Preeclampsia, Placental Insufficiency, and Autism Spectrum Disorder or Developmental Delay
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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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Recent evidence from human and animal studies suggests that under stress, placental transfer of nutrients to the fetus is disrupted, and factors such as prenatal stress and placental inflammation increase hyperactivity in offspring.
“Recent evidence from human and animal studies suggests that under stress, placental transfer of nutrients to the fetus is disrupted, and factors such as prenatal stress and placental inflammation increase hyperactivity in offspring3536.”
From Fetal and postnatal metal dysregulation in autism (2017) · cites this paper as [36]
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- Authors
- Walker, C. K., Krakowiak, P., Baker, A., Hansen, R. L., Ozonoff, S., & Hertz-Picciotto, I.
- Affiliations
- University of California, Davis (US)
- Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California, Davis3Department of Public Health Sciences, School of Medicine, University of California, Davis
- Venue
- JAMA Pediatrics
- Publisher
- American Medical Association (AMA)
- Published
- 2015-02-01
- Volume
- 169
- Issue
- 2
- Pages
- 154
- ISSN
- 1072-4710 (ISSN-L)
- 2168-6203
- PMC
- PMC4416484
- OpenAlex
- W2164516419
- Cited by
- 292
- References
- 38
- Citations by year
- 2026: 19 · 2025: 17 · 2024: 26 · 2023: 21 · 2022: 27 · 2021: 41 · 2020: 28 · 2019: 34 · 2018: 27 · 2017: 24 · 2016: 18 · 2015: 10
- FWCI
- 9.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of Pediatrics and Adolescent Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Environmental Protection Agency (R01ES015359)
- National Institutes of Health
- University of California, Davis
- National Institute of Environmental Health Sciences (1 P01-ES11269, R01ES015359, P01ES011269)
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD079125)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- placental insufficiency, autism spectrum disorder, developmental delay, prenatal exposure, severe preeclampsia, CHARGE study, autism risk factors, fetal development, pre-pregnancy obesity, maternal parity, maternal education, preeclampsia severity
- MeSH terms
- California, Developmental Disabilities, Child Development Disorders, Pervasive, Child, Preschool, Data Collection, Female, Humans, Infant, Infant, Newborn, Male, Placental Insufficiency, Pre-Eclampsia, Pregnancy, Severity of Illness Index, Case-Control Studies
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