Guangnan Mei, Jin Gan, Yafang Xia, Bingqian Chen
Prenatal glucocorticoid use was associated with modestly increased risks of ASD and ADHD. However, residual confounding by maternal disease severity remained a major limitation and a specific medication-related effect could not be conclusively established. Glucocorticoid use should focus on the lowest dose and shortest duration, with clear counselling. Further research is required.
AIM: A systematic review was conducted to clarify the association between long-term prenatal systemic glucocorticoid use of at least 7 days and offspring neurodevelopmental and neuropsychiatric outcomes.
METHODS: PubMed, Embase, Web of Science, the Cumulative Index to Nursing and Allied Health Literature, Cochrane Library and PsycINFO were searched from inception to March 8, 2026. We identified four observational studies that evaluated prenatal systemic glucocorticoid exposure and offspring neurodevelopmental outcomes, including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and intellectual disability (ID). Study quality was assessed, and a narrative synthesis was performed.
RESULTS: Three nationwide cohorts (covering more than 1.2 million pregnancies) reported significantly elevated risks of ASD and ADHD following prenatal glucocorticoid exposure (adjusted risk ratio 1.3-1.5). The association with ID was inconsistent and non-significant (risk ratio 1.1-1.4). A single-centre study of 74 subjects did not find any significant cognitive differences.
CONCLUSION: Prenatal glucocorticoid use was associated with modestly increased risks of ASD and ADHD. However, residual confounding by maternal disease severity remained a major limitation and a specific medication-related effect could not be conclusively established. Glucocorticoid use should focus on the lowest dose and shortest duration, with clear counselling. Further research is required.
TRIAL REGISTRATION: International Prospective Register of Systematic Reviews: CRD420261327850.