Abstract
BACKGROUND: Prenatal exposure to organophosphate insecticides may be associated with autism spectrum disorders and related behaviors. This association may be modified by single nucleotide polymorphisms in the paraoxonase (PON1) enzyme. OBJECTIVE: We examined the relationship of prenatal organophosphate insecticide biomarkers with reciprocal social, repetitive, and stereotypic behaviors in 8-year old children, and modification of this relationship by child PON1 polymorphisms. METHODS: Among 224 pregnant women, we quantified concentrations of six nonspecific dialkyl phosphate (DAP) metabolites of organophosphate insecticides in two urine samples collected at ~16 and ~26 weeks gestation. When children were eight years old, we administered the Social Responsiveness Scale (SRS), a continuous measure of various dimensions of interpersonal behavior, communication, and repetitive/stereotypic behaviors. We estimated the association between a 10-fold increase in the sum of six DAP concentrations (ΣDAP) and SRS scores. We examined whether child PON1(192) and PON1(-108) genotypes modified this association. RESULTS: After covariate adjustment, ΣDAP concentrations were not associated with SRS scores [β=-1.2; 95% confidence interval (CI): -4.0, 1.6]. Among children with the PON1(-108TT) genotype, ΣDAP concentrations were associated with 2.5-point higher (95% CI: -4.9, 9.8) SRS scores; however, the association was not different from the 1.8-point decrease (95% CI: -5.8, 2.2) among children with PON1(-108CT/CC) genotypes (ΣDAP × PON1(-108) p-value =0.54). The association between ΣDAP concentrations and SRS scores was not modified by PON1(192) (ΣDAP × PON1(192) p-value =0.89). CONCLUSIONS: In this cohort, prenatal urinary DAP concentrations were not associated with children's social behaviors; these associations were not modified by child PON1 genotype.