PULL-OUT SECTION www.australiandoctor.com.au
COMPLETE HOW TO TREAT QUIZZES ONLINE (www.australiandoctor.com.au/cpd) to earn CPD or PDP points.
Aetiology and risk
DR ANNEMARIE HENNESSY,
foundation chair of medicine,
University of Western Sydney,
and the Heart Research
Institute, Sydney, NSW.
hypertension in pregnancy DR ANGELA MAKRIS,
renal and obstetric physician,
Liverpool Hospital, Sydney, NSW.
Authors’ case study
SUSAN, 38, presents to her GP with family, including in pregnancy. She She was admitted to day-stay for clonus. Her cardiotocograph was
a plan for another pregnancy with was being seen by her GP for shared assessment of her hypertension and normal and her urine had ++++ pro-
her new partner. She had had a single care with her local hospital antena- started on a low dose of methyl- tein. She had a normal retinal fundal
live birth 13 years earlier, as well as tal clinic, her antenatal tests were dopa (250mg tds) under supervision examination without vessel changes
two miscarriages, with her first hus- all normal and initially her blood at the local hospital-based feto- or haemorrhages.
band. Her earlier full pregnancy with pressure was low at 110/60mmHg. maternal assessment unit. A car- An urgent caesarean delivery was
her son was complicated by early Her problems began at about 31 diotocograph was performed, which organised and Susan was started on
delivery at 33 weeks’ gestation, due weeks, when her GP noted her BP was “reassuring” in terms of base- intravenous hydralazine for BP con-
to upper abdominal pain, headache, to be 130/80. The GP noted that line fetal heart rate and baseline trol and magnesium sulfate for
high BP and proteinuria. there was no radiofemoral delay variability. seizure prophylaxis. She delivered a
Relevant clinical issues arising and no epigastric bruit, and there Susan’s blood tests showed a creati- 1050g baby boy. She was transferred
from this case include: was no hyperreflexia or clonus and nine concentration of 30μmol/L to ICU for 24 hours, but her BP set-
• What was the likely nature of the no epigastric tenderness, the uterus (non-pregnant reference range 60- tled to normal over the next six days
pregnancy complication 13 years was appropriate for 31 weeks’ ges- 90μmol/L) and uric acid concentra- and she was discharged on no med-
earlier? tation and there was no uterine ten- tion of 0.30mmol/L (0.15- ications. No further follow-up was
• What was the likely cause of that derness and no proteinuria. 0.35mmol/L); her LFTs were normal recommended on discharge from the
complication? The GP organised review at the and her platelet count was 175 × hospital.
• What is her risk of a repeat episode local hospital in the same week 109/L. Her BP reading was 140/90 Susan’s miscarriages had preceded
in a new pregnancy, and what can despite the patient having no new before treatment and settled to that pregnancy and were at eight and
be done to reduce that risk? symptoms. Notably there was no 120/80 over the next four hours after 10 weeks’ gestation. Both pregnan-
headache, no decrease in appetite starting methyldopa. cies had been confirmed by ultra-
Relevant history and no upper abdominal pain. Susan was returned to the care of sound investigation after a positive
Susan described her first full preg- Her BP reading at the local clinic her GP and the high-risk clinic, with pregnancy test. They were uncompli-
nancy in 1997 as uneventful in the was 140/90 and she was assessed a request to have her BP checked cated by bleeding or changes in BP.
early stages. She had a pre-preg- for pre-eclampsia. At that time, her twice a week. She remained well until Susan only had her BP checked
nancy BMI of 23kg/m and her examination was unremarkable, her 33 weeks, when she presented to the once in the intervening 12-year
medical notes reveal no personal urine protein dipstick was negative delivery suite with headache and period and that was described as
history of hypertension. There was and her baby was appropriately right upper quadrant pain. She was normal. She had no other medical or
a positive family history of hyper- grown for 32 weeks’ gestation (by noted at this time to have a BP of surgical issues.
tension on her mother’s side of the fundal height). 170/110 and brisk reflexes with cont’d next page
www.australiandoctor.com.au 14 January 2011 | Australian Doctor | 17
HOW TO TREAT Pre-eclampsia and hypertension in pregnancy
Definitions of hypertension in pregnancy and pre-eclampsia
WHILE prior definitions of ≥90mmHg occurring after 20 file of progression to superim-
Figure 1: Renal biopsy changes in ‘pure’ pre-eclampsia. Causes of secondary
hypertension in pregnancy weeks’ gestation and which posed pre-eclampsia as
Photomicrograph at high power (×80) demonstrating the hypertension identified
had up to 23 classifications unique feature of human pre-eclampsia — endothelial cell normalises by three months chronic hypertension and
(including peripheral oedema), swelling of the renal glomerular endothelial cells. This finding post-partum. There must be should be taken seriously and
we now use a four-category explains the clinical features of proteinuria, and, when severe, no prior history of hyperten- Vascular causes monitored carefully. However,
system relevant to patient risk the reduced renal function manifests as rising serum sion or renal disease for this treatment of white-coat hyper-
while pregnant and in the creatinine concentration and oliguria. diagnosis to be made. A Coarctation of the aorta tension is not usually recom-
immediate- and long-term family history is not relevant mended until the elevation in
Renal artery stenosis
post-period (see box below). here. BP is sustained above the
Pregnancy-specific diag- An increase of 25mmHg in Endocrine causes guideline limits of 140mmHg
noses are gestational hyper- systolic BP, or of 15mmHg in systolic or 90mmHg diastolic.
tension and pre-eclampsia. diastolic BP, should be a cause Phaeochromocytoma Secondary hypertension
Other diagnoses are chronic for concern and should trig- includes all known causes such
hypertension, which includes ger maternal and fetal moni- as renal disease (figure 2), dia-
essential hypertension and sec- toring. This is because of the Cushing’s syndrome betes, endocrine disease, reno-
ondary hypertension (eg, renal lower BP seen in a normal vascular disease or coarctation
disease, endocrine disease, pregnancy compared with the Hypothyroidism of the aorta (see box, left).
renovascular disease or coarc- BP of the non-pregnant state. Hypertension associated with
tation of the aorta [see box: the metabolic syndrome, oral
‘Causes of secondary hyper- Pre-eclampsia Polycystic ovary syndrome contraceptive pill use or poly-
tension identified in preg- The defining features of pre- cystic ovary syndrome also
nancy’, right]), and pre- eclampsia are listed in the box Hyperparathyroidism meets this criterion.
eclampsia superimposed on on the opposite page. The ‘must-not-miss’ causes
chronic hypertension. Renal causes include hypo- and hyperthy-
Hypertension in pregnancy as the risk of white-coat Chronic hypertension Diabetic nephropathy roidism, which also have an
Definitions of hypertension progressing to
is defined as a systolic BP of This is defined as an increase impact on the developmental
≥140mmHg or a diastolic BP pre-eclampsia. This indicates in BP before 20 weeks’ gesta- Reflux nephropathy outcomes for the baby and are
≥90mmHg. The blood pres- that any increase in BP is tion, or persisting beyond Polycystic kidney disease easily correctable. These are
sure must be elevated on two Gestational hypertension potentially pathological in three months post-partum. It relatively common. The
occasions at least four hours pregnancy. can be essential hypertension, Focal sclerosing glomerulo- maternal mortality associated
apart. It should be measured Pre-eclampsia/eclampsia white-coat hypertension or sclerosis with phaeochromocytoma is
in the right arm, with the Chronic hypertension: Gestational hypertension secondary hypertension. IgA disease always worrying, but these
patient sitting in the semi- Gestational hypertension is As mentioned above, white- women often have refractory
recumbent position, with the • Essential defined as a systolic BP coat hypertension in preg- Renin-secreting renal hypertension and the periodic
cuff fitted to the bare arm ≥140mmHg or a diastolic BP nancy has the same risk pro- tumours symptoms (flushing, tachy-
deflated appropriately slowly.
Too rapid deflation of the cuff • White-coat Figure 2: Renal biopsies of common renal diseases presenting in young women with hypertension and urinary abnormalities (proteinuria
can underestimate the systolic or haematuria).
Pre-eclampsia superimposed A: A normal glomerulus.
BP and overestimate the dias-
on chronic hypertension B: IgA disease causes mesangial expansion and is associated with hypertension and haematuria. Episodes of acute renal failure in
tolic reading. On the first
pregnancy can be difficult to distinguish from superimposed pre-eclampsia.
assessment the BP should be C: Focal sclerosis is demonstrated in the glomerulus on the right. Focal sclerosing glomerulosclerosis (FSGS) usually presents as
measured in both arms to Some of the basic proteinuria and hypertension with or without progressive renal failure. These women have a high likelihood of developing superimposed
ensure the readings are similar. preeclampsia.
Some of the basic physio- physiological D: PAS stain demonstrating the extent of fibrosis in a focal sclerosis lesion.
logical changes of pregnancy changes occur E: The globally sclerosed glomerulus in this photomicrograph illustrates advanced FSGS in a woman who had significantly worse
occur very early and result in renal failure after pre-eclampsia in her first pregnancy (creatinine 55mmol/L pre-partum and 101mmol/L at three months post-
a natural decrease in both sys- very early and partum).
tolic and diastolic BP. The car- result in a natural F: High-grade lupus nephritis with areas of focal necrosis. The glomerulus has a lobular appearance with inflammation and
diovascular responses to this
decrease in BP include:
decrease in both
• Activation of the systolic and A B
and thus sodium and water
retention and increased pressure.
• Increased heart rate (sinus
tachycardia up to 120bpm).
• Increased cardiac output.
The increase in blood
volume is further demon-
strated by reduced haemoglo-
bin concentration. The
decrease in serum creatinine
concentration seen in normal C D Segmental
pregnancy (<60μmol/L) sclerosis
reflects the increased glomeru- (PAS stain)
lar filtration rate due to
increased renal blood flow as
the renovascular resistance is
lowered by the natural preg-
The vasodilatory state man-
ifests in several ways, includ- Segmental
ing: BP decreasing from early sclerosis
pregnancy (6-8 weeks) to 24
weeks’ gestation then increas-
ing slightly towards term; and E F
BP being intrinsically more Nuclear ‘dust’
resistant to a ‘stress’ response
than is seen outside pregnancy.
This stress-resistant state
means that any increase in BP
in pregnancy is abnormal and
should therefore be considered
carefully and reviewed regu-
larly. The tendency of chronic
(ie, pre-existing) hypertension
to progress to pre-eclampsia
(17% of patients) is the same
18 | Australian Doctor | 14 January 2011 www.australiandoctor.com.au
cardia, acute anxiety and tional features of pre-eclamp- Defining features of pre-eclampsia
changes in skin colour) com- sia outlined in the box, right.
monly associated with cate- The presence of proteinuria Pre-eclampsia is defined as elevation in BP as for gestational hypertension plus one or more of the following:
cholamine excess. This is a in a patient with renal dis-
very rare cause of hyperten- ease cannot be used to define Renal involvement (figure 1) • Severe headache
sion in pregnancy. pre-eclampsia and the addi- • Significant proteinuria: dipstick proteinuria confirmed by a spot • Persistent visual disturbances: photopsia (flashes of light),
Hypertension due to tional features are required. urine protein:creatinine ratio ≥30mg/mmol scotomata, cortical blindness, retinal vasospasm
lifestyle factors such as obe- In the case of SLE with • Serum or plasma creatinine ≥ 90μmol/L (normal range 60- • Stroke
sity, illicit drug use (cocaine lupus nephropathy, the diag- 90μmol/L) Pulmonary oedema
and amphetamines) and caf- nosis of superimposed pre- • Oliguria (<0.5mL/kg for three consecutive hours) Fetal growth restriction
feine intake are not tradition- eclampsia can be more diffi- Haematological involvement Placental abruption
ally considered secondary cult still. • Thrombocytopenia (>30% reduction compared with baseline
causes, but attention to Reliance is needed on
lifestyle in the pre-pregnancy additional clinical features
• Haemolysis In the Australian guidelines for diagnosis:
period can dramatically such as intrauterine growth
reduce the risk of escalating restriction and abnormal (Both these indicate disseminated intravascular coagulation) • Proteinuria is not mandatory to make the clinical diagnosis
BP in pregnancy. LFTs. Cerebral signs can Liver involvement • Hyperuricaemia is a common but not diagnostic feature of
only be used in the absence • Raised serum transaminase levels (ALT and AST) pre-eclampsia
Superimposed of cerebral lupus, and • Severe epigastric or right upper-quadrant pain • The HELLP syndrome (haemolysis, elevated liver enzyme levels and a
pre-eclampsia platelet counts in the absence Neurological involvement low platelet count) represents a particular presentation of severe pre-
Superimposed pre-eclampsia of known antiplatelet • Convulsions (eclampsia) eclampsia, and separating it as a distinct disorder is not helpful
is defined as chronic hyperten- autoantibodies in the under- • Hyperreflexia with sustained clonus • Peripheral oedema is not a defining feature
sion (as above) with the addi- lying disease.
Aetiology and risk factors for pre-eclampsia
Aetiology and pathology Table 1: Recurrence rates for pre-eclampsia Thrombophilic abnormalities eclampsia is more common in
THE aetiology and pathology of pre- include: women with underlying renal or
Relative risk (95% confidence
eclampsia are not well understood. Risk factor • Non-pregnant protein S and pro- hypertensive disease, autoantibody
Pre-eclampsia is thought to be a two- tein C deficiency. diseases or diabetes. Recurrence rates
stage disease. Stage one occurs early Antiphospholipid antibodies 9.72 (4.34-21.75) • Antithrombin III deficiency. in women without underlying dis-
in pregnancy when there is a failure • Activated protein C resistance (usu- ease are higher in those with previous
Previous history of pre-eclampsia 7.19 (5.85-8.83)
of invasion by the (placental) tro- ally conferred by the factor V early severe pre-eclampsia without
phoblasts and inadequate remodel- Pre-exisiting diabetes 3.56 (2.54-4.99) Leiden mutation). other cause.
ling of the uterine spiral arteries. The • Hyperhomocystinaemia. The main risk factors for recur-
Multiple pregnancy 2.91 (2.04-4.21)
uterine spiral arteries do not ade- Antiphospholipid syndrome is rence of pre-eclampsia are sum-
quately invade the inner third of the Nulliparity 2.91 (1.28-6.61) defined as multiple miscarriages (three marised in table 1.
myometrium, as is normally the case. or more) or second-trimester losses
Family history of pre-eclampsia 2.90 (1.7-4.93)
As the pregnancy progresses, this in the setting of any of the following: Summary of Susan’s case
poor vascular invasion results in pla- Elevated BMI (>25kg/m ) 2
2.47 (1.66-3.67) • Abnormal APTT. Susan’s greatest risk factor is her pre-
cental dysfunction. The dysfunctional • Lupus inhibitor. vious history of early severe pre-
Maternal age >40 years 1.96 (1.34-2.87)
placenta mediates stage two of the • Lupus anticoagulant. eclampsia, which confers a risk of
disease, in which the maternal and Diastolic BP > 80mmHg at booking 1.38 (1.01-1.87) • Positive Russell’s pit viper test. recurrence of 18%. Having a new
fetal signs and symptoms of pre- • The presence of moderate or high partner confers a risk of about 10%
eclampsia are seen. The reasons why have a new partner are generally at Pre-eclampsia and miscarriage concentration of anticardiolipin for pre-eclampsia (baseline rate 5%
the trophoblasts fail to invade the increased risk of pre-eclampsia, are associated in patients with autoantibodies (IgG or IgM). for normal pregnancy). The inter-
myometrium adequately are thought which suggests that immunological obstetric lupus syndrome and can In some populations, dietary influ- pregnancy interval of more than 10
to be many, including immunological factors are involved. There is an be a manifestation of other throm- ences such as low calcium intake, years doubles the risk. However,
disturbances, vascular disease, increased risk with various forms of bophilias. These should be investi- high fat intake and soft drink con- thankfully, these risks are not addi-
endothelial dysfunction and a throm- assisted reproduction technology and gated in the settings of: sumption have been associated with tive. Susan’s diet is replete in cal-
botic tendency, to name but a few. with the number of fetuses (triplets > • Recurrent (three or more) mis- an increased risk of pre-eclampsia. A cium, and supplements are not rec-
twins > singletons). An inter-preg- carriages. dietary history for calcium and appro- ommended. Her thrombophilia and
Risk factors nancy interval of more than 10 years • Second- or third-trimester preg- priate advice regarding healthy eating anticardiolipin antibody screening
Women with a short duration of also increases the risk, but this may nancy loss. are essential for preventing pre- tests were normal. Her BP since her
cohabitation with their partner, those also reflect the risk associated with a • Early severe pre-eclampsia (deliv- eclampsia as well as general wellbeing first pregnancy has been normal.
who have used only barrier methods change in partner that may occur ery before 34 weeks of gesta- during pregnancy. Her overall risk of pre-eclampsia is
of contraception, and those who during that interval. tion). Recurrent superimposed pre- about 18%.
Physical examination for hypertension in pregnancy
PHYSICAL examination trophy or coarctation of the The systemic features of planned pregnancy.
Figure 3: Retinal changes in pre-eclampsia can represent
should be undertaken at the aorta. vasculitis (rash, abdominal malignant hypertension. The early findings of retinal oedema Biochemical screening is
first pregnancy review or as • Feeling for radiofemoral pain, joint swelling, neuropa- (the glistening retina) is a subtle change; the dramatic not a part of routine antena-
part of pre-conceptual coun- delay by simultaneously thy, confusion) should be changes of retinal haemorrhage, papilloedema and retinal tal care. In hypertensive
selling. The importance of assessing the femoral and obvious. The features of SLE infarction are advanced signs and indicate the need for urgent women a baseline creatinine
an accurate physical exami- radial pulses. such as malar rash, arthritis, delivery, as these changes reflect microvascular injury concentration is essential
nation cannot be underesti- • Listening in the epigastrium enlarged spleen, and rash may elsewhere in the white matter and cerebral cortex. (Note: the estimated GFR
mated in assessing hyperten- for a systolic bruit, indica- be more subtle. Features of [eGFR] has not been vali-
sion in pregnancy. In a tive of renal artery stenosis. endocrine conditions would dated in pregnancy). The
woman such as Susan in our Assessing urine has become include purple striae and finding of a low serum potas-
case study, who has a past less universal in regular ante- proximal muscle wasting in sium level can indicate pri-
history of pre-eclampsia and natal practice but is essential Cushing’s disease, which may mary hyperaldosteronism,
is planning another preg- in chronic or potentially also be associated with corticosteroid excess, cate-
nancy, any evidence of hypertensive women to depression and diabetes. Thy- cholamine excess or reno-
underlying causes for hyper- exclude the multitude of roid disease is best assessed vascular disease. Assessing
tension in pregnancy should glomerular possibilities. by thyroid function tests, but thyroid function can exclude
be sought, as well as look- Haematuria exists in 6.7% of a thyroid examination should either hyper or hypothy-
ing for evidence of end- the general Australian popula- include palpation and auscul- roidism as a cause of elevated
organ involvement due to tion and mostly indicates tation of the gland. BP in pregnancy, and a
hypertension. thin-membrane disease or A retinal examination is normal calcium concentra-
The initial assessment other benign forms of essential to identify hyperten- tion corrected for serum
should include: glomeular abnormality. How- sive changes (figure 3). Arter- albumin can exclude hyper-
• BP in both arms. ever, for haematuria in the ial bruits are very uncommon parathyroidism from a
• Identification of the apex presence of additional clinical in people of childbearing age parathyroid adenoma as a
beat and heart rate. features — proteinuria or with hypertension, but a renal Although also uncommon, superimposed pre-eclampsia. cause. Again, these are treat-
• Identification of an S4 or hypertension in particular — bruit can indicate fibromus- this a potentially correctable If present, consideration can able, reversible causes even if
systolic flow murmur, indi- a glomerular diagnosis should cular disease of the renal cause of refractory hyperten- be given to angioplastic or they are uncommon.
cating left ventricular hyper- be strongly considered. arteries in young women. sion associated with severe surgical correction before a cont’d page 22
14 January 2011 | Australian Doctor | 19
HOW TO TREAT Pre-eclampsia and hypertension in pregnancy
MONITORING for the cate- risk obstetric services in asso- tion, creatinine concentra-
Figure 4: Dipstick proteinuria indicates pathological proteinuria with a high degree of certainty at
gories of hypertension in preg- 2+ or greater. The diagnostic level of >300mg/day represents + or more in a standard specimen ciation with general practice tion, LFTs, platelet count
nancy should include frequent and may need to be confirmed with a 24-hour urine collection. The picture shows the dipstick shared care and midwifery and haemoglobin).
urine testing for proteinuria. result for a pre-eclamptic patient who had 42g of proteinuria, which resolved after delivery at 34 support. It would be usual for They allow appropriate
This is especially the case with weeks’ gestation. the high-risk service to review fetal monitoring, including
chronic hypertension, when a stable woman at least timely fetal ultrasound look-
BP increases alone become dif- monthly, then more frequently ing at rates of fetal growth,
ficult to interpret. Whenever if the BP is unstable, and as wellbeing and amniotic fluid
BP or antihypertensive med- the pregnancy advances. volume assessment. A car-
ication requirements increase, Adjuncts to the clinic-based diotocograph will commonly
urine testing, pre-eclampsia assessment can include the use be done in this setting. It
blood tests (platelet count, of day assessment units for involves the mother having 2-
LFTs and serum creatinine) monitoring BP and overall 4 hours of monitoring and
and fetal growth assessment wellbeing, and occasionally review by either a member of
are required to establish a admission to hospital to assess the obstetric team or the renal
diagnosis. Uric acid concen- 24-hour BP patterns and and/or obstetric medicine
tration is useful as a marker symptoms. team.
of disease progression, Given that the definition of
although this is not diagnostic. hypertension in pregnancy Summary of Susan’s case
These investigations need to requires a demonstration of Susan clearly had pre-eclamp-
be repeated as often as sustained high BP, the use of sia 13 years earlier, with a
required until delivery to mon- fetal–maternal or day-stay complete resolution of the
itor for progression to the assessment units to determine maternal complications by
more severe forms of the dis- elevated BP have a proven three months post-partum.
ease. benefit in the care of pregnant There was no history of renal
Assessing urinary protein women. These units are hospi- disease and the absence of any
includes screening via a uri- test. The ‘gold standard’ of urine is essential in early preg- text of intrauterine growth tal based and involve assessing proteinuria (or haematuria) in
nary dipstick (figure 4). 24-hour urinary protein still nancy hypertension to exclude restriction is an important the mother by: the post-partum follow-up
Greater accuracy can be stands, but can be difficult to underlying renal disease. adjunct to the diagnostic • Regular (half-hourly) BP would suggest that underlying
achieved with the use of a interpret due to inaccurate col- Screening for proteinuria at workup. checks. glomerular (renal) disease is
urine-protein:creatinine ratio lection (up to 50% of collec- the time of any change in BP, Monitoring for the progres- • Urine testing. unlikely. Her physical exami-
(>30mg/mmol) but this tions) and patient inconven- at the time of development of sion of hypertension in preg- • Assessing diagnostic blood nation did not reveal any
requires a formal laboratory ience. Initial screening of the new symptoms, or in the con- nancy usually involves high- tests (uric acid concentra- endocrine or vascular causes.
Management of pre-eclampsia risk in pregnancy
THE potential strategies for manag- Table 2: Low-dose aspirin therapy for prevention of pre-eclampsia sia in women with chronic hyperten- limited support for population-
ing the risk factors for pre-eclampsia sion, renal disease and those with a based calcium supplementation for
are limited. Diagnosis Baseline event rate (%) NNT* history of early severe pre-eclampsia preventing pre-eclampsia. However,
(prior delivery before 34 weeks’ ges- an individual history of a low-cal-
High-risk patients Low-risk pregnancy 2 500 tation) is supported by this study. cium diet should be corrected in
High-risk patients are women with Normal pregnancy 6 167 The number needed to treat to pre- pregnancy by either an increase in
several risk factors, as described in vent one case of pre-eclampsia is 25, calcium-containing foods or by
the ‘Causes’ box on page 18 and in Prior severe pre-eclampsia 18 56 34 and 56 for these groups respec- supplemental calcium. There is no
table 1, page 19. The mainstay of tively (table 2). clear evidence to suggest that bed
Renal disease 30 34
treatment of high-risk patients is pre- The greatest benefit in taking rest prevents pre-eclampsia and its
conception counselling. For women Chronic hypertension 40 25 aspirin is afforded if it is started complications in women with
with SLE or obstetric lupus (anti- before 20 weeks’ gestation. Although normal BP, although there is some
phospholipid syndrome), renal dis- *NNT is the number needed to treat to prevent one case of pre-eclampsia the larger trials were free from bleed- evidence to recommend reducing
ease or endocrine hypertension, it is ing complications, in individual physical and work activities.
important to carefully manage the diet with adequate fruit and vegeta- eclampsia. The vexing question of patients common complications of
underlying condition with multidis- bles and limits to high-fat food, soft whom to treat with aspirin has been aspirin such as gastric irritation, gingi- Summary of Susan’s case
ciplinary care throughout pregnancy. drinks and high salt intake. best addressed by a recent meta- val bleeding or haemorrhoidal bleed- In view of her 18% risk, low-dose
In patients with chronic hyperten- analysis of low-dose aspirin to pre- ing need to be monitored. aspirin is recommended for pro-
sion, appropriate control of BP Intermediate-risk patients vent pre-eclampsia.1 Indiscriminant phylaxis from 12 weeks’ to 34
throughout pregnancy is essential. The intermediate-risk group should use in primiparous women is not Low-risk patients weeks’ gestation in the absence of
Management of usual lifestyle issues be considered for low-dose aspirin supported. However, use of aspirin to For patients at low risk of pre- any early pregnancy ante-partum
is recommended, including a healthy therapy to prevent progression to pre- prevent progression to pre-eclamp- eclampsia (no risk factors) there is haemorrhage.
Management of hypertension in pregnancy
MANAGEMENT of hyper- It is not clear oping pre-eclampsia is not rec- pressure in pregnancy has not formal evidence that one agent also been implicated in fetal
tension in pregnancy is based ommended. Most trials in this been established. This is espe- is superior to another. Being skull ossification defects as
on two main strategies: con- whether tight area in the 1970s and 1980s cially the case in a woman familiar with the agent and its well as an increase in the fetal
trolling hypertension with blood pressure included bed rest as part of the with mild-moderate hyperten- characteristics is the most anomaly rate if used in the first
appropriate lifestyle advice protocol. A meta-analysis of sion. It is not clear whether important factor. Either a beta trimester.
and antihypertensives; and control improves studies including bed rest alone tight blood pressure control blocker or a centrally acting The long-acting, highly
timing the delivery based on outcomes confirms that this is not of improves outcomes compared agent is used as first-line ther- selective beta blockers atenolol
assessment of progression of proven benefit.2 However, in with less stringent blood pres- apy. Second-line treatment is and metoprolol have been
pre-eclampsia and the devel-
compared with the setting of the need for sure control. The current treat- usually a vasodilator, such as associated with fetal growth
opment of target-organ less stringent ongoing and frequent BP mon- ment target is a BP hydralazine, and third-line, restriction. The newer antihy-
effects, such as fetal growth itoring by the obstetric man- <140mmHg systolic and either a beta blocker or cen- pertensives such as lercanidip-
restriction and maternal
blood pressure agement team, including the <90mmHg diastolic. trally acting agent (depending ine should also be avoided due
organ involvement. A useful control. GP, a decrease in work com- There is strong evidence that on what was used as a first- to the lack of clinical experi-
managment algorithm is mitments is recommended and treating severe hypertension in line agent). ence and safety data.
shown in figure 5. bed rest should be considered pregnancy (>170mmHg sys- Fetal safety is a major con- Table 3 provides a summary
an option. tolic and/or >110mmHg dias- cern for the mother and, if this of antihypertensive agents in
Antihypertensives Hospital admission is often tolic) prevents episodes of issue is not adequately pregnancy.
Hypertension is best managed required when: extreme hypertension, intra- addressed with her, it will
by a combination of lifestyle • BP is not controlled. cerebral haemorrhage and pla- result in reduced compliance. Seizure prophylaxis
modification and antihyperten- • Biochemistry is abnormal. cental abruption. Several groups of agents have Anticonvulsant prophylaxis
sives. The evidence for rest is • Symptoms occur. Antihypertensive medication demonstrable fetal side effects. is reserved for cases of neu-
not conclusive, but continua- • Fetal compromise is sus- choice is influenced by famil- ACEIs and ARBs result in fetal rological irritability, and
tion of full-time work or high- pected. iarity with available agents, renal tract anomalies and severe hypertension (usually
level aerobic exercise in devel- The optimal target blood and fetal safety. There is no should be avoided. They have >170/110mmHg). This
22 | Australian Doctor | 14 January 2011 www.australiandoctor.com.au
involves the infusion of intra-
venous undiluted magnesium
Figure 5: Treatment of chronic hypertension of <20 weeks’ gestation, and gestational hypertension and pre-eclampsia
after 20 weeks’ gestation.
sulphate in a dedicated vein
and requires at least hourly FORMERLY it was consid-
observations for signs of toxi- ered that once pre-eclampsia
city (most notably, depressed BP ≥140mmHg systolic or ≥90 mmHg resolved, maternal cardiovas-
reflexes). The dose is adjusted diastolic cular risk returned to normal.
according to the urine output What is the gestation of the patient? It has become apparent that
and level of renal function. women who develop pre-
Magnesium is used at the eclampsia later in life have a
time of patient stabilisation <20 weeks’ gestation ≥20 weeks’ gestation significantly increased risk of
before delivery, then for 24 developing: hypertension
hours post-partum to prevent (odds ratio [OR] 3.7, 95%
seizures. In cases of severe Secondary cause of hypertension Is there significant proteinuria on confidence interval [CI] 2.7-
pre-eclampsia it has been evident urinalysis? 5.05), ischaemic heart disease
shown to decrease maternal Assessment must include a urine (OR 2.16, 95% CI 1.86-2.5)
mortality. analysis or stroke (OR 2.03, 95% CI
No Yes 1.64-2.67).
Seizure (eclampsia) Compared with known
treatment Yes No conventional risk factors such
Seizures are treated with a Is the booking BP Refer for urgent as smoking (relative risk 2.1,
similar protocol to that for ≥130/80mmHg? review 95%CI 1.5-2.9) pre-eclamp-
prophylaxis, and preferably Start an antihypertensive sia is a significant risk factor.
with magnesium sulfate alone. Refer for specialist agent to reduce risk of What is unclear is whether
Ongoing seizure activity, review or manage as superimposed vigilant monitoring and early
which is rare on a magnesium appropriate pre-eclampsia management of known car-
Are there any systemic Chronic
infusion, indicates a possible Counselling diovascular risk factors such
symptoms / blood hypertension
structural cause (eg, intracere- Regular review as obesity, smoking, exercise
abnormalities to suggest likely
bral haemorrhage). If benzodi- pre-eclampsia? levels, dietary factors, hyper-
azepines are used as an tension, glycaemic monitor-
adjunct to control seizures, Yes No ing and lipid abnormalities,
respiratory suppression is will reduce the future mater-
almost guaranteed. The most nal cardiovascular risk. Until
common complication of a Start an antihypertensive agent, frequent (twice weekly) evidence is available to guide
magnesium infusion is pain at Pre-eclampsia regular review, review by specialist as soon as possible clinical practice, women who
the site of the intravenous can- Refer for urgent review Several diagnostic possibilities — gestational or chronic have had pre-eclampsia
nula. hypertension but may evolve into pre-eclampsia should be counselled to avoid
smoking, exercise regularly
After delivery and maintain a healthy
After delivery the BP does not weight, and should have their
immediately normalise, taking BP measured and urinalysis
up to six weeks to return to Table 3: Antihypertensive choices in pregnancy assessed yearly. Other cardio-
normal. Thus, after delivery vascular assessments should
and on discharge antihyper- Dosing Usual Max dose Side effects Notes Mechanism also be undertaken, such as
tensives usually need to be starting dose of action fasting glucose and lipids on
continued. In the weeks after a 3-5-yearly basis, depending
delivery it is important not to Methyldopa tds or 250mg 2000mg/ Drowsiness, Contraindicated in people Centrally acting on the individual profile.
abruptly stop the antihyper- qid day headache, increased taking monoamine oxidase anti-adrenergic
tensives but to wean gradu- risk of postnatal inhibitors or lithium, and those
ally. depression, postural with liver disease or positive References
Uncommonly the BP can hypotension, liver Coomb’s test 1. Duley L, et al.
actually increase after deliv- dysfunction, Antiplatelet agents for
ery. In this instance the med- leukopenia, preventing pre-eclampsia
ication dosages will also have haemolytic anaemia and its complications.
to be increased and titrated to Cochrane Database of
control the elevated BP. Clonidine qid 75μg 300μg qid Drowsiness, dry Avoid stopping suddenly due Centrally acting Systematic Reviews 2007;
NSAIDs are contraindicated mouth, dry eyes, to pressor effect sympathetic 18 Apr(2):CD004659.2.
in women with hypertension nausea, reduced inhibitor 2. Meher S, et al. Bed rest
in the post-partum period, in fetal heart rate with or without
which context they have been hospitalisation for
shown to exacerbate hyper- Oxprenolol tds 40mg 120mg tds Nightmares Contraindicated in people Beta blocker hypertension during
tension. The specific mecha- with asthma. pregnancy. Cochrane
nism is not clear but is prob- Avoid in possible Database of Systematic
ably multifactorial, including phaechromocytoma, in heart Reviews 2005;
reduced renal prostaglandin failure, bradycardia, peripheral (4):CD003514.
synthesis, increased endothe- vascular disease, or patients
lin (a potent vasoconstrictor) with Raynaud’s phenomenon Online resources
production, as well as • Preeclampsia Research
sodium and water retention. Laboratories (PEARLS):
Labetolol bd/tds 100mg 2.4g/day Worsening asthma, Contraindicated in asthmatics. Alpha- and beta
If antihypertensives are still www.preeclampsia.org.au
(no thera- cough, nightmares, Avoid in possible blocker
required at six weeks post- • Australian Action on
peutic bradycardia phaechromocytoma, in heart
partum, consideration needs Preeclampsia (AAPEC):
benefit failure, bradycardia, peripheral
to given to whether the www.aapec.org.au
above vascular disease or patients
woman has chronic hyperten-
600mg tds) with Raynaud’s phenomenon
sion rather than pregnancy-
related hypertension. Com-
plete resolution is expected by Nifedipine tds 10mg 30mg tds Headache, Metabolised through CYT Calcium-channel
three months post-partum for oedema, palpitations, P450-3A4 —consider blocker
gestational hypertension and nausea dizziness interaction with, eg,
pre-eclampsia. phenytoin and cisapride
The urine analysis also
needs to be rechecked to Hydralazine qid 12.5mg 50mg qid Flushing, palpitations, Should be a second- or third- Peripheral vasodilator
ensure the resolution of the headaches, nausea line agent to minimise side
proteinuria and to exclude effects. Can cause
the possibility of underlying autoimmune lupus
renal disease. The protein-
uria related to pre-eclampsia
may take up to three months will have completely is difficult to interpret changes, such as an elevated
to completely resolve. Ideally resolved or at least should because of the ongoing vagi- creatinine, LFTs or haema-
a urinalysis should be per- be considerably reduced at nal blood loss. tological abnormalities, they
formed at six weeks and in six weeks post-partum. A Similarly, if there were any should be repeated about
most cases the proteinuria urinalysis before six weeks residual biochemical one week after discharge. cont’d next page
www.australiandoctor.com.au 14 January 2011 | Australian Doctor | 23
HOW TO TREAT Pre-eclampsia and hypertension in pregnancy
day. She was started on but was in otherwise good study from Peru in 2007 support their use in the man- was strongly influenced by
oxprenolol and low-dose condition, with Apgar scores showed a doubling of the odds agement of pre-eclampsia. The the pattern of growth in early
aspirin. 9 and 9, at one and five min- for pre-eclampsia.2 It is unclear importance of pre-eclampsia neonatal life and predicted
When I saw her three weeks utes, respectively. whether this is significant in as an independent risk factor both BMI and risk of hyper-
later at 31 weeks’ gestation her Eight weeks later Gayle other cultural settings. for CVD is a recent finding tension. Despite these theoret-
BP was well controlled on her brought her son for vaccina- and work needs to be done to ical links, there is no current
medication but she was feel- tion. Her BP had normalised Aspirin and calcium are used determine which patients recommendation to screen
ing sad and emotional. We dis- and she was taking no med- for prevention of pre-eclamp- would likely benefit from such these children for cardiovas-
DR RENATA CHAPMAN
cussed eventual referral to a ications at all. All biochemical sia in pregnant women with a an intervention. cular risk factors in child-
counsellor, and Gayle was abnormalities had resolved but past history of the condition, hood, other than that which
going to consider that option. Gayle admitted that she did or the presence of risk factors How would this recommen- would be undertaken due to
Case study She did not attend the rou- not feel well — she was very for it. We know that women dation relate to the recently their prematurity.
GAYLE, 32, came to see me tine follow-up but phoned me emotional, crying a lot and with a history of pre-eclampsia published meta-analysis in the
for confirmation of her preg- five weeks later, complaining unable to bond well with her are at higher risk of developing BMJ indicating higher risk of Is there any evidence of the
nancy. She had two previous of a sudden-onset upper-quad- child. Her Edinburgh Postna- hypertension and other cardio- cardiac events in women benefit of heparin in the man-
early miscarriages at six weeks. rant abdominal pain, nausea tal Depression Scale score was vascular diseases in the future. taking calcium supplements?5 agement of pre-eclampsia?
This time she was nine weeks and vomiting. When I saw her 22, indicating depression. Would there be a place for This is clearly one of the major Heparin benefit in preg-
pregnant. She was overweight, that day her BP was 160/100 long-term use of aspirin and potential detrimental effects of nancy for prevention of pre-
with a BMI of 29 kg/m2, and and she had significant right Questions for the author calcium in Gayle, who with long-term calcium use and eclampsia is indicated in
had background of mild poly- abdominal tenderness, bruises It seems that pre-eclampsia her PCOS has additional risk needs to balanced against any women with antiphospholipid
cystic ovary syndrome with and hyperreflexia. There was and cardiovascular diseases of developing CVD? proven benefit in prevention syndrome and other thrombo-
axillary acanthosis nigricans marked albuminuria (+++) on have similar risk factors. A benefit for the use of cal- of CVD. philias. There is no current rec-
and facial acne. Her routine her urine examination. Her Depression is now a well- cium for prophylaxis was ini- ommendation for its global
examinations included BP of blood tests performed later in recognised independent risk tially shown in developing Gayle’s son was born with use in the prevention or treat-
110/70mmHg and blood and hospital showed thrombocy- factor for cardiovascular dis- countries, but its usefulness signs of mild growth retarda- ment of pre-eclampsia.
urine tests, which were topenia and elevated AST and eases. Could it also be an inde- was not replicated in a large- tion. Are there any particular
normal. uric acid levels. pendent risk factor for pre- scale trial in the US.3 However, problems I should be looking References
Gayle returned to me at 28 Once in hospital Gayle was eclampsia? the meta-analysis of several for in children of mothers who 1. Obstetrics and Gynecology
weeks for review, complaining given hydralazine and methyl- Depression is not currently smaller trials did show a bene- experienced pre-eclampsia? 2000; 95:487-90.
of worsening peripheral dopa (Aldomet) to control her recognised as a risk factor for fit in pre-eclampsia preven- The Barker hypothesis, 2. BMC Women’s Health 2007;
oedema and headache. Her BP BP and was started on IV pre-eclampsia. A single study tion.4 now known as the develop- 7:15.
was 140/90 and there was + magnesium sulfate infusion to from Finland showed an Use of aspirin and calcium mental origins of health and 3. New England Journal of
albumin on the urinary dip- prevent convulsions. increased risk of pre-eclampsia in the long term as a primary disease theory, indicates that Medicine 1997; 337:69-77.
stick. I phoned my local hospi- A caesarean section was in women who were identified prevention strategy for CVD growth restriction is a risk 4. Cochrane Database of
tal and Gayle was seen by the performed and a baby boy as having anxiety or depres- should be the subject of future factor for future (later-life) Systematic Reviews 2006;
maternal–fetal medicine assess- delivered. He showed mild sion at 15-18 weeks’ gestation.1 randomised controlled trials. CVD. In the Raine cohort Issue 3, CD001059.
ment unit physician the same signs of growth retardation A subsequent case–control There are no current data to from Perth, being born small 5. BMJ 2010; 341:c3586.
How to Treat Quiz Complete this quiz online and fill in the GP evaluation form to earn 2 CPD or PDP points. We no longer accept quizzes
by post or fax.
The mark required to obtain points is 80%. Please note that some questions have more than one correct answer.
Pre-eclampsia and hypertension in
pregnancy — 14 January 2011 www.australiandoctor.com.au/cpd/ for immediate feedback
1. Which TWO of the following are regarded diastolic from baseline BP should trigger 6. Which TWO statements are correct? c) Risk factors for pre-eclampsia include barrier
as relating to elevated blood pressure only maternal and fetal monitoring, even if the BP a) Antenatal urine assessment is essential in methods of contraception, a new partner and
in pregnancy? is <140/90mmHg women with chronic hypertension or with risk multiple-fetus pregnancy
a) Gestational hypertension d) Proteinuria is mandatory for a diagnosis of factors for hypertension d) High calcium intake is a risk factor for pre-
b) Pre-eclampsia pre-eclampsia in a pregnant patient with b) In a hypertensive pregnant woman, a baseline eclampsia
c) Chronic hypertension hypertension creatinine concentration is inaccurate and
d) Pre-eclampsia superimposed on chronic unhelpful in monitoring renal function 9. Which TWO statements are correct?
hypertension 4. Which TWO statements are correct c) Calcium, potassium and thyroid function tests a) Use of aspirin for prophylaxis against pre-
regarding pre-eclampsia? may identify treatable secondary causes of eclampsia is appropriate for women with
2. Which TWO statements are correct? a) Thrombocytopenia and haemolysis reflect hypertension prior severe pre-eclampsia, renal disease or
a) Hypertension in pregnancy is defined as a disseminated intravascular coagulation d) Uric acid concentration is not useful as a chronic hypertension
systolic blood pressure ≥140mmHg or a b) Peripheral oedema is a defining feature marker of pre-eclampsia disease progression b) Aspirin prophylaxis against pre-eclampsia is
diastolic blood pressure ≥90mmHg c) Hyperreflexia, severe headache or visual appropriate in all primiparous women
b) Too rapid deflation of the cuff can disturbances are some of the neurological 7. Which THREE statements are correct c) Aspirin prophylaxis for pre-eclampsia should
overestimate the systolic blood pressure and manifestations regarding monitoring for the development be started after 20 weeks’ gestation
underestimate the diastolic reading d) Hyperuricaemia is a common diagnostic of pre-eclampsia? d) Continuation of full-time work or high-level
c) Normally blood pressure decreases from feature a) An increase in blood pressure should trigger a aerobic exercise in women developing pre-
early pregnancy (6-8 weeks) to 24 weeks’ platelet count, LFTs and a serum creatinine eclampsia is not recommended
gestation then increases slightly towards 5. Which TWO statements are correct? test
term a) Chronic hypertension presents after 20 b) Fetal ultrasound monitors fetal growth rate, 10. Which TWO statements are correct?
d) In a normal pregnancy, the BP response to weeks’ gestation wellbeing and amniotic fluid volume a) Centrally acting agents or certain beta
‘stress’ is augmented b) Chronic hypertension in pregnancy includes c) Urine assessment by dipstick is unhelpful blockers are first-line therapy for
essential hypertension and secondary d) Monitoring ideally should involve high-risk hypertension in pregnancy
3. Which TWO statements are correct? hypertension obstetric services at least monthly b) ACEIs or ARBs are second-line therapy for
a) The decrease in the concentrations of c) Hypothyroidism and hyperthyroidism are hypertension in pregnancy
haemoglobin and creatinine in a normal correctable causes of hypertension that also 8. Which THREE statements are correct? c) Seizure prophylaxis with IV magnesium
pregnancy reflect an increase in blood have an impact on developmental outcomes a) In pre-eclampsia there is placental dysfunction sulfate is used where there is neurological
volume for the baby due to failure of the placental trophoblast to irritability or severe hypertension.
b) Gestational hypertension occurs within the d) White-coat hypertension in pregnancy is invade the uterine spiral arteries in the d) Once pre-eclampsia has resolved, the
first trimester benign and not associated with an increased myometrium normally maternal cardiovascular risk returns to
c) An increase of 25mmHg systolic or 15mmHg risk of pre-eclampsia b) Definitive treatment of pre-eclampsia is delivery normal
CPD QUIZ UPDATE
The RACGP requires that a brief GP evaluation form be completed with every quiz to obtain category 2 CPD or PDP points for the 2011-13 triennium. You can
complete this online along with the quiz at www.australiandoctor.com.au. Because this is a requirement, we are no longer able to accept the quiz by post or HOW TO TREAT Editor: Dr Giovanna Zingarelli
fax. However, we have included the quiz questions here for those who like to prepare the answers before completing the quiz online. Co-ordinator: Julian McAllan
Quiz: Dr Giovanna Zingarelli
NEXT WEEK The next How to Treat confronts the anxiety-producing, real or perceived abnormalities in the head shape of an infant or child. The author is Professor David John David, clinical professor of
craniomaxillofacial surgery, University of Adelaide, and head of the Australian craniofacial unit at the Women’s and Children’s Hospital, North Adelaide, SA.
24 | Australian Doctor | 14 January 2011 www.australiandoctor.com.au