Is maternal diabetes during pregnancy associated with attention deficit hyperactivity disorder and autism spectrum disorder in children? Insights from individual participant data meta-analysis in ten birth cohorts

Abstract

Background Growing evidence shows that dysregulated metabolic intrauterine environments can affect neurodevelopment, cognitive and behaviour in offspring. However, results of individual cohort studies have been inconsistent. We aimed to investigate the association between maternal diabetes before pregnancy and gestational diabetes mellitus (GDM) with neurodevelopment, cognitive and behaviour outcomes in children. Methods Harmonized data from > 200 000 mother-child pairs across ten birth cohorts in Europe and Australia were available. Mother-child pairs were included for analysis to determine whether GDM was recorded (yes or no) and whether at least one neurodevelopmental, cognitive and behavioural outcome was available in children aged 3 to 13. Confounder-adjusted regression models were used to estimate associations between maternal diabetes and child outcomes using individual participant data (IPD) meta-analysis. Minimal adjustment model (model 1) included adjustments for child sex and maternal age. Full adjustment model (model 2) included adjustment for child sex and maternal age, birth weight, pre-pregnancy BMI, pregnancy weight gain, maternal smoking during pregnancy, plurality, parity, maternal education, and income. Results Children (aged 7–10 years) born to mothers with GDM had consistently higher attention-deficient hyperactive disorder (ADHD) symptoms compared to non-exposed controls (model 2, regression coefficient (β) 2.40 (95% CI 0.07, 4.73), P = 0.044)). Moreover, children (aged 4–6 years) born to mothers with GDM consistently exhibited more externalising problems than those born to mothers without GDM (model 2, β 2.50 (95% CI 0.15, 4.85), P = 0.039). In the secondary analysis, maternal history of type 1 and type 2 diabetes mellitus was associated with ADHD symptoms at 4–6 years (model 1, β 9.52 (95% CI 3.03, 16.01, P = 0.004) and β 8.73 (95% CI 1.72, 15.74, P = 0.001), respectively), the association was no longer apparent in further adjustments. Conclusions This study found that children between 4–6 and 7–10 years of age born to mothers with GDM have a greater likelihood of developing externalising problems and ADHD symptoms. Externalising problems often co-exist with ADHD symptoms and appear before medical intervention, particularly during school entry years (ages 4–6). Overall, this large-scale multi-cohort study suggested that a dysregulated metabolic environment during pregnancy may contribute to ADHD symptoms and externalising problems in young children.