68: Prenatal exposure to gestational diabetes mellitus as an independent risk factor for long- term neurologic morbidity of the offspring Academic Article uri icon


  • Background: The reported rates of gestational diabetes mellitus are constantly escalating and little is known about the long term complications in the offspring. Evidence from the field of epigenetics strongly advocates the need for research on the neuropsychiatric complications in offspring prenatally exposed to gestational diabetes mellitus. Objective: To assess whether in utero exposure to gestational diabetes mellitus increases the risk of long- term neuropsychiatric morbidity in the offspring. Methods: 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 confounders and for maternal clusters. Results: 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.

publication date

  • January 1, 2016