2007 Progress Report: Pesticides, Endocrine Disruptors, Childhood Growth and Development (Birth Cohort)
EPA Grant Number: R831711C002Subproject: this is subproject number 002 , established and managed by the Center Director under grant R831711
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Mount Sinai Center for Children’s Health and the Environment
Center Director: Wolff, Mary S.
Title: Pesticides, Endocrine Disruptors, Childhood Growth and Development (Birth Cohort)
Investigators: Wolff, Mary S.
Institution: Mount Sinai School of Medicine
EPA Project Officer: Fields, Nigel
Project Period: November 1, 2003 through October 31, 2008
Project Period Covered by this Report: November 1, 2006 through October 31,2007
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003)
Research Category: Children's Health , Health Effects
Description:
Objective:Project 2: Pesticides, Endocrine Disruptors, Childhood Growth and Development
Specific Aims
The specific aims of the study are:
SAl. To assess prenatal and postnatal exposures to potentially endocrine disrupting synthetic chemicals, specifically phthalates and bisphenol A, and their association with early and late childhood growth and neurodevelopment;
SA2. To assess prenatal and postnatal exposures to pesticides, particularly organophosphates and pyrethroids, and their relationships to long-term childhood growth and cognitive, motor and behavioral development;
SA3. To assess possible modulation of associations among pesticides, potentially endocrine disrupting chemicals and childhood growth and neurodevelopment by genetically determined variation in individual susceptibility factors
Progress Summary:Studies and Results
Enrollment is ongoing as subjects became eligible for each visit. To date we have reconsented 215 participants. Among these women, we have completed 143 four-year visits, 133 six-year visits, and 747-year visits. During these follow up visits we collected 132 child urine samples at the 4-year visit (samples are not available when the child could not urinate), 138 saliva samples at the 4-year visit, 120 urine samples at the 6-year visit, 126 saliva samples at the 6-year visit, 74 urine samples at the 7-year visit and 61 saliva samples at the 7 year visit.
Study visits continue to progress well. We developed a referral protocol for the BASC in which children who score in a clinically significant or at-risk range have their study material reviewed by Dr. Canfield, and are then referred either to their Pediatrician or to local low-cost counseling resources if needed. Quality control assessments of all standardized neurodevelopmental assessment tools have been completed for all appointments to date. Seasonal and birthday cards, in addition to newsletters are being mailed to our participants in order to facilitate recruitment and retention of study subjects. Data entry has been completed for all assessments to date.
In February 2007 we began our 7-year assessments and have completed 74 to date. We have replaced the CANTAB with the WISC in order to facilitate pooling of data with other Children’s Centers. We have also added the Social Responsiveness Survey (SRS) to our 7-year protocol, in order to measure aberrations in social behavior that may relate to exposure to these environmental toxicants.
During the past year we have completed statistical analyses for organophosphate metabolites and organochlorines with regard to birth outcomes, Brazelton neonatal behavioral tests, and Bayley Scales of Infant Development neurobehavioral tests. The birth outcome and Brazelton papers have been published. The Bayley paper will be submitted shortly.
Maternal prenatal urine samples have been analyzed by the CDC for phthalates and bisphenol A. Statistical analyses relating these exposures to birth outcomes have been completed and will be submitted for publication shortly. We have begun statistical analyses relating these exposures to the neurodevelopment endpoints. We are also contrasting prenatal exposure to phthalates and bisphenol A with performance on the BASC at ages 4 and 6 years. We will be presenting preliminary findings relating OPs, PCBs, DDE, BPA and phthalates to birth, neurodevelopmental, and behavioral endpoints at the 2007 International Society for Environmental Epidemiology in Mexico City, Mexico.
Significance
Berkowitz et al. (2004) described our analysis of the relationship among pesticide exposure, paraoxonase (PON) polymorphisms and expression, and neonatal head circumference. When PON activity was taken into account, maternal levels of TCPy above the level of detection, combined with low maternal PON activity, were associated with a significant reduction in the head circumference of the infant. The PON gene is responsible for detoxification of chlorpyrifos. These findings are of importance, as small head size has been found to be predictive of subsequent cognitive functioning.
Our current findings support the importance of maternal susceptibility, i.e. PON metabolite capacity, in organophosphate toxic effects on birth outcomes. Relationships were observed between DDE and birthweight and head circumference, but these associations have been ascribed to maternal characteristics of weight-gain and adiposity.
Of potential importance are the maternal prenatal exposures to phthalates and phenols, which are known reproductive toxins. Whereas the urinary alkylphosphate levels are (median) <10 ug/L and DDE/PCB levels are <1 ug/L in plasma, newly received data on prenatal urinary phthalate and phenol metabolites have median levels >10 ug/L for 2 phenols and 6 phthalate biomarkers. Lower-molecular-weight phthalate monoesters (low-MWP, <250d) were elevated compared with higher-molecular-weight compounds, mainly due to mono-ethylphthalate (median 380 ug/L). Medians of the two highest phenol metabolites were 11 and 54 ug/L (of 9 measured). Therefore, in terms of risk assessment these hormonally active agents have potential to affect fetal and infant growth and development. These analyses will occupy much of the coming year.
Prenatal exposure to pesticides also appears to have an impact on infant neurodevelopment. MDA levels above the limit of detection were associated with a 2.24-fold increase in the number of abnormal reflexes at birth (95% CI 1.55, 3.24). Likewise, higher levels of ΣDEP and ΣDAP were associated with an increases in abnormal reflexes, as was ΣDMP after considering paraoxonase expression. There were no adverse associations with PCB or DDE levels and any behavior.We have uncovered additional evidence that prenatal levels of OP metabolites are associated with anomalies in primitive reflexes which are a critical marker of neurological integrity.
For phthalate biomarkers weakly positive associations were found with gestational age, the strongest being with low- molecular-weight metabolites. There was an interaction between 3 phenols and infant sex, such that for example mothers with higher prenatal exposure to 2,5-dichlorophenol (25DCP) had smaller boy infants (-71 g birthweight per log-25DCP). Relationships among maternal BMI, urinary creatinine and phthalate biomarkers indicated that collinearity among these factors may require care in interpretation of findings. In summary phthalate and phenol exposures during pregnancy were high in our population. Effects of these exposures on birth outcomes are not likely to be clinically significant in healthy populations, but may be important in early births. Maternal susceptibility factors may contribute to the effects for some phenols.
Future Activities:During the next year we plan to continue 4, 6 and 7 year follow up visits.
We are finalizing a paper describing the relationship between prenatal OP and OC exposure the Bayley and Infant and Toddler behavior at ages 1 and 2 and the BASC at ages 4-7 yr. We will also finalize a paper relating prenatal exposure to bisphenol A and phthalates to birth outcomes, and begin our analyses of these exposures in relation to neurodevelopmental endpoints.
Journal Articles on this Report: 3 Displayed | Download in RIS Format
Other subproject views: | All 155 publications | 88 publications in selected types | All 80 journal articles |
Other center views: | All 168 publications | 96 publications in selected types | All 86 journal articles |
Type | Citation | ||
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Engel SM, Levy B, Liu Z, Kaplan D, Wolff MS. Xenobiotic phenols in early pregnancy amniotic fluid. Reproductive Toxicology 2006;21(1):110-112. |
R831711 (2005) R831711 (2006) R831711 (2007) R831711C001 (2006) R831711C002 (2006) R831711C002 (2007) R831711C003 (2006) |
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Engel SM, Berkowitz GS, Barr DB, Teitelbaum SL, Siskind J, Meisel SJ, Wetmur JG, Wolff MS. Prenatal organophosphate metabolite and organochlorine levels and performance on the Brazelton Neonatal Behavioral Assessment Scale in a multiethnic pregnancy cohort. American Journal of Epidemiology 2007;165(12):1397-1404. |
R831711C002 (2007) R831711C003 (2007) |
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Wolff MS, Engel S, Berkowitz G, Teitelbaum S, Siskind J, Barr DB, Wetmur J. Prenatal pesticide and PCB exposures and birth outcomes. Pediatric Research 2007;61(2):243-250. |
R831711 (2005) R831711 (2006) R831711 (2007) R831711C001 (2006) R831711C002 (2006) R831711C002 (2007) R831711C003 (2006) R831711C003 (2007) |
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, POLLUTANTS/TOXICS, ENVIRONMENTAL MANAGEMENT, Scientific Discipline, Health, RFA, Endocrine Disruptors - Environmental Exposure & Risk, Risk Assessment, Health Risk Assessment, endocrine disruptors, Chemicals, Children's Health, Biochemistry, Environmental Chemistry, Endocrine Disruptors - Human Health, neurodevelopmental toxicity, endocrine disrupting chemicals, children's environmental health, childhood development, exposure pathways, pesticide exposure, environmental health, phthalates, phtalates, pesticides, children's vulnerablity, exposure studies
Progress and Final Reports:
2004 Progress Report
2005 Progress Report
2006 Progress Report
Original Abstract
Main Center Abstract and Reports:
R831711 Mount Sinai Center for Children’s Health and the Environment