Prenatal exposure to systemic glucocorticoids is associated with a 2.3% absolute risk increase for autism spectrum disorders and a 1.5% increase for attention-deficit hyperactivity disorder, reflecting relative risk increases of up to 50%, according to a study published in JAMA Network Open.

The Danish cohort study included 1,061,548 live births (1996–2016) and assessed systemic glucocorticoid use in two maternal groups: those at risk of preterm delivery and those with autoimmune or inflammatory disorders. Researchers used Danish national registries and propensity score-weighted analyses to adjust for confounding factors.

For mothers at risk of preterm delivery, adjusted 15-year risks increased from 4.3% to 6.6% for autism spectrum disorders (adjusted relative risk [aRR], 1.5; 95% CI, 1.2–1.9), from 4.3% to 5.8% for ADHD (aRR, 1.3; 95% CI, 1.0–1.7), and from 4.6% to 7.2% for mood and anxiety disorders (aRR, 1.5; 95% CI, 1.1–2.0). Risks for intellectual disabilities increased from 1.3% to 1.6% (aRR, 1.3; 95% CI, 0.8–1.8), but this association was not statistically significant.

For mothers with autoimmune or inflammatory disorders, adjusted risks also rose for autism spectrum disorders (4.8% vs 3.8%; aRR, 1.3; 95% CI, 1.1–1.5), ADHD (5.5% vs 4.4%; aRR, 1.3; 95% CI, 1.0–1.5), and mood and anxiety disorders (6.6% vs 4.6%; aRR, 1.4; 95% CI, 1.2–1.8).

The findings remained consistent across sensitivity analyses, including sibling-matched comparisons and an active comparator cohort of mothers using other immunosuppressive treatments. Study limitations included incomplete paternal data, potential residual confounding by disease severity, and a median follow-up of 9 years, which may not fully capture long-term outcomes.

The study reported moderate increases in absolute risk associated with glucocorticoid use during pregnancy. Short-term benefits, including reduced neonatal morbidity and mortality, were noted, but these were weighed against potential long-term risks. The authors noted the importance of improved risk stratification to minimize unnecessary glucocorticoid exposure, particularly in women delivering at term.

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