Antenatal corticosteroids may affect neurodevelopment differently based on gestational age

1. In a systematic review and meta-analysis of 30 cohort studies, antenatal corticosteroid use was associated with significantly decreased rates of later neurodevelopmental impairment in children born extremely preterm.

2. In children born late preterm or full term, exposure to antenatal corticosteroids was significantly associated with higher risk of adverse neurological and psychological outcomes.

Evidence Rating Level: 2 (Good)

Study Rundown: Antenatal corticosteroids (ACS) are used to foster fetal lung maturity and reduce neonatal mortality in the setting of likely preterm delivery. However, ACS use has been linked to negative effects on neurological development, which remain poorly understood. This review and meta-analysis assessed neurodevelopmental and psychological outcomes beyond 1 year of age using data from 30 cohort studies of over 1.25 million children. Based on 2 studies comparing children exposed to a single course of ACS to those unexposed, children born extremely premature were 31% less likely to have later neurodevelopmental impairment. Exposure to ACS was not associated with a significant difference in risk of impairment in the broader preterm population based on 5 studies. However, one study showed a significantly increased risk of neurocognitive disorders in children born late preterm (34-37 weeks), while another found significantly higher rates of mental or behavioral disorders and neurocognitive disorders in children born at full term who received ACS. This systematic review supports the positive impact of ACS on neurologic — not just overall — outcomes for extremely preterm infants, perhaps via reduced rates of neonatal complications such as intraventricular hemorrhage. However, it suggests that the harms of ACS may outweigh benefits in infants born later. Currently, administration of ACS to pregnant patients is recommended only before 34 weeks’ gestation, but predicting pregnancy and delivery courses to determine which infants will be delivered before this mark presents obvious difficulty.

Click to read the study in JAMA Pediatrics

Click to read an accompanying editorial in JAMA Pediatrics

Relevant Reading: Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth

In-Depth [systematic review and meta-analysis]: Studies examining neurodevelopmental or psychological outcomes in children at least 1 year old born in or after 2000 who were exposed to ACS were included. Randomized controlled trials (RCTs) and quasi-RCTs were included in initial review but not the final study. The Newcastle-Ottawa scale was used to assess risk of bias; the median score was 5.75 out of 9, with 9 indicating highest comparability. The GRADE tool was used to rate the certainty of outcomes as high, moderate, low or very low. A random-effects meta-analysis was used for pooled outcomes. The adjusted odds ratio for neurodevelopmental impairment with ACS exposure was 0.69 [95% confidence interval (CI) 0.57-0.84], with low certainty but an I² statistic of 0% indicating homogeneity of studies. For ACS-exposed children born at term, the hazard ratio for any mental or behavioral disorder was 1.47 (95% CI 1.36-1.60) and for any neurocognitive disorder was 1.16 (1.10-1.21), both with low certainty.

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