Abstract
BackgroundEpidemiologic studies suggest that maternal organophosphorus (OP) pesticide exposure is associated with poorer fetal growth, but findings are inconsistent. We explored whether paraoxonase (PON1), a key enzyme involved in detoxification of OPs, could be an effect modifier in this association.MethodsThe study population included 470 pregnant women enrolled in the CHAMACOS Study, a longitudinal cohort study of mothers and children living in an agricultural region of California. We analyzed urine samples collected from mothers twice during pregnancy for dialkyl phosphate (DAP) metabolites of OP pesticides. We analyzed maternal and fetal (cord) blood samples for PON1 genotype (PON1192 and PON1−108) and enzyme activity (paraoxonase and arylesterase). Infant birth weight, head circumference, and gestational age were obtained from medical records.ResultsInfants' PON1 genotype and activity were associated with birth outcome, but mothers' were not. Infants with the susceptible PON1−108TT genotype had shorter gestational age (β = −0.5 weeks, 95% Confidence Interval (CI): −0.9, 0.0) and smaller head circumference (β = −0.4 cm, 95% CI: −0.7, 0.0) than those with the PON1−108CC genotype. Infants' arylesterase and paraoxonase activity were positively associated with gestational age. There was some evidence of effect modification with DAPs: maternal DAP concentrations were associated with shorter gestational age only among infants of the susceptible PON1−108TT genotype (p-valueinteraction = 0.09). However, maternal DAP concentrations were associated with larger birth weight (p-valueinteraction = 0.06) and head circumference (p-valueinteraction<0.01) in infants with non-susceptible genotypes.ConclusionsInfants whose PON1 genotype and enzyme activity levels suggested that they might be more susceptible to the effects of OP pesticide exposure had decreased fetal growth and length of gestation. PON1 may be another factor contributing to preterm or low birth weight birth.
Highlights
Organophosphorus (OP) pesticides are a class of widely used, neurotoxic insecticides that include compounds such as chlorpyrifos, diazinon, and malathion
In a study of low-income women living in an agricultural community, we previously reported no association of maternal urinary dialkyl phosphate (DAP) metabolites with decreased birth weight, length, or head circumference, but did find an association with shorter length of gestation [12]
The geometric mean (GM) for the average DAP concentrations during pregnancy was 146 nmol/L (95% confidence interval (CI) = 133, 160); of this, a larger proportion was dimethyl phosphate (DM) metabolites (GM = 109 nmol/L; 95% CI = 98, 120) than diethyl phosphate (DE) (GM = 23 nmol/L; 95% CI = 21, 25)
Summary
Organophosphorus (OP) pesticides are a class of widely used, neurotoxic insecticides that include compounds such as chlorpyrifos, diazinon, and malathion. Chlorpyrifos and diazinon were used in household pest control products until 2000–2001, when they were voluntarily phased out by the manufacturers Use of these and other OP pesticides in agriculture continues, with approximately 73 million pounds applied in the United States each year [1]. Whyatt et al [9] found that concentrations of chlorpyrifos in umbilical cord blood were negatively associated with birth weight and length among infants born to low-income minority mothers in New York City before the year 2001. A separate study carried out in New York City before the residential phase-out found no association of dialkyl phosphate (DAP) OP pesticide metabolites in maternal urine with birth weight or length, but did find a statistically significant inverse association with head circumference [11]. We explored whether paraoxonase (PON1), a key enzyme involved in detoxification of OPs, could be an effect modifier in this association
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