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Preeclampsia, placental insufficiency, and autism spectrum disorder or developmental delay
Cheryl K Walker1, Paula Krakowiak2, Alice Baker3
1Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, School of Medicine, University of California, Davis2Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California, Davis.
Insights
Preeclampsia, a pregnancy complication, is linked to a higher risk of autism spectrum disorder (ASD) and developmental delay (DD) in children. Severe preeclampsia significantly increases these risks, suggesting a connection to fetal neurodevelopment.
Area of Science:
- Neurodevelopmental disorders
- Maternal-fetal medicine
- Public health
Background:
- Autism spectrum disorder (ASD) and developmental delay (DD) are increasingly understood to originate during fetal development.
- Preeclampsia, a condition during pregnancy, may disrupt normal neurodevelopment through various physiological pathways affecting the mother, placenta, and fetus.
Purpose of the Study:
- To investigate the association between preeclampsia exposure in utero and the subsequent development of ASD and/or DD in children.
- To determine if the severity of preeclampsia influences the risk of these neurodevelopmental outcomes.
Main Methods:
- The study utilized data from the Childhood Autism Risks from Genetics and the Environment (CHARGE) study, a population-based case-control investigation.
- Children aged 24-60 months with ASD (n=517) or DD (n=194) and typically developing controls (n=350) were enrolled.
- Preeclampsia and placental insufficiency were assessed through self-reporting and medical record abstraction, with researchers masked to neurodevelopmental outcomes and preeclampsia status.
Main Results:
- Children exposed to preeclampsia in utero were twice as likely to have ASD compared to controls, even after adjusting for confounding factors (adjusted odds ratio, 2.36).
- The risk of ASD associated with preeclampsia increased with greater disease severity.
- Severe preeclampsia was strongly linked to an increased risk of DD, with placental insufficiency identified as a likely mediator (adjusted odds ratio, 5.49).
Conclusions:
- Preeclampsia, especially severe forms, is significantly associated with an increased risk of both ASD and DD.
- The study highlights faulty placentation, leading to maternal vascular damage, inflammation, insulin resistance, placental dysfunction, and fetal compromise (growth restriction, hypoxemia), as potential mechanisms for neurodevelopmental issues.
- These findings underscore the critical role of placental health in fetal neurodevelopment and the potential long-term consequences of preeclampsia.
Importance:
Increasing evidence suggests that autism spectrum disorder (ASD) and many forms of developmental delay (DD) originate during fetal development. Preeclampsia may trigger aberrant neurodevelopment through placental, maternal, and fetal physiologic mechanisms.
Objective:
To determine whether preeclampsia is associated with ASD and/or DD.
Design, Setting, And Participants:
The Childhood Autism Risks from Genetics and the Environment (CHARGE) study is a population-based, case-control investigation of ASD and/or DD origins. Children from 20 California counties aged 24 to 60 months at the time of recruitment and living in catchment areas with a biological parent fluent in English or Spanish were enrolled from January 29, 2003, through April 7, 2011. Children with ASD (n = 517) and DD (n = 194) were recruited through the California Department of Developmental Services, the Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, and referrals. Controls with typical development (TD) (n = 350) were randomly selected from birth records and frequency matched on age, sex, and broad geographic region. Physicians diagnosing preeclampsia were masked to neurodevelopmental outcome, and those assessing neurodevelopmental function were masked to preeclampsia status.
Exposures:
Preeclampsia and placental insufficiency were self-reported and abstracted from medical records.
Main Outcomes And Measures:
The Autism Diagnostic Observation Schedule and Autism Diagnostic Interview-Revised were used to confirm ASD, whereas children with DD and TD were confirmed by Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales and were free of autistic symptoms. Hypotheses were formulated before data collection.
Results:
Children with ASD were twice as likely to have been exposed in utero to preeclampsia as controls with TD after adjustment for maternal educational level, parity, and prepregnancy obesity (adjusted odds ratio, 2.36; 95% CI, 1.18-4.68); risk increased with greater preeclampsia severity (test for trend, P = .02). Placental insufficiency appeared responsible for the increase in DD risk associated with severe preeclampsia (adjusted odds ratio, 5.49; 95% CI, 2.06-14.64).
Conclusions And Relevance:
Preeclampsia, particularly severe disease, is associated with ASD and DD. Faulty placentation manifests in the mother as preeclampsia with vascular damage, enhanced systemic inflammation, and insulin resistance; in the placenta as oxygen and nutrient transfer restriction and oxidative stress; and in the fetus as growth restriction and progressive hypoxemia. All are potential mechanisms for neurodevelopmental compromise.
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