Study of Parental Occupational Exposures to Solvents and Risk of Autism Spectrum Disorder in Offspring

BACKGROUND AND AIM: Solvents can accumulate in fat and later metabolize during pregnancy. Additionally, these toxicants could lead to germline mutations. We investigated associations between multiple parental occupational solvent exposures and odds of autism spectrum disorder (ASD) diagnosis in offspring. METHODS: Using population-based data from the Danish National Patient Registry, we identified a subset of ASD cases from 1982 to 2016 and 1:100 sex and birth-year matched controls obtained from the Central Population Register. We determined parental occupation history from age 16 years through 6 months post-childbirth from the Danish Pension Fund and estimated cumulative benzene, methylcyclohexane, toluene, trichloroethylene, perchloroethylene, and 1,1,1-trichloroethane exposure for mothers and fathers based on job exposure matrices (JEMs). Conditional logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for exposures one year prior to conception and during pregnancy. RESULTS: In analysis of data from 1898 people with ASD and 141,702 without ASD, there were no observed associations between maternal solvent exposures during pregnancy and risk of ASD in offspring. However, analysis for maternal benzene exposure one year prior to conception revealed higher adjusted odds for those with any exposure (aOR=1.55; 95% CI 1.02, 2.37). Additionally, although there were no significant associations between paternal solvent exposures during pregnancy and ASD risk, there were significantly increased odds of ASD in offspring whose fathers were exposed to benzene (aOR=3.07; 95% CI 1.72, 5.46) and toluene (aOR=1.66; 95% CI 1.05, 2.62) one year before conception. CONCLUSIONS: Although previous studies have suggested parental solvent exposure during pregnancy can contribute to pathogenesis of ASD, our findings suggest that risk may be increased through exposures prior to conception. However, unavoidable non-differential misclassification from the use of JEMs may have masked truly increased risk during pregnancy.