title: Preeclampsia, placental insufficiency, and autism spectrum disorder or developmental delay.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Preeclampsia and placental insufficiency were self-reported and abstracted from medical records.
  
  
  METHODS
  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
  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.
authors.affiliation: Division 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.
authors.forename: Cheryl K
authors.initials: CK
authors.lastname: Walker
authors.affiliation: Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California, Davis3Department of Public Health Sciences, School of Medicine, University of California, Davis.
authors.forename: Paula
authors.initials: P
authors.lastname: Krakowiak
authors.affiliation: Department of Public Health Sciences, School of Medicine, University of California, Davis.
authors.forename: Alice
authors.initials: A
authors.lastname: Baker
authors.affiliation: Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California, Davis4Department of Pediatrics, School of Medicine, University of California, Davis.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Hansen
authors.affiliation: Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California, Davis5Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California, Davis.
authors.forename: Sally
authors.initials: S
authors.lastname: Ozonoff
authors.affiliation: Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California, Davis3Department of Public Health Sciences, School of Medicine, University of California, Davis.
authors.forename: Irva
authors.initials: I
authors.lastname: Hertz-Picciotto
mesh_terms: D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology*; D002675:Child, Preschool; D003625:Data Collection; D002658:Developmental Disabilities / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010927:Placental Insufficiency / Q000453:epidemiology*; D011225:Pre-Eclampsia / Q000453:epidemiology*; D011247:Pregnancy; D012720:Severity of Illness Index