Autism spectrum disorder, flea and tick medication, and adjustments for exposure misclassification: the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study

Abstract

Background: The environmental contribution to autism spectrum disorders (ASD) is largely unknown, but household pesticides are receiving increased attention. We examined associations between ASD and maternally-reported use of imidacloprid, a common flea and tick treatment for pets.

Methods: Bayesian logistic models were used to estimate the association between ASD and imidacloprid and to correct for potential differential exposure misclassification due to recall in a case control study of ASD.

Results: Our analytic dataset included complete information for 262 typically developing controls and 407 children with ASD. Compared with exposure among controls, the odds of prenatal imidacloprid exposure among children with ASD were slightly higher, with an odds ratio (OR) of 1.3 (95% Credible Interval [CrI] 0.78, 2.2). A susceptibility window analysis yielded higher ORs for exposures during pregnancy than for early life exposures, whereas limiting to frequent users of imidacloprid, the OR increased to 2.0 (95% CI 1.0, 3.9).

Conclusions: Within plausible estimates of sensitivity and specificity, the association could result from exposure misclassification alone. The association between imidacloprid exposure and ASD warrants further investigation, and this work highlights the need for validation studies regarding prenatal exposures in ASD.

Figure 1

Adjusted odds ratios and 95% confidence intervals comparing imidacloprid exposure of children with autism spectrum disorder with typically developing controls from the CHARGE data. Estimates are from separate frequentist, unconditional logistic models for each time period. All models were adjusted for child’s sex, regional center of birth, and age, maternal education, race/ethnicity, and parity and pet ownership during the prenatal period.

Figure 2

Adjusted odds ratios and 95% confidence intervals comparing imidacloprid exposure of all children with an autism spectrum disorder (ASD) to that of typically developing (typically developing) controls. This sensitivity analysis varies sensitivity (Sens) and false positive probability (FPP, 1-specificity) priors used in the Bayesian models assuming known exposure misclassification (certain misclassification models). Models are broken into four groups; 1: sensitivity and FPP are greater among controls; 2: sensitivity and FPP are equal between cases and controls (non-differential misclassification); 3: sensitivity and FPP are greater among cases; 4: sensitivity greater among cases, FPP is equal between cases and controls.