Jonathan Chevrier

Prenatal Exposure to Organophosphate Pesticides and IQ in 7-Year-Old Children

Context: Organophosphate (OP) pesticides are neurotoxic at high doses. Few studies have examined whether chronic exposure at lower levels could adversely affect children’s cognitive development. Objective: We examined associations between prenatal and postnatal exposure to OP pesticides and cognitive abilities in school-age children. Methods: We conducted a birth cohort study (Center for the Health Assessment of Mothers and Children of Salinas study) among predominantly Latino farmworker families from an agricultural community in California. We assessed exposure to OP pesticides by measuring dialkyl phosphate (DAP) metabolites in urine collected during pregnancy and from children at 6 months and 1, 2, 3.5, and 5 years of age. We administered the Wechsler Intelligence Scale for Children, 4th edition, to 329 children 7 years of age. Analyses were adjusted for maternal education and intelligence, Home Observation for Measurement of the Environment score, and language of cognitive assessment. Results: Urinary DAP concentrations measured during the first and second half of pregnancy had similar relations to cognitive scores, so we used the average of concentrations measured during pregnancy in further analyses. Averaged maternal DAP concentrations were associated with poorer scores for Working Memory, Processing Speed, Verbal Comprehension, Perceptual Reasoning, and Full-Scale intelligence quotient (IQ). Children in the highest quintile of maternal DAP concentrations had an average deficit of 7.0 IQ points compared with those in the lowest quintile. However, children’s urinary DAP concentrations were not consistently associated with cognitive scores. Conclusions: Prenatal but not postnatal urinary DAP concentrations were associated with poorer intellectual development in 7-year-old children. Maternal urinary DAP concentrations in the present study were higher but nonetheless within the range of levels measured in the general U.S. population.

In Utero and Childhood Polybrominated Diphenyl Ether (PBDE) Exposures and Neurodevelopment in the CHAMACOS Study

background: California children’s exposures to polybrominated diphenyl ether flame retardants (PBDEs) are among the highest worldwide. PBDEs are known endocrine disruptors and neurotoxicants in animals. Objective: Here we investigate the relation of in utero and child PBDE exposure to neurobehavioral development among participants in CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a California birth cohort. Methods: We measured PBDEs in maternal prenatal and child serum samples and examined the association of PBDE concentrations with children’s attention, motor functioning, and cognition at 5 (n = 310) and 7 years of age (n = 323). Results: Maternal prenatal PBDE concentrations were associated with impaired attention as measured by a continuous performance task at 5 years and maternal report at 5 and 7 years of age, with poorer fine motor coordination—particularly in the nondominant—at both age points, and with decrements in Verbal and Full-Scale IQ at 7 years. PBDE concentrations in children 7 years of age were significantly or marginally associated with concurrent teacher reports of attention problems and decrements in Processing Speed, Perceptual Reasoning, Verbal Comprehension, and Full-Scale IQ. These associations were not altered by adjustment for birth weight, gestational age, or maternal thyroid hormone levels. Conclusions: Both prenatal and childhood PBDE exposures were associated with poorer attention, fine motor coordination, and cognition in the CHAMACOS cohort of school-age children. This study, the largest to date, contributes to growing evidence suggesting that PBDEs have adverse impacts on child neurobehavioral development.

Polybrominated Diphenyl Ether (PBDE) Flame Retardants and Thyroid Hormone during Pregnancy

Background Human exposure to polybrominated diphenyl ether (PBDE) flame retardants has increased exponentially over the last three decades. Animal and human studies suggest that PBDEs may disrupt thyroid function. Although thyroid hormone (TH) of maternal origin plays an essential role in normal fetal brain development, there is a paucity of human data regarding associations between exposure to PBDEs and maternal TH levels during pregnancy. Objectives Our goal was to determine whether PBDE serum concentrations are associated with TH levels in pregnant women. Methods We measured the concentration of 10 PBDE congeners, free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in 270 pregnant women around the 27th week of gestation. Results Serum concentrations of individual PBDE congeners with detection frequencies > 50% (BDEs 28, 47, 99, 100, and 153) and their sum (∑PBDEs) were inversely associated with TSH levels. Decreases in TSH ranged between 10.9% [95% confidence interval (CI), −20.6 to 0.0] and 18.7% (95% CI, −29.2 to −4.5) for every 10-fold increase in the concentration of individual congeners. Odds of subclinical hyperthyroidism (low TSH but normal T4) were also significantly elevated in participants in the highest quartile of ∑PBDEs and BDEs 100 and 153 relative to those in the first quartile. Associations between PBDEs and free and total T4 were not statistically significant. Results were not substantially altered after the removal of outliers and were independent of the method used to adjust for blood lipid levels and to express ∑PBDEs. Conclusions Results suggest that exposure to PBDEs is associated with lower TSH during pregnancy. Findings may have implications for maternal health and fetal development.

The pine river statement: human health consequences of DDT use.

Objectives Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. Data sources and extraction We conducted a PubMed search in October 2008 and retrieved 494 studies. Data synthesis Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Conclusions Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDT.

PBDE Concentrations in Women’s Serum and Fecundability

Background Exposure to polybrominated diphenyl ether (PBDE) flame retardants is widespread, with 97% of Americans having detectable levels. Although PBDEs have been associated with reproductive and hormonal effects in animals, no human studies have examined their association with fertility. Objectives This study was designed to determine whether maternal concentrations of PBDEs in serum collected during pregnancy are associated with time to pregnancy and menstrual cycle characteristics. Methods Pregnant women (n = 223) living in a low-income, predominantly Mexican-immigrant community in California were interviewed to determine how many months they took to become pregnant. Blood samples were collected and analyzed for PBDEs. PBDE concentrations were lipid adjusted and log10 transformed. Analyses were limited to PBDE congeners detected in > 75% of the population (BDEs 47, 99, 100, 153). Cox proportional hazards models modified for discrete time were used to obtain fecundability odds ratios (fORs) for the association of PBDEs and time to pregnancy. Results We detected all four congeners in > 97% of women. Increasing levels of BDEs 47, 99, 100, 153 and the sum of these four congeners were all associated with longer time to pregnancy. We observed significantly reduced fORs for BDE-100 [adjusted fOR = 0.6; 95% confidence interval (CI), 0.4–0.9], BDE-153 (adjusted fOR = 0.5; 95% CI, 0.3–0.8), and the sum of the four congeners (adjusted fOR = 0.7; 95% CI, 0.5–1.0). PBDEs were not associated with menstrual cycle characteristics. Conclusions We found significant decreases in fecundability associated with PBDE exposure in women. Future studies are needed to replicate and confirm this finding.

Organophosphate Urinary Metabolite Levels during Pregnancy and after Delivery in Women Living in an Agricultural Community

Little information has been published about pesticide exposures experienced by pregnant women. We measured six dialkyl phosphate (DAP) urinary metabolites of organophosphate (OP) pesticides in 600 pregnant, low-income women living in the Salinas Valley, California, an agricultural area. A total of 28% were employed as farm fieldworkers during pregnancy, and 81% had at least one household member who worked in agriculture. Samples were collected twice during pregnancy (mean = 13 and 26 weeks’ gestation, respectively) and just after delivery (mean = 9 days). As in other studies, dimethyldithiophosphate levels were higher than those of other urinary OP metabolites. Total DAP metabolite levels in samples collected after delivery were higher than in samples collected during pregnancy. Median metabolite levels at the first and second prenatal sampling points and at the postpartum collection were 102.8, 106.8, and 227.2 nmol/L, respectively. Both prenatal and postpartum metabolite levels were higher in these Salinas Valley women than in a sample of women of childbearing age in the general U.S. population (National Health and Nutrition Examination Survey), although the deviation from U.S. reference levels was most pronounced after delivery. Higher DAP metabolite levels in the immediate postpartum period may have implications for estimating dose during pregnancy and for exposure during lactation.

Prenatal and postnatal bisphenol A exposure and body mass index in childhood in the CHAMACOS cohort

Background: Bisphenol A (BPA), a widely used endocrine-disrupting chemical, has been associated with increased body weight and fat deposition in rodents. Objectives: We examined whether prenatal and postnatal urinary BPA concentrations were associated with body mass index (BMI), waist circumference, percent body fat, and obesity in 9-year-old children (n = 311) in the CHAMACOS longitudinal cohort study. Methods: BPA was measured in spot urine samples collected from mothers twice during pregnancy and from children at 5 and 9 years of age. Results: Prenatal urinary BPA concentrations were associated with decreased BMI at 9 years of age in girls but not boys. Among girls, being in the highest tertile of prenatal BPA concentrations was associated with decreased BMI z-score (β = –0.47, 95% CI: –0.87, –0.07) and percent body fat (β = –4.36, 95% CI: –8.37, –0.34) and decreased odds of overweight/obesity [odds ratio (OR) = 0.37, 95% CI: 0.16, 0.91] compared with girls in the lowest tertile. These findings were strongest in prepubertal girls. Urinary BPA concentrations at 5 years of age were not associated with any anthropometric parameters at 5 or 9 years, but BPA concentrations at 9 years were positively associated with BMI, waist circumference, fat mass, and overweight/obesity at 9 years in boys and girls. Conclusions: Consistent with other cross-sectional studies, higher urinary BPA concentrations at 9 years of age were associated with increased adiposity at 9 years. However, increasing BPA concentrations in mothers during pregnancy were associated with decreased BMI, body fat, and overweight/obesity among their daughters at 9 years of age.

Maternal Urinary Bisphenol A during Pregnancy and Maternal and Neonatal Thyroid Function in the CHAMACOS Study

Background: Bisphenol A (BPA) is widely used in the manufacture of polycarbonate plastic bottles, food and beverage can linings, thermal receipts, and dental sealants. Animal and human studies suggest that BPA may disrupt thyroid function. Although thyroid hormones play a determinant role in human growth and brain development, no studies have investigated relations between BPA exposure and thyroid function in pregnant women or neonates. Objective: Our goal was to evaluate whether exposure to BPA during pregnancy is related to thyroid hormone levels in pregnant women and neonates. Methods: We measured BPA concentration in urine samples collected during the first and second half of pregnancy in 476 women participating in the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study. We also measured free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in women during pregnancy, and TSH in neonates. Results: Associations between the average of the two BPA measurements and maternal thyroid hormone levels were not statistically significant. Of the two BPA measurements, only the one taken closest in time to the TH measurement was significantly associated with a reduction in total T4 (β = –0.13 µg/dL per log2 unit; 95% CI: –0.25, 0.00). The average of the maternal BPA concentrations was associated with reduced TSH in boys (–9.9% per log2 unit; 95% CI: –15.9%, –3.5%) but not in girls. Among boys, the relation was stronger when BPA was measured in the third trimester of pregnancy and decreased with time between BPA and TH measurements. Conclusion: Results suggest that exposure to BPA during pregnancy is related to reduced total T4 in pregnant women and decreased TSH in male neonates. Findings may have implications for fetal and neonatal development.

Associations between prenatal exposure to polychlorinated biphenyls and neonatal thyroid-stimulating hormone levels in a Mexican-American population, Salinas Valley, California.

Background Studies have reported that prenatal exposure to polychlorinated biphenyls (PCBs) may alter neurodevelopment in both humans and animals. Furthermore, prenatal exposure to some PCB congeners and commercial mixtures has been shown to decrease free and total thyroxine (T4) blood levels in animals. Because thyroid hormones (TH) are essential for normal neurologic development, it has been suggested that the deleterious neurodevelopmental effect of PCBs may occur through TH disruption. PCBs may in turn affect TH levels by inducing the microsomal enzyme uridinediphosphate glucuronosyltransferase (UDP-GT), which is involved in TH elimination. Objectives Our goals were to group PCB congeners based on their potential to induce microsomal enzymes in animals, and to examine the relationship between neonatal TSH levels and prenatal exposure to PCB congeners grouped according to their structure and potential mechanisms of action. Methods We measured the concentration of 34 PCB congeners in serum samples collected from 285 pregnant women and the thyroid-stimulating hormone (TSH) levels in their children’s blood collected shortly after birth. Results We found no association between the sum of PCB congeners, the toxic equivalents, or structure-based groupings (mono- or di-ortho substituted congeners), and TSH blood concentration. However, we found a positive association between the sum of congeners suspected to be UDP-GT inducers (more specifically cytochrome P450 2B inducers) in animals and neonatal TSH levels. In individual congener analyses, PCBs 99, 138, 153, 180, 183, 187, 194, and 199 were positively associated with neonatal TSH levels after adjustment for covariates. PCBs 194 and 199 remained significant after adjustment for multiple hypothesis testing. Conclusions Our results support grouping PCB congeners based on their potential mechanism of action of enzyme induction when investigating associations with TH. Findings also suggest that PCBs affect TH homeostasis even at the low background level of exposure found in the CHAMA-COS (Center for the Health Assessment of Mothers and Children of Salinas) population.

Association of Prenatal Exposure to Polybrominated Diphenyl Ethers and Infant Birth Weight

Polybrominated diphenyl ethers (PBDEs) are a class of persistent compounds that have been used as flame retardants in vehicles, household furnishings, and consumer electronics. This study examined whether concentrations of PBDEs in maternal serum during pregnancy were associated with infant birth weight, length, head circumference, and length of gestation. Participants were pregnant women (n = 286) enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Study, a longitudinal cohort study of low-income, predominantly Mexican families living in the Salinas Valley, California. Blood samples were collected near the 26th week of pregnancy in 1999-2000, and concentrations of 10 PBDE congeners (BDE-17, -28, -47, -66, -85, -99, -100, -153, -154, and -183) were measured. Multiple linear regression models were used to investigate the association of lipid-adjusted, log(10)-transformed PBDE concentrations and birth outcome. In adjusted analyses, negative associations with birth weight were seen with BDE-47 (β = -115 g, 95% confidence interval (CI): -229, -2), BDE-99 (β = -114 g, 95% CI: -225, -4), and BDE-100 (β = -122 g, 95% CI: -235, -9). These findings were diminished slightly and were no longer statistically significant when maternal weight gain was included in the models. PBDE congeners were not associated with birth length, head circumference, or gestational duration.