Parental exposures to occupational asthmagens and risk of autism spectrum disorder in a Danish population-based case-control study

Abstract

Background: Environmental exposures and immune conditions during pregnancy could influence development of autism spectrum disorder (ASD) in offspring. However, few studies have examined immune-triggering exposures in relation to ASD. We evaluated the association between parental workplace exposures to risk factors for asthma ("asthmagens") and ASD.

Methods: We conducted a population-based case-control study in the Danish population using register linkage. Our study population consisted of 11,869 ASD cases and 48,046 controls born from 1993 through 2007. Cases were identified by ICD-10 codes in the Danish Psychiatric Central Register. ASD cases and controls were linked to parental Danish International Standard Classification of Occupations (DISCO-88) job codes. Parental occupational asthmagen exposure was estimated by linking DISCO-88 codes to an asthma-specific job-exposure matrix.

Results: Our maternal analyses included 6706 case mothers and 29,359 control mothers employed during the pregnancy period. We found a weak inverse association between ASD and any maternal occupational asthmagen exposure, adjusting for sociodemographic covariates (adjusted OR: 0.92, 95% CI: 0.86-0.99). In adjusted analyses, including 7647 cases and 31,947 controls with employed fathers, paternal occupational asthmagen exposure was not associated with ASD (adjusted OR: 0.98, 95% CI: 0.92-1.05).

Conclusions: We found a weak inverse association between maternal occupational asthmagen exposure and ASD, and a null association between paternal occupational exposure and ASD. We suggest that unmeasured confounding negatively biased the estimate, but that this unmeasured confounding is likely not strong enough to bring the effect above the null. Overall, our results were consistent with no positive association between parental asthmagen exposure and ASD in the children.

Keywords: Autism; Epidemiology; Neurodevelopment; Occupational asthma; Prenatal exposure.

Fig. 1

Adjusted odds ratios and 95% confidence intervals for maternal occupational asthmagen exposure and ASD. Maternal model is adjusted for child’s year of birth, child’s sex, maternal age at birth, paternal age of birth, total income of parents, parity, highest parental education, history of parental psychiatric diagnosis prior to child’s date of birth, urbanicity of birth place, maternal immigrant status, and maternal smoking (6706 cases and 29,359 controls). ^aHMW = High Molecular Weight. ^bLMW = Low Molecular Weight

Fig. 2

Adjusted odds ratios and 95% confidence intervals for paternal occupational asthmagen exposure and ASD. Paternal model is adjusted for child’s year of birth, child’s sex, maternal age at birth, paternal age of birth, total income of parents, parity, highest parental education, history of parental psychiatric diagnosis prior to child’s date of birth, urbanicity of birth place, paternal immigrant status, and maternal smoking (7647 cases and 31,947 controls). ^aHMW = High Molecular Weight. ^bLMW = Low Molecular Weight. ^cPaternal mites odds ratio could not be estimated

Fig. 3

Sensitivity to unobserved confounder for the association between maternal occupational asthmagen exposure and ASD. Sensitivity analysis assumed fixed prevalence of unmeasured confounder among unexposed of 30%. ORyu = association between the unmeasured confounder and ASD. ORxu = association between the unmeasured confounder and maternal occupational asthmagen exposure