Diabetes and Hypertension in Pregnancy in Association with Autism Spectrum Disorder in the Child

Background:   Previous studies have shown complications of pregnancy, labor, and the neonatal period to be associated with autism spectrum disorder (ASD). However, because specific conditions are relatively rare, multiple conditions of pregnancy have often been examined in aggregate and with inconsistent results. More common complications in pregnancy should be investigated independently. 

Objectives:   To examine the association between 1) maternal diabetes and 2) maternal hypertension active during pregnancy and the development of ASD in the child. 

Methods:   Our analysis uses the Study to Explore Early Development (SEED), a multi-site, case-control study. Children born from 2003-2006 were enrolled in SEED at 2 to 5 years of age. Developmental assessment in the clinic was used to classify children into three groups based on presence of ASD (n=702), non-ASD developmental delay (DD; n= 893), or non-ASD controls drawn from the general population (POP; n=982). Mothers who had an active diagnosis of diabetes or a hypertensive disorder during pregnancy were identified from prenatal medical records, maternal interviews, and questionnaires. We examined the associations between diabetes, hypertension, and case status (ASD and DD groups to POP) using adjusted multivariable logistic regression models. We examined the impact of diabetes and hypertension independently, as well as adjusted for the co-occurrence of each condition. Odds ratios were further adjusted (aOR) for maternal age, race/ethnicity, education, smoking during pregnancy, and pre-pregnancy body mass index.  Models of hypertension were additionally adjusted for parity and plurality. 

Results:   From a sample of 2,577, we identified 244 mothers (9.5%) with diabetes and 433 mothers (16.8%) with hypertension in pregnancy. The crude OR=1.32 (95% confidence interval (CI) 0.94, 1.86) for diabetes was attenuated after adjusting for covariates, aOR=0.99 (95% CI 0.68, 1.45). No differences in association were seen between mothers with gestational diabetes (n=199) and preexisting diabetes (n=45). For hypertension, the crude OR=1.71 (95%CI 1.32, 2.23) was attenuated slightly with covariate adjustment, but remained elevated, aOR=1.37 (95% CI 1.02, 1.84). A stronger association was observed for mothers with a preexisting diagnosis of hypertension (n=134) that persisted into pregnancy and ASD relative to mothers without a diagnosis of hypertension (adjusted OR=1.61 [95% CI 1.00, 2.58]. Associations were slightly stronger when comparing DD vs. POP, diabetes aOR=1.22 (95% CI 0.87, 1.71) and hypertension aOR=1.49 (95% CI 1.13, 1.96).

Conclusions:   Our results did not show an association between diabetes during pregnancy and ASD in the child. An association was found with hypertension during pregnancy. A stronger association was observed with preexisting hypertension, which may highlight the importance of the early prenatal period in the development of ASD. In general, most associations between mother’s conditions and child outcomes were slightly stronger when examining children with a non-ASD developmental delay. Further analysis will be conducted to examine these differences and explore additional factors related to the etiology of ASD.