race, history of pre-
                    conditions.                             term births, anemia.
Carroli 01          7 RCTs. 5/7           4 trials in       To demonstrate          No differences for pre-        Precog group        Systematic         Ia
(review)            trials were           developed         equivalence in terms    eclampsia, UTI, postpartum     note that neither   review and
                    conducted in          countries (1 in   of efficacy of          anaemia, maternal              the meta-           meta-analyses
                    women defined         the UK – see      intervention.           mortality, low birth weight.   analysis nor        of RCTs
                    as low risk           Sikorski); 2 in   Outcomes included                                      individual trials
                    (various              Zimbabwe; one     pre-eclampsia, UTI,     OR pooled for pre-             are powered to
                    definitions). 2/7     a multicentre     postpartum              eclampsia 0.91 (95% CI         demonstrate
                    trials included all   trial in          anaemia, maternal       0.66-1.26) did not show        equivalence in
                    women                 Argentina,        mortality, low birth    statistical equivalence        maternal
                    attending             Cuba, Thailand    weight and perinatal    within the upper margin        mortality.
                    antenatal care        and Saudi         mortality.              established for birth weight   Confirmed by
                    clinics.              Arabia (see                               (a 20% increase).              NICE group in
                                          Villar 01).       Poor outcome                                           correspondence.
                                                            measures                Formal statistical




Section: new hypertension                                                                                                                       page 32
                                                         associated with pre-   equivalence for perinatal     Author of SR
                                                         eclampsia in           mortality was not obtained    note that in
                                                         individual trials      because of rarity of          developed
                                                         included low birth     outcome.                      countries the
                                                         weight, SGA,                                         difference
                                                         induction of labour,   Actual visits achieved in     between
                                                         preterm delivery and   standard and new model        interventions
                                                         antepartum/            was (median number):          was very small,
                                                         postpartum                 • 8 and 5 (with           therefore
                                                         haemorrhage.                   women requiring       outcome results
                                                                                        more care referred    are expected to
                                                                                        to a higher level –   be similar.
                                                                                        see Villar 01)
                                                                                    • 6 and 4                 Villar J et al
                                                                                    • 11 and 8                (same authors)
                                                                                    • 15 and 12               note in
                                                                                    • 11 and 9                Cochrane
                                                                                    • 11 and 8                review of same
                                                                                    • 4 and 4                 7 trials that no
                                                                                                              intervention
                                                                                                              occurred in the 4
                                                                                                              trials in
                                                                                                              developed
                                                                                                              countries due to
                                                                                                              similarity of
                                                                                                              number of visits.
Conde Agudelo       125 cases of        N=24 women       Risk factors           Risk factors associated                           Retrospective     IIb
 97                 eclampsia           with eclampsia   associated with        with the development of                           case control
(Colombia)          managed in a        complicated by   complicated            complicated eclampsia: no
                    tertiary referral   intracerebral    eclampsia.             prenatal care (adjusted OR
                    centre between      haemorrhage,                            3.3, 95% CI 1.25, 9.60) in
                    1993 and 1995.      pulmonary                               15 (63%) of cases and 29
                                        oedema, renal,                          (29%) of controls.
                                        hepatic or
                                        respiratory




Section: new hypertension                                                                                                                 page 33
                                     failure, DIC,
                                     placental
                                     abruption,
                                     pulmonary
                                     aspiration or
                                     HELLP
                                     compared with
                                     101
                                     uncomplicated
                                     eclamptic
                                     controls.
Henderson 2000                       Two schedules     Economic evaluation   Savings that arose            Economic arm         RCT              Ib
UK)                                  of antenatal                            antenatally in the reduced    of Sikorski 96
                                     care in the UK                          schedule (£225 v £251)        (one of the trials
                                                                             were offset by increased      included in
                                                                             costs (£181 vs. £126)         Carroli
                                                                             because a greater number      systematic
                                                                             of babies in this group       review)
                                                                             required special or
                                                                             intensive care and for a
                                                                             longer duration.
                                                                             Sensitivity analyses based
                                                                             on possible variations in
                                                                             unit costs and resource use
                                                                             and modelled postnatal
                                                                             stay showed considerable
                                                                             variation and substantial
                                                                             overlap in costs.
Porapakkham         N=298 cases of   Race,             Eclampsia             90% of eclamptic women                             Case series      III
79                  eclampsia in     residence,                              did not receive antenatal
(Thailand).         one hospital     occupation,                             care v 15% (n=137,995) of
                    between 1967     nutritional                             population of women who
                    and 1974         status, age and                         delivered in the hospital
                                     parity, type of                         during the same period.
                                     antenatal care,




Section: new hypertension                                                                                                              page 34
                                    seasonal
                                    occurrence,
                                    onset in
                                    relation to
                                    delivery,
                                    clinical
                                    findings,
                                    gestational age
                                    at onset,
                                    pregnancy
                                    outcome were
                                    considered.
Sikorski 96         N=2794 women    Two schedules      Rate of Caesarean         Actual mean number of          Authors         RCT             Ib
(UK)                between June    of antenatal       section for pre-          visits achieved were 10.8 in   recognise
                    1993 and July   care in the UK:    eclampsia (as a           the traditional care arm and   inadequacy of
                    1994.           protocol           surrogate marker for      8.6 visits in the reduced      surrogate
                                    required either    late detection or         visit arm.                     marker.
                                    traditional care   failure to detect, pre-
                                    of 13 visits or    eclampsia and             Sample size was too small      See Henderson
                                    reduced            therefore morbidity       to identify rare but serious   et al for
                                    schedule of 7      associated with           events such as perinatal       economic
                                    visits for         pregnancy related         loss, eclampsia and            evaluation.
                                    nulliparous and    hypertensive              maternal mortality.
                                    6 visits for       disorders). Other
                                    multiparous        measures of fetal         Sample size was
                                    women.             and maternal              marginally too small
                                                       morbidity, health         (79.6%) to test primary
                                                       service use,              hypothesis that Caesarean
                                                       psychosocial              section would be increased
                                                       outcomes, maternal        with reduced antenatal care
                                                       and professional          (unidirectional).
                                                       satisfaction.
                                                                                 Women having reduced
                                                                                 care had fewer day
                                                                                 admissions (0.8 v 1.0:




Section: new hypertension                                                                                                             page 35
                                                                                p=0.002) and ultrasound
                                                                                scans (1.6 v 1.7:p=0.003)
                                                                                and less often suspected of
                                                                                carrying SGA fetuses (OR
                                                                                0.73; 95% CI 0.54 to 0.99).
                                                                                They were more worried
                                                                                about fetal well-being
                                                                                antenatally and coping with
                                                                                the baby postnatally, had
                                                                                more negative attitudes to
                                                                                their babies and were more
                                                                                dissatisfied with the
                                                                                number of visits they
                                                                                received (OR 2.50; 2.00 to
                                                                                3.11)
Villar 01(a)        7 RCTs (same        Provision of    Perinatal outcomes.     Authors note that no            Cochrane        Systematic       Ia
(review)            trials as Carroli   reduced         Relevant morbid         intervention occurred in the    review          review of RCTs
                    01 systematic       number of       outcomes (HELLP,        4 trials in developed           (published as
                    review)             visits          eclampsia) not          countries due to the            Carroli 01)
                                        compared with   measured and            similarity in number of
                                        standard        severe pre-             visits.
                                        schedule of     eclampsia only
                                        visits.         measured as an          N not powered for maternal
                                                        outcome in one trial.   mortality, perinatal
                                                                                mortality.

                                                                                No significant differences in
                                                                                preterm delivery (<37
                                                                                weeks), pre-eclampsia,
                                                                                caesarean section,
                                                                                induction of labour,
                                                                                antenatal haemorrhage,
                                                                                postnatal haemorrhage,
                                                                                low birth weight, SGA,
                                                                                postpartum anaemia,




Section: new hypertension                                                                                                              page 36
                                                                              admission to neonatal
                                                                              intensive care unit,
                                                                              perinatal mortality,
                                                                              maternal mortality and UTI
                                                                              were found.

                                                                              Equivalence for pre-
                                                                              eclampsia did not have
                                                                              adequate sample size
                                                                              (63%). Statistical
                                                                              equivalence for pre-
                                                                              eclampsia was not shown
                                                                              within the upper margin of
                                                                              20% increase (26%
                                                                              increase shown).

                                                                              Women from developed
                                                                              countries in reduced arm
                                                                              were less satisfied with
                                                                              frequency of visits (OR
                                                                              0.61, 95%CI 0.52, 0.72)
Villar 01(b)        53 clinics         New model        Low birthweight       Median number of visits      Women in new         RCT             Ib
(Argentina,         randomly           care consisted   (<2500g), pre-        were five (new model) and    model group
Saudi Arabia,       assigned to        of 4 visits      eclampsia/eclampsia   eight (standard model). In   had a urine test
Cuba, Thailand)     traditional care   (booking, 26,                          the new model those who      for protein at all
                    (n=11, 958         32, 38 weeks).                         were eligible for basic      antenatal visits.
                    women) or new      Women                                  component care had a         Women in
                    model care         deemed at                              median of 4 visits, women    standard group
                    (n=12, 568         higher risk                            requiring further            had a urine test
                    women)             remained in                            assessment or care a         for protein at the
                                       new-model                              median of 6 visits.          first visit and if
                                       group for                                                           the woman had
                                       analysis but                           Pre-eclampsia/ eclampsia     hypertension.
                                       were given                             rate 1.69% (new model) vs.
                                       usual care for                         1.38% (standard model).




Section: new hypertension                                                                                                             page 37
                                    their condition.                         OR 1.26 (1.02-1.56) (see
                                    Factors                                  comment).
                                    considered
                                    higher risk                              Similar rates of low
                                    included                                 birthweight (new model
                                    previous poor                            7.68% vs standard model
                                    fetal outcome,                           7.14%)
                                    3 or more
                                    consecutive                              More women in the new
                                    miscarriages,                            model group were referred
                                    previous                                 to higher levels of care
                                    hospital                                 (13.4% vs 7.3%).
                                    admission of
                                    hypertension,                            Higher (non-significant)
                                    pre-eclampsia                            rate of fetal death at 36
                                    or eclampsia,                            weeks of gestation or
                                    multiple                                 earlier in the new model
                                    pregnancy,                               (1.0% vs 0.7%)(p=0.08).
                                    age over 40,                             More SGA fetuses among
                                    diastolic ≥                              those who died at or before
                                    90mmHg at                                36 weeks (40.2% vs
                                    booking,                                 28.6%).
                                    diabetes, renal
                                    or cardiac
                                    condition.
Witlin 99           445                                Risk factors for      Greatest morbidity            Case series      III
(USA)               consecutively                      placental abruption   associated with eclampsia
                    managed                            and eclampsia         occurred in women with
                    women with                                               preterm gestations not
                    severe pre-                                              receiving medical attention
                    eclampsia and                                            (figures not shown).
                    eclampsia




Section: new hypertension                                                                                         page 38
Section: new hypertension

Study                Population         Intervention          Outcomes              Results                          Comments   Study Type       Evidence
                                        details                                                                                                  Level
Barton 01            N= 748 women       Women with mild       Progression to pre-   343 (46%) developed                         Case series      III
(USA)                with mild          gestational           eclampsia             proteinuria and 72 (9.6%)
                     gestational        hypertension          (proteinuria ≥ 1+     severe pre-eclampsia.
                     hypertension (≥    participating in an   on at least 2
                     140/90 mmHg)       outpatient            occasions); rate of   The likelihood of having
                     between 24-35      hypertension          progression to        pre-eclampsia increased
                     weeks gestation    monitoring            severe pre-           with earlier gestational age
                     on enrolment,      programme.            eclampsia             at presentation. There was
                     between Feb                              (160/110mmHg on       a significant difference in
                     1995 – Feb                               at least 2            the rate of progression
                     1998.                                    occasions with        between those enrolled at
                                                              proteinuria or mild   34-35 weeks gestation and
                                                              hypertension with     those a) at less than 30
                                                              ≥ 3+ proteinuria or   weeks (p=0.008) and b) at
                                                              thrombocytopenia),    32-33 weeks (p=0.009).
                                                              obstetric
                                                              complications,        <30 weeks 52.1%
                                                              neonatal              progressed; 30-31 weeks
                                                              outcomes.             50.0% progressed; 32-33
                                                                                    weeks 49.3% progressed
                                                                                    and 34-35 weeks 37.3%
                                                                                    progressed.

Douglas 94           All episodes of    Information           Incidence of          325 (85%) women had                         Prospective      III
(UK)                 eclampsia in the   collected from        eclampsia in the      been seen by a doctor or                    case series
                     UK in 1992         review of hospital    UK; maternal          midwife in the week before
                                        case notes and        complications;        their first convulsion. At the
                                        questionnaires to     neonatal mortality;   time of the last antenatal
                                        general               type of eclampsia     visit:
                                        practitioners.        (ante, intra and      36 (11%) had no recorded
                                                              post partum) and      hypertension or proteinuria,



Section: hypertension and proteinuria                                                                                                  page 39
                                        Hypertension        gestational             71 (22%) had hypertension
                                        defined as a        maturity (before 31     alone and 186 (57%) had
                                        booking diastolic   weeks, before 37        proteinuria and
                                        blood pressure of   completed weeks,        hypertension.
                                        < 90mmHg, a         at term.);
                                        maximum diastolic   prodromal signs         Of the 294 (77%) women in
                                        ≥ 90mmHg and an     and symptoms            hospital at time of onset of
                                        increment of ≥                              seizures, in 100 (34%) the
                                        25mmHg.             Eclampsia defined       highest recorded blood
                                        Proteinuria         as occurrence of        pressure before onset of
                                        defined as ≥ 1+     convulsions during      seizures was 100mmHg or
                                        on a random         pregnancy or in the     less. Within 1 hour of onset
                                        sample or ≥         first 10 days           the mean (SD) diastolic bp
                                        0.3g/24 hour        postpartum              was 97 (14.6) mmHg.
                                                            together with at
                                                            least 2 of the
                                                            following features
                                                            within 24 hours
                                                            after the
                                                            convulsions:
                                                            hypertension;
                                                            proteinuria;
                                                            thrombocytopenia;
                                                            increased plasma
                                                            aspartate
                                                            transaminase
                                                            concentration.
Ferrazani 90         n-=444             98 women with       Birth weight (BW),                                     Case series      III
                                                                                    %SGA
(Italy)              hypertensive       chronic             birth percentile
                                                                                    GH (n=199)      18%**
                     women with         hypertension (CH)   (BP) gestational        Control(n=9774) 10%
                     singleton          – documented        age (GA), SGA (<
                     pregnancies        before 20 weeks     10th percentile by      **p<0.0001 v. control
                     between 1984-      or before           national standard
                     88.                pregnancy; 199      criteria), serum uric
                                        with non-           acid (mg/dl) – last




Section: hypertension and proteinuria                                                                                     page 40
                     Hypertension          proteinuric           value before
                     defined as            hypertension (GH)     delivery. Higher
                     bp≥90mmHg in 2        after 20 weeks        value of proteinuria
                     consecutive           and 147 with          (g/l in a random
                     measurements 6        hypertension and      sample) before
                     hours apart (4th      proteinuria –         delivery, preterm
                     K). Proteinuria >     n=126 with            delivery (PD),
                     0.3gm/l or >1+        hypertension after    perinatal death
                     dipstick in a         20 weeks and          (PND), stillbirth
                     random sample         n=21 with chronic     (SB), neonatal
                     with no urinary       hypertension          death (NND)
                     infection.            superimposed
                                           with significant
                                           proteinuria and an
                                           exacerbation of
                                           hypertension
                                           (Pre). The two
                                           groups were
                                           combined as they
                                           showed the same
                                           rate of SGA
                                           (52%).
Hauth 2000           N=4589 healthy        Outcome of            Comparative            Fetal growth restriction:    Observational    III
(USA)                singleton             women who             endpoints were         135/3229 (4.2%)in the no     study
                     nulliparas (bp        developed             clinically             hypertension group; 49/715
                     below                 pregnancy             diagnosed              (6.9%) in the mild
                     135/85mmHg            induced               placental              hypertension group; 3/32
                     and no                hypertension          abruption, acute       (9.7%) in the severe
                     proteinuria by        (PIH) (≥ 90mmHg       renal dysfunction,     hypertension group.
                     dipstick at           on 2 occasions 4-     caesarean
                     randomisation)        168 hrs apart):       delivery, preterm      Women with mild
                     enrolled in a         severe PIH            birth. Perinatal       hypertension had a
                     randomised,           (diastolic bp of at   outcomes were          significantly higher birth
                     placebo-              least 110mmHg         admission to           weight (mean 3303g,
                     controlled trial of   on two occasions,     NICU, RDS,             p<0.001) compared with




Section: hypertension and proteinuria                                                                                       page 41
                     calcium            or one if receiving    ventilator support,    the no hypertension group
                     supplementation.   antihypertensives)     intraventricular       (mean 3205g) and a
                     N=4302 women       or if complicated      haemorrhage, birth     correspondingly
                     observed to or     by oliguria,           weight under           significantly longer
                     beyond 20          pulmonary              2500g, fetal growth    gestation (mean no of days
                     weeks gestation.   oedema, or             restriction (FGR)      278 v 275, p<0.001) and a
                                        thrombocytopenia.      below tenth            smaller number of women
                                        or pre-eclampsia (     percentile             with gestation under 34
                                        PIH plus               according to           weeks (7(1.0%) v 102
                                        proteinuria            Brenner et al, fetal   (3.2%)). They also had a
                                        (300mg/ 24 hour        or neonatal death.     higher percentage of
                                        collection or single                          babies who were admitted
                                        2+ protein by                                 to NICU (18.2% v 12.9%,
                                        dipstick or single                            p<0.001)
                                        protein/ creatinine
                                        ratio of 0.35, or
                                        two 1+ protein by
                                        dipstick 4-168 hrs
                                        apart) within 7
                                        days of each
                                        other).
Mattar 2000          399 consecutive    Eclampsia defined      Relative risk of       63 (16%) of women with        Retrospective     IIa
(USA).               women with         as new onset           maternal and           eclampsia had a diastolic     cohort
                     eclampsia          convulsions            neonatal outcomes      blood pressure of ≤
                     between 1977-      during or              before or after 32     90mmHg and 14% had
                     1998 in USA.       postpartum             weeks gestation        absent or trace of
                     113 women          pregnancy                                     proteinuria.
                     onset at 32        unrelated to other
                     weeks or before,   cerebral                                      Women with antepartum
                     286 women          pathological                                  eclampsia were more likely
                     onset at 32        conditions in                                 to have diastolic pressures
                     weeks or after.    women with pre-                               ≥ 110mmHg (58% vs. 45%,
                                        eclampsia.                                    p=0.015) and to have
                                                                                      proteinuria ≥3+ on dipstick
                                                                                      (55% vs. 28%,




Section: hypertension and proteinuria                                                                                       page 42
                                                                                     p=0.000002) compared
                                                                                     with postpartum eclampsia.

                                                                                     Women who develop
                                                                                     eclampsia at 32 weeks or
                                                                                     before were more likely to
                                                                                     have diastolic pressures ≥
                                                                                     110mmHg (71% vs. 48%,
                                                                                     p<0.0001), to have absent
                                                                                     or trace proteinuria
                                                                                     (p<0.0001) and were less
                                                                                     likely to have severe
                                                                                     proteinuria (25% vs. 57%,
                                                                                     p<0.0001)

Long (80)            N=2434             Pre-eclampsia         Fetal growth           Overall the prevalence of      Case series      III
(Australia)          consecutive        defined as two of     restriction,           fetal growth restriction was
                     singleton women    the following signs   subnormal oestriol     8.7% (compared with a
                     with pre-          after 20 weeks:       excretion,             total hospital population of
                     eclampsia          hypertension          abnormal glucose       8.6%).
                                        140/90mmHg or         tolerance, perinatal
                                        more, generalised     mortality              In women with proteinuria
                                        oedema,                                      and hypertension after 37
                                        proteinuria. Early                           weeks fetal growth
                                        onset defined as                             restriction occurred in
                                        before the                                   51/581 (8.8%) of
                                        beginning of the                             primagravid women and
                                        37th week of                                 14/218 (6.4%) of
                                        gestation. Small                             multigravid women.
                                        for dates defined
                                        as a birthweight                             In women with late-onset
                                        below the 10th                               pre-eclampsia, without
                                        centile according                            proteinuria (i.e.
                                        to gestational age.                          hypertension and oedema),
                                        Urinary oestriol                             39/1042 (3.7%) had fetal




Section: hypertension and proteinuria                                                                                      page 43
                                        excretion defined                           growth restriction and there
                                        as low when                                 were no perinatal deaths.
                                        below the line                              The rate of fetal growth
                                        joining 27.8                                restriction for all women
                                        micromol/24 hr at                           with late onset pre-
                                        30 weeks and                                eclampsia was 5.6%.
                                        41.6 micromole/24
                                        hours at 40
                                        weeks.
McCowan 2001         N= 224             Serial uterine and    Pre-eclampsia,        N= 174 remained                                Case series       III
(New Zealand)        normotensive       umbilical Doppler     gestational           normotensive, 50 (22%)
                     women with         studies were          hypertension          developed hypertension of
                     small for          performed from                              which 8 (3%) had pre-
                     gestational age    detection of SGA                            eclampsia and 42 (19%)
                     pregnancies        until delivery.                             gestational hypertension at
                                                                                    a median (interquartile
                                                                                    range) of 19 (12-32 days)
                                                                                    after recognition of SGA.

Naeye 79             N=41,241           N=1339 cases of       Perinatal mortality   Perinatal mortality rate:                      Population        IIa
(USA)                singleton          hypertension-         rate: perinatal       17.2 per 1000 birth for                        based
                     pregnancies        proteinuria with      death by placental    normotensive gestations                        retrospective
                     between 1959       max diastolic ≥       infarcts > 3cm in     without proteinuria v                          cohort
                     and 1966 in 12     85mmHg and            diameter, placental   hypertension alone 26.6
                     urban hospitals    proteinuria 1+ or     abruption, growth-    per 1000 births (p<0.01)
                     across the US.     more. N=1865          retarded placenta,
                                        cases of              acute infection of
                                        hypertension          amniotic fluid, all
                                        without proteinuria   other disorders
                                        when max              including
                                        diastolic ≥           “diagnosis
                                        95mmHg and            unknown”.
                                        proteinuria absent
                                        or trace.
North 99             N=1496 healthy     Gestational           Severe maternal       In gestational hypertension    Six (3.2%) of   Prospective,      IIb




Section: hypertension and proteinuria                                                                                                      page 44
(Australia)          nulliparous        hypertension          disease (defined      the presence of proteinuria   the             nested, case-
                     women. Women       defined as systolic   as any of the         1+ was associated with a      hypertensive    control study
                     with gestational   bp ≥ 140mmHg          following: systolic   3.8 fold increase in severe   women only
                     hypertension       with a rise of ≥      bp ≥ 160mmHg,         maternal disease (41.7%       had systolic
                     (GH)(n=117,        30mmHg and/or         diastolic bp ≥        vs. 15.9%: OR 3.8; 95% CI     hypertension.
                     7.8%) or pre-      diastolic bp ≥        110mmHg,              1.5-9.8).
                     eclampsia (PRE)    90mmHg with a         platelets <
                     (n=71, 4.8%)       rise of ≥ 15mmHg.     100x109/L, renal      The 56 (27%) women with
                     were compared      Pre-eclampsia         insufficiency         a rise in blood pressure ≥
                     with a control     defined as            (serum creatinine     30/15mmHg which did not
                     group of 223       gestational           > 0.10mmol.L),        exceed 140/90mmHg had
                     randomly           hypertension with     liver involvement     uncomplicated
                     selected           ≥2+ on dipstick or    (hepatic pain or      pregnancies.
                     normotensive       0.3g/24 hour.         AST>40IU/L),
                     women.                                   imminent              Severe maternal disease
                                                              eclampsia),           occurred in 26.5% of GH
                                                              preterm birth, SGA    (21.4% severe
                                                              infant                hypertension, 5.1%
                                                                                    multisystem disease) and
                                                                                    63.4% of PRE (21.1%
                                                                                    severe hypertension and
                                                                                    42.3% multisystem
                                                                                    disease): OR 4.8 (2.4-9.5)
                                                                                    PRE v GH.

                                                                                    Within the GH group
                                                                                    severe maternal disease
                                                                                    occurred in 11/69 (15.9%)
                                                                                    of women with no or a trace
                                                                                    of proteinuria (1.5%
                                                                                    multisystem disease and
                                                                                    14.5% severe
                                                                                    hypertension) and 20/48
                                                                                    (41.7%) women with 1+
                                                                                    proteinuria (10.4%
                                                                                    multisystem disease and



Section: hypertension and proteinuria                                                                                                     page 45
                                                                                    33.3% severe
                                                                                    hypertension): OR 3.8 (1.5-
                                                                                    9.8), p=0.002.

                                                                                    SGA infants were more
                                                                                    likely in the GH group (OR
                                                                                    2.0; 1.0-3.7) and PRE
                                                                                    group (OR 2.6 (1.2-5.3))
                                                                                    compared with the
                                                                                    normotensive group.

                                                                                    Preterm birth was more
                                                                                    likely in the GH group (OR
                                                                                    1.7 (0.5-5.4) and PRE
                                                                                    group (OR 14.6 (5.8-37.8)
                                                                                    compared with the
                                                                                    normotensive group.

Page 76              N=12,954 gravid     Eight categories     Pregnancy             n        SB         PND       MAP               Case series      III
(US)                 women between       combining levels     outcome (stillbirth   NT 94/10629      174/10629    calculated as
                     1959 and 1967       of mean arterial     (SB) perinatal        GH    3/307          4/307    2D/3+ S/3
                     with single live    pressure (MAP)       death (PND),          Pre    2/49          2/49     such that
                                                                                    CH+Pre 5/33            5/33
                     births or           and proteinuria.     FGR, neonatal         Prot    9/246         9/46
                                                                                                                  140/90mmHg
                     stillbirths after   MAP-2 is mean        morbidity)                                          translates to a
                     180 days and        MAP in 5th and 6th                         Rate per 1000                 MAP of 107.
                     requiring blood     month. MAP-3 is                            NT      8.8        16.4
                     pressure and        mean of two                                GH       9.8       13.0       Clinical
                     proteinuria         highest MAP prior                          Pre      40.8       40.8      diagnosis of
                     assessments in      to delivery.                               CH+Pre 151.5        151.5     pre-eclampsia
                     both middle and     Proteinuria (Prot)                         Prot      36.6       52.8     was made in
                     third trimesters    defined as 2+ or                                                         all 8
                                         more. Pre-                                 Stillbirth rate compared to   categories.
                                         eclampsia group                            normotensive group:
                                         (Pre) defined as                           gestational hypertension      Note a
                                         proteinuria 2+ or                          (p=0.45), chronic             diagnosis of
                                                                                    hypertension (p<0.001), all



Section: hypertension and proteinuria                                                                                                      page 46
                                        more, MAP-2 <                     with significant proteinuria    pre-eclampsia
                                        90, MAP-3 ≥ 105                   (p<0.001).                      required a
                                        (n=49). Chronic                                                   MAP-2 (mean
                                        hypertension plus                 Perinatal death rate            MAP in 5th and
                                        pre-eclampsia                     compared to normotensive        6th month) of <
                                        (CH+Pre) defined                  group: gestational              90
                                        as proteinuria 2+                 hypertension (p=0.70),
                                        or more, MAP-2 ≥                  chronic hypertension
                                        90, MAP-3 ≥ 105                   (p<0.001), all combined
                                        (n=33).                           groups with significant
                                        Gestational                       proteinuria (p<0.001)
                                        hypertension (GH)
                                        defined as                        Live-born infants SGA
                                        proteinuria <2+,                  (<2500g, ≥ 37 weeks –
                                        MAP-2< 90, MAP-                   figures not given)
                                        3 ≥ 105 (n=307).                  compared to normotensive:
                                        Normotensive                      gestational hypertension
                                        (NT) defined as                   (p=0.13), chronic
                                        proteinuria <2+,                  hypertension (p<0.001), all
                                        MAP-2<90, MAP-                    with significant proteinuria
                                        3<105 (n=10,629).                 (p<0.001)
                                        Other groups not
                                        defined here.
Porapakkham          N=298 cases of     Race, residence,      Eclampsia   122 (41%) women had                               Case series      III
79                   eclampsia in one   occupation,                       no/trace proteinuria, 140
(Thailand).          hospital between   nutritional status,               (47%) had 1+ or 2+ and 36
                     1967 and 1974      age and parity,                   (12%) had 3+ or 4+.
                                        type of antenatal
                                        care, seasonal                    Significant proteinuria (≥1+)
                                        occurrence, onset                 (n=176) was associated
                                        in relation to                    with antepartum eclampsia
                                        delivery, clinical                in 84 patients (47.7%),
                                        findings,                         intrapartum eclampsia in 65
                                        gestational age at                patients (36.9%) and
                                        onset, pregnancy                  postpartum eclampsia in 27




Section: hypertension and proteinuria                                                                                              page 47
                                        outcome were                              patients (15.4%).
                                        considered.
                                                                                  There was no consistent
                                                                                  relationship between
                                                                                  amount of proteinuria and
                                                                                  blood pressure.

Saudan 98            N= 845 pregnant    661 in a           Likelihood of          62/416 women in               Definition of     Case series       III
(Australia)          women with new     retrospective      progression from       retrospective analysis and    pre-eclampsia
                     hypertension (bp   analysis and 184   gestational            29/112 women in the           did not require
                     ≥ 140/90 mmHg      in a prospective   hypertension to        prospective study             proteinuria.
                     using phase IV)    study.             pre-eclampsia.         progressed to pre-
                     in the second                         Definition did not     eclampsia. Using
                     half of                               require proteinuria    proteinuria and/or HELLP
                     pregnancy                             but one of the         as a definition, rate of
                                                           following as well as   progression was 6%
                                                           hypertension:          (retrospective) and 18%
                                                           proteinuria ≥ 300      (prospective). Early
                                                           mg/day or              gestation at presentation
                                                           persistently ≥ 2+,     was associated with
                                                           renal impairment,      increased likelihood of
                                                           hepatic dysfunction    progression (combined
                                                           , haematological       data OR (95% CI) 0.82
                                                           abnormalities,         (0.77-0.87) with p value of
                                                           cerebral disorder      < 0.0001) with 42%
                                                           or severe              progressing in those
                                                           hypertension. Also     presenting at or before 30
                                                           used hypertension      weeks and 7% at or after
                                                           plus proteinuria       38 weeks .
                                                           and/or HELLP
                                                           syndrome or
                                                           eclampsia for
                                                           some analysis.
Stamilio 2000        49 women with      Clinical and       Severe pre-            High MAP > 90mmHg at          High MAP at       Retrospective     IIa
(USA)                severe pre-        biochemical        eclampsia as           24-28 weeks gestation was     24-28 weeks       cohort




Section: hypertension and proteinuria                                                                                                     page 48
                     eclampsia and       markers to predict    defined by ACOG:       predictive for severe pre-    was excluded
                     1949 women          development of        a)systolic bp ≥        eclampsia.                    from the
                     without severe      severe pre-           160mmHg or                                           predictive
                     pre-eclampsia       eclampsia (64         diastolic bp ≥         11.2% of controls (n=1949)    model for
                     delivered at one    variables were        110mmHg b)             and 28.6% of cases. RR        severe pre-
                     centre between      considered). A        proteinuria ≥ 5g/24    (unadjusted) 3.0;95% CI       eclampsia as it
                     1995-1997           predictive model      hr or 3+ or 4+         1.5-6.2 (p=0.002)             was
                                         was constructed.      c)oliguria (urinary                                  moderately
                                                               volume < 500ml/24                                    collinear with
                                                               hr) d)cerebral or                                    the screening
                                                               visual disturbances                                  MAP variable,
                                                               e) epigastic pain f)                                 had a weaker
                                                               pulmonary oedema                                     association
                                                               or cyanosis                                          and was
                                                                                                                    considered
                                                                                                                    less useful for
                                                                                                                    clinical
                                                                                                                    prediction as it
                                                                                                                    occurred later.
Witlin 99            N=445               Characteristics       Eclampsia (n=39)       There was no association      Most eclamptic     Case series      III
(USA)                consecutively       related to clinical   or placental           between eclampsia and         seizures
                     managed             presentation or       abruption (n=32) or    placental abruption and       occurred in
                     women from          laboratory            both (n=1)             systolic, diastolic or mean   women who
                     1992-1997 with      variables                                    arterial pressure,            were not
                     severe pre-         predictive of                                quantitative proteinuria,     receiving
                     eclampsia and       outcome                                      epigastric pain.              medical
                     eclampsia,                                                                                     attention. Uric
                     defined                                                                                        acid and blood
                     according to                                                                                   pressure
                     ACOG and                                                                                       determinations
                     managed in a                                                                                   and degree of
                     regional referral                                                                              proteinuria
                     centre in the                                                                                  would not have
                     USA.                                                                                           been available
                                                                                                                    for the majority




Section: hypertension and proteinuria                                                                                                         page 49
                                                                                                                    of women
                                                                                                                    before seizure
                                                                                                                    (author
                                                                                                                    comment).
                                                                                                                    Individual
                                                                                                                    records show
                                                                                                                    all three were
                                                                                                                    recorded after
                                                                                                                    seizure.
Xiong 99             N=16,938 births    Gestational           Gestational age,       The risk of low birth weight   Exclusion        Observational    III
(China)              from 1989-1990     hypertension          preterm birth, birth   was not increased              criteria         study
                                        (GH), pre-            weight, low birth      significantly for GH           included
                                        eclampsia (pre) or    weight (<2500g),       (adjusted odds ratio 1.56      women with
                                        severe pre-           fetal growth           [1.00-2.41]).                  diabetes.
                                        eclampsia/            restriction (birth                                    Results were
                                        eclampsia (spre).     weight less than       Pre-eclampsia and severe       adjusted for
                                                              10th percentile of     pre-eclampsia increased        confounding
                                        GH defined as a       expected weight        the risk of FGR and low        variables
                                        blood pressure ≥      for gestational age    birth weight (adjusted odds    including
                                        130/90mmHg            according to a         ratio of low birth weight      maternal
                                        (using K4) or a       Chinese birth          were 2.65 (1.73-4.39) for      obesity.
                                        rise of systolic bp   weight distribution    pre-eclampsia and 2.53
                                        ≥ 30mmHg and a        plot.                  (1.19-4.93) for severe pre-
                                        diastolic rise ≥                             eclampsia.
                                        15mmHg with
                                        absent or trace
                                        proteinuria.

                                        Pre-eclampsia
                                        was defined as a
                                        hypertension of >
                                        130/90 to <
                                        160mmHg with
                                        proteinuria (1+
                                        and 2+) in 2




Section: hypertension and proteinuria                                                                                                       page 50
                                        dipstick samples
                                        or with > 0.3g
                                        protein in a 24
                                        hour collection.

                                        Severe pre-
                                        eclampsia was
                                        defined as a
                                        systolic ≥
                                        160mmHg or a
                                        diastolic ≥
                                        110mmHg and/or
                                        >2+ on dipstick or
                                        5g/24 hours.
                                        Eclampsia was
                                        defined as
                                        convulsions with
                                        pre-eclampsia.
Xiong 2000           N=87,798           Gestational           Low birth weight       84,658 had normal bp,            Retrospective     IIa
(Canada)             pregnancies        hypertension (GH)     (LBW) defined as       2395 (2.7%) had GH, 740          population
                     between 1991       defined as bp ≥       < 2500g. Preterm       (0.8%) had pre-eclampsia         based cohort
                     and 1996 from a    140/90mmHg or a       delivery defined as    and 5 had eclampsia (pre-
                     registry of 35     rise of systolic bp   before 37 weeks        eclampsia and eclampsia
                     hospitals.         ≥ 30mmHg and a        gestation. High        group were combined).
                     Exclusions         diastolic rise ≥      birth weight (HBW)            Nor GH pre
                     included pre-      15mmHg on two         ≥ 4200g. LGA was       HBW: 5.6% 7.3%* 5.0%
                     existing chronic   or more occasions     defined as birth       LGA: 2.2% 4.5%* 4.7%*
                     hypertension,      > 6 hrs apart with    weight > 90th          LBW: 5.2% 10.6%* 26.0%*
                                                                                     SGA: 2.9% 5.1%* 7.4% *
                     hypertension       no or a trace of      percentile of
                     before 20 weeks,   proteinuria, after    expected weight        *p<0.001, all for adjusted OR.
                     use of             20 weeks              for gestational age,
                     antihypertensive   gestation.            SGA defined as         GH adjusted OR for HBW
                     drugs before                             birth weight < 10th    1.44(1.21-1.70), LGA 1.50
                     pregnancy,         Pre-eclampsia         percentile of          (1.22-1.85), LBW 2.49(2.13-
                     transient          (pre) defined as >    expected weight        2.93), SGA 2.04 (1.68-2.48).




Section: hypertension and proteinuria                                                                                         page 51
                     hypertension           140/90 mmHg           for gestational age   Pre adjusted OR for HBW
                     during labour,         with proteinuria ≥    according to a        1.40 (0.99-1.98), LGA 1.87
                     multiple               1+ in 2 samples 6     Canadian birth        (1.31-2.67), LBW 4.14 (3.32-
                     pregnancies,           hours apart or >      weight distribution   5.15), SGA 2.56 (1.92-3.41)
                     prior diabetes,        0.3g/24 hrs.          plot.
                     gestational            Eclampsia defined
                     diabetes,              as pre-eclampsia      Results adjusted
                     cardiovascular         with convulsions.     for confounding
                     disease, chronic                             variables (history
                     kidney disease.        Normal bp (nor)       of smoking,
                     All birth weight ≥                           maternal age ≤ 19
                     500g were                                    and ≥ 35, parity,
                     included                                     obesity, maternal
                     regardless of                                weight ≤ 45 kg,
                     sign of life.                                prior SGA, prior
                                                                  LGA, prior
                                                                  spontaneous/
                                                                  induced abortions).
Zhang 01             9133 singleton         5 definitions of      Severe maternal       The last bp before delivery    Prospective       III
(USA)                pregnancies            hypertension in       and perinatal         with proteinuria was           observational
                     from a cohort          pregnancy were        morbidity and         predictive of a bad            study
                     study between          tested for            mortality.            outcome. Mild hypertension
                     1959-65. All           sensitivity,                                occurring for the first time
                     women had a            specificity and                             in labour and isolated mild
                     first prenatal visit   positive predictive                         systolic hypertension were
                     at or before 22        value. Factors                              not associated with
                     weeks, and at          included baseline                           adverse outcomes. An
                     least 3 prenatal       bp, last                                    increase of 15mmHg
                     visits.                antepartum bp                               diastolic bp that did not
                                            before onset of                             achieve an absolute value
                                            labour or delivery                          of 90mmHg did not predict
                                            (considered the                             adverse outcome.
                                            highest
                                            antepartum bp),
                                            highest




Section: hypertension and proteinuria                                                                                          page 52
                                        intrapartum bp,
                                        overall highest bp,
                                        rise in bp,
                                        antepartum rise in
                                        bp, proteinuria (at
                                        least two 1+ or
                                        one 2+ or greater
                                        dipstick during
                                        pregnancy)




Section: hypertension and proteinuria                         page 53
Section: hypertension and proteinuria

Study              Population             Intervention details      Outcomes              Results                       Comments         Study Type     Evidence
                                                                                                                                                        Level
Barton 01          N= 748 women           Women with mild           Progression to pre-   343 (46%) developed                            Case series    III
(USA)              with mild              gestational               eclampsia             proteinuria and 72 (9.6%)
                   gestational            hypertension              (proteinuria ≥ 1+     severe pre-eclampsia.
                   hypertension (≥        participating in an       on at least 2
                   140/90 mmHg)           outpatient hypertension   occasions); rate of   The development of
                   between 24-35          monitoring programme.     progression to        proteinuria was
                   weeks gestation                                  severe pre-           associated with earlier
                   on enrolment,                                    eclampsia             gestational age at
                   between Feb                                      (160/110mmHg on       delivery, lower birth
                   1995 – Feb                                       at least 2            weight, an increased
                   1998.                                            occasions with        incidence of SGA infants
                                                                    proteinuria or mild   and a longer duration of
                                                                    hypertension with     neonatal hospital stay
                                                                    ≥ 3+ proteinuria or   (p<0.001 for all).
                                                                    thrombocytopenia),
                                                                    obstetric             Gestational age at
                                                                    complications,        delivery (36.5+/-2.4 vs.
                                                                    neonatal              37.4+/-2.0 weeks); birth
                                                                    outcomes.             weight 2752 +/-767g vs.
                                                                                          3038 +/- 715g); incidence
                                                                                          of SGA infants (24.8%
                                                                                          vs. 13.8%); duration of
                                                                                          neonatal hospital stay
                                                                                          (7.1 +/- 10 vs. 5.0 +/- 9.3
                                                                                          days)

 Buchbinder        N= 598 women           Pre-eclampsia was         Maternal and           In women with recurrent       One of the      Case series    III
02                 with previous          defined as                perinatal             pre-eclampsia, if             seven centres
(USA)              pre-eclampsia          hypertension plus         outcomes:             hypertension is severe in     had a high
                   who were               proteinuria (≥                                  second pregnancy the          incidence of
                   considered at          300mg/24 hours or 2                             perinatal outcome is          pre-eclampsia.



Section: hypertension and proteinuria (correlation studies)                                                                                            page 54
                   high risk of re-       dipstick test results of ≥                      poorer compared with
                   occurrence.            2+), thrombocytopenia                           mild hypertension, with     Aspirin and
                   Subset of women        or pulmonary oedema,                            or without proteinuria.     non-aspirin
                   from 2 RCTs            and further defined as                          These women had a           group were
                   who were               mild (≥ 140/90mmHg                              significantly increased     combined for
                   followed               with proteinuria) or                            risk of preterm delivery    analysis.
                   prospectively          severe (≥                                       and of delivery of an
                   throughout a           160/110mmHg on 2                                SGA infant similar to       Definitions
                   subsequent             successive                                      patients who developed      indicate that
                   pregnancy.             measurements 4 hours                            severe pre-eclampsia.       proteinuria
                                          apart or one diastolic                                                      was not
                   Secondary              bp of ≥ 110mmHg                                 401 (67.1%) remained        required in
                   analysis of data       treated with                                    normotensive, 66(11%)       order to define
                   from women             antihypertensive                                had mild gestational        severe pre-
                   enrolled in two        medication or ≥5g                               hypertension, 24 (4.0%)     eclampsia, in
                   multicentre trials     proteinuria or                                  had severe gestational      which case
                   of aspirin 60mg        thrombocytopenia or                             hypertension. Pre-          the
                   for the                HELLP syndrome or                               eclampsia occurred in       differentiation
                   prevention of          pulmonary oedema or                             107 (17.8%) of              between
                   pre-eclampsia.         eclampsia ) .                                   pregnancies and was         severe
                   Half the women                                                         mild in 62 (10.3%) and      hypertension
                   were receiving         Gestational                                     severe in 45 (7.5%).        and severe
                   aspirin                hypertension defined                                                        pre-eclampsia
                   (randomised).          as bp elevation without                         Fetal death rate was        is not clear.
                                          proteinuria detected for                        highest for the patients
                   Exclusion criteria     first time after mid-                           who experienced severe
                   included multiple      pregnancy (mild or                              pre-eclampsia (rate of 67
                   pregnancy;             severe)                                         per 1000)
                   diabetes, chronic
                   hypertension or
                   proteinuria at
                   baseline.
Douglas 94         All episodes of        Information collected        Incidence of       383 confirmed cases of                        Prospective    III
(UK)               eclampsia in the       from review of hospital      eclampsia in the   eclampsia: 81 (21%)                           case series
                   UK in 1992             case notes and               UK; maternal       presented before 31




Section: hypertension and proteinuria (correlation studies)                                                                                           page 55
                                          questionnaires to        complications;        weeks, 169 (44%) before
                                          general practitioners.   neonatal mortality;   37 completed weeks,
                                                                   type of eclampsia     and 214 (56%) at term.
                                          Hypertension defined     (ante, intra and
                                          as a booking diastolic   post partum) and      325 (85%) women had
                                          blood pressure of <      gestational           been seen by a doctor or
                                          90mmHg, a maximum        maturity (before 31   midwife in the week
                                          diastolic ≥ 90mmHg       weeks, before 37      before their first
                                          and an increment of ≥    completed weeks,      convulsion. At the time of
                                          25mmHg. Proteinuria      at term.);            the last antenatal visit:
                                          defined as ≥ 1+ on a     prodromal signs       36 (11%): no recorded
                                          random sample or ≥       and symptoms          hypertension or
                                          0.3g/24 hour                                   proteinuria
                                                                   Eclampsia defined     32 (10%) had proteinuria
                                                                   as occurrence of      only
                                                                   convulsions during    71 (22%) had
                                                                   pregnancy or in the   hypertension alone
                                                                   first 10 days         186 (57%) had
                                                                   postpartum            proteinuria and
                                                                   together with at      hypertension.
                                                                   least 2 of the
                                                                   following features
                                                                   within 24 hours
                                                                   after the
                                                                   convulsions:
                                                                   hypertension;
                                                                   proteinuria;
                                                                   thrombocytopenia;
                                                                   increased plasma
                                                                   aspartate
                                                                   transaminase
                                                                   concentration.
Ferrazani 90       n-=444                 98 women with chronic    Birth weight (BW),    GH (n=199)       Pre (n=147)     Case series    III
                                                                                         BW: 2922+/-733   1997+/-927*
(Italy)            hypertensive           hypertension (CH) –      birth percentile
                                                                                         BP 42.3+/-29.6    22.5+/-28.1*
                   women with             documented before 20     (BP) gestational      UA 5.7+/-1.5     7.2+/-1.7*




Section: hypertension and proteinuria (correlation studies)                                                                             page 56
                   singleton              weeks or before           age (GA), SGA (<        GA 38.6+/-2.4     35.3+/-3.4*
                                                                                            PD 20 (10.1%)     86 (58.5%)
                   pregnancies            pregnancy; 199 with       10th percentile by
                                                                                            PND 6(3.0%)       19(12.9%)**
                   between 1984-          non-proteinuric           national standard       SB 1              2
                   88.                    hypertension (GH) after   criteria), serum uric   NND 5             17
                                          20 weeks and 147 with     acid (mg/dl) – last
                                                                                            Key:
                   Hypertension           hypertension and          value before
                                                                                            * p<0.05 pre v GH
                   defined as             proteinuria – n=126       delivery. Higher        **p<0.001, pre v GH
                   bp≥90mmHg in 2         with hypertension after   value of proteinuria
                   consecutive            20 weeks and n=21         (g/l in a random        %SGA
                                                                                            GH (n=199)      18%**
                   measurements 6         with chronic              sample) before
                                                                                            Pre (n=147)     52%**
                   hours apart (4th       hypertension              delivery, preterm       Control(n=9774) 10%
                   K). Proteinuria >      superimposed with         delivery (PD),
                   0.3gm/l or >1+         significant proteinuria   perinatal death         **p<0.0001 v. control
                                                                                            ***p<0.0005 v. control
                   dipstick in a          and an exacerbation of    (PND), stillbirth
                   random sample          hypertension (Pre). The   (SB), neonatal          Pre-eclampsia primips (n=86) v
                   with no urinary        two groups were           death (NND)             multips (n=61): no sig dif in
                   infection.             combined as they                                  terms of SGA, birth weight,
                                                                                            birth percentile, week of
                                          showed the same rate                              delivery and perinatal
                                          of SGA (52%).                                     mortality.

                                                                                            CH not associated with poor
                                                                                            perinatal outcome, except when
                                                                                            complicated with superimposed
                                                                                            pre-eclampsia.

                                                                                            In pre-eclampsia group,
                                                                                            proteinuria as a function of BW
                                                                                            showed a negative correlation
                                                                                            (R=-0.25, p<0.01).

                                                                                            Correlation between proteinuria
                                                                                            and week of delivery (R=-0.22,
                                                                                            p<0.05) and relative BW (R=-
                                                                                            0.21,p<0.05) were negative –
                                                                                            the latter an expression of fetal
                                                                                            growth restriction (author
                                                                                            opinion).

                                                                                            Pre-eclampsia group showed
                                                                                            exponential +ive relationship




Section: hypertension and proteinuria (correlation studies)                                                                     page 57
                                                                                           between relative BW and week
                                                                                           of delivery (R=0.51,p<0.001) –
                                                                                           implying increased frequency of
                                                                                           FGR in early onset ad delivery .



Martin 99          N= 970 women           Predictive value of       Significant            Proteinuria: 568 women             Excluded        Retrospective    III
(US).              with severe pre-       admission battery of      maternal morbidity     had admission lab data             eclamptic       case series
                   eclampsia with or      symptoms and              involving 3 major      associated with (n=148)            women (as
                   without HELLP          laboratory tests. Three   morbidity              or without (n=420)                 these women
                   syndrome (class        risk categories for       groupings:             morbidity. For proteinuria         had obvious
                   1, 2 and 3)            significant maternal      I)haematological       by dipstick, there was             morbidity).
                   between 1981           morbidity were defined:   and coagulation,       significant difference in          The category
                   and 1997, using        low risk (18 women, no    ii)cardiopulmonary     values between those               of central
                   the ACOG               morbidity); moderate      and iii) hepatorenal   with and without                   nervous
                   diagnostic             risk (223 women, 28       systems.               morbidity (p=0.002):               system
                   criteria. N=82         (17%) with morbidity,                            median value (50th                 morbidity was
                   women with             representing 26% of                              percentile) for those              not
                   antepartum or          total morbidity) and                             without morbidity was 2+           considered.
                   postpartum             high risk (327 women,                            and with morbidity was
                   eclampsia were         108 (22%) with                                   3+. Using the following            Numbers of
                   excluded. N=888        morbidity, representing                          criteria of <2+ for low            women with
                   women were             74% of total morbidity)                          risk, 2+-3+ for moderate           symptoms not
                   therefore                                                               risk and 4+ as high risk,          given.
                   studied.                                                                19%, 30% and 33%,
                                                                                           respectively, had
                                                                                           significant maternal
                                                                                           morbidity in each group.

Mattar 2000        399 consecutive        Eclampsia defined as      Relative risk of       63 (16%) of women with                             Retrospective    IIa
(USA).             women with             new onset convulsions     maternal and           eclampsia had a diastolic                          cohort
                   eclampsia              during or postpartum      neonatal outcomes      blood pressure of ≤
                   between 1977-          pregnancy unrelated to    before or after 32     90mmHg and 14% had
                   1998 in USA.           other cerebral            weeks gestation        absent or trace of
                   113 women              pathological conditions                          proteinuria.
                   onset at 32            in women with pre-



Section: hypertension and proteinuria (correlation studies)                                                                                                   page 58
                   weeks or before,       eclampsia.                                       Women with antepartum
                   286 women                                                               eclampsia were more
                   onset at 32                                                             likely to have diastolic
                   weeks or after.                                                         pressures ≥ 110mmHg
                                                                                           (58% vs. 45%, p=0.015)
                                                                                           and to have proteinuria
                                                                                           ≥3+ on dipstick (55% vs.
                                                                                           28%, p=0.000002)
                                                                                           compared with
                                                                                           postpartum eclampsia.

                                                                                           Women who develop
                                                                                           eclampsia at 32 weeks or
                                                                                           before were more likely
                                                                                           to have diastolic
                                                                                           pressures ≥ 110mmHg
                                                                                           (71% vs. 48%,
                                                                                           p<0.0001), to have
                                                                                           absent or trace
                                                                                           proteinuria (p<0.0001)
                                                                                           and were less likely to
                                                                                           have severe proteinuria
                                                                                           (25% vs. 57%, p<0.0001)

Moore 83           N=24 women             Cases required: rise of     Mode of delivery,     Mean (range) weeks of      Case control    IIb
(UK)               with pre-              30 and 15mmHg,              perinatal outcome,   gestation at delivery:
                   eclampsia              respectively, of systolic   history, patient     39.1(33-42) control v
                   diagnosed before       and diastolic (K1 and       characteristics      31.4(25-36) case.
                   34 weeks, with         IV), max antenatal                               IUD: 0/48 control v. 2/24
                   n=48 controls          readings ≥140 and                                case
                   randomly               90mmHg; persistent                               NND:0/48 control v 2/24
                   selected were          proteinuria of 2+ or                             case
                   matched for age        more.                                            BW centile < 10:
                   and parity.                                                             4/48(control) v 18/22
                                                                                           (82%) case




Section: hypertension and proteinuria (correlation studies)                                                                           page 59
                                                                                         Eight pre-eclamptic
                                                                                         women (33%) v 3 control
                                                                                         women (6%) described
                                                                                         headaches accompanied
                                                                                         by nausea, vomiting or
                                                                                         visual disturbances
                                                                                         (p<0.01) – typical
                                                                                         characteristics of
                                                                                         migraine headache.

Naeye 79           N=41,241               N=1339 cases of          Perinatal mortality   Perinatal mortality rate:                   Population       IIa
(USA)              singleton              hypertension-            rate: perinatal       37.9 per 1000 births                        based
                   pregnancies            proteinuria with max     death by placental    (when associated with                       retrospective
                   between 1959           diastolic ≥ 85mmHg       infarcts > 3cm in     gestational hypertension                    cohort
                   and 1966 in 12         and proteinuria 1+ or    diameter, placental   and proteinuria) v 17.2
                   urban hospitals        more. N=1865 cases of    abruption, growth-    per 1000 birth for
                   across the US.         hypertension without     retarded placenta,    normotensive gestations
                                          proteinuria when max     acute infection of    without proteinuria
                                          diastolic ≥ 95mmHg       amniotic fluid, all   (p<0.001). Rate for
                                          and proteinuria absent   other disorders       hypertension alone 26.6
                                          or trace.                including             per 1000 births (p<0.01 v
                                                                   “diagnosis            normotensive gestations.
                                                                   unknown”.
North 99           N=1496 healthy         Gestational              Severe maternal       In gestational              Six (3.2%) of   Prospective,     IIb
(Australia)        nulliparous            hypertension defined     disease (defined      hypertension the            the             nested, case-
                   women. Women           as systolic bp ≥         as any of the         presence of proteinuria     hypertensive    control study
                   with gestational       140mmHg with a rise of   following: systolic   1+ was associated with a    women only
                   hypertension           ≥ 30mmHg and/or          bp ≥ 160mmHg,         3.8 fold increase in        had systolic
                   (GH)(n=117,            diastolic bp ≥ 90mmHg    diastolic bp ≥        severe maternal disease     hypertension.
                   7.8%) or pre-          with a rise of ≥         110mmHg,              (41.7% vs. 15.9%: OR
                   eclampsia (PRE)        15mmHg. Pre-             platelets <           3.8; 95% CI 1.5-9.8).
                   (n=71, 4.8%)           eclampsia defined as     100x109/L, renal
                   were compared          gestational              insufficiency         Severe maternal disease
                   with a control         hypertension with ≥2+    (serum creatinine     occurred in 26.5% of GH




Section: hypertension and proteinuria (correlation studies)                                                                                          page 60
                   group of 223           on dipstick or 0.3g/24   > 0.10mmol.L),       (21.4% severe
                   randomly               hour.                    liver involvement    hypertension, 5.1%
                   selected                                        (hepatic pain or     multisystem disease) and
                   normotensive                                    AST>40IU/L),         63.4% of PRE (21.1%
                   women.                                          imminent             severe hypertension and
                                                                   eclampsia),          42.3% multisystem
                                                                   preterm birth, SGA   disease): OR 4.8 (2.4-
                                                                   infant               9.5) PRE v GH.

                                                                                        Within the GH group
                                                                                        severe maternal disease
                                                                                        occurred in 11/69
                                                                                        (15.9%) of women with
                                                                                        no or a trace of
                                                                                        proteinuria (1.5%
                                                                                        multisystem disease and
                                                                                        14.5% severe
                                                                                        hypertension) and 20/48
                                                                                        (41.7%) women with 1+
                                                                                        proteinuria (10.4%
                                                                                        multisystem disease and
                                                                                        33.3% severe
                                                                                        hypertension): OR 3.8
                                                                                        (1.5-9.8), p=0.002.

                                                                                        SGA infants were more
                                                                                        likely in the GH group
                                                                                        (OR 2.0; 1.0-3.7) and
                                                                                        PRE group (OR 2.6 (1.2-
                                                                                        5.3)) compared with the
                                                                                        normotensive group.

                                                                                        Preterm birth was more
                                                                                        likely in the GH group
                                                                                        (OR 1.7 (0.5-5.4) and
                                                                                        PRE group (OR 14.6



Section: hypertension and proteinuria (correlation studies)                                                        page 61
                                                                                          (5.8-37.8) compared with
                                                                                          the normotensive group.

Page 76            N=12,954 gravid        Eight categories          Pregnancy              n        SB      PND       MAP               Case series    III
(US)               women between          combining levels of       outcome (stillbirth   NT 94/10629                 calculated as
                   1959 and 1967          mean arterial pressure    (SB) perinatal        174/10629                   2D/3+ S/3
                   with single live       (MAP) and proteinuria.    death (PND),          GH     3/307       4/307    such that
                                                                                          Pre     2/49       2/49
                   births or              MAP-2 is mean MAP in      FGR, neonatal         CH+Pre 5/33          5/33
                                                                                                                      140/90mmHg
                   stillbirths after      5th and 6th month.        morbidity)            Prot     9/246      9/46    translates to a
                   180 days and           MAP-3 is mean of two                                                        MAP of 107.
                   requiring blood        highest MAP prior to                            Rate per 1000
                   pressure and           delivery. Proteinuria                           NT      8.8       16.4      Clinical
                   proteinuria            (Prot) defined as 2+ or                         GH       9.8      13.0      diagnosis of
                   assessments in         more. Pre-eclampsia                             Pre      40.8      40.8     pre-eclampsia
                   both middle and        group (Pre) defined as                          CH+Pre 151.5       151.5    was made in
                   third trimesters       proteinuria 2+ or more,                         Prot      36.6      52.8    all 8
                                          MAP-2 < 90, MAP-3 ≥                                                         categories.
                                                                                          Stillbirth rate compared
                                          105 (n=49). Chronic
                                                                                          to normotensive group:
                                          hypertension plus pre-                                                      Note a
                                                                                          gestational hypertension
                                          eclampsia (CH+Pre)                                                          diagnosis of
                                                                                          (p=0.45), chronic
                                          defined as proteinuria                                                      pre-eclampsia
                                                                                          hypertension (p<0.001),
                                          2+ or more, MAP-2 ≥                                                         required a
                                                                                          all with significant
                                          90, MAP-3 ≥ 105                                                             MAP-2 (mean
                                                                                          proteinuria (p<0.001).
                                          (n=33). Gestational                                                         MAP in 5th and
                                          hypertension (GH)                                                           6th month) of <
                                          defined as proteinuria                          Perinatal death rate        90
                                          <2+, MAP-2< 90, MAP-                            compared to
                                          3 ≥ 105 (n=307).                                normotensive group:
                                          Normotensive (NT)                               gestational hypertension
                                          defined as proteinuria                          (p=0.70), chronic
                                          <2+, MAP-2<90, MAP-                             hypertension (p<0.001),
                                          3<105 (n=10,629).                               all combined groups with
                                          Other groups not                                significant proteinuria
                                          defined here.                                   (p<0.001)

                                                                                          Live-born infants SGA



Section: hypertension and proteinuria (correlation studies)                                                                                           page 62
                                                                                        (<2500g, ≥ 37 weeks –
                                                                                        figures not given)
                                                                                        compared to
                                                                                        normotensive:
                                                                                        gestational hypertension
                                                                                        (p=0.13), chronic
                                                                                        hypertension (p<0.001),
                                                                                        all with significant
                                                                                        proteinuria (p<0.001)


Schiff 96          N= 66 women            N= 24 women with an      Maternal and fetal   No differences between        Case series    III
(USA)              with severe pre-       increase in 24 hour      outcomes             the two groups: no cases
                   eclampsia before       urinary protein                               of eclampsia or stillbirth,
                   32 weeks of            excretion of ≥ 2gm and                        similar rate of HELLP
                   gestation.             n=7 had a decrease or                         syndrome, placental
                   Severe pre-            n=35 had an increase                          abruption, caesarean
                   eclampsia              of less than 2gm                              delivery because of fetal
                   defined as new-                                                      distress, 5 minute
                   onset                                                                APGAR scores ≤ 6,
                   hypertension (bp                                                     admission to delivery
                   persistently >                                                       intervals.
                   140mmHg or >
                   90mmHg
                   diastolic), urinary
                   protein excretion
                   ≥ 300mg/24 hr,
                   serum uric acid >
                   5mg/dl and one
                   of: bp
                   persistently >
                   160mmHg
                   systolic or
                   110mmHg
                   diastolic, urinary




Section: hypertension and proteinuria (correlation studies)                                                                         page 63
                   protein excretion
                   ≥ 5gm/24 hr,
                   serum aspartate
                   aminotransferase
                   > 72 U/L
Seshadri 97        N=118 women            Hypertension defined       Maternal                  GH     pre     p<                          Cohort         IIa
(India)            with non-              as bp ≥ 140/90 mmHg        complications         PL 4/118 27/96 .001
                   proteinuric            on two consecutive         (MC), stillbirths     PND 2/118 26/96 .0001
                   hypertension           occasions 6 hours          (SB), perinatal       SB 1/118   9/96 .008
                                                                                           NND 1/118 17/96 .001
                   (GH), n=98 with        apart after 20 weeks       deaths (PND),         FGR19/118 50/96 .001
                   proteinuric            gestation (Karotkoff 4).   neonatal death        MC 0/118 7/96     .009
                   hypertension           Proteinuria defined as     (NND), SGA
                   (pre)                  ≥ 1+ on dipstick in a      infants (<10th
                                          random sample. All         percentile),
                                          delivered at 40 weeks.     preterm labour
                                                                     (PL), intrauterine
                                                                     growth restriction
                                                                     (FGR)
Witlin 99          N=445                  Characteristics related    Eclampsia (n=39)      Characteristics              Most              Case series    III
(USA)              consecutively          to clinical presentation   or placental          associated with              eclamptic
                   managed women          or laboratory variables    abruption (n=32) or   eclampsia (after             seizures
                   from 1992-1997         predictive of outcome      both (n=1)            univariate analysis): uric   occurred in
                   with severe pre-                                                        acid concentration >         women who
                   eclampsia and                                                           8.1mg/dl, proteinuria        were not
                   eclampsia,                                                              (3+), headache, visual       receiving
                   defined                                                                 symptoms, deep tendon        medical
                   according to                                                            reflexes > 3+, serum         attention. Uric
                   ACOG and                                                                albumin concentration <      acid and blood
                   managed in a                                                            3mg/dl, serum creatinine     pressure
                   regional referral                                                       concentration > 1.3          determinations
                   centre in the                                                           mg/dl.                       and degree of
                   USA.                                                                                                 proteinuria
                                                                                           After multivariate           would not
                                                                                           analysis (to show            have been
                                                                                           independently related        available for




Section: hypertension and proteinuria (correlation studies)                                                                                             page 64
                                                                                           variables) only headache     the majority of
                                                                                           and deep tendon reflexes     women before
                                                                                           >3+ remained significant.    seizure
                                                                                           62.5% of women with          (author
                                                                                           eclampsia and 44% of         comment).
                                                                                           women with no                Individual
                                                                                           eclampsia had headache       records show
                                                                                           (OR 2.13(1.04-4.38)).        all three were
                                                                                           35% of women with            recorded after
                                                                                           eclampsia and 20.5% of       seizure.
                                                                                           women without
                                                                                           eclampsia had visual
                                                                                           symptoms (OR 2.09
                                                                                           (0.99-4.39)

                                                                                           There was no
                                                                                           association between
                                                                                           eclampsia and placental
                                                                                           abruption and systolic,
                                                                                           diastolic or mean arterial
                                                                                           pressure, quantitative
                                                                                           proteinuria, epigastric
                                                                                           pain. Univariate analysis
                                                                                           showed an association
                                                                                           between bleeding and
                                                                                           platelet count <
                                                                                           60,000/mm3

Xiong 99           N=16,938 births        Gestational               Gestational age,       The risk of low birth                          Observational    III
(China)            from 1989-1990         hypertension (GH), pre-   preterm birth, birth   weight was not increased                       study
                                          eclampsia (pre) or        weight, low birth      significantly for GH
                                          severe pre-eclampsia/     weight (<2500g),       (adjusted odds ratio 1.56
                                          eclampsia (spre).         fetal growth           [1.00-2.41]).
                                                                    restriction (birth
                                          GH defined as a blood     weight less than       Pre-eclampsia and




Section: hypertension and proteinuria (correlation studies)                                                                                               page 65
                                          pressure ≥                  10th percentile of    severe pre-eclampsia
                                          130/90mmHg (using           expected weight       increased the risk of
                                          K4) or a rise of systolic   for gestational age   FGR and low birth weight
                                          bp ≥ 30mmHg and a           according to a        (adjusted odds ratio of
                                          diastolic rise ≥            Chinese birth         low birth weight were
                                          15mmHg with absent          weight distribution   2.65 (1.73-4.39) for pre-
                                          or trace proteinuria.       plot.                 eclampsia and 2.53
                                                                                            (1.19-4.93) for severe
                                          Pre-eclampsia was                                 pre-eclampsia.
                                          defined as a
                                          hypertension of >
                                          130/90 to < 160mmHg
                                          with proteinuria (1+ and
                                          2+) in 2 dipstick
                                          samples or with > 0.3g
                                          protein in a 24 hour
                                          collection.

                                          Severe pre-eclampsia
                                          was defined as a
                                          systolic ≥ 160mmHg or
                                          a diastolic ≥ 110mmHg
                                          and/or >2+ on dipstick
                                          or 5g/24 hours.
                                          Eclampsia was defined
                                          as convulsions with
                                          pre-eclampsia.
Xiong 2000         N=87,798               Gestational                 Low birth weight      84,658 had normal bp,       Retrospective    IIa
(Canada)           pregnancies            hypertension (GH)           (LBW) defined as      2395 (2.7%) had GH,         population
                   between 1991           defined as bp ≥             < 2500g. Preterm      740 (0.8%) had pre-         based cohort
                   and 1996 from a        140/90mmHg or a rise        delivery defined as   eclampsia and 5 had
                   registry of 35         of systolic bp ≥            before 37 weeks       eclampsia (pre-
                   hospitals.             30mmHg and a                gestation. High       eclampsia and eclampsia
                   Exclusions             diastolic rise ≥            birth weight (HBW)    group were combined).
                   included pre-          15mmHg on two or            ≥ 4200g. LGA was            Nor GH pre
                                                                                            HBW: 5.6% 7.3%* 5.0%




Section: hypertension and proteinuria (correlation studies)                                                                             page 66
                   existing chronic       more occasions > 6 hrs     defined as birth       LGA: 2.2% 4.5%* 4.7%*
                   hypertension,          apart with no or a trace   weight > 90th          LBW: 5.2% 10.6%* 26.0%*
                   hypertension           of proteinuria, after 20   percentile of          SGA: 2.9% 5.1%* 7.4% *
                   before 20 weeks,       weeks gestation.           expected weight
                                                                                            *p<0.001, all for adjusted
                   use of                                            for gestational age,   OR.
                   antihypertensive       Pre-eclampsia (pre)        SGA defined as
                   drugs before           defined as > 140/90        birth weight < 10th    GH adjusted OR for HBW
                   pregnancy,             mmHg with proteinuria      percentile of          1.44(1.21-1.70), LGA 1.50
                   transient              ≥ 1+ in 2 samples 6        expected weight        (1.22-1.85), LBW 2.49(2.13-
                   hypertension           hours apart or >           for gestational age    2.93), SGA 2.04 (1.68-
                   during labour,         0.3g/24 hrs. Eclampsia     according to a         2.48).
                   multiple               defined as pre-            Canadian birth
                   pregnancies,           eclampsia with             weight distribution    Pre adjusted OR for HBW
                                                                                            1.40 (0.99-1.98), LGA 1.87
                   prior diabetes,        convulsions.               plot.                  (1.31-2.67), LBW 4.14
                   gestational                                                              (3.32-5.15), SGA 2.56
                   diabetes,              Normal bp (nor)            Results adjusted       (1.92-3.41)
                   cardiovascular                                    for confounding
                   disease, chronic                                  variables (history
                   kidney disease.                                   of smoking,
                   All birth weight ≥                                maternal age ≤ 19
                   500g were                                         and ≥ 35, parity,
                   included                                          obesity, maternal
                   regardless of                                     weight ≤ 45 kg,
                   sign of life.                                     prior SGA, prior
                                                                     LGA, prior
                                                                     spontaneous/
                                                                     induced abortions).




Section: hypertension and proteinuria (correlation studies)                                                               page 67
Section: hypertension and proteinuria (correlation studies)

Brown 95              N=230                  To determine       24-hour urine        Dipstick before 24 hour          Authors             Correlation    III
(Australia)           consecutive            the accuracy of    protein excretion    urine collection: negative       conclude that       study
                      hypertensive           ward urinalysis    compared with a      predictive value 86%, positive   when dipstick
                      women admitted         and the            mid-stream           predictive value 38%             urinalysis
                      to hospital over a     sensitivity of     sample before        Dipstick after 24 hour urine     shows 0.3g/L
                      2 year period          dipstick testing   and after the 24-    collection: negative             or greater (i.e.
                                             in the             hour collection.     predictive value 88%, positive   1+ or more),
                                             assessment of      As a control for     predictive value 46%             more than half
                                             proteinuria.       dipstick accuracy,   Dipstick from aliquot:           the times this
                                                                urinalysis was       negative predictive value        will not reflect
                                                                also performed       87%, positive predictive value   true proteinuria.
                                                                on a mixed           60%.                             When ward
                                                                aliquot of each of                                    analysis shows
                                                                the 24-hour          Dipstick of 1+: 17% (15/89),     either nil or a
                                                                samples by a         25% (20/79) and 33% (16/48)      trace of
                                                                single observer      of 1+ dipstick samples had       proteinuria,
                                                                experienced in       proteinuria ≥ 300mg/day          approximately
                                                                urinalysis. True     (respectively, before, after     1 in 8 patients
                                                                proteinuria was      and aliquot). False positive     will have
                                                                considered as >      rates 83%, 75%, and 67%.         increased
                                                                300mg/day.                                            protein
                                                                Positive             Dipstick of 2+: 50% (22/44),     excretion. 3+
                                                                urinalysis was 1+    68% (17/25) and 82% (14/17)      (3g/L) or 4+
                                                                (0.3g/L) or more.    had true proteinuria (before,    (≥20g/L) will
                                                                Positive             after, and aliquot,              rarely be false
                                                                predictive value     respectively). False positive    positive
                                                                (%) was number       rates 50%, 32%, and 18%.         (ranged from 0-
                                                                of true positive                                      17%).
                                                                24-hour results      Dipstick of negative or
                                                                divided by the       trace: false negative rates of   An independent
                                                                number of            8-18%. 2/27, 3/24 and 6/58       reviewer
                                                                positive dipstick    negative dipstick and 8/45,      commented
                                                                urinalysis.          9/79 and 12/85 trace dipstick    that the
                                                                Negative                                              research



Section: hypertension and proteinuria (correlation studies)                                                                                             page 68
                                                                predictive values      had true proteinuria              midwife in the
                                                                were calculate by      (respectively before, after and   study may have
                                                                urinalysis of nil or   aliquot)                          been trained to
                                                                trace to be                                              identify small
                                                                negative and 24-                                         changes as a
                                                                hour protein <                                           positive
                                                                300mg/day to be                                          dipstick. This
                                                                true negatives.                                          is evident in the
                                                                                                                         results.
Durnwald 2003         N=220 women            Protein            Abnormal protein       The test showed a sensitivity     Note that a         Correlation    III
(US)                  with suspected         creatinine ratio   creatinine ratio       of 81%, specificity 56%,          different           study
                      pre-eclampsia of       followed by 24     defined as             positive predictive value of      method was
                      24 or more             hour urine         300mg/g                86% and a negative                used to
                      weeks gestation        evaluation         (equivalent to         predictive value of 48% for       measure
                      (excluding                                approximately 34       300mg protein.                    proteinuria (a
                      women with                                mg/mmol)                                                 biuret reaction)
                      chronic                                                                                            to Saudan
                      hypertension,                                                                                      1997
                      diabetes or                                                                                        (benzethonium
                      preexisting renal                                                                                  chloride
                      disease.                                                                                           turbidometric
                                                                                                                         method)
Kuo 92                N= 68                  Volume,            Results for            There was a significant                               Correlation    III
(Australia)           consecutive new        protein and        protein were           relationship (r=0.639)                                study
                      hypertensive           creatinine         negative, 30 (+),      between the two measures of
                      (diastolic blood       concentrations     100 (++), or 500       protein, but with a wide
                      pressure ≥ 90          from a 24 hour     (+++) mg/dl.           scatter, with both false-
                      mmHg) pregnant         urine sample       Inter-observer         negative and false-positive
                      women admitted         were measured      variability in         results.
                      to hospital with       and compared       dipstick analyses
                      0.3g/L, ≥ 1+           with dipstick      of urine samples       Two subjects (3%) had
                      proteinuria on         analysis of an     of known protein       negative dipstick tests with ≥
                      urinalysis.            early morning      content was            1000mg per 24-hour
                                             midstream          assessed with          proteinuria.
                                             urine sample       the aid of 66




Section: hypertension and proteinuria (correlation studies)                                                                                                page 69
                                             collected at the   volunteers from        Dipstick protein values of
                                             end of the 24      the hospital staff     1+ were associated with a
                                             hour period.       (40 nurse-             scatter of value for 24-hour
                                                                midwives, 14           protein excretion from 0 to
                                                                medical                2400mg.
                                                                graduates, 12
                                                                scientific officers)   Dipstick protein values of
                                                                who each               2+ were associated with a
                                                                assessed six           range from 700 to 4000mg,
                                                                urine samples.         and 3+ with values ranging
                                                                                       from 1200 to 7000mg per 24
                                                                                       hours.




Lindow & Davey        N=22 women             Urine volume,      Urinary protein/       A large coefficient of variation             Correlation      III
92 (S Africa)         with gestational       protein            creatinine ratio,      in urine volume (41%),                       study
                      proteinuric            excretion and      Multistix              amount of protein excreted
                      hypertension (2+       creatinine         examination to         (44%) and the amount of
                      or greater on          excretion in       estimate 24-hour       creatinine excreted (22%)
                      routine spot           eight hourly       protein excretion.     and protein/ creatinine ratio
                      testing)               periods were                              (27%) in the eight-hour
                                             measured                                  specimens was noted. The
                                             using an                                  protein creatinine ratio did not
                                             indwelling                                accurately predict the 24 h
                                             urinary catheter                          protein excretion. The
                                             placed for 24                             Multistix examination was
                                             hours.                                    less accurate with increasing
                                                                                       amounts of proteinuria. The
                                                                                       amount of creatinine excreted
                                                                                       correlated with the volume of
                                                                                       urine passed (r=0.43).
Meyer 1994            Review of n=300        24-hour                                   123 samples had negative           Authors   Retrospective    III




Section: hypertension and proteinuria (correlation studies)                                                                                         page 70
(USA)                 samples from           collection and   or trace protein on dipstick       comment that       correlation
                      hypertensive           at least two     on two occasions at least 6        these results      study
                      pregnant women         urinalysis       hours apart. Of these 81           are obtained by
                                             during the 24    (66%) women were false             retrospective
                                             hours.           negative with a urinary            review of
                                                              protein above 300mg/24             hospitalised
                                                              hours. This is a negative          hypertensive
                                                              predictive value of 34%            patients and
                                                              (42/123).                          are therefore
                                                                                                 applicable only
                                                              101 patients had 1+ or 2+          to a similar
                                                              dipstick of whom 89 (88%)          group and
                                                              had significant proteinuria        should not be
                                                              and 12 (12%) normal protein        applied to a
                                                              excretion.                         population of
                                                                                                 normal patients
                                                              Urinary protein dipstick           whose baseline
                                                              values of ≥1+ had a positive       incidence of
                                                              predictive value of 92%            proteinuria will
                                                              (162/177) for predicting ≥         be much lower
                                                              300mg per 24 hours, a              with very
                                                              negative predictive value of       different
                                                              34% (81/123 or 66% false           positive and
                                                              negative rate), a sensitivity of   negative
                                                              67% and a specificity of 74%       predictive
                                                              (15/57 or 26% false positive       values.
                                                              rate).

                                                              Dipstick values of 1+ were
                                                              associated with protein
                                                              excretion ranging between
                                                              94.2 to 8100 mg in a 24-hour
                                                              collection.

                                                              76 samples had 3+ or 4+




Section: hypertension and proteinuria (correlation studies)                                                                       page 71
                                                                                   protein in at least two
                                                                                   samples of which 27 (36%)
                                                                                   had ≥5gm per 24 hours and
                                                                                   42 (55%) had ≥3.5gm per 24
                                                                                   hours. Positive predictive
                                                                                   value of 3+ to 4+ was 36%
                                                                                   (27/76) for ≥5gm (definition of
                                                                                   severe proteinuria).

                                                                                   ≥2+ was associated with a
                                                                                   10.5% false positive rate
                                                                                   (specificity 89.5%)..
Quadri 94             N=34 pregnant          Assessment of                         A urine P:C ratio ≤ 0.3                            Correlation    III
(USA)                 women with             renal function                        corresponded to a normal                           study
                      underlying renal       using a random                        protein excretion (≤ 300mg/
                      disease (normal        urine protein/                        24 hr ) with a positive
                      or mildly              creatinine ratio                      predictive value of 88.1% and
                      impaired renal         to estimate                           a negative predictive value of
                      function               protein                               93.9%, a sensitivity of 90.1%
                      creatinine ≤ 1.4       excretion                             and a specificity of 86.1%.
                      mg/dl)                 serially (16
                                             comparisons in                        A random P/C ratio of ≥ 3.0
                                             the first                             corresponded to a “nephritic-
                                             trimester,                            range” proteinuria of ≥
                                             second                                3.5g/24 hr with a sensitivity of
                                             trimester (29                         100% and a specificity of
                                             comparisons),                         94.2%. The positive
                                             third trimester                       predictive value (P/C ≥ 3.0;
                                             15                                    proteinuria ≥ 3.5g/24 hr) was
                                             comparisons)                          72.7% and the negative
                                             and postpartum                        predictive value (P/C ratio ≤
                                             (15                                   3.0; proteinuria ≤ 3.5g/24 hr)
                                             comparisons)                          was 100%.
Ramos 99              N= 47                  Urinary protein/   Protein            All women had urinary              Authors         Correlation    III
(Brazil)              hypertensive           creatinine ratio   determination in   creatinine excretion higher        conclude that   study



Section: hypertension and proteinuria (correlation studies)                                                                                         page 72
                      (arterial blood        in women who      24-hour urine.     than 800 mg/24 hr. The             0.5 mg/mg is a
                      pressure of            were              Women were         correlation coefficient            suitable cut-off
                      140/90mmHg or          hospitalised. A   divided into two   between the P/C ratio and the      for significant
                      higher in two          midstream         groups             24 hr proteinuria was 0.94.        proteinuria.
                      different              sample prior to   dependant on the
                      measurements at        the 24 hour       presence of        A ratio ≥ 0.8 gave a specificity   This translates
                      intervals of more      collection was    significant        and positive predictive value      to 30 mg/mmol
                      than 6 h)              used for the      proteinuria.       of 100%.
                      pregnant women         P/C ratio         Significant
                      > 20 weeks             determination     proteinuria was    A ratio of 0.5 gave a
                      gestation              (mg/dl urinary    defined as ≥       sensitivity of 0.96, a
                                             protein divided   300mg in 24        specificity of 0.96, a positive
                                             by mg/dl          hours.             predictive value of 0.96 and a
                                             urinary                              negative predictive value of
                                             creatinine)                          0.96 for significant proteinuria
                                                                                  and was considered the
                                                                                  optimal ratio.

                                                                                  1/26 women with a ratio of
                                                                                  <0.3 had significant
                                                                                  proteinuria (mean 24 hr
                                                                                  proteinuria for this group was
                                                                                  124 (range 24-315). 0/5
                                                                                  women with a P/C ratio of
                                                                                  0.3-0.5 had a 24 hour protein
                                                                                  excretion of more than
                                                                                  300mg/24 hour (mean 186
                                                                                  (range 144-277)).

                                                                                  If P/C ratio were calculated as
                                                                                  mg protein/mmol creatinine,
                                                                                  30 mg/mmol was the best
                                                                                  result for the diagnosis of
                                                                                  significant proteinuria (>
                                                                                  300mg) with 94% sensitivity,
                                                                                  80% specificity, 72% positive



Section: hypertension and proteinuria (correlation studies)                                                                             page 73
                                                                                     predictive value, and 96%
                                                                                     negative predictive value.
Saudan 97             N= 100 women           Assessing          True proteinuria     Spot urine protein: creatinine                       Correlation    III
(Australia)           with hypertensive      proteinuria by     defined as ≥         ratio correlated well with                           study
                      pregnancy              spot protein       300mg/ 24 hours      subsequent 24-hour urine
                      admitted to            creatinine ratio   and true negative    proteinuria (r=0.93, p<0.001).
                      hospital or            followed by a      as < 300mg/ 24
                      managed within         24-hour            hours.               Protein/ creatinine ratio > 30
                      the Day Unit.          collection.                             (mg protein/ mmol creatinine)
                                                                Urine protein/       can discriminate ≥ 300mg
                                                                creatinine ratio     protein with 94% sensitivity,
                                                                was calculated by    92% specificity, 95% positive
                                                                dividing the urine   predictive value and 90%
                                                                protein              negative predictive value.
                                                                concentration
                                                                (mg/L) by the
                                                                urine creatinine
                                                                concentration
                                                                (mmol/L)
Saudan 97             N= 103 samples         a) comparing       True proteinuria     True positive results were        Authors            Correlation    III
(Australia)           from                   routine dipstick   defined as ≥         significantly more frequent       comment that       study
                      hypertensive           urinalysis with    300mg/ 24 hours      with the automated urinalysis     there was a
                      women (as              laboratory urine   and true negative    (p=0.024).                        reduced
                      above)                 protein            as < 300mg/ 24       A dipstick of 1+ had              accuracy of the
                                             concentration      hours.               (respectively from the ward       protein/
                                             measurement                             urinalysis and automated          creatinine ratio
                                             and b)                                  device) a sensitivity of 100%     in the presence
                                             comparing                               and 90%, a specificity of 62%     of heavy
                                             urinalysis done                         and 86% and a PPV of 24%          proteinuria, but
                                             by an                                   and 47%.                          there was good
                                             automated                                                                 agreement for
                                             device on the                           A dipstick of negative or trace   patients with <
                                             same sample                             had a NPV of 100% and 98%,        500mg
                                             as a) with                              respectively, from the ward       proteinuria/ 24
                                             laboratory urine                        urinalysis and automated          hours.




Section: hypertension and proteinuria (correlation studies)                                                                                             page 74
                                             protein          device.
                                             concentration
                                                              A dipstick of 2+ had
                                                              (respectively from the ward
                                                              urinalysis and automated
                                                              device) a sensitivity of 100%
                                                              and 83%, a specificity of 85%
                                                              and 98%, and a PPV of 53%
                                                              and 83%.




Section: hypertension and proteinuria (correlation studies)                                   page 75
Section: new proteinuria

Study                Population         Intervention      Outcomes              Results                          Comments   Study Type        Evidence
                                        details                                                                                               Level
Douglas 94           All episodes of    Information       Incidence of          383 confirmed cases of                      Prospective       III
(UK)                 eclampsia in the   collected from    eclampsia in the      eclampsia: 81 (21%)                         case series
                     UK in 1992         review of         UK; maternal          presented before 31 weeks,
                                        hospital case     complications;        169 (44%) before 37
                                        notes and         neonatal mortality;   completed weeks, and 214
                                        questionnaires    type of eclampsia     (56%) at term.
                                        to general        (ante, intra and
                                        practitioners.    post partum) and      325 (85%) women had been
                                                          gestational           seen by a doctor or midwife
                                        Hypertension      maturity (before      in the week before their first
                                        defined as a      31 weeks, before      convulsion. At the time of the
                                        booking           37 completed          last antenatal visit:
                                        diastolic blood   weeks, at term.);     36 (11%): no recorded
                                        pressure of <     prodromal signs       hypertension or proteinuria
                                        90mmHg, a         and symptoms          32 (10%) had proteinuria
                                        maximum                                 only
                                        diastolic ≥       Eclampsia defined     71 (22%) had hypertension
                                        90mmHg and        as occurrence of      alone
                                        an increment of   convulsions           186 (57%) had proteinuria
                                        ≥ 25mmHg.         during pregnancy      and hypertension.
                                        Proteinuria       or in the first 10
                                        defined as ≥ 1+   days postpartum
                                        on a random       together with at
                                        sample or ≥       least 2 of the
                                        0.3g/24 hour      following features
                                                          within 24 hours
                                                          after the
                                                          convulsions:
                                                          hypertension;
                                                          proteinuria;
                                                          thrombocytopenia;




Section: new proteinuria                                                                                                            page 76
                                                            increased plasma
                                                            aspartate
                                                            transaminase
                                                            concentration.
Murray 02            N=1000              Proteinuria        Diagnosis of           6/26 women with pre-          Timing of first     Prospective       III
(Australia)          pregnant            defined as ≥       chronic                eclampsia developed           and                 observational
                     women, 87 lost      1+. All other      hypertension,          proteinuria before            subsequent
                     to follow up,       definitions of     gestational            hypertension. 2/26 women      visits not stated
                     attending two       hypertensive       hypertension, pre-     with pre-eclampsia had        in paper.
                     hospital            disorders of       eclampsia, pre-        dipstick proteinuria at
                     antenatal care      pregnancy as       eclampsia              baseline (first visit)
                     units. Women        defined by         superimposed on
                     had blood           Australasian       chronic
                     pressure and        Society for the    hypertension.
                     dipstick            Study of
                     urinalysis on the   Hypertension
                     first and           in Pregnancy.
                     subsequent
                     antenatal visits.
Stettler 92          Chronic             65 pregnancies     Perinatal outcome      48/65 pregnancies (74%) had   The perinatal       Case series       III
(USA)                proteinuria         in 53 women        by proteinuria +/-     associated renal              morbidity rate
                     complicating        with proteinuria   renal insufficiency,   insufficiency, 26/65 (40%)    was also five
                     pregnancy           ≥500mg/24          chronic                had chronic hypertension.     times greater
                     between 1970-       hours (            hypertension.                                        than in
                     1990.               quantified after                          62% case and 12% of           uncomplicated
                                         ≥2+ or             Preterm delivery       controls had pre-eclampsia    pregnancies.
                                         persistent 1+),    defined as             (p<0.001), 23 (43%) of case
                                         no known renal     delivery < 38          and 17% of controls had
                                         disease, no        completed weeks.       preterm delivery (p<0.001),
                                         reversible renal   Fetal growth           23% of case and 10% of
                                         dysfunction        restriction as         controls had fetal growth
                                         and no             determined by          restriction (p=0.01).
                                         evidence of        Brenner et al.
                                         pre-eclampsia                             Excluding 8 abortions, the
                                         at discovery of    Outcome                following incidence of




Section: new proteinuria                                                                                                                     page 77
                           proteinuria.       compared with       complications occurred
                           Renal              general obstetric   during 57 pregnancies.
                           insufficiency      population from
                           defined as         the same hospital   Preterm birth occurred in
                           serum              (controls).         1/14 (7%) women with
                           creatinine                             proteinuria alone, 8/19 (42%)
                           concentration                          women with proteinuria and
                           of > 0.8 mg/dl                         renal insufficiency, ½ (50%)
                           that persisted                         women with proteinuria and
                           throughout                             chronic hypertension, and
                           pregnancy.                             17/22 (77%) women with
                           Chronic                                proteinuria and both renal
                           hypertension                           insufficiency and chronic
                           defined as bp ≥                        hypertension. Proteinuria
                           140/90mmHg                             with renal insufficiency, and
                           before 20                              proteinuria with both renal
                           weeks or                               insufficiency and chronic
                           before                                 hypertension were both more
                           pregnancy.                             likely to result in preterm birth
                           Superimposed                           (p=0.01, OR 3.4 and
                           pre-eclampsia                          p<0.001, OR 15.9,
                           diagnosed                              respectively), compared with
                           clinically as an                       the general obstetric
                           acute                                  population. Proteinuria alone,
                           elevations in                          and with chronic
                           bp, marked                             hypertension were not
                           increases in                           significantly different from the
                           proteinuria,                           general population (OR 0.36
                           characteristic                         and 4.68, respectively).
                           symptoms,
                           and/ or lab                            Growth restriction occurred in
                           evidence.                              1/14 (7%) women with
                                                                  proteinuria alone4/19 (21%)
                                                                  women with proteinuria and
                                                                  renal insufficiency, no women
                                                                  with proteinuria and chronic



Section: new proteinuria                                                                              page 78
                                                                             hypertension, and 7/22 (32%)
                                                                             women with proteinuria and
                                                                             both renal insufficiency and
                                                                             chronic hypertension.
                                                                             Proteinuria with both renal
                                                                             insufficiency and chronic
                                                                             hypertension was more likely
                                                                             to result in growth restriction
                                                                             (p=0.004, OR 4.2), compared
                                                                             with the general obstetric
                                                                             population. The other groups
                                                                             were not significantly
                                                                             different from the general
                                                                             population.
Theron 98            N= 99 women      Weight gain       Pre-eclampsia,       Of the 96 pre-eclamptic           Case control      IIb
(S Africa)           who developed    spurts            defined as new       women evaluated (3
                     pre-eclampsia,   identified by     proteinuria ≥        excluded because height was
                     n=675 women      90th percentile   0.3g/l(one plus or   not recorded), 19 were first
                     with normal      of the adaptive   more on dipstick)    diagnosed by a change in
                     pregnancies,     maternal          and bp of ≥          diastolic bp ≥ 15mmHg, 34
                     randomly         weight chart      140/90mmHg on        by diastolic bp ≥ 90mmHg,
                     selected from    and average       two separate         13 by proteinuria and 30 by
                     6851 singleton   change in         occasions at least   both proteinuria and diastolic
                     pregnancies      weight            4 hours apart.       ≥ 90mmHg. Sudden weight
                     from 1989 to     between                                gain occurred on average 1.9
                     1990, matched    successive                             weeks (standard deviation
                     for age and      clinic visits.                         7.3 weeks) before onset of
                     parity.          Compared                               clinical symptoms.
                                      temporally with
                                      abnormal blood                         Of the women with pre-
                                      pressure                               eclampsia identified by 90th
                                      observations                           percentile of the adaptive
                                      (≥15mmHg rise                          chart, 62.0% were identified
                                      or ≥90mmHg                             by a change in their weight
                                      diastolic).                            gain prior to the onset of




Section: new proteinuria                                                                                               page 79
                                            abnormal observations of
                           Frequency of     blood pressure or proteinuria.
                           antenatal
                           appointments
                           is not given,
                           but one women
                           with pre-
                           eclampsia had
                           appointments
                           at 20, 24, 28,
                           30, 32 and 34
                           weeks)




Section: new proteinuria                                                     page 80
Section: new proteinuria   page 81
Section: headache and visual disturbances

Study                Population             Intervention      Outcomes              Results                          Comments   Study Type        Evidence
                                            details                                                                                               Level
Douglas 94           All episodes of        Information       Incidence of          383 confirmed cases of                      Prospective       III
(UK)                 eclampsia in the       collected from    eclampsia in the      eclampsia: 81 (21%)                         case series
                     UK in 1992             review of         UK; maternal          presented before 31 weeks,
                                            hospital case     complications;        169 (44%) before 37
                                            notes and         neonatal mortality;   completed weeks, and 214
                                            questionnaires    type of eclampsia     (56%) at term.
                                            to general        (ante, intra and
                                            practitioners.    post partum) and      325 (85%) women had been
                                                              gestational           seen by a doctor or midwife
                                            Hypertension      maturity (before      in the week before their first
                                            defined as a      31 weeks, before      convulsion. At the time of the
                                            booking           37 completed          last antenatal visit:
                                            diastolic blood   weeks, at term.);     36 (11%): no recorded
                                            pressure of <     prodromal signs       hypertension or proteinuria
                                            90mmHg, a         and symptoms          32 (10%) had proteinuria only
                                            maximum                                 71 (22%) had hypertension
                                            diastolic ≥       Eclampsia defined     alone
                                            90mmHg and        as occurrence of      186 (57%) had proteinuria
                                            an increment of   convulsions           and hypertension.
                                            ≥ 25mmHg.         during pregnancy
                                            Proteinuria       or in the first 10
                                            defined as ≥ 1+   days postpartum
                                            on a random       together with at
                                            sample or ≥       least 2 of the
                                            0.3g/24 hour      following features
                                                              within 24 hours
                                                              after the
                                                              convulsions:
                                                              hypertension;
                                                              proteinuria;
                                                              thrombocytopenia;




Section: headache and visual disturbances                                                                                               page 82
                                                              increased plasma
                                                              aspartate
                                                              transaminase
                                                              concentration.
Martin 99            N= 970 women           Predictive        Significant          Initial symptoms                 Excluded          Retrospective     III
(US).                with severe pre-       value of          maternal morbidity                                    eclamptic         case series
                     eclampsia with or      admission         involving 3 major    Headache was not                 women (as
                     without HELLP          battery of        morbidity            associated with the              these women
                     syndrome (class        symptoms and      groupings:           development of subsequent        had obvious
                     1, 2 and 3)            laboratory        I)haematological     significant maternal morbidity   morbidity). The
                     between 1981           tests. Three      and coagulation,     of any type (p=0.592).           category of
                     and 1997, using        risk categories   ii)cardiopulmonary                                    central nervous
                     the ACOG               for significant   and iii)                                              system
                     diagnostic             maternal          hepatorenal                                           morbidity was
                     criteria. N=82         morbidity were    systems.                                              not considered.
                     women with             defined: low
                     antepartum or          risk (18                                                                Numbers of
                     postpartum             women, no                                                               women with
                     eclampsia were         morbidity);                                                             symptoms not
                     excluded. N=888        moderate risk                                                           given.
                     women were             (223 women,
                     therefore              28 (17%) with
                     studied.               morbidity,
                                            representing
                                            26% of total
                                            morbidity) and
                                            high risk (327
                                            women, 108
                                            (22%) with
                                            morbidity,
                                            representing
                                            74% of total
                                            morbidity)
Porapakkham 79       N=298 cases of         Race,             Eclampsia            211 (70.8%) eclamptic                              Case series       III
(Thailand).          eclampsia in one       residence,                             women had headache/




Section: headache and visual disturbances                                                                                                     page 83
                     hospital between       occupation,                             blurred vision prior to their
                     1967 and 1974          nutritional                             eclamptic fit.
                                            status, age and
                                            parity, type of
                                            antenatal care,
                                            seasonal
                                            occurrence,
                                            onset in
                                            relation to
                                            delivery,
                                            clinical
                                            findings,
                                            gestational age
                                            at onset,
                                            pregnancy
                                            outcome were
                                            considered.
Sibai 81             N=67 cases of          Patient            All women had        Most frequent premonitory         Retrospective     III
(USA)                eclampsia              characteristics,   eclamptogenic        symptoms were headache            observational
                     between 1977           clinical           convulsions (not     (82.5%), visual disturbance       case series
                     and 1980               findings,          further defined in   (44.4%), and right upper
                     managed at a           gestational age    paper)               quadrant/ epigastric pain
                     referral centre in     and birth                               (19%).
                     the USA                weight, labour
                                            and delivery,                           N=14 (21%) had a diastolic <
                                            and perinatal                           90mmHg, n=14 (21%) had
                                            and maternal                            no proteinuria, n=18 (27%)
                                            outcome were                            had 2+ or less proteinuria,
                                            considered.                             n=35 (52%) had 3+ or 4+
                                                                                    proteinuria.

                                                                                    Presence of significant
                                                                                    proteinuria was associated
                                                                                    with all SGA infants, all cases
                                                                                    of placental abruption, and all




Section: headache and visual disturbances                                                                                     page 84
                                                                                 cases of perinatal death or
                                                                                 neonatal complications.
Witlin 99            N=445                  Characteristics   Eclampsia (n=39)   Characteristics associated        Most eclamptic     Prospective       III
(USA)                consecutively          related to        or placental       with eclampsia (after             seizures           case series
                     managed women          clinical          abruption (n=32)   univariate analysis): uric acid   occurred in
                     from 1992-1997         presentation or   or both (n=1)      concentration > 8.1mg/dl,         women who
                     with severe pre-       laboratory                           proteinuria (3+), headache,       were not
                     eclampsia and          variables                            visual symptoms, deep             receiving
                     eclampsia,             predictive of                        tendon reflexes > 3+, serum       medical
                     defined                outcome                              albumin concentration <           attention. Uric
                     according to                                                3mg/dl, serum creatinine          acid and blood
                     ACOG and                                                    concentration > 1.3 mg/dl.        pressure
                     managed in a                                                                                  determinations
                     regional referral                                           After multivariate analysis (to   and degree of
                     centre in the                                               show independently related        proteinuria
                     USA.                                                        variables) only headache and      would not have
                                                                                 deep tendon reflexes >3+          been available
                                                                                 remained significant. 62.5%       for the majority
                                                                                 of women with eclampsia and       of women
                                                                                 44% of women with no              before seizure
                                                                                 eclampsia had headache            (author
                                                                                 (OR 2.13(1.04-4.38)). 35% of      comment).
                                                                                 women with eclampsia and          Individual
                                                                                 20.5% of women without            records show
                                                                                 eclampsia had visual              all three were
                                                                                 symptoms (OR 2.09 (0.99-          recorded after
                                                                                 4.39)                             seizure.

                                                                                 There was no association
                                                                                 between eclampsia and
                                                                                 placental abruption and
                                                                                 systolic, diastolic or mean
                                                                                 arterial pressure, quantitative
                                                                                 proteinuria, epigastric pain.
                                                                                 Univariate analysis showed




Section: headache and visual disturbances                                                                                                     page 85
                                            an association between
                                            bleeding and platelet count <
                                            60,000/mm3




Section: headache and visual disturbances                                   page 86
Section: epigastric pain

Study                 Population         Intervention      Outcomes              Results                          Comments   Study Type        Evidence
                                         details                                                                                               Level
Douglas 94            All episodes of    Information       Incidence of          383 confirmed cases of                      Prospective       III
(UK)                  eclampsia in the   collected from    eclampsia in the      eclampsia: 81 (21%)                         case series
                      UK in 1992         review of         UK; maternal          presented before 31 weeks,
                                         hospital case     complications;        169 (44%) before 37
                                         notes and         neonatal mortality;   completed weeks, and 214
                                         questionnaires    type of eclampsia     (56%) at term.
                                         to general        (ante, intra and
                                         practitioners.    post partum) and      325 (85%) women had been
                                                           gestational           seen by a doctor or midwife
                                         Hypertension      maturity (before      in the week before their first
                                         defined as a      31 weeks, before      convulsion. At the time of the
                                         booking           37 completed          last antenatal visit:
                                         diastolic blood   weeks, at term.);     36 (11%): no recorded
                                         pressure of <     prodromal signs       hypertension or proteinuria
                                         90mmHg, a         and symptoms          32 (10%) had proteinuria only
                                         maximum                                 71 (22%) had hypertension
                                         diastolic ≥       Eclampsia defined     alone
                                         90mmHg and        as occurrence of      186 (57%) had proteinuria
                                         an increment of   convulsions           and hypertension.
                                         ≥ 25mmHg.         during pregnancy
                                         Proteinuria       or in the first 10
                                         defined as ≥ 1+   days postpartum
                                         on a random       together with at
                                         sample or ≥       least 2 of the
                                         0.3g/24 hour      following features
                                                           within 24 hours
                                                           after the
                                                           convulsions:
                                                           hypertension;
                                                           proteinuria;
                                                           thrombocytopenia;




Section: epigastric pain                                                                                                             page 87
                                                           increased plasma
                                                           aspartate
                                                           transaminase
                                                           concentration.
Martin 99             N= 970 women       Predictive        Significant          Initial symptoms: women          Excluded          Retrospective     III
(US).                 with severe pre-   value of          maternal morbidity   with nausea and vomiting         eclamptic         case series
                      eclampsia with     admission         involving 3 major    were significantly more likely   women (as
                      or without         battery of        morbidity            to have haematological and       these women
                      HELLP              symptoms and      groupings:           coagulation (p<0.006) and        had obvious
                      syndrome (class    laboratory        I)haematological     hepatorenal (p<0.017)            morbidity). The
                      1, 2 and 3)        tests. Three      and coagulation,     complications develop than       category of
                      between 1981       risk categories   ii)cardiopulmonary   were symptom-free patients       central nervous
                      and 1997, using    for significant   and iii)             with renal insult (p<0.001).     system
                      the ACOG           maternal          hepatorenal          but no relation with             morbidity was
                      diagnostic         morbidity were    systems.             cardiopulmonary (p=0.281)        not considered.
                      criteria. N=82     defined: low                           morbidity. They had
                      women with         risk (18                               significantly higher LDH         Numbers of
                      antepartum or      women, no                              levels, AST levels and ALT       women with
                      postpartum         morbidity);                            levels than symptom-free         symptoms not
                      eclampsia were     moderate risk                          mothers, significantly lower     given.
                      excluded. N=888    (223 women,                            APGAR scores at 1 and 5
                      women were         28 (17%) with                          minutes after delivery
                      therefore          morbidity,                             (p<0.007 and p<0.001,
                      studied.           representing                           respectively) and remained
                                         26% of total                           hospitalised significantly
                                         morbidity) and                         longer (p<0.001).
                                         high risk (327
                                         women, 108                             Epigastric or upper
                                         (22%) with                             abdominal pain of any type
                                         morbidity,                             was significantly associated
                                         representing                           with various morbidities
                                         74% of total                           (p<0.001): increased LDH
                                         morbidity)                             values, AST values, ALT
                                                                                values, significantly
                                                                                decreased Apgar scores at 1




Section: epigastric pain                                                                                                                   page 88
                                                                                   minute (p<0.001) and 5
                                                                                   minutes (p=0.005), with
                                                                                   respect to women with
                                                                                   HELLP syndrome without
                                                                                   epigastric pain on admission.

                                                                                   Nausea and vomiting,
                                                                                   epigastric pain in association
                                                                                   with lactate dehydrogenase
                                                                                   (>1400 IU/L), AST ( > 150
                                                                                   IU/L) and uric acid conc. (>
                                                                                   7.8 mg/dl) were predictive of
                                                                                   high risk of morbidity in
                                                                                   patients with severe pre-
                                                                                   eclampsia.
Sibai 81              N=67 cases of        Patient            All women had        Most frequent premonitory                           Retrospective     III
(USA)                 eclampsia            characteristics,   eclamptogenic        symptoms were headache                              observational
                      between 1977         clinical           convulsions (not     (82.5%), visual disturbance                         case series
                      and 1980             findings,          further defined in   (44.4%), and right upper
                      managed at a         gestational age    paper)               quadrant/ epigastric pain
                      referral centre in   and birth                               (19%).
                      the USA              weight, labour
                                           and delivery,
                                           and perinatal
                                           and maternal
                                           outcome were
                                           considered.
Witlin 99             N=445                Characteristics    Eclampsia (n=39)     There was no association          Most eclamptic    Case series       III
(USA)                 consecutively        related to         or placental         between eclampsia and             seizures
                      managed women        clinical           abruption (n=32)     placental abruption and           occurred in
                      from 1992-1997       presentation or    or both (n=1)        systolic, diastolic or mean       women who
                      with severe pre-     laboratory                              arterial pressure, quantitative   were not
                      eclampsia and        variables                               proteinuria, epigastric pain.     receiving
                      eclampsia,           predictive of                           Univariate analysis showed        medical
                      defined              outcome                                 an association between            attention. Uric




Section: epigastric pain                                                                                                                       page 89
                      according to        bleeding and platelet count <   acid and blood
                      ACOG and            60,000/mm3                      pressure
                      managed in a                                        determinations
                      regional referral                                   and degree of
                      centre in the                                       proteinuria
                      USA.                                                would not have
                                                                          been available
                                                                          for the majority
                                                                          of women
                                                                          before seizure
                                                                          (author
                                                                          comment).
                                                                          Individual
                                                                          records show
                                                                          all three were
                                                                          recorded after
                                                                          seizure.




Section: epigastric pain                                                                     page 90
Section: weight change

Study               Population         Intervention      Outcomes             Results                          Comments   Study Type        Evidence
                                       details                                                                                              Level
Theron 98           N= 99 women        Weight gain       Pre-eclampsia,       Weight gain exceeding 90th                  Case control      IIb
(S Africa)          who developed      spurts            defined as new       percentile had estimated
                    pre-eclampsia,     identified by     proteinuria ≥        sensitivity and specificity of
                    n=675 women        90th percentile   0.3g/l(one plus or   52% (50/96) and 66% (446/
                    with normal        of the adaptive   more on dipstick)    675) and weight gain > 0.9kg
                    pregnancies,       maternal          and bp of ≥          per week between visits in
                    randomly           weight chart      140/90mmHg on        76% (75/99) and 29% (194/
                    selected from      and average       two separate         675) respectively.
                    6851 singleton     change in         occasions at
                    pregnancies from   weight between    least 4 hours        Of the 96 pre-eclamptic
                    1989 to 1990,      successive        apart.               women evaluated (3 excluded
                    matched for age    clinic visits.                         because height was not
                    and parity.        Compared                               recorded), 19 were first
                                       temporally with                        diagnosed by a change in
                                       abnormal blood                         diastolic bp ≥ 15mmHg, 34 by
                                       pressure                               diastolic bp ≥ 90mmHg, 13 by
                                       observations                           proteinuria and 30 by both
                                       (≥15mmHg rise                          proteinuria and diastolic ≥
                                       or ≥90mmHg                             90mmHg. Sudden weight
                                       diastolic).                            gain occurred on average 1.9
                                                                              weeks (standard deviation 7.3
                                       Frequency of                           weeks) before onset of
                                       antenatal                              clinical symptoms.
                                       appointments
                                       is not given,                          Of the women with pre-
                                       but one women                          eclampsia identified by 90th
                                       with pre-                              percentile of the adaptive
                                       eclampsia had                          chart, 62.0% were identified
                                       appointments                           by a change in their weight
                                       at 20, 24, 28,                         gain prior to the onset of
                                       30, 32 and 34                          abnormal observations of




Section: weight change                                                                                                            page 91
                         weeks)   blood pressure or proteinuria.




Section: weight change                                             page 92
Section: fetal compromise

Study               Population            Intervention           Outcomes            Results                         Comments   Study Type       Evidence
                                          details                                                                                                Level
Hauth 2000          N=4589 healthy        Outcome of             Comparative         Fetal growth restriction:                  Observational    III
(USA)               singleton             women who              endpoints were      135/3229 (4.2%)in the no                   study
                    nulliparas (bp        developed              clinically          hypertension group; 49/715
                    below                 pregnancy              diagnosed           (6.9%) in the mild
                    135/85mmHg            induced                placental           hypertension group; 3/32
                    and no                hypertension           abruption, acute    (9.7%) in the severe
                    proteinuria by        (PIH) (≥ 90mmHg        renal               hypertension group; 22/217
                    dipstick at           on 2 occasions 4-      dysfunction,        (10.2%) in the mild pre-
                    randomisation)        168 hrs apart):        caesarean           eclampsia group; 20/109
                    enrolled in a         severe PIH             delivery, preterm   (18.5%) in the severe pre-
                    randomised,           (diastolic bp of at    birth. Perinatal    eclampsia group. Both mild
                    placebo-              least 110mmHg          outcomes were       and severe pre-eclampsia
                    controlled trial of   on two occasions,      admission to        groups were significantly
                    calcium               or one if receiving    NICU, RDS,          different (p<0.001)
                    supplementation.      antihypertensives)     ventilator          compared with no
                    N=4302 women          or if complicated      support,            hypertension.
                    observed to or        by oliguria,           intraventricular
                    beyond 20             pulmonary              haemorrhage,        Women with mild
                    weeks gestation.      oedema, or             birth weight        hypertension had a
                                          thrombocytopenia.      under 2500g,        significantly higher birth
                                          or pre-eclampsia (     fetal growth        weight (mean 3303g,
                                          PIH plus               restriction (FGR)   p<0.001) compared with the
                                          proteinuria            below tenth         no hypertension group
                                          (300mg/ 24 hour        percentile          (mean 3205g) and a
                                          collection or single   according to        correspondingly significantly
                                          2+ protein by          Brenner et al,      longer gestation (mean no of
                                          dipstick or single     fetal or neonatal   days 278 v 275, p<0.001)
                                          protein/ creatinine    death. Mild PIH     and a smaller number of
                                          ratio of 0.35, or      and mild pre-       women with gestation under
                                          two 1+ protein by      eclampsia           34 weeks (7(1.0%) v 102
                                          dipstick 4-168 hrs     groups were         (3.2%)). They also had a




Section: fetal compromise                                                                                                              page 93
                            apart) within 7     combined after         higher percentage of babies
                            days of each        initial analysis, as   who were admitted to NICU
                            other). Severe      were severe PIH        (18.2% v 12.9%, p<0.001)
                            proteinuria was     and severe pre-
                            3.5g protein/ 24    eclampsia              Combining the mild
                            hours of two        groups for             hypertension and mild pre-
                            random              analysis of            eclampsia groups (n=932):
                            specimens of at     incidence rates.       significantly (p<0.001)
                            least 3+ by                                longer gestation (mean 278
                            dipstick. Severe                           v 275 days), higher birth
                            pre-eclampsia                              weight (3282 v 3205g), more
                            defined as severe                          fetal growth restriction
                            hypertension with                          (7.6v4.2%) and more NICU
                            proteinuria, mild                          admission (20.3% v 12.9%)
                            hypertension with                          compared with the no
                            severe                                     hypertension group. Also
                            proteinuria,                               significantly (p<0.005) less
                            HELLP syndrome                             women with gestation under
                            or eclampsia.                              34 weeks (1.2% v 3.2%).
                                                                       Combining severe
                                                                       hypertension and severe
                                                                       pre-eclampsia (n=141),
                                                                       significantly (p<0.001)
                                                                       shorter gestation (mean 261
                                                                       v 275 days), more women
                                                                       with gestation less than 34
                                                                       weeks (15.1% v 3.2%),
                                                                       lower birth weight (2714 v
                                                                       3205g), more babies with
                                                                       birth weight under 2500g
                                                                       (34.5% v 8.3%), more fetal
                                                                       growth restriction (16.5% v
                                                                       4.2%) compared with
                                                                       women with no
                                                                       hypertension.




Section: fetal compromise                                                                             page 94
Magpie Trial        N=10141 women       N=5071 were         Eclampsia, death      The following complication      RCT             Ib
Collaborative       who had not         randomised to       of baby (for          rate was reported in the
Group (02)          given birth or      received            women                 5055 babies born of mothers
(multi-country)     were less than      magnesium           randomised            with pre-eclampsia: perinatal
                    24 h postpartum     sulphate and        before delivery).     death rate 11.5%; stillbirth
                    with blood          n=5070 to receive                         8.6%; macerated stillbirth
                    pressure of         placebo             Severe pre-           3.7%; low birth weight
                    140/90mmHg or                           eclampsia             (<2500g) 48.0%. In total,
                    more and                                defined as (for all   19.8% of women with
                    proteinuria of 1+                       women) diastolic      severe pre-eclampsia and
                    (30mg/dl) or                            bp ≥ 110mmHg          9.7% of women with mild-
                    more.                                   on two                moderate pre-eclampsia had
                                                            occasions, or         babies who died.
                                                            systolic bp ≥         Risk of death in utero after
                                                            170mmHg on            trial entry for severe pre-
                                                            two occasions         eclampsia was twice that for
                                                            and proteinuria ≥     not severe pre-eclampsia
                                                            3+                    (severe 132 of 1159, 11.5%,
                                                            Or                    not severe 181 of 3307,
                                                            Diastolic bp ≥        5.4%, vs 142 of 1187,
                                                            100mmHg on            11.9% vs 164 of 3208,
                                                            two occasions or      5.1%)
                                                            systolic bp ≥
                                                            150mmHg on
                                                            two occasions
                                                            and proteinuria
                                                            ≥2+ and at least
                                                            2 signs or
                                                            symptoms of
                                                            imminent
                                                            eclampsia
                                                            (alternative
                                                            definition for
                                                            women who had




Section: fetal compromise                                                                                               page 95
                                                             antihypertensive
                                                             in the 48 h before
                                                             randomisation –
                                                             see paper)
McCowan 2001        N= 224             Serial uterine and    Pre-eclampsia,       N= 174 remained                                    Case series      III
(New Zealand)       normotensive       umbilical Doppler     gestational          normotensive, 50 (22%)
                    women with         studies were          hypertension         developed hypertension of
                    small for          performed from                             which 8 (3%) had pre-
                    gestational age    detection of SGA                           eclampsia and 42 (19%)
                    pregnancies        until delivery.                            gestational hypertension at
                                                                                  a median (interquartile
                                                                                  range) of 19 (12-32 days)
                                                                                  after recognition of SGA.

Xiong 2000          N=87,798           Gestational           Low birth weight     84,658 had normal bp, 2395       Note this is a    Retrospective    IIa
(Canada)            pregnancies        hypertension (GH)     (LBW) defined as     (2.7%) had GH, 740 (0.8%)        low risk          population
                    between 1991       defined as bp ≥       < 2500g. Preterm     had pre-eclampsia and 5          population (see   based cohort
                    and 1996 from a    140/90mmHg or a       delivery defined     had eclampsia (pre-              exclusions)
                    registry of 35     rise of systolic bp   as before 37         eclampsia and eclampsia          and a low
                    hospitals.         ≥ 30mmHg and a        weeks gestation.     group were combined).            percentage of
                    Exclusions         diastolic rise ≥      High birth weight           Nor GH pre                pre-eclampsia
                    included pre-      15mmHg on two         (HBW) ≥ 4200g.       HBW: 5.6% 7.3%* 5.0%
                    existing chronic   or more occasions     LGA was defined      LGA: 2.2% 4.5%* 4.7%*
                    hypertension,      > 6 hrs apart with    as birth weight >    LBW: 5.2% 10.6%* 26.0%*
                                                                                  SGA: 2.9% 5.1%* 7.4% *
                    hypertension       no or a trace of      90th percentile of
                    before 20 weeks,   proteinuria, after    expected weight      *p<0.001, all for adjusted OR.
                    use of             20 weeks              for gestational
                    antihypertensive   gestation.            age, SGA             GH adjusted OR for HBW
                    drugs before                             defined as birth     1.44(1.21-1.70), LGA 1.50
                    pregnancy,         Pre-eclampsia         weight < 10th        (1.22-1.85), LBW 2.49(2.13-
                    transient          (pre) defined as >    percentile of        2.93), SGA 2.04 (1.68-2.48).
                    hypertension       140/90 mmHg           expected weight
                    during labour,     with proteinuria ≥    for gestational      Pre adjusted OR for HBW 1.40
                                                                                  (0.99-1.98), LGA 1.87 (1.31-
                    multiple           1+ in 2 samples 6     age according to     2.67), LBW 4.14 (3.32-5.15),
                    pregnancies,       hours apart or >      a Canadian birth     SGA 2.56 (1.92-3.41)




Section: fetal compromise                                                                                                                   page 96
                    prior diabetes,      0.3g/24 hrs.        weight
                    gestational          Eclampsia defined   distribution plot.
                    diabetes,            as pre-eclampsia
                    cardiovascular       with convulsions.   Results adjusted
                    disease, chronic                         for confounding
                    kidney disease.      Normal bp (nor)     variables (history
                    All birth weight ≥                       of smoking,
                    500g were                                maternal age ≤
                    included                                 19 and ≥ 35,
                    regardless of                            parity, obesity,
                    sign of life.                            maternal weight
                                                             ≤ 45 kg, prior
                                                             SGA, prior LGA,
                                                             prior
                                                             spontaneous/
                                                             induced
                                                             abortions).




Section: fetal compromise                                                         page 97
Section: quality of care

See appendices for Confidential Enquiries into Maternal Deaths (CEMD) and Confidential Enquiry into Stillbirth and Deaths in Infancy (CESDI) reports




Section: quality of care                                                                                                                page 98
Section: provision of step-up care

Study                 Population         Intervention        Outcomes             Results                            Comments            Study Type          Evidence
                                         details                                                                                                             Level
Twaddle &             Women with         Evaluation of       Maternal             There was not significant                              Observational       III
Harper 92             hypertension in    daycare             hypertensive         difference in any of the                               study
(Scotland)            pregnancy from     compared with       complications,       measured pregnancy
                      two hospitals,     inpatient           gestation at         outcomes.
                      one with and one   management          delivery , mode of
                      without an         with prior          delivery , birth     Daycare management of
                      established        domiciliary         weight, Apgar        hypertension in pregnancy
                      daycare unit.      visits. Three       scores,              was more efficient (cheaper)
                                         groups were         admission rates      than inpatient care with prior
                                         identified: mild    and length of        domiciliary visits for most
                                         hypertension        admission to         women, but less efficient for
                                         (diastolic          special care baby    women with transient or
                                         between 90          unit. Economic       previous hypertension).
                                         and 99mmHg),        evaluation.
                                         a mix of mild                            The majority of women were
                                         and severe                               willing to attend daycare five
                                         (diastolic >                             times per week to avoid
                                         99mmHg or                                admission.
                                         significant
                                         proteinuria).
Villar 01             3 RCTs, n=3041     Midwife/GP          Incidence of pre-    In all 3 trials midwife led care   All 3 trials        Systematic          Ia
(multi-country)                          managed care        eclampsia and        identified a statistically         conducted in        review and
                                         vs. obstetrician/   PIH (pregnancy       significant lower rate of PIH      developed           meta-analysis
                                         gynaecologist       induced              and pre-eclampsia and less         countries.          of randomised
                                         led shared care     hypertension, as     early recognition of fetal                             controlled trials
                                                             defined in the       malpresentation. There was         Authors
                                                             studies)             no detrimental effect on           conclude that
                                                                                  perinatal outcome.                 the significantly
                                                                                                                     lower rate
                                                                                  Pre-eclampsia (2 RCTs,             points to a
                                                                                  n=2952): OR 0.37, 95% CI           decreased




Section: provision of step-up care                                                                                                                 page 99
                                     0.22, 0.64.                   incidence or
                                                                   failure of
                                     Pregnancy induced             detection.
                                     hypertension (3 RCTs,
                                     n=3041): OR 0.56, 95%CI,
                                     0.45, 0.70

                                     Satisfaction was similar or
                                     higher for those with
                                     midwife/GP led care.




Section: provision of step-up care                                                page 100
Section: Blood pressure measurement

Study              Population             Intervention      Outcomes           Results                         Comments   Study Type         Evidence
                                          details                                                                                            Level
Brown 98           N=220 pregnant         N=103             Maternal and       Pregnancy was prolonged                    RCT                Ib
(Australia)        women with             randomly          fetal outcomes     by an average of 2 weeks in
                   hypertensive           assigned to       and likelihood     both groups, no significant
                   pregnancies            management        that episodes of   difference between groups
                   (K4≥90mmHg)            with K4 and       severe             in lab data, requirements for
                                          n=117             hypertension       antihypertensive treatment,
                                          assigned to       (systolic ≥ 170,   birth weight, fetal growth
                                          management        diastolic ≥        restriction, or perinatal
                                          with K5 for the   110mmHg, or        mortality. There was no
                                          remainder of      both) would be     eclampsia or significant
                                          the pregnancy.    recorded.          maternal morbidity in either
                                                                               group.

                                                                               An episode of severe
                                                                               hypertension was more
                                                                               likely to be recorded with
                                                                               use of K4 than K5 (38% v
                                                                               26% women, p=0.051). The
                                                                               frequency of severe systolic
                                                                               hypertension and severe
                                                                               systolic and diastolic
                                                                               hypertension did not differ
                                                                               between groups.
Maxwell 82         N=84 000 blood         Replicate                            In 5838 comparisons for                    Observational      III
(USA)              pressure               measurements                         which a regular cuff was                   study
                   measurements in        were made                            appropriate (AC<33cm), the
                   1240 obese             during 24,723                        use of a large cuff
                   subjects using cuffs   clinic visits                        misdiagnosed 30% of truly
                   of three standard      (mean                                hypertensive subjects as
                   sizes in a             calculated of                        normotensive. In 5052
                   randomised order in    two to four                          comparisons in moderately




Section: blood pressure measurement                                                                                               page 101
                   a weight reduction     replicate                              obese subjects (AC 33-
                   clinic over 3 years.   measurements)                          41cm), use of a regular
                                          before and                             rather than a large cuff
                                          during rapid                           incorrectly classified 37% of
                                          weight                                 the normotensive subjects
                                          reduction. Cuff                        as hypertensive.
                                          sizes were
                                          regular                                The differences in readings
                                          (12x23cm),                             between the three cuff sizes
                                          large                                  were smallest in non-obese
                                          (15x33cm) and                          subjects and became
                                          thigh                                  progressively greater with
                                          (18x36cm).                             increasing arm
                                                                                 circumference (AC).

Perry 91           Questionnaire sent                                            Response rate was 72%.          Cross sectional    III
(UK)               to 116 midwives                                               Only 9 (10%) of respondents     study
                   and 11 obstetricians                                          reported that they record
                   working in a UK                                               blood pressure to the
                   obstetric unit to                                             nearest 2mmHg and 22
                   assess their                                                  (23%) reported that they
                   methodology in                                                round blood pressure
                   measuring blood                                               reading to the nearest
                   pressure in                                                   10mmHg. 53% of
                   pregnancy.                                                    respondents use the fifth
                                                                                 phase diastolic end point.
Shennan 96         Measurement of         Five pairs of     The                  K5 was identified in all        Correlation        III
(UK)               blood pressure         observers took    reproducibility      measurements by both            study
                   during pregnancy       1120              and identification   observers and never
                   by mercury             measurements      of K4 and K5 by      approached zero. K4 was
                   sphygmomanometry       in 80 pregnant    observers            heard in only 52% of
                                          and 80 non-       unaware of each      measurements and by only
                                          pregnant          other’s results.     one of the pair of observers
                                          women.                                 in 33% of cases. When
                                                                                 heard by both observers




Section: blood pressure measurement                                                                                      page 102
                                                                              agreement on its value was
                                                                              poor (78% within 5 mmHg
                                                                              vs. 86% for K5, p<0.05).
Steer 99           Review of blood         Data stored on   Distribution of   Only nine values of diastolic   Observational      III
(UK)               pressure at booking     St Mary’s        booking blood     blood pressure were             study
                   of 179,993 women        Maternity        pressure          recorded with a frequency of
                   at 13 maternity units   Information      measurements in   greater than 1%: 50 (4.8%),
                   in the UK from          System.          a population.     55 (1.9%), 60 (32.5%), 65
                   1994-1996.                                                 (5.5%), 70 (35.4%), 75
                                                                              (4.2%), 80 (11%), 85 (1%)
                                                                              and 90 (1%). These
                                                                              accounted for 97.3% of all
                                                                              blood pressures recorded:
                                                                              84.7% ended in zero.
                                                                              Similar findings were
                                                                              observed for the highest
                                                                              diastolic blood pressure
                                                                              during pregnancy.




Section: blood pressure measurement                                                                                   page 103
Section: proteinuria assessment

Study                Population          Intervention       Outcomes            Results                          Comments   Study Type         Evidence
                                         details                                                                                               Level
Bell 99              20 midwives, 20     Antenatal          Negative or         Negative solutions (120 and                 Correlation        III
(UK)                 nursing             dipstick           positive dipstick   160 microgram/ ml): false                   study
                     auxiliaries and 9   proteinuria        results. True       positive rates of 40% and
                     untrained and       analysis of five   assessment was      55% for nursing auxiliaries,
                     inexperienced       standard           2 negative and 3    5% and 30% for midwives,
                     laboratory          solutions of       positive results    67% and 89% for untrained
                     technicians         serum albumin.     (120, 160, 200,     lab. technicians and 0% and
                                         Untrained          240 and 280         22% for trained technicians, .
                                         laboratory         microgram/ml).
                                         technicians        Solutions           Positive solutions (200, 240,
                                         were tested,       containing ≥ 192    280 microgram per ml): false
                                         trained            micrograms          negative rates of 30%, 15%
                                         (instructed to     human serum         and 3% for nursing auxiliaries
                                         adhere strictly    albumin per ml      and 55%, 10% and 15% for
                                         to the             should score ≥      midwives, 11% for untrained
                                         manufacturer’s     1+)                 lab technicians (all 3
                                         recommended                            solutions) and 22%, 11% and
                                         procedure and                          11% for trained technicians.
                                         to assign a
                                         solution an                            The effect of training is
                                         appropriate                            significant at 160
                                         positive score                         microgram/ml (p=0.023) with
                                         only when the                          little difference at the three
                                         colour of the                          highest concentrations.
                                         dipstick was
                                         equal to, or
                                         greater than,
                                         the colour on
                                         the indicator
                                         strip).
Bell 2000            Urine samples       Use of an          Intra- and inter-   The same operator                           Correlation        III




Section: proteinuria assessment                                                                                                     page 104
(UK)                 (unknown origin)   automated        observation          conducting five replicates on   study
                                        urinalysis       precision.           32 urine samples for protein
                                        system to read                        gave 96.3% exact agreement
                                        Multistix        Urine samples        and 99.4% agreement to
                                        reagent strips   were tested by       within one colour block.
                                                         seven operators
                                                         (ward nurses of      Testing the same sample with
                                                         different grades     different operators, ( seven
                                                         trained in the use   urine samples tested by four
                                                         of the automated     operators), protein gave
                                                         urinalysis           89.3% exact agreement and
                                                         system), in          100% agreement within one
                                                         duplicate and in     colour block.
                                                         replicates of five
                                                         by the same
                                                         operators, and by
                                                         groups of four
                                                         operators on the
                                                         same sample.
                                                         Precision was
                                                         assessed using
                                                         true urine
                                                         samples and
                                                         Chek-Stix
                                                         controls.




Section: proteinuria assessment                                                                                       page 105
Section: assessment of fetal compromise in the community

See appendices for a summary of the evidence-based RCOG guideline No 31, 2002 (UK); Investigation and management of the small for
gestational age fetus.

REFERENCE CITATIONS

Reference citations for all the studies summarised in this Evidence Table can be found in the appendices to the PRECOG guideline.




Section: assessment of fetal compromise in the community                                                                            page 106

								
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