Objective: To provide a comprehensive review and meta-analysis of the association between perinatal and neonatal factors and autism risk; further, to discuss the heterogeneous evidence regarding obstetric suboptimality and autism, and share recommendations to improve methodological rigor.
Data Sources and study selection: PubMed, Embase, and PsycInfo databases were searched for studies that examined the association between perinatal and neonatal factors and autism through March, 2007. Forty studies were eligible for the meta-analysis.
Data extraction: For each exposure, a summary effect estimate was calculated using a random effects model. Heterogeneity in effect estimates across studies was examined and, if found, a meta-regression was conducted to identify measured methodological factors that could explain between-study variability
Results: Over 60 perinatal and neonatal factors have been examined. Factors associated with autism risk in the meta-analysis were abnormal presentation, umbilical cord complications, fetal distress, birth injury/trauma, multiple birth, maternal hemorrhage, summer birth, low birthweight, small for gestational age, congenital malformation, low 5-minute Apgar score, feeding difficulties, meconium aspiration, neonatal anemia, ABO or Rh incompatibility, and hyperbilirubinemia. Factors not associated with autism risk included anesthesia, assisted vaginal delivery, post-term birth, high birthweight, and head circumference.
Conclusions: There is insufficient evidence to implicate any one perinatal or neonatal factor in autism aetiology, although there is some evidence to suggest that exposure to a broad class of conditions reflecting general compromises to perinatal and neonatal health may increase the risk. Methodological variations were likely sources of heterogeneity of risk factor effects across studies