Meconium Exposure, but Not Meconium Aspiration Syndrome, Is Associated with Autism

Background:  As the incidence of Autism Spectrum Disorder (ASD) has risen, much effort has been invested into understanding the genetics involved in this condition. However, a recent twin study concluded that environmental influences feature more prominently than heritability in ASD susceptibility.  Studies investigating the prenatal, perinatal, and neonatal risk factors for ASD sometimes offer conflicting results, often failing to consider confounding by numerous covariates and erroneously adjusting for pathway intermediates. One marker of a stressful in-utero environment is fetal passage of meconium, the tar-like primary feces. This fecal matter may coat the lung surface and impair breathing in a condition called meconium aspiration syndrome.  Meconium passage and aspiration have both been associated with neurodevelopmental compromise.

Objectives:  Our goals are to determine whether fetal meconium passage and/or MAS are associated with autism, and the degree to which any associations could be attributed to the meconium itself or risk factors for and complications of meconium passage.

Methods:  This is a retrospective population-based cohort study. We merged the 1991-2001 California birth cohort database provided by the Office of Statewide Health Planning and Development (n=6,088,159) with data from the California Department of Developmental Services to identify children later diagnosed with autism (n=20,326). We searched ICD-9 codes for perinatal stressors, meconium status, and downstream complications. Univariate analyses (autism risk by meconium or MAS) were followed by multinomial logistic regression analyses to account for the effects of confounders and mediators within the causal pathway.

Results:  Fetal meconium passage was significantly associated with autism (OR 1.68, CI 1.44-1.86), but not MAS (OR 1.08, CI 0.93-1.25), prior to adjustment. Surprisingly, odds decreased by only a small margin and maintained significance after controlling for confounders and downstream adverse events (OR 1.48, CI 1.31-1.69).

Conclusions:  As a marker of fetal stress, meconium’s association with autism was expected. The persistent significance following adjustment for perinatal complications is novel, and may reflect our inability to control for other stressors or that meconium represents trauma beyond its antecedents. The lack of association between the most severe presentation of fetal meconium exposure, MAS, and autism is counter to the expected dose-response effect. We postulate that our findings reflect the benefits of aggressive resuscitation received by neonates with MAS.  Hydration, oxygenation, and supportive care may mitigate long-term damage and reduce autism risk in neonates with in-utero meconium exposure.