Use of antenatal corticosteroids in special circumstances: a comprehensive review EVERETT F. MAGANN1 , KJELL HARAM2 , SONGTHIP OUNPRASEUTH1 , JAN H. MORTENSEN2 , HORACE J. SPENCER2 & JOHN C. MORRISON3 1Department of Obstetrics and Gynecology, Department of Biostatistics, University of Arkansas for the Medical Sciences, Little Rock, AR, USA, 2Haukeland University Hospital, Department of Public and Primary Care, University of Bergen, Bergen, Norway, and 3Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS, USA ACTA Obstetricia et Gynecologica Scandinavica Journal Club -Obstetrics- April 2017 Edited by Francesco D’Antonio

Background Corticosteroids have been proved to reduce perinatal neonatal morbidity/mortality in at-risk pregnancies and result in substantial health cost savings. Steroid treatment is currently recommended by the National Institutes of Health, the American Congress of Obstetrics and Gynecology (ACOG), and the American Academy of Pediatrics (AAP) as well as other groups for women at risk for preterm delivery (>26–34 weeks). There are patients with special circumstances where antenatal corticosteroids have not been fully evaluated, such as those with preterm premature rupture of the membranes (PPROM), hypertension, intrauterine growth restriction (IUGR), near-term delivery (34–38 weeks), multi-fetal pregnancies, and the very preterm (23–26 weeks’ gestation).

Aim of the study To determine, in pregnancies complicated by preterm premature rupture of membranes (PPROM), hypertension, intrauterine growth restriction, multi-fetal gestations and pregnancies 23–26 weeks and ≥34 weeks’ gestation, whether antenatal corticosteroids benefit the fetus.

Methodology Study design: Systematic review. Methods: Literature search: PubMed, Web of Science, clinical trials.gov, Cochrane Database of Systematic Reviews). Inclusion criteria: Pregnancies complicated by preterm premature rupture of membranes (PPROM), hypertension, intrauterine growth restriction, multi-fetal gestations and pregnancies 23–26 weeks and ≥34 weeks’ gestation. Statistical analysis: For outcomes of interest, the calculated effect estimates were pooled to obtain the overall effect. Heterogeneity between studies was assessed using the Q-statistic and Higgins’ I 2 statistic. Heterogeneity was defined as an I 2 ≤ 25% as low heterogeneity, 25–75% as moderate, and >75% as high heterogeneity. Data weer pooled using a random effects model. Finally, to evaluate the constancy of our results, sensitivity analysis was conducted using a leave-one-out method.

Results (1) 468 abstracts were identified from the literature search 49 studies were included

Results (PPROM) 17 trials. Corticosteroids reduce the risks of intraventricular hemorrhage (IVH), grade III and IV [relative risk (RR) = 0.49, 95% confidence interval (CI)0.25–0.96], IVH grade I–IV (RR = 0.52, 95% CI 0.37–0.72), and RDS (RR = 0.81, 95% CI 0.67–0.98). No difference was observed between steroid and control groups concerning the risk for necrotizing enterocolitis (NEC), neonatal sepsis, Apgar score <7 at five minutes (Figure 3). Perinatal/neonatal mortality and maternal chorioamnionitis was also similar between steroid and control groups.

Results (Twin pregnancies) 3 trials. No difference in risk for RDS between the steroid group and the control group (RR = 0.66, 95% CI 0.37–1.19)

Results (Intrauterine growth restriction) 4 trials. No difference between the steroid group and the control group as regards the risk for: RDS (RR = 0.89. 95% CI 0.74–1.07). IVH overall (RR = 1.28, 95% CI 0.78–2.11). IVH grade III and IV (RR = 0.38, 95% CI 0.13–1.15). NEC (RR = 1.21, 95% CI 0.53–2.76). Perinatal/neonatal death (RR = 1.00, 95% CI 0.60–1.67). Neonatal sepsis (RR = 0.96, 95% CI 0.76–1.21). Patent ductus arteriosus (RR = 1.19, 95% CI 0.74–1.94). Bronchopulmonary dysplasia (RR = 0.86, 95% CI 0.52–1.44)

Results (Pregnancies after 34 weeks) 3 trials. The risk for RDS was reduced by steroid treatment (RR = 0.38, 95% CI 0.14–1.00) (Figure 7).

Recomendation for antenatal corticosteroids

Antenatal corticosteroids are beneficial for PPROM up to 32–34 weeks. Conclusion Antenatal corticosteroids are beneficial for PPROM up to 32–34 weeks. Corticosteroids in twin pregnancies decrease respiratory distress syndrome but the effect is less than in singleton pregnancies. Corticosteroid effects in pregancies affected by IUGR are conflicting. Corticosteroid use in pregnancies at risk of delivering at 23–26 weeks reduces neonatal mortality but not morbidity. Corticosteroids reduce respiratory distress syndrome in pregnancies between 34 and 36 6/7 weeks of gestation.