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2004 Progress Report: Measurement of Non-Persistent Pesticides in Postpartum Meconium as a Biomarker of Prenatal Exposure: A Validation Study

EPA Grant Number: R828609
Title: Measurement of Non-Persistent Pesticides in Postpartum Meconium as a Biomarker of Prenatal Exposure: A Validation Study
Investigators: Whyatt, Robin M. , Barr, Dana , Camann, David , Kinney, Patrick L. , Matseoane, Stephen , Perera, Frederica P. , Tsai, Wei-Yann
Institution: Columbia University - Mailman School of Public Health , Centers for Disease Control and Prevention , Southwest Research Institute
EPA Project Officer: Laessig, Susan A.
Project Period: September 28, 2000 through March 28, 2005 (Extended to June 28, 2005)
Project Period Covered by this Report: September 28, 2004 through March 28, 2005
Project Amount: $744,866
RFA: Biomarkers for the Assessment of Exposure and Toxicity in Children (2000)
Research Category: Children's Health , Health Effects

Description:

Objective:

The overall objective of this research project is to validate a new biomarker of cumulative prenatal exposure to organophosphates and other nonpersistent pesticides. Specifically the research project seeks to determine if the levels of the pesticides in postpartum meconium reflect exposures during the last 2 months of pregnancy. A cumulative biomarker is needed to facilitate the evaluation of health impacts associated with exposures during pregnancy, given the widespread residential use of these pesticides. Experimental data have linked prenatal organophosphate exposure to adverse neurocognitive development. Exposures during the spurt in brain growth (beginning in humans during the third trimester) appear particularly deleterious. Epidemiologic research on this relationship, however, has been hampered by the lack of reliable dosimeters. Existing biomarkers (including urine and blood levels) reflect short-term exposure only. Our prior research has shown that the pesticides can be quantified in meconium. Meconium begins to form during the second trimester but is generally not excreted until after delivery. Xenobiotics enter meconium through bile secretion and/or swallowing by the fetus of amniotic fluid. Evidence suggests significant trapping of xenobiotics in meconium, with measured levels reflecting months of exposure.

Progress Summary:

Enrollment, Indoor Air Monitoring, and Biologic Sample Collection

Enrollment into the study began in February 2001, and was completed in May 2004. We had originally planned to enroll 140-146 women but increased the number of enrollment to 220 women to achieve our goal of 100 mother/newborn pairs followed from the 32nd week of pregnancy until delivery with the collection of environmental and biologic samples. This increase in enrollment was necessary to offset the loss to followup, which has been higher than anticipated. The anticipated loss to follow-up rate (29-31%) was based on our experience to date in enrolling and following a similar cohort of pregnant women under the Columbia Center for Children’s Environmental Health study. Our actual loss to follow-up rate in the current study, however, was higher (55%) than in the Center study because the air monitoring protocol is more intensive. We finalized the collection of all indoor air monitoring and biologic samples in July 2004. Analysis of pesticide levels in the indoor air samples collected over the final 2 months of pregnancy from 100 homes (355 air samples) was completed at the Southwest Research Institute in November 2004. Analysis of pesticide levels in the biologic samples is ongoing at the Centers for Disease Control and Prevention, and will be completed by February 2005. Pesticides are being measured in the following biologic samples: 249 urine samples collected from the mothers during pregnancy; 148 urine samples collected from the mothers and newborns at delivery; 174 blood samples collected from the mothers and newborns at delivery; and 91 meconium samples collected from the newborns at delivery.

Results on Self-Reported Pesticide Use

Questionnaire data on pesticide use has been gathered from study women every 2 weeks during the eighth and ninth month of pregnancy. Questions include whether pests were seen in the home during the 2-week period, whether pest control measures were used and, if so, which methods were used and how frequently they were used. To date, 323 2-week questionnaires collected from 97 women have been entered into the database and data analysis has been completed for 79 women who were enrolled between 2001-2003. Of these, 61 percent reported that some form of pest control was used over the final 2 months of pregnancy and 20 percent reported using an exterminator. Forty-seven percent reported using one or more of the higher toxicity methods (can spays, sprays by exterminators, pest bombs, and illegal street pesticides). There was no change in self-reported pest control between 2001 and 2003 (chi-square = 3.7, p = 0.5).

Results on Pesticide Levels in Indoor Air Samples

The indoor air monitoring was conducted continuously between the 32nd week of pregnancy until the woman delivered. Integrated indoor air samples were collected every 2 weeks throughout the monitoring period. A personal air sample also was collected from the mother over a 48 hour period during the 32nd week of pregnancy. Analysis of pesticide levels in personal air (n = 76) and indoor air (n = 288) samples has been completed for 79 women who were monitored between 2001-2003. Of the 10 target pesticides, 3 (chlorpyrifos, diazinon, and propoxur) were detected in 99.6 percent to 100 percent of the personal and indoor air samples. Chorpyrifos and diazinon were detected in almost all air samples 1 to 2 years after the U.S. Environmental Protection Agency ban on their residential use. Air concentrations of the insecticides seldom declined during the 6-10 weeks of sequential integrated sampling, and the correlations among concentrations detected in each 2-week period were highly significant (r-values ≥ 0.8, p < 0.001, Spearman’s rank) for both insecticides. Air levels decreased, however, two- to three-fold among homes monitored in 2001 compared to those monitored in 2003: from 48.8 to 21.5 ng/m3 for diazinon (p = 0.002, ANOVA) and from 12.7 to 4.0 ng/m3 for chlorpyrifos (p = 0.35, ANOVA). Diazinon levels were significantly associated with maternal self-reported pesticide use (p = 0.005, ANOVA). Indoor air levels of both insecticides also were highly correlated with maternal personal air levels (r > 0.8, p < 0.001). The remaining pesticides were detected less frequently in the indoor air samples (in 0-40% of samples).

Results on Pesticide Levels in Biologic Samples

We have completed analysis of pesticide metabolites in prenatal urine samples collected from 42 mothers who were fully enrolled into the study (total 118 urine samples). Both the chemical specific metabolite of chlorpyrifos (3,5,6-trichloro-2-pyridinol [TCPY]) and the chemical specific metabolite of diazinon (2-isopropyl-4-methyl-6-hydroxypryimidine [IMPY]) were analyzed. TCPY was detected in 79 percent of the urine samples; IMPY was detected less frequently and was found in 23 percent. A significant correlation was seen between average chlorpyrifos in the indoor air samples and TCPY in the urine samples during the 2 months of monitoring. The correlation between diazinon in the indoor air samples and IMPY in the urine samples was generally weaker. Chlorpyrifos and diazinon levels also have been measured in blood samples collected from the mothers (n = 68) and newborns (n = 38) at delivery. Chlorpyrifos was detected in 20 percent of the maternal blood samples and 21 percent of the cord blood samples, while diazinon was detected in 24 percent of the maternal and 36 percent of the cord blood samples. Maternal and cord blood levels for both pesticides were highly correlated (r ≥ 0.9, p < 0.001). Diethylphosphate and diethylthiophosphate (metabolites common to both chlorpyrifos and diazinon) have been analyzed in 33 meconium samples collected from the newborns after delivery. Diethylphosphate was detected in 73 percent of the samples but diethylthiophosphate was not detected. No correlation was seen between the indoor air levels of chlorpyrifos or diazinon during the eighth and ninth months of pregnancy and the levels of these pesticides or their metabolites in blood and meconium samples collected from the mothers and/or newborns at delivery.

Future Activities:

We will continue data analysis and complete the final report by June 2005.


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

Other project views: All 17 publications 5 publications in selected types All 5 journal articles

Type Citation Project Document Sources
Journal Article Whyatt RM, Barr DB, Camann DE, Kinney PL, Barr JR, Andrews HF, Hoepner LA, Garfinkel R, Hazi Y, Reyes A, Ramirez J, Cosme Y, Perera FP. Contemporary-use pesticides in personal air samples during pregnancy and blood samples at delivery among urban minority mothers and newborns. Environmental Health Perspectives 2003;111(5):749-756. R828609 (2002)
R828609 (2004)
R828609 (Final)
R827027 (2002)
R832141 (2005)
R832141 (2006)
  • Abstract from PubMed
  • Full-text: Environmental Health Perspectives Full Text
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  • Other: Environmental Health Perspectives PDF
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  • Journal Article Whyatt RM, Camann D, Perera FP, Rauh VA, Tang D, Kinney PL, Garfinkel R, Andrews H, Hoepner L, Barr DB. Biomarkers in assessing residential insecticide exposures during pregnancy and effects on fetal growth. Toxicology and Applied Pharmacology 2005;206(2):246-254. R828609 (2004)
    R828609 (Final)
    R827027 (2002)
    R832141 (2005)
    R832141 (2006)
  • Abstract from PubMed
  • Full-text: Science Direct Full Text
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  • Other: Science Direct PDF
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  • Journal Article Whyattt RM, Rauh V, Barr DB, Camann DE, Andrews HF, Garfinkel R, Hoepner LA, Diaz D, Dietrich J, Reyes A, Tang D, Kinney PL, Perera FP. Prenatal insecticide exposures and birth weight and length among an urban minority cohort. Environmental Health Perspectives 2004;112(10):1125-1132. R828609 (2004)
    R828609 (Final)
    R832141 (2005)
    R832141 (2006)
  • Abstract from PubMed
  • Full-text: Environmental Health Perspectives Full Text
    Exit EPA Disclaimer
  • Other: Environmental Health Perspectives PDF
    Exit EPA Disclaimer
  • Supplemental Keywords:

    pesticides, insecticides, organophosphates, indoor air, monitoring, exposure assessment, biomarkers, fetus, newborn, human health, vulnerability, sensitive populations, ethnic groups, developmental, epidemiology, northeast, NY, nonpersistent pesticides, meconium, exposure, urine samples, blood samples, chlorpyrifos levels, diazinon levels, , Toxics, Geographic Area, Scientific Discipline, Health, RFA, Susceptibility/Sensitive Population/Genetic Susceptibility, Toxicology, Biology, genetic susceptability, Health Risk Assessment, Children's Health, pesticides, Environmental Chemistry, State, biomarkers, exposure assessment, insecticides, risk assessment, xenobiotics, environmental hazard exposures, developmental disorders, health effects, postpartum meconium, environmental toxicant, organophosphate pesticides, prenatal exposure, growth and development, pesticide residues, New York (NY), maternal exposure, pesticide exposure, sensitive populations, biological markers, children, validation study, exposure, growth & development, neurobehavioral effects, minority population, neurodevelopmental
    Relevant Websites:

    http://cpmcnet.columbia.edu/dept/sph/ccceh/index.htmlexit EPA
    Synthesis Report of Research from EPA’s Science to Achieve Results (STAR) Grant Program: Feasibility of Estimating Pesticide Exposure and Dose in Children Using Biological Measurements (PDF) (42 pp, 3.87 MB)

    Progress and Final Reports:
    2000 Progress Report
    2002 Progress Report
    Original Abstract
    Final Report

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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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