Long-term outcomes of antenatal corticosteroids for preterm birth: An overview of systematic reviews

Antenatal corticosteroids (ACS) is a critical preterm birth intervention that reduces neonatal mortality and short-term morbidities when administered to women at risk of preterm birth <34 weeks’ gestation. While numerous systematic reviews have evaluated the effects of ACS on child health outcomes, this body of evidence has not been comprehensively assessed. This overview of systematic reviews thus aimed to comprehensively summarize the findings on the effects of ACS for preterm birth on long-term outcomes in children. We searched six electronic databases, with no date and language restrictions. Systematic reviews of randomized, non-randomized trials or observational studies that evaluated childhood health outcomes (assessed at age 12 months or older) for any ACS exposure compared to no ACS exposure, including comparisons between different types and regimens of ACS were eligible. We used the AMSTAR-2 tool to assess the quality of the included reviews. We included 19 systematic reviews. We identified a wide range of outcomes across the included reviews and categorized them as neurodevelopmental, psychological, physical growth, respiratory, cardiovascular, and survival/mortality outcomes. The reported outcomes were substantially varied in terms of operational definitions, terminology, timing of assessment, and measurement. No benefits or harms were observed for most of the reported outcomes following ACS exposure, though many outcomes had few participants. Available evidence suggested that a single course of ACS possibly has positive effects on selected neurodevelopmental outcomes. However, ACS exposure might also have adverse effects on psychological and some neurodevelopmental outcome in children born at late preterm or at term. Heterogeneity in outcome measurements and reporting, including overall confidence in results, contributes to uncertainties about long-term effect of ACS and warrants caution while interpreting the findings. Further high-quality research is required to generate robust evidence base on the effects of ACS on long-term child health outcomes.