Marisa E Millenson1, Joseph M Braun2, Antonia M Calafat3, Dana Boyd Barr4, Yen-Tsung Huang5, Aimin Chen6, Bruce P Lanphear7, Kimberly Yolton8. 1. Department of Epidemiology, Brown University, Providence, RI 02912, USA. 2. Department of Epidemiology, Brown University, Providence, RI 02912, USA. Electronic address: joseph_braun_1@brown.edu. 3. Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA. 4. Department of Environmental Health, Emory University, Atlanta, GA, USA. 5. Institute of Statistical Science, Academia Sinica, Taipei, Taiwan. 6. Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA. 7. Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada. 8. Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
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.
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 childPON1 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 childPON1 genotype.
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