Meta-analysis reveals antenatal corticosteroids reduce composite neonatal mortality and morbidity in low-birth-weight preterm infants, indicating benefits despite unchanged isolated lung injury risk.
Early antenatal corticosteroids (ACS) are widely recommended for women at risk of preterm delivery to prevent neonatal death and neurocognitive impairment, yet inconsistent evidence has reported its impact on bronchopulmonary dysplasia (BPD). We aimed to systematically investigate risks of BPD as well as other major neonatal adverse outcomes among preterm infants. This meta-analysis searched PubMed, EMBASE, Cochrane CENTRAL, Web of Science, CINAHL Plus, PsycInfo (OvidSP), and ClinicalTrials.gov from 1st January 1990 to 31st March 2026. Four reviewers independently screened records, extracted data, and assessed risk of bias using Cochrane tools for randomized clinical trials (RCTs) and the Newcastle-Ottawa Scale for cohort studies. Exposures was the administration of early ACS prior to preterm delivery. The primary outcome was a composite of neonatal death or BPD, and BPD alone among survivors. Secondary outcomes included composites of neonatal death or retinopathy of prematurity (ROP) and neonatal death or neurodevelopmental impairment (NDI), alongside incidences of chorioamnionitis, respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and periventricular leukomalacia (PVL). Pooled risk ratios (RRs) with 95% CIs were calculated using random-effects models. Thirty-four studies (4 RCTs, 30 cohorts) with 55,284 infants were included. ACS reduced the risk of the death/BPD composite (RR, 0.90; 95% CI, 0.83–0.98) but not BPD alone (RR, 1.04; 95% CI, 0.93–1.15). ACS reduced risks for the death/ROP composite (RR, 0.79; 95% CI, 0.72–0.87), the death/NDI composite (RR, 0.72; 95% CI, 0.67–0.78), NDI alone (RR, 0.78; 95% CI, 0.73–0.82), RDS, IVH, and PVL. ACS did not affect ROP alone or NEC, but increased chorioamnionitis risk (RR, 1.32; 95% CI, 1.10–1.58). Stratification by gestational age (≤28 weeks versus >28 weeks of gestation) or birth weight (<1500 g versus 1500–2500 g) did not alter findings. In non-late preterm, low-birth-weight infants, early ACS demonstrated overall neonatal benefits but did not reduce the risk of BPD or ROP when assessed independently among survivors. The associated increased risk of chorioamnionitis warrants careful clinical consideration. Future research requires extended follow-up to evaluate multi-systemic developmental outcomes. PROSPERO (CRD420251154695)
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