Parental Exposure to Occupational Asthmagens and Risk of Autism Spectrum Disorders in a Danish Population-Based Case-Control Study

Background:   There is some evidence that maternal immune activity during pregnancy may be linked to autism spectrum disorders (ASD). Some occupational and environmental exposures, such as asthmagens, can also trigger immune responses.  In order to better understand environmental risk factors for ASD, we have sought to determine if occupational asthmagens are associated with ASD.

Objectives:   To evaluate the association between maternal and paternal prenatal workplace exposures to asthmagens and ASD in a Danish population-based case-control study.

Methods: We selected our study population from singleton children born at 23-43 weeks gestation in Denmark from June 1993 through December 2007 with a linkage to the mother through the Danish Civil Registration System.   ASD cases were identified in the Danish Psychiatric Central Register using ICD-10 codes.  We randomly sampled 4 controls for every case.  The study population was further restricted to only include the oldest child for each mother and to exclude those lost to follow-up before age one, children with inconsistent maternal identification numbers across different registers, and children with extreme birth-weights for gestational age.  We estimated maternal and paternal occupational exposure to asthmagens by linking Danish International Standard Classification of Occupations codes to an asthma-specific job exposure matrix that yields dichotomous exposure estimates.  Maternal and paternal analyses were further restricted to employed mothers and employed fathers, respectively, with sufficient job information to estimate asthmagen exposure. We used logistic regression models to examine the association between parental exposure to any asthmagen and ASD, adjusting for available potential confounders, such as child’s sex, child’s year of birth, maternal age, paternal age, parity, parental income, parental education, parental psychiatric diagnosis, and parental asthma diagnosis.

Results:   We included 6,830 cases and 29,670 controls in our maternal asthmagen analyses.  18.9% of case mothers and 20.6% of control mothers were exposed to asthmagens.  The most common maternal asthmagen exposed jobs were nursing associate professionals, institution-based personal care workers, and cleaning staff in non-domestic settings.  In our paternal asthmagen analysis (7,799 cases and 32,335 controls), the exposure prevalence was 20.2% and 21.2% among fathers of cases and controls, respectively.  The most common paternal asthmagen exposed jobs were carpenters and joiners, market-oriented crop and animal producers, and meat and fish processing machine operators. ASD in the children was inversely associated with both maternal exposures to asthmagens (adjusted OR: 0.88; 95% CI: 0.82 – 0.95) and paternal exposures to asthmagens (adjusted OR: 0.92, 95% CI: 0.86 – 0.98).   Among parents without an asthma diagnosis prior to the child’s birth, the adjusted odds ratios for maternal and paternal asthmagen exposure and ASD were 0.89 (95% CI: 0.83 – 0.95) and 0.91 (95% CI: 0.85 – 0.97), respectively.

Conclusions:   We observe an inverse association between both maternal and paternal exposures to asthmagens and ASD.  Our results may be sensitive to exposure misclassification as well as confounding but they do not suggest that occupational asthmagen exposure is a risk factor for ASD.