Urinary organophosphate insecticide metabolite concentrations during pregnancy and children's interpersonal, communication, repetitive, and stereotypic behaviors at 8 years of age: The home study

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 PON1₁₉₂ 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 PON1₁₉₂ (ΣDAP × PON1₁₉₂ 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.

Keywords: And neurodevelopment; Autism spectrum disorders; Children; Insecticides; Prenatal.

Fig 1

Absolute difference in each participant’s urinary ΣDAP concentration measured at 16 weeks gestation and 26 weeks gestation. Each bar represents the absolute difference in ΣDAP concentration measured at 16 weeks gestation and 26 weeks gestation for one participant (n = 224). The bars are ordered from least difference to greatest difference, with the participant with the smallest absolute difference located at the far left and the participant with the largest absolute difference located at the far right.

Fig 2

Unadjusted and adjusted mean difference (95% confidence interval) in children’s SRS scores at 8 years of age with a 10-fold increase in maternal urinary ΣDAP concentrations during pregnancy (n = 224). Each point estimate is the association of prenatal urinary DAP concentrations with child SRS scores from separate models without any covariate adjustment (Unadjusted), adjustment for each covariate, and fully adjusted for all the listed covariates (All).

Fig 3

Adjusted mean change in SRS Scores per 10-fold Increase in maternal ΣDAPs: Stratified by child PON1₋₁₀₈.^a,b,c, a- Adjusted for maternal race, age, education, marital status, household income, health insurance, maternal depression, parity, prenatal vitamins, child sex, maternal serum cotinine concentrations, and frequency of fresh fruit and vegetable consumption during pregnancy. b-Effect measure modification p-values for three and two category PON1₋₁₀₈ equal to 0.61 and 0.33, respectively, c-N’s for CC, CT, and TT equal to 96, 76, and 34, respectively.

Fig 4

Adjusted mean change in SRS Scores per 10-fold Increase in maternal ΣDAPs: Stratified by child PON1₁₉₂.^a,b,c, a- Adjusted for maternal race, age, education, marital status, household income, health insurance, maternal depression, parity, prenatal vitamins, child sex, maternal serum cotinine concentrations, and frequency of fresh fruit and vegetable consumption during pregnancy. b-Effect measure modification p-values for three and two category PON1₁₉₂ equal to 0.92 and 0.94, respectively. c-N’s for CC, CT, and TT equal to 75, 76, and 54, respectively.