The Role of Preeclampsia in Autism Spectrum Disorders and Cognitive Function

Background:  Preeclampsia evolves late in pregnancy and is characterized by marked increases in maternal peripheral vascular resistance, vascular permeability and coagulation abnormalities.  The resulting physiologic alterations in maternal immune, metabolic and other major organ systems can be substantial and may affect the fetus adversely.  

Objectives:  This study examined whether fetal exposure to maternal preeclampsia was associated with an increased odds of developing either ASD or cognitive impairments.

Methods:   The CHARGE (Childhood Autism Risk from Genetics and the Environment) Study is an ongoing case-control study of the etiology of autism.  Data from maternal self-report and medical records documenting maternal conditions during pregnancy were available for the mothers of 517 children with a diagnosis of autism spectrum disorder (ASD) and 350 population-based frequency-matched controls with typical development.  We collected demographic data and information about the pregnancy, delivery, and child’s early life in the Environmental Exposure Questionnaire, a telephone-administered interview.  Covariates related to clinical conditions, therapeutic interventions and the labor and delivery process were abstracted in a systematic fashion from medical records.  All children were scored on both the Vineland Scales of Adaptive Behavior (VABS) and the Mullen Scales of Early Learning (MSEL), and we performed the Autism Diagnostic Interview–Revised and the Autism Diagnostic Observation Schedule to confirm the diagnosis of ASD.   Cognitive function among children with ASD was categorized as follows:  low (<70 on MSEL and VABS), mixed (<70 on either MSEL or VABS), high (>70 on MSEL and VABS).  Adjusting for maternal education, delivery payer, parity, obesity (body mass index > 30), and frequency-matching variables child’s age at study entry and Regional Center catchment, we developed logistic regression models to examine the relationships between preeclampsia and (1) case status and (2) ASD cognitive function level.

Results:  Women with preeclampsia had a nearly three-fold increased risk of having a child with ASD compared to women without this condition (adjusted odds ratio [aOR] 2.75, 95% confidence interval [CI] 1.30, 5.80).  The association between preeclampsia and ASD was only detected among children with low cognitive function compared to children with typical development (aOR 2.75, 95% CI 1.27, 5.97).

Conclusions:   We propose multiple mechanisms for the role preeclampsia in the pathogenesis of ASD with low cognitive function.  Inadequate placentation results in insufficient circulation leading to progressive hypoxia and oxidative stress in the placenta and fetus.  Further, generalized systemic maternal endothelial activation exacerbates the maternal systemic inflammation and insulin resistance seen in normal pregnancy.