Introduction:
Prenatal exposure to glucocorticoids, such as betamethasone and dexamethasone, is common in cases of risk of preterm birth and maternal autoimmune disorders, aiming to mitigate neonatal complications. Although glucocorticoids play critical roles in the development of the central nervous system (CNS), excessive exposure during pregnancy can induce neurobiological alterations, being associated with later mental disorders in the offspring.
Methods:
Danish population-based cohort study from 1996-2016, including 1,061,548 children, with maternal glucocorticoid exposure assessed by medical and pharmacy records. Two subcohorts were analyzed: mothers at risk of preterm birth (n=31,518) and mothers with autoimmune/inflammatory disorders (n=288,747). Primary outcomes included autism spectrum disorders (ASD), intellectual disability, ADHD, and mood, anxiety, and stress disorders, monitored for up to 15 years. Analyses included risk ratios (RR) adjusted via Kaplan-Meier estimator and propensity score weighting.
Results:
Among children of mothers at risk of preterm birth, adjusted rates of ASD were 6.6% in exposed vs. 4.3% in unexposed (RR: 1.5; 95% CI: 1.2-1.9). Similarly, children of mothers with autoimmune disorders had an increased risk of ASD (4.8% exposed vs. 3.8% unexposed; RR: 1.3; 95% CI: 1.1-1.5) and ADHD (5.5% exposed vs. 4.4% unexposed; RR: 1.3; 95% CI: 1.0-1.5). Cumulative exposure to doses greater than 500 mg prednisolone equivalents exacerbated the risks of affective and neurodevelopmental disorders.
Discussion:
The findings suggest that prenatal exposure to glucocorticoids, even when clinically indicated, may adversely impact the neuropsychiatric development of offspring, highlighting the need for caution in obstetric management. Potential confounders, such as maternal disease severity, were not completely eliminated, highlighting the relevance of future research for accurate risk stratification and development of therapeutic alternatives.
Reference:
Laugesen, K., Skajaa, N., Petersen, I., Andersen, M.S., Feldt-Rasmussen, U., Kejlberg Al-Mashhadi, S., Stewart, P., Lunde Jørgensen, JO, & Sørensen, H.T. (2025 ). Mental Disorders Among Offspring Prenatally Exposed to Systemic Glucocorticoids. JAMA Network Open, 8(1), e2453245. [https://doi.org/10.1001/jamanetworkopen.2024.53245](https://doi.org/10.1001/jamanetworkopen.2024.53245)
