Preterm Labor

							Preterm Labor:
Evidence Based View
   Dr.Mohamed El Sherbiny
     MD Obstetrics&Gynecology
        Senior Consultant
     Damietta General Hospital
         Damietta Egypt
Evidence Based Sources:

PubMed
Cochrean library
RCOG Guidelines
ACOG Issues Guidelines
National Guideline Clearinghouse
MOH Sing. Guideline
           Definition
 Preterm labor is the presence of
contractions of sufficient strength
and frequency to effect
progressive effacement and
dilation of the cervix between 20
and 37 weeks' gestation

             WHO
      Preterm Labor
        Incidence : 6- 10%

• Spontaneous          : 40-50%

• PROM                : 25-40%

• Obstetrically indicated : 20-25%
  Preterm Labor
Most mortality and
morbidity is experienced
by babies born before 34
weeks.
Major Risks Of Preterm Delivery
•   Death
•   Respiratory distress syndrome
•   Hypothermia
•   Hypoglycaemia
•   Necrotising enterocolitis
•   Jaundice
•   Infection
•   Retinopathy of prematurity
    Goldenberg , Obstetrics &Gynecology 11-2002
Can preterm
labor be
predicted?
       Prediction
1. Assessment of risk factors
2. Vaginal examination to assess the
   cervical status
3. Ultrasound visualization of
   cervical length and dilatation
4. Detection of foetal fibronectin in
   cervicovaginal secretions
   1-Risk Factors
While the exact cause of
 preterm labor is often
 unknown, there is strong
 evidence that intrauterine
 infection may play a role in
 very early preterm labor.
 ACOG NEWS RELEASE November 2002
                 1-Risk Factors
               Bacterial Vaginosis
    Bacterial vaginosis increased the
     risk of preterm delivery >2-fold .
    Risks were higher for those
     screened at <16 weeks (odds ratio,
     7.55; 95% CI, 1.80-31.65) than those
     at <20 weeks of gestation (odds
     ratio, 4.20; 95% CI, 2.11-8.39).
Leitich et al Am J Obstet Gynecol. 2003 Jul;189(1):139 ( Meta-Analysis)
      1-Risk Factors
     Other Risk Factors
Multiple pregnancy: risk >50%
Previous preterm delivery: risk 20- 40%
Cigarette smoking: risk 20-30%
Cervical incompetence
 Uterine abnormalities

MOH Sing. Guideline Grade C Recommendation 2001
      1-Risk Factors
         Other Risk Factors
Young age of mother - less than 16 years of age.
•Lower socioeconomic class.
Reduced body mass index (BMI) - BMI less than
19.0.
Antiphosphlipid syndrome.
 Obstetric complications, including hypertension in
pregnancy,antepartum haemorrhage, infection,
polyhydramnios, foetalabnormalities.
MOH Sing. Guideline Grade C Recommendation 2001
   2-Vaginal examination




Digital examination is the traditional
   method used to detect cervical
   maturation, but quantifying these
   changes is often difficult.
      3-Vaginal U/S
Vaginal ultrasonography
 allows a more objective
 approach to examination
 of the cervix.

 Goldenberg , Obstetrics &Gynecology 11-2002
               4-Fibronectin Test
    Outcome                             Sensitivity specificity

        Delivery <37                       52%            85%

        Delivery <34                       53%            89%
   Delivery within 1 Week                   71%           89%
   Delivery within 2 Week                   67%           89%
   Delivery within 3 Week                   59%           92%
Leitich & Kaider ,BJOG. 2003 Apr;110 , 20:66-70. Meta-Analysis 40 studies
Prevention
Prevention of Preterm Labor

Women at increased risk of
 preterm delivery may be
 identified by various risk
 factors in the obstetric
 history and treated.

American Academy of Pediatrician & ACOG 1997
 17 Hydroxy -Progesterone Caproate

  Prophylactic use of 17 hydroxy
   progesterone caproate to prevent
   preterm labor revealed a significant
   decrease in preterm birth .
 However, it has not successfully inhibited
  active preterm labor.
Keirse. Br J Obstet Gynaecol 1990;97:149-54. Meta-anlysis of 6RCTs.

Meis et al. N Engl J Med. 2003 Jun 12;348(24):2379-85.RCT (19 centers )
Treatment Of Vaginosis
 Treatment of asymptomatic abnormal
  vaginal flora and bacterial vaginosis
   with oral clindamycin early in the
   2nd trimester significantly reduces
   the rate of late miscarriage and
   spontaneous preterm birth.

Ugwumadu et al. Lancet. 2003 Mar 22;361:983-8. ) RCT
Diagnosis
             Diagnosis
3 criteria to document PTL(20-37w)
1-Regular uterine contractions occur
  at 4/20 min. or 8/60 min. Plus:
  progressive change in the cervix.
2- Cervical dilatation > 1 cm
                _
3- Effacement > 80%.
American Academy of Pediatrician & ACOG 1997
Vaginal U/S+ Fibronectin Test
Suspected preterm labor with no
 cervical changes :
Negative fetal fibronectin +
Cervical length > 30 mm
the likelihood of delivering in the next week
 is less than 1%.
Thus most women with a negative test can
 safely be sent home without treatment.
    Goldenberg , Obstetrics &Gynecology 11-2002
  Treatment
•Inhibition of labor
• Corticosteroid
• Antibiotics
•Others.
Inhibition Of Labor
•Bed rest :DVT
•Hydration &sedation
• Tocolytics
     Most Efforts to Prevent
   Preterm Labor Not Effective
Until effective strategies are found, efforts
  should be aimed at preventing newborn
  complications by :
• Corticosteroids
• Antibiotics against group B strep
• Avoiding traumatic deliveries.
• Delivery in a center with experienced
  resuscitation teams and neonatal intensive
  care
  ACOG NEWS RELEASE: November 2002
  Incidence of preterm birth in USA, 1981-1999.




National Center for Health Statistics. Goldenberg.. Obstet Gynecol 2002
             Hydration
  • Intravenous hydration does not seem
    to be beneficial, even during the
    period of evaluation soon after
    admission,
  • Women with evidence of dehydration
    may, however, benefit from the
    intervention.

Stan et al (Cochrane Review 2000). In:
The Cochrane Library, Issue 1 2003. Oxford
   Is Tocolysis Better Than No
  Tocolysis For Preterm Labour?
  • It is reasonable not to use tocolytic
    drugs, as there is no clear evidence
    that they improve outcome. However,
    tocolysis should be considered if the
    few days gained would be put to good
    use, such as completing a course of
    corticosteroids, or in utero transfer


RCOG Guideline Grade A recommendation 2002 (Valid:2005)
           Tocolytics
Most authorities do not
 recommend use of tocolytics
 at or after 34 weeks' .
There is no consensus on a
 lower gestational age limit for
 the use of tocolytic agents.
 Goldenberg , Obstetrics &Gynecology 11-2002
Choice Of Tocolytic Drug
B –Sympathomimetic
(Ritodrine)
Magnesium sulphate
Indomethacin

Nifedipine = Epilate
Atosiban= Tractocile
     Choice Of Tocolytic Drug
If a tocolytic drug is used, ritodrine no
   longer seems the best choice.
 Atosiban or nifedipine appear
   preferable as they have fewer adverse
   effects and seem to have comparable
   effectiveness.

RCOG Guideline Grade A recommendation 2002 (Valid:2005)
     B -Sympathomimetic Agents.
  • Use of beta-agonists should be
    restricted to the management of
    preterm labour between 20 and
    35 completed weeks, including
    women with ruptured membranes.
    (Grade A)

RCOG Guideline Grade A recommendation 1997
• Clinical Green Top Guidelines
Tocolytic Drugs for Women in Preterm Labour (1B)




(Replaces Guideline No.1A Beta-agonists and No.1
  Ritodrine)
         Valid until October 2005
         unless otherwise indicated
  B -Sympathomimetic Agents.
• Maternal: pulmonary edema, myocardial
  ischemia, arrhythmia, and even maternal
  death.
• Fetal : arrhythmia, cardiac septal
  hypertrophy , hydrops, pulmonary edema,
  and cardiac failure. hypoglycemia,
  periventricular-intraventricular
  hemorrhage, and fetal and neonatal death.
  .
     Magnesium Sulfate
 Magnesium sulphate is ineffective
   at delaying birth or preventing
   preterm birth, and its use is
   associated with an increased
   mortality for the infant.

Crowther et al, (Cochrane Review) August 2002. In: The
Cochrane Library, Issue 1 2003. Oxford: Update Software.
      Nitric Oxide Donors
There is insufficient evidence to
 support the routine
 administration of nitric oxide
 donors (nitroglycerin )in the
 treatment of preterm labor.

Duckitt& Thornton , (Cochrane Review) March 2002. In: The
Cochrane Library, Issue 1 2003. Oxford: Update Software.
        Indomethacin
  Compared with ritodrine there is
  insufficient evidence for any
  differential effect on delay in
  delivery, but indomethacin does
  seem to have fewer maternal
  adverse effects than the beta-
  agonists
RCOG Guideline Grade B Recommendation 2002 (Valid:2005)
        Indomethacin
Fetal risk:
Premature closure of the ductus.
Renal and cerebral vasoconstriction.
Necrotising enterocolitis
Common with high dose and
 prolonged exposure.
RCOG Guideline Grade B Recommendation 2002 (Valid:2005)
      Indomethacin
 Indomethacin therapy for
< 48 hours
< 30-32 weeks' gestation)
Not > 200mg/day.
appears to be a relatively safe and
  effective tocolytic agent
Goldenberg , Obstetrics &Gynecology 11-2002
    Indomethacin
 Indomethacin can be
used as a second-line
tocolytic agent in early
gestational age preterm
labors.
 Goldenberg , Obstetrics &Gynecology 11-2002
    Indomethacin
  Indomethacin may be a first-
  line tocolytic in:
• Associated polyhydramnios :
     ( to have renal effects of
  indomethacin)
          Newton eMedicine 2002
      Indomethacin
Capsule         25mg oral
Amp             50mg
Rectal Supp     100 mg

   50 mg Loading dose
    Then 25-50mg /6hs
  Newton eMedicine 2002
Atosiban: Tractocil
  Atosiban, a synthetic
 peptide, is a competitive
 antagonist of oxytocin at
     uterine oxytocin
        receptors.
   Atosiban: Tractocil
Atosiban - compared with beta-agonists-
  has:
Little difference in the effect of these agents on
  delayed delivery
Fewer maternal adverse effects than beta-agonists,
  such as chest pain, palpitations , tachycardia ,
  hypotension , dyspnoea ,vomiting , and headache.


Worldwide Atosiban Vs Beta-agonists Study Group. BJOG 2001;108:133–42(   RCT)
                     Nifedipine
 Nifedipine- compared with ritodrine -
    has:
  Higher delaying of delivery for >48 H.
  Lower risk of RDS &Neonatal jundice.
 Lower admission to NN ICU
 Fewer maternal adverse effects
Tsatsaris et al, . Obstet Gynecol 2001;97:840–7. (Meta-analysis)
                Nifedipine
 When tocolysis is indicated for women in
   preterm labor, calcium channel blockers
   are preferable to other tocolytic agents
   compared, mainly betamimetics.
 Further research should address the
   effects of different dosage regimens and
   formulations
King et al, (Cochrane Review) 9-2002. In: The Cochrane
Library, Issue 1 2003. Oxford: Update Software.
                     Nifedipine
 20mg initial
 10-20 mg /4-6 h
    Epilate capsule                                  :10mg
    Epilate retard Tablet: 20 mg

Tsatsaris et al, . Obstet Gynecol 2001;97:840–7. (Meta-analysis)
   Maintenance Tocolysis Is Not
Recommended For Routine Practice.

  There is insufficient evidence for any
   firm conclusions about whether or not
   maintenance tocolytic therapy
   following threatened preterm labor is
   worthwhile. Therefore maintenance
   therapy cannot be recommended for
   routine practice.
RCOG Guideline Grade A recommendation 2002 (Valid:2005)
     Corticosteroids
Antenatal corticosteroids are associated
  with a significant reduction in rates of
  RDS, neonatal death and
  intraventricular haemorrhage, although
  the numbers needed to treat increase
  significantly after 34 weeks' gestation.

RCOG Guidelines : Grade A Recommendation
     Corticosteroids
The optimal treatment-delivery
  interval for administration of
  antenatal corticosteroids is
  after 24 hours but < 7 days after
  the start of treatment.

RCOG Guidelines : Grade A Recommendation
    Corticosteroids
Two 12 mg doses of betamethasone
 given IM 24 hours apart, Or
Four 6 mg doses of dexamethasone
 given IM 12 hours apart (I-A).
There is no proof of efficacy for any
 other regimen.

SOGC Recommendation Jan. 2003
              Antibiotics
   There is no evidence of clear
    overall benefit from
    prophylactic antibiotics for
    preterm labour with intact
    membranes on neonatal
    outcomes.
King & Flenady (Cochrane Review August 2002). In: The
Cochrane Library, Issue 1 2003. Oxford: Update Software.
Screening for GB Strep.
ACOG Advises
 Screening All
 Pregnant Women
 for Group B Strep.
 ACOG NEWS RELEASE November 2002
Group B Streptococci (GBS) Prophylaxis

 All patients in preterm labor are
  considered at high risk for
  neonatal GBS sepsis and
  should receive prophylactic
  antibiotics regardless of
  culture status.
   Goldenberg , Obstetrics &Gynecology 11-2002
Group B Streptococci (GBS) Prophylaxis

 The goal of this strategy is
  to prevent neonatal
  sepsis, and not to
  prevent preterm birth.

   Goldenberg , Obstetrics &Gynecology 11-2002
Prophylactic Vitamin K Or Phenobarbital
   Have not been shown to
    significantly prevent
    periventricular
    haemorrhages in preterm
    infants.
Crowther & Henderson-Smart (Cochrane Review Novemb. 2000 )
In:The Cochrane Library, Issue 1 2003. Oxford: Update Software
Crowther & Henderson-Smart (Cochrane Review May 2003 )
      Cochrane Library, Issue 1 2003. Oxford: Update Software
In:TheGoldenberg , May 2003
     Conclusions
Various strategies that have been
used to prevent or treat preterm
labor, haven't proven effective.

Tocolysis should be considered only
for 2 days- if needed - for
corticosteroids thereby , or in utero
transfer to a tertiary center .
   Conclusions
If a tocolytic drug is
 used, ritodrine no
 longer seems the
 best choice.
       Conclusions
Other drugs with fewer adverse effects and
 comparable effectiveness are now
 recommended
 Atosiban or nifedipine have been
 recommended by RCOG
 endomethacin may be used as a 2nd line
 tocolytic or if there is polyhydramnous
   Conclusions
Maintenance tocolytic
 therapy has no proven
 effect.
It cannot be recommended
 for routine practice.
Thank You