Maternal urinary concentrations of pyrethroid and chlorpyrifos metabolites and attention deficit hyperactivity disorder (ADHD) symptoms in 2-4-year old children from the Odense Child Cohort

Background: Pyrethroids and chlorpyrifos are widely used insecticides, but the potential impact of prenatal exposure on child neurodevelopment has only been addressed in few longitudinal studies. Objectives: To investigate associations between prenatal exposure to pyrethroids and chlorpyrifos and traits of ADHD in 2-4-year-old children. Methods: Metabolites of chlorpyrifos and pyrethroids were measured in maternal urine collected at gestational week 28 among 1207 women from the Odense Child Cohort. Of these, 948 completed the Child Behavior Check List for ages 1.5-5 years (CBCL: 11/2-5). Negative binomial and logistic regression models were used to estimate relative differences in ADHD problem scores (CBCL: 11/2-5 subscale) expressed as the ratio of expected scores between exposure groups and the odds (OR) of scoring equal to or above the 90th percentile in relation to maternal urinary metabolite concentrations (continuous ln(2)-transformed or categorized into tertiles). The analyses were adjusted for maternal education level, parental psychiatric diagnosis, child age and sex. Results: The chlorpyrifos metabolite, 3,5,6-trichloro-2-pyridinol (TCPY), the generic pyrethroid metabolite, 3-phenoxybenzoic acid (3-PBA), and the metabolite of trans-isomers of permethrin, cypermethrin, and cyfluthrin, trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-l-carboxylic acid (trans-DCCA), were detected in 90%, 94%, and 11%, respectively, of the urine samples. Each doubling in maternel 3-PBA concentration was associated with a 3% increase in the ADHD score (Ratio: 1.03 (95% CI: 1.00, 1.07)) and a 13% higher odds of having a ADHD score >= the 90th percentile (OR: 1.13 (1.04, 1.38)). Similar associations were seen for 3-PBA as categorical variable (p-trend = 0.052 in negative binimoal regression, p-trend = 0.007 in logistic regression). Furthermore, concurrent concentrations of 3-PBA and TCPY above their medians were associated with higher ADHD score (Ratio: 1.20 (1.04, 1.38)) and higher odds of scoring >= the 90th percentile (OR: 1.98 (1.26, 3.11)). Maternal trans-DCCA above the detection level increased the odds of ADHD symptoms (OR: 1.76 (1.08, 2.86)). The associations were not modified by sex. Conclusions: Prenatal exposure to pyrethroids was associated with ADHD related traits at 2-4 years of age. Considering the widespread use of pyrethroids these results are of concern.