Abstract
Prenatal exposure to metabolic disturbances is associated with increased risk of offspring neurodevelopmental impairment and autism spectrum disorder, while little is known about the joint effect of maternal obesity and diabetes. With this study, we aim to assess the joint effect of maternal obesity and diabetes on the risk for offspring psychiatric and mild neurodevelopmental disorders. Nationwide registries were used to link data of all live births in Finland between 2004 and 2014 (n = 649 043). Cox proportional hazards modeling adjusting for potential confounders was applied to estimate the effect of maternal obesity, pregestational diabetes mellitus (PGDM), and gestational diabetes mellitus, as well as their joint effects, on the outcomes of offspring psychiatric and mild neurodevelopmental diagnoses and offspring prescription of psychotropic drugs. Among mothers without diabetes, severely obese mothers had 67% to 88% increased risk of having a child with mild neurodevelopmental disorders (hazard risk ratio [HR] = 1.69; 95% confidence interval [CI] = 1.54-1.86), attention-deficit/hyperactivity disorder or conduct disorder (HR = 1.88; 95% CI = 1.58-2.23), and psychotic, mood, and stress-related disorders (HR = 1.67; 95% CI = 1.31-2.13) compared with mothers with a normal BMI. PGDM implied a further risk increase for all groups of psychiatric diagnoses with onset in childhood or adolescence in mothers with severe obesity. Marked effects were found particularly for autism spectrum disorder (HR = 6.49; 95% CI = 3.08-13.69), attention-deficit/hyperactivity disorder and conduct disorder (HR = 6.03; 95% CI = 3.23-11.24), and mixed disorders of conduct and emotions (HR = 4.29; 95% CI = 2.14-8.60). Gestational diabetes mellitus did not increase the risk highly for these offspring disorders. Maternal PGDM combined with severe maternal obesity markedly increases the risk of several children's psychiatric and mild neurodevelopmental disorders.
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