Long-term neurodevelopmental and psychological outcomes after prenatal exposure to antenatal corticosteroids: a systematic review and meta-analysis

Objectives Our objective was to systematically review and meta-analyse long-term neurodevelopmental and psychological outcomes of children (>1 year) exposed to antenatal corticosteroids (ACS), with planned stratification by timing of birth. Methods We systematically searched seven electronic databases from Jan 2000 (reflecting recent neonatal care) to June 2020. We included follow-up studies of randomized controlled trials (RCTs) and cohort studies on neurodevelopmental and psychological outcomes in ACS-exposed vs unexposed children, and with random-effects meta-analysis, data permitting. Results Thirty-two publications met inclusion criteria (five follow-up studies of three RCTs and 27 cohort studies). Most studies were published within the last five years with follow-up of children ranging from 1 to 10 years of age. A total of over 70 outcomes were identified. Three cohort studies of 2,926 children found that children born preterm after exposure to a single course of ACS was associated with a significantly decreased risk of cerebral palsy vs. non-exposure (RR=0.70, 95% CI=0.49-0.99, I2=30%). However, the largest cohort study (N=670,097) found a higher risk of any mental and behavioral disorders in preterm/term-born children exposed to ACS vs. those unexposed (absolute difference=5.56%, 95% CI=5.04%-6.19%; HR=1.33, 95% CI=1.26-1.41; with the largest effects in term-born children). Conclusions While ACS exposure is associated with significantly lower risks of cerebral palsy after preterm birth, it is also associated with increased mental and behavioral disorders following preterm or term birth, particularly those at term. These data suggest a need to consider cautious ACS administration.