Prenatal Air Pollution, Maternal Immune Activation, and Autism Spectrum Disorders

Abstract

BACKGROUND AND AIM: Early-life causes of autism spectrum disorders (ASD) are multifactorial, including prenatal air pollution and gestational conditions with maternal immune activation (MIA) which may share common biological mechanisms. This study examined the potential synergistic effects of prenatal air pollution and MIA on ASD risk. METHODS: This retrospective cohort study included 311,617 mother-child pairs with singleton deliveries in Kaiser Permanente Southern California (KPSC) hospitals in 2001-2014. Children were followed through electronic medical records (EMR) until ASD diagnosis, non-KPSC membership, death, or December 31, 2019, whichever came first. The presence of five broad categories of MIA during pregnancy (asthma, infections, any hypertension, allergies, and autoimmune diseases) were identified by International Classification of Diseases, Ninth Revision (ICD-9). Pregnancy average PM2.5, NO2, and O3 exposures were estimated using high spatio-temporal resolution models based on maternal residential address history during pregnancy. Hazard ratios of ASD associated with air pollution and MIA were estimated using Cox regression models adjusted for birth year, KPSC medical center, child sex, and maternal sociodemographic characteristics. Multiplicative interactions were assessed in Cox models using interaction terms; additive interactions were assessed using relative excess risk due to interaction (RERI). RESULTS:The prevalence of maternal asthma, infection, hypertension, allergy, and autoimmune diseases was 7.17%, 48.6%, 9.6%, 13.7%, and 11.2%, respectively. During follow-up 6,291 children were diagnosed with ASD. Higher levels of average pregnancy PM2.5, and each of the five categories of MIA exposures was associated with ASD risk (p-value0.05). However, no statistically significant interactions were found between the five categories of MIA and any of the three air pollutants on either multiplicative or the additive scales. CONCLUSIONS:This study found little evidence that MIA and prenatal air pollution have synergistic effects on ASD. MIA and prenatal air pollution may contribute independently to ASD risk. KEYWORDS: Air pollution, Neurodevelopmental outcomes, Pregnancy outcomes