Mental Disorders Among Offspring Prenatally Exposed to Systemic Glucocorticoids.

Summary

In a nationwide cohort of 1,061,548 births, prenatal systemic glucocorticoid exposure was associated with increased risks of autism spectrum disorder, ADHD, and mood/anxiety/stress-related disorders by age 15, across maternal risk strata. Results remained in active-comparator and sibling analyses, though residual confounding by disease severity cannot be excluded.

Key Findings

• Among mothers at risk for preterm delivery, exposure increased ASD risk (6.6% vs 4.3%; RR 1.5), ADHD (5.8% vs 4.3%; RR 1.3), and mood/anxiety/stress disorders (7.2% vs 4.6%; RR 1.5).
• Among mothers with autoimmune/inflammatory disorders, exposure increased ASD (RR 1.3), ADHD (RR 1.3), and mood/anxiety/stress disorders (RR 1.4).
• Active comparator and sibling analyses supported the associations, though disease severity confounding remains possible.

Clinical Implications

Counsel pregnant patients on potential neurodevelopmental and mood/anxiety risks with systemic glucocorticoids, emphasizing judicious use, lowest effective dose and duration, and alternative strategies when feasible.

Limitations

• Observational design with potential residual confounding by disease severity and indication.
• Exposure and outcome ascertainment rely on registries; misclassification is possible.

Future Directions

Investigate dose–response, timing, and specific glucocorticoid agents; integrate mechanistic studies and causal inference methods to refine risk estimates.