Nogueira Avelar E Silva · JAMA network open 2021 · population-based cohort study · n=2413335

Associations of Maternal Diabetes During Pregnancy With Psychiatric Disorders in Offspring During the First 4 Decades of Life in a Population-Based Danish Birth Cohort.

Cited 64 times in the scientific literature.

Level 3 - non-randomized controlled study

Nationwide non-randomized prospective cohort study

PubMed 34648013 · doi:10.1001/jamanetworkopen.2021.28005 · record verified 2026-08-26

What was done

This population-based cohort study analyzed data from Danish nationwide medical and administrative registries covering 2,413,335 live births between 1978 and 2016 (median age 19.0 years, IQR 5.8-20.8 years; follow-up up to 39 years). Exposures were any maternal diabetes diagnosis during pregnancy (56,206 offspring, 2.3%) and subtypes: pregestational type 1 diabetes (22,614 offspring), pregestational type 2 diabetes (6,713 offspring), and gestational diabetes (26,879 offspring). Cox proportional hazards models estimated hazard ratios for 10 psychiatric disorder categories, adjusting for parental psychiatric history, birth period, singleton status, offspring sex, and maternal factors (age, parity, education, smoking, cohabitation, residence, BMI), with sibship and competing risk analyses.

What was found

During follow-up, 151,208 offspring (6.4%) were diagnosed with a psychiatric disorder. Maternal diabetes during pregnancy was associated with increased risks of any psychiatric disorder (HR, 1.15; 95% CI, 1.10-1.20), schizophrenia (HR, 1.55; 95% CI, 1.15-2.08), anxiety disorders (HR, 1.22; 95% CI, 1.09-1.36), intellectual disabilities (HR, 1.29; 95% CI, 1.11-1.50), developmental disorders (HR, 1.16; 95% CI, 1.03-1.30), and behavioral disorders (HR, 1.17; 95% CI, 1.08-1.27). No association was observed for substance use disorders, mood disorders, eating disorders, and personality disorders.

Why it matters

This study provides large-scale population evidence that maternal diabetes is associated with a broader spectrum of offspring psychiatric conditions—including schizophrenia and anxiety—extending into early adulthood.

Limits

As an observational registry study, unmeasured confounding and shared familial or environmental factors cannot be fully excluded. Case identification relied on hospital-based registry diagnoses, likely underrepresenting milder psychiatric conditions managed exclusively in primary care. Findings from this Danish cohort may not generalize to populations with different healthcare access or ethnic diversity.

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