Can Association Between Preterm Birth and Autism be Explained by Maternal or Neonatal Morbidity?
ABSTRACT We examined whether an association between preterm birth and risk of autistic disorders could be explained by pregnancy complications or neonatal morbidity.
This Swedish, population-based, case-control study included 1216 case subjects with autistic disorders who were born between 1987 and 2002 and 6080 control subjects who were matched with respect to gender, birth year, and birth hospital. We assessed associations between gestational age and autistic disorders and adjusted for maternal, birth, and neonatal characteristics. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
Compared with infants born at term, the unadjusted ORs for autistic disorders among very and moderately preterm infants were 2.05 [95% CI: 1.26-3.34] and 1.55 [95% CI: 1.22-1.96], respectively. When we controlled for maternal, pregnancy, and birth characteristics, ORs were reduced to 1.48 [95% CI: 0.77-2.84] and 1.33 [95% CI: 0.98-1.81], respectively. When we also controlled for neonatal complications, ORs were 0.98 [95% CI: 0.45-2.16] and 1.25 [95% CI: 0.90-1.75], respectively. Reductions in risks of autistic disorders related to preterm birth were primarily attributable to preeclampsia, small-for-gestational age birth, congenital malformations, low Apgar scores at 5 minutes, and intracranial bleeding, cerebral edema, or seizures in the neonatal period. Neonatal hypoglycemia, respiratory distress, and neonatal jaundice were associated with increased risk of autistic disorders for term but not preterm infants.
The increased risk of autistic disorders related to preterm birth is mediated primarily by prenatal and neonatal complications that occur more commonly among preterm infants.
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ABSTRACT: We probed the developmental and behavioral consequences of a single episode of kainic acid-induced early-life seizures (KA-ELS) in the rat on postnatal day 7. Correlates of developmental trajectory were not altered, demonstrating that long-term consequences following KA-ELS are not initiated by secondary causes, such as malnourishment or alterations in maternal care. We report reduced marble burying in adult rats, suggestive of restricted interests, a trait common to experimental and clinical autism. We did not detect increased repetitive grooming during habituated cage behavior. However, we did detect reduced grooming in adult KA-ELS rats in the presence of an unfamiliar rat, supporting altered social anxiety following KA-ELS. Reanalysis of a social approach task further indicated abnormal social interactions. Taken together with previous physiological and behavioral data, these data support the hypothesis that KA-ELS lead to a latent autistic phenotype in adult rats not attributable to other early alterations in development.Epilepsy & Behavior 03/2015; 44. DOI:10.1016/j.yebeh.2015.01.006 · 2.06 Impact Factor
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ABSTRACT: 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. To determine whether preeclampsia is associated with ASD and/or DD. 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. Preeclampsia and placental insufficiency were self-reported and abstracted from medical records. 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. 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). 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.JAMA Pediatrics 12/2014; 169(2). DOI:10.1001/jamapediatrics.2014.2645 · 4.25 Impact Factor
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ABSTRACT: Preterm children seem to be at increased risk for autism spectrum disorders (ASD). Parents of 157 children with birth weights less than 1,500 g (age 2 years, corrected for prematurity; 88 boys, 69 girls) completed screening questionnaires. The screening battery included the Modified Checklist for Autism in Toddlers (M-CHAT), Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist (CSBS-DP-ITC), and the Infant/Toddler Sensory Profile (ITSP). Children with disabilities were excluded. All children who screened positive on any of the screening tools were subsequently assessed by clinical examination including the Autism Diagnostic Observation Schedule. Fifty-six children (35.7%) screened positive on at least one of the parental screening questionnaires. Of the 56 children who tested positive, 33 participated in the detailed clinical follow-up assessment. A diagnosis of ASD was confirmed in 13 of the 33 children. The ASD prevalence was 9.7% of the sample. Analysis of children with and without an ASD diagnosis found significant differences relative to gestational age (26.9 weeks vs 28.3 weeks, P=0.033) and length of the stay in hospital (89.5 days vs 75.4 days, P=0.042). The screening tool with the most positive results was CSBS-DP-ITC (42 positive screens [PS]), followed by M-CHAT (28 PS), and ITSP (22 PS). Differences in the frequency of PS among the tests were significant (P=0.008). CSBS-DP-ITC had the highest sensitivity (0.846), followed by M-CHAT (0.692) and ITSP (0.462). Our results indicate a higher prevalence of autism in children with birth weights <1,500 g at 2 years of age compared to the general population prevalence. The ASD diagnosis was associated with shorter gestation times and longer hospital stays. Our findings support the simultaneous use of more than one screening tests in order to increase screening sensitivity.Neuropsychiatric Disease and Treatment 01/2014; 10:2201-2208. DOI:10.2147/NDT.S72921 · 2.15 Impact Factor