Antenatal Corticosteroid Use in Twin Pregnancies: A Systematic Review and Meta-analysis.

Abstract

Objective: To synthesize evidence on the benefit-risk profile of antenatal corticosteroid (ACS) exposure in twin pregnancies and to explore effect modification by gestational age at birth.

Data sources: PubMed, Embase, ClinicalTrials.gov , and Cochrane Central Register of Controlled Trials (from inception to October 2025) were searched using terms for twin pregnancy or multiple gestation and antenatal corticosteroids (eg, betamethasone, dexamethasone).

Methods of study selection: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-analysis (PROSPERO CRD420251275650), we included a randomized controlled trial (RCT) and observational studies comparing ACS exposure with no ACS in twin pregnancies and reporting neonatal outcomes. Observational studies were eligible if they reported sufficient raw outcome data to permit quantitative synthesis. Primary outcomes were neonatal mortality and neonatal hypoglycemia; key secondary outcomes included neonatal intensive care unit (NICU) or special care unit admission and major respiratory outcomes. Risk of bias was assessed with version 2 of the Cochrane Risk of Bias tool and Risk of Bias in Non-randomized Studies of Interventions.

Tabulation, integration, and results: Random-effects meta-analyses were conducted to estimate risk ratios (RRs) with 95% CIs. Heterogeneity was assessed with the I2 statistic, and small-study effects were evaluated when feasible. Prespecified subgroup analyses examined gestational age (less than 34 weeks vs 34 or more weeks). Sixteen studies (18,367 neonates, 8,723 ACS exposed) were included. Overall, the certainty of evidence was moderate to low. Exposure to ACS was not significantly associated with a reduction in neonatal mortality (RR 0.77, 95% CI, 0.59-1.01). Antenatal corticosteroid was not associated with a reduction in respiratory distress syndrome (RDS) overall (RR 1.11, 95% CI, 0.81-1.52), and gestational age-stratified analyses were nonsignificant. Exposure to ACS was associated with increased supplemental oxygen requirement (RR 1.72, 95% CI, 1.07-2.74), neonatal hypoglycemia (RR 1.80, 95% CI, 1.30-2.51), and NICU or special care unit admission (RR 1.33, 95% CI, 1.07-1.64), with consistent hypoglycemia effects across gestational ages.

Conclusion: In twin pregnancies, ACS exposure was not consistently associated with improved neonatal outcomes, with no overall reduction in RDS and neonatal mortality. Associations with increased risks of hypoglycemia, oxygen requirement, and NICU or special care unit admission were observed. Given the moderate-to-low certainty of the available evidence, these findings should be interpreted cautiously.

Systematic review registration: PROSPERO, CRD420251275650.