Background: Despite evidence of atrazine toxicity in developing organisms from experimental studies, few studies—and fewer epidemiologic investigations—have examined the potential effects of prenatal exposure.Objectives: We assessed the association between adverse birth outcomes and urinary biomarkers of prenatal atrazine exposure, while taking into account exposures to other herbicides used on corn crops (simazine, alachlor, metolachlor, and acetochlor).Methods: This study used a case-cohort design nested in a prospective birth cohort conducted in the Brittany region of France from 2002 through 2006. We collected maternal urine samples to examine pesticide exposure biomarkers before the 19th week of gestation.Results: We found quantifiable levels of atrazine or atrazine mercapturate in urine samples from 5.5% of 579 pregnant women, and dealkylated and identified hydroxylated triazine metabolites in 20% and 40% of samples, respectively. The presence versus absence of quantifiable levels of atrazine or a specific atrazine metabolite was associated with fetal growth restriction [odds ratio (OR) = 1.5; 95% confidence interval (CI), 1.0–2.2] and small head circumference for sex and gestational age (OR = 1.7; 95% CI, 1.0–2.7). Associations with major congenital anomalies were not evident with atrazine or its specific metabolites. Head circumference was inversely associated with the presence of quantifiable urinary metolachlor.Conclusions: This study is the first to assess associations of birth outcomes with multiple urinary biomarkers of exposure to triazine and chloroacetanilide herbicides. Evidence of associations with adverse birth outcomes raises particular concerns for countries where atrazine is still in use.

Pyrethroid insecticides are widely used in agriculture and in homes. Despite the neurotoxicity of these insecticides at high doses, few studies have examined whether lower-level exposures could adversely affect children's neurodevelopment. The PELAGIE cohort included 3421 pregnant women from Brittany, France between 2002 and 2006. When their children reached their sixth birthday, 428 mothers from the cohort were randomly selected, successfully contacted and found eligible. A total of 287 (67%) mothers agreed to participate with their children in the neuropsychological follow-up. Two cognitive domains were assessed by the Wechsler Intelligence Scale for Children: verbal comprehension and working memory. Five pyrethroid and two organophosphate insecticide metabolites were measured in maternal and child first-void urine samples collected between 6 and 19 gestational weeks and at 6years of age, respectively. Linear regression models were used to estimate associations between cognitive scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders. Maternal prenatal pyrethroid metabolite concentrations were not consistently associated with any children's cognitive scores. By contrast, childhood 3-PBA and cis-DBCA concentrations were both negatively associated with verbal comprehension scores (P-trend=0.04 and P-trend<0.01, respectively) and with working memory scores (P-trend=0.05 and P-trend<0.01, respectively). No associations were observed for the three other childhood pyrethroid metabolite concentrations (4-F-3-PBA, cis-DCCA, and trans-DCCA). Low-level childhood exposures to deltamethrin (as cis-DBCA is its principal and selective metabolite), in particular, and to pyrethroid insecticides, in general (as reflected in levels of the 3-PBA metabolite) may negatively affect neurocognitive development by 6years of age. Whatever their etiology, these cognitive deficits may be of importance educationally, because cognitive impairments in children interfere with learning and social development. Potential causes that can be prevented are of paramount public health importance.

BackgroundPesticide use is widespread in agriculture. Several studies have shown that pesticides used in agricultural fields can contaminate the domestic environment and thus be an important source of pesticide exposure of populations residing nearby. Epidemiological studies that have examined the health effects of in utero pesticide exposure from residence near agricultural activities suggest adverse effects, but the results are inconsistent. Our purpose was to investigate the effect on intrauterine growth of such exposure due to agricultural activities in the residential municipality.MethodsA prospective birth cohort recruited 3421 pregnant women in a French agricultural region (Brittany, 2002-2006) through gynecologists, ultrasonographers, and maternity hospitals during routine prenatal care visits before 19 weeks of gestation. The national agricultural census in 2000 provided the percentages of the municipality area devoted to cultivation of corn, wheat, colza, peas, potatoes, and fresh vegetables.ResultsBirth weight and the risk of fetal growth restriction were not associated with agricultural activities in the municipality of residence in early pregnancy. Children whose mother lived in a municipality where peas were grown had a smaller head circumference at birth than those in municipalities not growing peas (-0.2 cm, p = 0.0002). Head circumference also tended to be lower when wheat was grown, but not to a statistically significant degree (p-trend = 0.10). Risk of an infant with a small head circumference was higher for mothers living in a municipality where peas (OR = 2.2; 95% CI = 1.2-3.6) or potatoes (OR = 1.5; 95% CI = 0.9-2.4) were grown.ConclusionsAgricultural activities in the municipality of residence may have negative effects on cranial growth. Cultivation of pea crops and, to a lesser degree, potato and wheat crops, may negatively affect head circumference. Insecticides, including organophosphate insecticides, were applied to most of the area devoted to pea and potato crops; this was less true for corn and wheat crops. These results must be interpreted in light of the study's limitations, in particular, the scale at which we could assess pesticide exposure.

Background:Several studies suggest that exposure to organophosphate insecticides (OP) during pregnancy impairs neurodevelopment in children.Objectives:We evaluated associations between biomarkers of prenatal and postnatal OP exposure and cognitive function of 6-year-olds in a French longitudinal birth cohort.Methods:In 2002–2006, the PELAGIE mother–child cohort enrolled pregnant women from Brittany. For a random subcohort, we measured nonspecific dialkylphosphate metabolites (DAP) of OP in one maternal urine sample, collected before 19 weeks’ gestation, and in one urine sample collected from their 6-year-old children. Six subtests of the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV) were administered when the children were 6 years of age to evaluate cognitive function (n = 231). Linear regression models controlling for factors including maternal intelligence and the Home Observation for Measurement of the Environment score were used.Results:WISC-IV scores were not significantly associated with prenatal or childhood total DAP metabolites. WISC verbal comprehension score was significantly higher in association with the highest maternal urinary concentrations of diethylphosphate (DE) metabolites (5.5; 95% CI: 0.8, 10.3 for > 13.2 nmol/L vs. < LOQ), whereas WISC working memory score was significantly lower in association with the highest urinary concentrations of DE metabolites at age 6 years (–3.6; 95% CI: –7.8, –0.6 for > 11.1 nmol/L vs. < LOD).Conclusion:We found no evidence that prenatal OP exposure adversely affected cognitive function in 6-year-olds, perhaps because of the population’s socioeconomic status, which was higher than in previous studies, though other causal and noncausal explanations are also possible. The negative association between WISC score and concurrent DE urinary concentrations requires replication by longitudinal studies investigating childhood OP exposure.Citation:Cartier C, Warembourg C, Le Maner-Idrissi G, Lacroix A, Rouget F, Monfort C, Limon G, Durand G, Saint-Amour D, Cordier S, Chevrier C. 2016. Organophosphate insecticide metabolites in prenatal and childhood urine samples and intelligence scores at 6 years of age: results from the mother–child PELAGIE cohort (France). Environ Health Perspect 124:674–680; http://dx.doi.org/10.1289/ehp.1409472