Can Association Between Preterm Birth and Autism be Explained by Maternal or Neonatal Morbidity?

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.