Untangling the relationships between autism spectrum disorder and non-genetic risk factors

Autism spectrum disorder (ASD) has been attributed to genetic and non-genetic risk factors. Of the non-genetic factors, prenatal and perinatal complications have been extensively investigated, though few associations have been replicated consistently. We selected 2,562 families with at least one individual with ASD and one unaffected sibling. We investigated the relationships between 29 prenatal and perinatal complications and ASD, while considering the influences of confounding factors, comorbid conditions, and different ASD definitions. Although many complications were associated with ASD in the pairwise comparisons, only haematological disorders of the newborn and lower Apgar scores remained significant after adjusting for the effects of the confounders. After removing individuals with congenital anomalies, only 5-minute Apgar scores were associated with ASD. In conclusion, after considering confounding effects and four ASD definitions, several perinatal complications were associated with ASD with moderate effect sizes. Furthermore, comorbid conditions with ASD appear to be intertwined in these relationships.