Maternal Pregestational and Gestational Diabetes and Neuropsychiatric Risk in Offspring: A Binational Cohort Study

Maternal diabetes during pregnancy has been associated with long-term health outcomes in offspring, but studies on specific neuropsychiatric outcomes remain limited. We aimed to evaluate the association between maternal diabetes and neuropsychiatric disorders.

This binational cohort study included 2 722 687 mother-child pairs from South Korea and 181 134 mother-child pairs from Japan, from 2010 to 2017, followed until December 31, 2023. Maternal diabetes was categorized as pregestational or gestational using ICD-10 codes. Offspring outcomes included severe neuropsychiatric disorder, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models in a stabilized inverse probability of treatment weighted cohort and sibling-comparison cohort. Sibling-comparison analyses were conducted and validated in an independent Japanese cohort.

Among 2 722 687 mother-child pairs (mean follow-up, 10.3 years) in the full cohort, 783 265 offspring (26.7%) were exposed to maternal diabetes (756 193 gestational; 20 815 pregestational). Pregestational diabetes was associated with increased risks of any neuropsychiatric disorder (aHR, 1.29 [95% CI, 1.22-1.36]), severe neuropsychiatric disorder (1.33 [1.16-1.53]), ADHD (1.24 [1.16-1.31]), ASD (1.39 [1.25-1.55]), and intellectual disability (1.57 [1.40-1.77]). Associations remained consistent across maternal and perinatal subgroups. Gestational diabetes showed only modest associations (aHR, 1.05 [95% CI, 1.00-1.08]) and was nonsignificant in sibling analyses in both Korea (1.01 [0.98-1.05]) and Japan (0.90 [0.76-1.06]).

Pregestational diabetes was associated with increased neuropsychiatric risk in offspring, whereas gestational diabetes showed no meaningful association in sibling analyses, and adequate management before and during pregnancy remains important.