Preterm Exposure to Corticosteroids and Risk for Mental or Behavioral Disorders

In a systematic review and meta-analysis, researchers assessed the long-term neurodevelopmental, psychological, or other outcomes among children exposed to antenatal corticosteroids.

Exposure to antenatal corticosteroids is associated with a reduced risk for neurodevelopmental impairment in children with extremely preterm birth but an increased risk for adverse neurocognitive or psychological outcomes in children born full term, according to new research from JAMA Pediatrics.

Clinical guidelines often promote using antenatal corticosteroids in pregnancies at risk of preterm birth because in these circumstances they reduce mortality risk and morbidity of the newborn. Studies of animals indicate exposure to the corticosteroids is associated with higher risk of reduced blood flow in the brain, essential synaptic proteins, and cortical surface, along with harmful impacts on other organs.

The objective of the current study was to compare long-term outcomes of 1 course of antenatal exposure to antenatal corticosteroids with unspecified courses of exposure or no exposure among children born preterm and full term.

The researchers searched academic databases from 2000 through October 29, 2021, for studies that assessed neurodevelopmental, psychological, or other outcomes of children at least 1 year old who had preterm exposure to antenatal corticosteroids.

They selected 30 cohort studies, which together involved more than 1.25 million children.

Median risk for bias was 5.75 out of 9.0 points on the Newcastle-Ottawa Scale (NOS) for studies comparing 1 course of antenatal exposure to no exposure. Median risk of bias for unspecified exposure to no exposure was 6.5 out of 9.0 points.

All but 1 study addressed no more than 3 of 6 confounders researchers examined in the scoring: use of postnatal steroids, gestational age at birth, intrauterine growth restriction, family or maternal history of neurodevelopmental and psychological problems, socioeconomic status, and maternal substance use.

Children with extremely preterm birth who had exposure to 1 course of antenatal corticosteroids had lower risk of neurodevelopmental impairment (adjusted odds ratio [aOR], 0.69; 95% CI, 0.57-0.84). Children born at 34 to 36 weeks of gestation (n=25,668) who had that exposure had a higher risk of investigation for neurocognitive disorders (aOR, 1.12; 95% CI,1.05-1.20).

Children born full term with such exposure had higher risk of mental or behavioral disorders (n=641,487 children; adjusted HR [aHR], 1.47; 95% CI, 1.36-1.60) and proven or suspected neurocognitive disorders (n=529, 205 children; aHR, 1.16; 95% CI, 1.10-1.21).

Study limitations included little availability of randomized follow-up data, possible bias of observational data, and variations in meaning of child development scores based on age of assessment.

Exposure to a single dose of antenatal corticosteroids was associated with a lower risk for neurodevelopmental impairment in children born extremely preterm, but children born late preterm or full term were at a significantly higher risk for adverse neurocognitive and/or psychological outcomes.

“Given that approximately 50% of children who had preterm exposure to antenatal corticosteroids exceeded expectations and were born full term, the timing and dose of antenatal corticosteroid administration should be carefully considered,” the researchers concluded.


Ninan K, Liyanage SK, Murphy KE, et al. Evaluation of long-term outcomes associated with preterm exposure to antenatal corticosteroids: a systematic review and meta-analysis. JAMA Pediatrics. Published online April 11, 2022. doi: 10.1001/jamapediatrics.2022.0483