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

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.