Repeated antenatal corticosteroid treatment: a systematic review and meta-analysis


Outi M. Peltoniemi, MD, Department of Paediatrics, University of Oulu, PO Box 5000, FIN-90014 University of Oulu, Finland. E-mail:

Conflict of interest
The authors have stated explicitly that there are no conflicts of interest in connection with this article.


Objective. To systematically review the efficacy and safety of repeated antenatal corticosteroid on neonatal morbidity, growth and later development. Design. MEDLINE, Cochrane database and a bibliography of identified articles were searched for English language studies. Design. Meta-analysis of randomized controlled trials. Sample. Randomized, controlled trials studying the efficacy and safety of repeat antenatal corticosteroid treatment on neonatal morbidity and early childhood development. Main outcome measures. Respiratory distress syndrome, intrauterine growth, neurodevelopment. Methods. Two reviewers independently assessed titles, abstracts and full studies, extracted data and assessed quality. Meta-analyses were performed, calculating risk ratios and weighted differences of means with 95% confidence intervals using a random-effects model. Results. Eight trials were included. Repeated betamethasone treatment decreased the risk of respiratory distress syndrome (relative risk 0.85, 95% confidence interval 0.77–0.93). Trials involving weekly or biweekly repeated betamethasone and those involving a single rescue dose decreased the risk of respiratory distress syndrome. Intrauterine growth was significantly restricted among preterm infants exposed to weekly or biweekly repeated betamethasone. A single rescue course did not affect growth. Four follow-up studies did not reveal any disturbances in neurodevelopment or growth at two years of corrected age. Conclusions. Repeated corticosteroid treatment decreased the risk of respiratory distress syndrome among preterm infants. Weekly or biweekly repeated betamethasone restricted intrauterine growth, which raises concerns about long-term consequences on neurodevelopment and metabolism. More follow-up studies are needed to confirm the long-term safety of repeated betamethasone.