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Extramural Research

2007 Progress Report: Pesticides, Endocrine Disruptors, Childhood Growth and Development (Birth Cohort)

EPA Grant Number: R831711C002
Subproject: 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.
Current Investigators: Wolff, Mary S. , Engel, Stephanie M.
Institution: Mount Sinai School of Medicine
EPA Project Officer: Callan, Richard
Project Period: November 1, 2003 through October 31, 2008 (Extended to October 31, 2010)
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:

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:

Enrollment is ongoing as subjects became eligible for each visit. To date we have completed 148 four-year visits, 163 six-year visits, and 168 7-year visits. During these follow up visits we collected child urine and maternal saliva samples at each visit. We have completed the 4 and 6 year assessments, and are continuing the 7-year assessments.

At each visit, parents completed the Behavior Rating Inventory of Executive Function (BRIEF) and the Behavioral Assessment Scale for Children (BASC). The BRIEF is designed to assess children’s executive functioning in the home, and it includes two clinical scales (behavioral regulation and metacognition). The BRIEF has proven useful for evaluating children with a wide spectrum of developmental and acquired neurological conditions, including learning disabilities, low birth weight, and ADHD. Parent reported behavioral and attention problems will be assessed using the BASC, a parent report questionnaire, which will serve as a global measure of children’s behavior problems and attention problems. The most general measure from the BASC is the Behavioral Symptoms Index, but it also offers scales for externalizing problems, internalizing problems, school problems, and adaptive skills. In addition, at the four year visit the children were administered a battery of assessments which provide measures of specific neuropsychological functions, including attention, learning, memory, and executive functioning. At the 6-year assessment we evaluate children’s psychometric intelligence using the Wechsler Preschool and Primary School Scales of Intelligence, third edition (WPPSI-III, 2002). And at the 7-year visit we administer the WISC-IV.

We provide a number of services to our participants to help to address the issues of greatest concern to them. Each BASC is immediately scored by our research staff. Those with clinically significant scores in any domain are referred to our study psychologist for expert review. If the psychologist deems it necessary, we contact the parent and provide a referral to a low cost/no cost counseling service and offer to send a copy of their exam to their Pediatrician. We also provide copies of the WPPSI and/or WISC-IV to the parent if requested, and contact parents whose children score greater than 1.5 standard deviations below the mean to suggest that they get in touch with their child’s school principal for a full educational assessment. Large deviations between the full-scale IQ and specific subdomains may indicate learning problems that could be addressed within the school system. Therefore, we look for discrepancy patterns and offer to provide copies of all exams to parents for their child’s school report.

Each visit also includes measurements of the child’s growth, including weight, height, hip circumference, waist circumference, and lean body mass. Since growth measurements have been collected from each child from birth, we have a detailed trajectory of that child’s growth. We are creating a growth report card for each child to be mailed out at the end of the study which includes all of their growth measurements and their relationship to the CDC national norms.

Maternal prenatal urine samples have been analyzed by the CDC for organophosphate pesticide metabolites, phthalates and phenols, including bisphenol A. Statistical analyses relating these exposures to birth outcomes have been completed. 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 also presented 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. We will be presenting our final results relating to prenatal phthalate exposure and neonatal performance on the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) at ISEE in Pasadena, 2008.

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.

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 (Engel, SM 2007).

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 (Wolff, MS 2008).

Concern is mounting that phthalates may pose human health risks based on numerous animal studies and a limited number of observational studies in humans. There have been no studies to investigate the relationship between phthalates and neurodevelopment. The Mount Sinai Children’s Environmental Health Center undertook an investigation of maternal prenatal phthalate exposure on pregnancy outcome and child neurodevelopment in an inner-city multiethnic cohort between 1998 and 2002. The majority of participants were Black or Latina women aged 25 years or younger who were unmarried at the time of enrollment and had a relatively low educational attainment. Severely preterm births were excluded by design; therefore, most delivered term babies (92.9%) of normal birthweight (97.8%). The Brazelton Neonatal Behavioral Assessment Scale was administered before hospital discharge (n = 311). All babies were evaluated by 5 days of age, the majority by day 2. Maternal third trimester urine samples were analyzed by the Centers for Disease Control and Prevention (CDC) for ten phthalate metabolites. Metabolites were summed into three groups: di(2-ethylhexyl) (DEHP) metabolites, monoester metabolites of high (>250 dalton) (high-MWP) and low (<250 dalton) (low-MWP) molecular weight. Groups were chosen to represent similar molecular structure, biological activity, and sources of exposure. In multivariate adjusted generalized linear models, third trimester log-DEHP was associated with poorer neonatal orientation (beta = -0.20, 95% CI -0.40, -0.01), and log high-MWP was associated with poorer regulation of state (beta = -0.21, 95% CI -0.39, -0.04). There was a significant interaction among infant gender, log low-MWP, and the infant motor domain, such that increasing log low-MWP was associated with better motor performance among boys, but worse motor performance among girls (interaction p-value = 0.04). Infant gender, log high-MWP and orientation interacted such that increasing log high-MWP was associated with significantly worse orientation among girls (beta = -0.45, p = 0.01), with no effect among boys (interaction p-value 0.02). These data suggest that third trimester maternal phthalate metabolite urinary concentrations may be predictive of measures of neonatal behavior as measured shortly after delivery, and may indicate the importance of phthalates in human neurodevelopment. We will be presenting our findings relating to prenatal phthalate exposure and neonatal behavior at ISEE in Pasadena, 2008.


Journal Articles on this Report : 3 Displayed | Download in RIS Format

Other subproject views: All 94 publications 53 publications in selected types All 49 journal articles
Other center views: All 254 publications 140 publications in selected types All 118 journal articles

Type Citation Sub Project Document Sources
Journal Article Engel SM, Levy B, Liu Z, Kaplan D, Wolff MS. Xenobiotic phenols in early pregnancy amniotic fluid. Reproductive Toxicology 2006;21(1):110-112.
abstract available   full text available
R831711 (2005)
R831711 (2006)
R831711 (2007)
R831711 (Final)
R831711C001 (2006)
R831711C002 (2006)
R831711C002 (2007)
R831711C003 (2006)
  • Abstract from PubMed
  • Full-text: Science Direct-Full Text HTML
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  • Abstract: Science Direct-Abstract
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  • Other: Science Direct-Full Text PDF
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  • Journal Article 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.
    abstract available   full text available
    R831711 (2007)
    R831711 (Final)
    R831711C002 (2007)
    R831711C003 (2007)
  • Abstract from PubMed
  • Full-text: Oxford-Full Text HTML
    Exit
  • Abstract: Oxford-Abstract
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  • Other: Oxford-Full Text PDF
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  • Journal Article 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.
    abstract available   full text available
    R831711 (2005)
    R831711 (2006)
    R831711 (2007)
    R831711 (Final)
    R831711C001 (2006)
    R831711C002 (2006)
    R831711C002 (2007)
    R831711C003 (2006)
    R831711C003 (2007)
  • Abstract from PubMed
  • Full-text: Nature-Full Text HTML
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  • Abstract: Nature-Abstract
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  • Other: Nature-Full Text PDF
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  • Supplemental Keywords:

    RFA, Health, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, POLLUTANTS/TOXICS, Environmental Chemistry, Health Risk Assessment, Chemicals, Endocrine Disruptors - Environmental Exposure & Risk, endocrine disruptors, Biochemistry, Children's Health, Endocrine Disruptors - Human Health, Risk Assessment, pesticide exposure, environmental health, childhood development, endocrine disrupting chemicals, exposure studies, pesticides, phtalates, Human Health Risk Assessment, children's vulnerablity, neurodevelopmental toxicity, exposure pathways, children's environmental health

    Progress and Final Reports:
    Original Abstract
    2004 Progress Report
    2005 Progress Report
    2006 Progress Report
    Final Report


    Main Center Abstract and Reports:
    R831711    Mount Sinai Center for Children’s Health and the Environment

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R831711C001 Growing Up Healthy in East Harlem (Community-Based Participatory Research)
    R831711C002 Pesticides, Endocrine Disruptors, Childhood Growth and Development (Birth Cohort)
    R831711C003 Genetics of Phthalate and Bisphenol A Risk in Minority Populations (Individual Susceptibility)

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    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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