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Grand Rounds

Cochrane Update: Antenatal Corticosteroids and Impact on Respiratory Morbidity or Death in Preterm Births

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BACKGROUND AND PURPOSE:

  • In this second update to a 2006 review, McGoldrick et al. (Cochrane Database of Systematic Reviews, 2020) assess the effects of administering corticosteroids to women prior to anticipated preterm birth (<37 weeks), including maternal, fetal, and newborn outcomes

METHODS:

  • Systematic review and meta-analysis (through September 3, 2020)
  • Data sources
    • Cochrane Pregnancy and Childbirth Group’s Trials Register | ClinicalTrials.gov | WHO International Clinical Trials Registry Platform (ICTRP)
    • Reference lists of retrieved studies
  • Inclusion criteria
    • RCTs
    • Studies that compared antenatal corticosteroids with placebo or no treatment prior to anticipated preterm delivery in women with a singleton or multiple pregnancy
    • Preterm delivery could be elective or following rupture of membranes or spontaneous labor
  • Study design
    • Two review authors independently assessed trials for inclusion
    • Authors then extracted data and checked them for accuracy
    • Certainty of evidence was assessed using GRADE criteria
  • Primary outcomes
    • Perinatal death
    • Neonatal death
    • RDS
    • IVH
    • Birthweight
    • Developmental delay in childhood
    • Maternal death

RESULTS:

Trials and Data Included

  • 27 studies | 11,272 women | 11,925 neonates | 20 countries
    • 10 trials (4422 women) were conducted in lower- or middle-resource settings
  • 6 trials were removed from analysis that were included in a previous version of this review because they did not meet pre-defined trustworthiness criteria
  • Course of steroids prescribed
    • Single course: 19 trials
    • Repeated courses: 8 trials
  • Risk of bias
    • Low risk: 15 trials
    • High risk due to lack of blinding: 10 trials
  • Certainty of evidence
    • Overall: moderate to high
    • Certainty was downgraded for IVH, developmental delay, and for maternal adverse outcomes (death, chorioamnionitis and endometritis)

Neonatal & Child Outcomes

  • Antenatal corticosteroids reduce the risk of
    • Perinatal death
      • RR 0.85 (95% CI, 0.77 to 0.93)
      • 9833 infants; 14 studies; high-certainty evidence
      • 2.3% fewer (95% CI, 1.1% to 3.6% fewer)
    • Neonatal death
      • RR 0.78 (95% CI, 0.70 to 0.87)
      • 10,609 infants; 22 studies; high-certainty evidence
      • 2.6% fewer (95% CI, 1.5% to 3.6% fewer)
    • Respiratory distress syndrome
      • RR 0.71 (95% CI, 0.65 to 0.78)
      • 11,183 infants; 26 studies; high-certainty evidence
      • 4.3% fewer (95% CI, 3.2% to 5.2% fewer)
  • Antenatal corticosteroids probably reduce the risk of
    • IVH
      • RR 0.58 (95% CI, 0.45 to 0.75)
      • 8475 infants; 12 studies; moderate-certainty evidence
      • 1.4% fewer (95% CI, 0.8% to 1.8% fewer)
  • Antenatal corticosteroids probably have little to no effect on
    • Birthweight
      • Mean difference (MD) -14.02 g (95% CI, -33.79 to 5.76)
      • 9551 infants; 19 studies; high-certainty evidence
  • Antenatal corticosteroids probably lead to a reduction in
    • Developmental delay in childhood
      • RR 0.51 (95% CI, 0.27 to 0.97)
      • 600 children; 3 studies; moderate-certainty evidence
      • 3.8% fewer (95% CI, 0.2% to 5.7% fewer)

Maternal outcomes

  • Antenatal corticosteroids probably result in little to no difference in
    • maternal death
      • RR 1.19 (95% CI, 0.36 to 3.89)
      • 6244 women; 6 studies; moderate-certainty evidence
      • 0.0% fewer (95% CI, 0.1% fewer to 0.5% more)
    • Chorioamnionitis
      • RR 0.86 (95% CI, 0.69 to 1.08)
      • 8374 women; 15 studies; moderate-certainty evidence
      • 0.5% fewer (95% CI, 1.1% fewer to 0.3% more)
    • Endometritis
      • RR 1.14 (95% CI, 0.82 to 1.58)
      • 6764 women; 10 studies; moderate-certainty
      • 0.3% more (95% CI, 0.3% fewer to 1.1% more)
  • Note: Wide 95% CIs in all of these outcomes include possible benefit and possible harm

CONCLUSION:

  • The use of antenatal corticosteroids in women at risk of preterm delivery reduces the risk of perinatal and neonatal death, RDS, and probably reduces the risk of IVH
    • This robust evidence supports the continued use of antenatal corticosteroids, even in variable resource settings
  • Evidence remains limited regarding
    • Multiple gestation
    • Hypertensive disorders in pregnancy
    • PPROM
    • Dosing
  • The authors state

Further research should focus on variations in the treatment regimen, effectiveness of the intervention in specific understudied subgroups such as multiple pregnancies and other high‐risk obstetric groups, and the risks and benefits in the very early or very late preterm periods

Learn More – Primary Sources:

Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth

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Related ObG Topics:

Is Labor Independently Associated with Reduced Neonatal Respiratory Complications?
Antenatal Corticosteroids – When to Administer?
Results from the PRECISE Study: Repeat Prenatal Corticosteroid Treatment for Preterm Birth
In Women at Risk of Late Preterm Delivery, is Corticosteroid Therapy Still Cost-Effective?

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