XXXX , placental insufficiency, and autism spectrum disorder or developmental delay.

@entity1 @entity32 @entity28 @entity26 @entity245 @entity2438 @entity1504 @entity519 @entity72 @entity1468
IMPORTANCE: Increasing evidence suggests that @entity72 ( @entity72 ) and many forms of developmental delay ( @entity245 ) originate during fetal development. @entity1468 may trigger aberrant neurodevelopment through placental, maternal, and fetal physiologic mechanisms. OBJECTIVE: To determine whether @entity1468 is associated with @entity72 and/or @entity245 . DESIGN, SETTING, AND @entity1 : The Childhood Autism Risks from Genetics and the Environment (CHARGE) study is a population-based, case-control investigation of @entity72 and/or @entity245 origins. @entity1 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. @entity1 with @entity72 (n   =   517) and @entity245 (n   =   194) were recruited through the California Department of Developmental Services, the Medical Investigation of @entity245 (MIND) Institute, and referrals. Controls with @entity245 ( @entity245 ) (n   =   350) were randomly selected from birth records and frequency matched on age, sex, and broad geographic region. Physicians diagnosing @entity1468 were masked to neurodevelopmental outcome, and those assessing neurodevelopmental function were masked to @entity1468 status. EXPOSURES: @entity1468 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 @entity72 , whereas @entity1 with @entity245 and @entity245 were confirmed by Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales and were free of @entity2438 . Hypotheses were formulated before data collection. RESULTS: @entity1 with @entity72 were twice as likely to have been exposed in utero to @entity1468 as controls with @entity245 after adjustment for maternal educational level, parity, and prepregnancy @entity28 (adjusted odds ratio, 2.36; 95% CI, 1.18-4.68); risk increased with greater @entity1468 severity (test for trend, P   =   .02). Placental insufficiency appeared responsible for the increase in @entity245 risk associated with severe @entity1468 (adjusted odds ratio, 5.49; 95% CI, 2.06-14.64). CONCLUSIONS AND RELEVANCE: @entity1468 , particularly severe disease, is associated with @entity72 and @entity245 . Faulty placentation manifests in the mother as @entity1468 with @entity1504 , enhanced systemic @entity32 , and insulin resistance; in the placenta as @entity26 and nutrient transfer restriction and oxidative stress; and in the fetus as growth restriction and progressive @entity519 . All are potential mechanisms for neurodevelopmental compromise.
