TOPLINE:

Maternal pregestational diabetes was associated with an increased risk for subsequent neuropsychiatric disorders in offspring — including severe neuropsychiatric disorders, attention-deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and intellectual disability — compared to offspring of mothers without diabetes.

METHODOLOGY:

• Maternal diabetes is increasingly common and has been linked to a higher risk for neurodevelopmental and psychiatric disorders in offspring; however, prior studies have focused on single outcomes, leaving uncertainty about associations across a broader spectrum.
• Researchers conducted a cohort study of 2,568,006 mother-child pairs (after SIPTW weighting) in South Korea (mean maternal age, 32 years) to examine the association between maternal diabetes and a spectrum of neuropsychiatric disorders in offspring.
• Mothers with diabetes were classified as having pregestational (n = 20,815) or gestational diabetes (n = 756,193) and compared with mothers without diabetes (n = 1,790,998); infants with severe pediatric disorders or who died within the first year were excluded.
• The outcome was the first postnatal diagnosis of a neuropsychiatric disorder, including severe neuropsychiatric disorder, obsessive-compulsive disorder, ADHD, ASD, and intellectual disability, in the offspring; the mean follow-up duration was 10.3 years.
• To address familial confounding, sibling-matched analyses was conducted in the Korean cohort, comprising 358,679 sibling pairs (181,981 unexposed and 176,698 exposed to gestational diabetes); findings were validated in an independent Japanese dataset.

TAKEAWAY:

• Pregestational diabetes was associated with an increased risk for any neuropsychiatric disorder (adjusted hazard ratio [aHR], 1.29; 95% CI, 1.22-1.36), severe neuropsychiatric disorder (aHR, 1.33; 95% CI, 1.16-1.53), ADHD (aHR, 1.24; 95% CI, 1.16-1.31), ASD (aHR, 1.39; 95% CI, 1.25-1.55), and intellectual disability (aHR, 1.57; 95% CI, 1.40-1.77).
• In the full cohort, gestational diabetes showed no or only modest associations with specific neuropsychiatric outcomes; however, some associations were more pronounced among offspring of mothers who required pharmacologic therapy for their diabetes.
• In sibling-matched analyses of both the main and validation cohorts, gestational diabetes was not significantly associated with any neuropsychiatric disorder in the offspring.
• Associations with pregestational diabetes were consistent across maternal age groups, household income levels, parity, and maternal psychiatric history.

IN PRACTICE:

“These findings extend prior research by showing that maternal diabetes is associated with a broader spectrum of psychiatric outcomes than previously recognized, and that both the timing and severity of hyperglycemia are important determinants of offspring risk,” the authors wrote.

SOURCE:

The study was led by Hyesu Jo, Kyung Hee University College of Medicine, Seoul, South Korea. It was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

Because this was an observational study, residual confounding could not be ruled out. Unknown factors — such as genetic susceptibility to neuropsychiatric disorders — could not be assessed, and maternal A1c levels were unavailable. Pregestational diabetes was treated as a single category of prepregnancy diabetes, without distinguishing type 1 from type 2 diabetes.

DISCLOSURES:

The study was supported by the Ministry of Science and Information and Communications Technology and the Ministry of Health and Welfare of the Republic of Korea. Additional funding was provided by the BK21 FOUR Program at the Graduate School of Kyung Hee University. The authors disclosed having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.