Prenatal Exposure to Gestational Diabetes Mellitus as an Independent Risk Factor for Long- term Neuropsychiatric Morbidity of the Offspring.

A population-based cohort study compared the incidence of hospitalizations due to neuropsychiatric disease between singletons exposed and unexposed to gestational diabetes mellitus. Deliveries occurred between the years 1991-2014 in a regional tertiary medical center. Perinatal deaths, multiple gestations, mothers with pre-gestational diabetes or lack of prenatal care, and children with congenital malformations were excluded from the study. A multivariate generalized estimating equation logistic regression model analysis was used to control for co During the study period 231,271 deliveries met the inclusion criteria; 5.4% of the births were to mothers diagnosed with gestational diabetes mellitus (n=12642), of which 4.3% with gestational diabetes type A1 (n=10,076) and 1.1% with gestational diabetes type A2 (n=2,566). During the follow-up period, a significant linear association was noted between the severity of the gestational diabetes (no gestational diabetes, gestational diabetes mellitus A1, gestational diabetes mellitus A2) and neuropsychiatric disease of the offspring (1.02%, vs. 1.36% vs. 1.68% respectively, p<0.001). A Kaplan Meier curve demonstrated that children born to women with gestational diabetes mellitus had higher cumulative incidence of neuropsychiatric morbidity. Using a generalized estimating equation multivariable logistic regression model, controlling for time-to-event, maternal age and gestational age at delivery, maternal gestational diabetes mellitus was found to be an independent risk factor for long-term neuropsychiatric disease of the offspring (gestational diabetes mellitus A1; adjusted OR =1.90; 95% CI 1.59-2.28, gestational diabetes mellitus A2; adjusted OR =1.73; 95% CI 1.26-2.39). Within the limits of our database, our findings also point to a possible association between in utero exposure to gestational diabetes mellitus and autistic spectrum disorder of the offspring (adjusted OR=4.44; 95% CI 1.55-12.69), which was found significant also after controlling for time-to-event, maternal age, gestational age at delivery and offspring weight at birth. CONCLUSION: Exposure to maternal gestational diabetes mellitus is an independent risk factor for long-term neuropsychiatric morbidity in the offspring.