2002 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 Boyd , Camann, David , Kinney, Patrick L. , Matseoane, Stephen , Perera, Frederica P. , Tsai, Wei-Yann
Institution: Columbia University in the City of New York , Centers for Disease Control and Prevention , Southwest Research Institute
EPA Project Officer: Hahn, Intaek
Project Period: September 28, 2000 through March 28, 2005 (Extended to June 28, 2005)
Project Period Covered by this Report: September 28, 2002 through March 28, 2003
Project Amount: $744,866
RFA: Biomarkers for the Assessment of Exposure and Toxicity in Children (2000) RFA Text |  Recipients Lists
Research Category: Children's Health , Health Effects , Human Health , Health

Objective:

The objective of this research project is to validate a new biomarker of cumulative prenatal exposure to organophosphates and other nonpersistent pesticides. Specifically, this research project seeks to determine if 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 3rd trimester) appear particularly deleterious. However, epidemiologic research on this relationship 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 2nd trimester, but is not generally 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:

This research project began with a 3-month startup to hire and train personnel, develop questionnaires, pilot monitoring strategies, and conduct quality assurance assessments (see below). The indoor air monitoring protocols were revised to operate pumps continuously throughout the 8th and 9th months of pregnancy, which should ensure that peak exposures are not missed.

Enrollment and Indoor Air Monitoring. Enrollment in the study began in February 2001. As of December 1, 2002, a total of 116 women had been enrolled into the study at an average rate of 5.3 women/month. Two-week integrated indoor air samples during the 8th and 9th month of pregnancy have been collected on 69 women. The monitoring is scheduled or currently is ongoing for an additional 10 women; 37 women have been lost to followup between enrollment and the indoor air monitoring. Laboratory analysis of the 10 target pesticides has been completed for 194 indoor air monitoring filters collected from 49 women. Data analyses of results have been completed for 38 women (see results below).

Questionnaires and Data Inputting. Questionnaires are being administered to all study women every 2 weeks during the 8th and 9th month of pregnancy. Questions on pesticide use 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. The database for the questionnaires, air monitoring results, and results of the biologic samples has been constructed and data input is ongoing. To date, a total of 223 2-week questionnaires collected from 64 women have been entered into the database.

Biologic Samples Collection. A maternal urine sample is being collected biweekly from all women during the indoor air monitoring. To date, 176 urine samples have been collected. Fifty-eight women in the cohort have delivered and the following biologic samples have been collected at delivery: a postpartum meconium sample from 50 (86 percent) newborns; a postpartum urine sample from 46 (79 percent) newborns and 45 (78 percent) mothers; and a blood sample (maternal and/or umbilical cord) from 58 (100 percent) of the mother/newborn pairs. Samples are being shipped to the Center for Disease Control on dry ice and laboratory analyzes are currently ongoing.

Pesticide Levels, Indoor Air Samples, and Biologic Samples. Data analysis has been completed on levels of pesticides in 152 2-week integrated indoor air samples collected from 38 women over the final 2 months of pregnancy. Questionnaire data on pesticide use also have been analyzed for these 38 women; 27 (71 percent) reported that some form of pest control had been used during the 2 months of the indoor air monitoring. Specifically, 15 (39 percent) reported the use of the lower toxicity pest control methods only (gels, baits, and traps) and 12 (32 percent) reported use of higher toxicity methods (can sprays, pest bombs, and/or exterminator sprays). Of the 10 pesticides measured in the 2-week integrated indoor air samples, 3 were detected in all (100 percent) samples. They were chlorpyrifos, diazinon, and propoxur.

As seen in Figure 1, chlorpyrifos levels were generally low (range 0.5-171 ng/m3) with only two women showing indoor air levels > 30 ng/m3. Propoxur levels were somewhat higher (range 1.1-317 ng/m3). No association was seen between the woman's self-reported pesticide use during the 2 months of the monitoring and indoor air levels of either chlorpyrifos and propoxur. Indoor air levels of diazinon were higher than either chlorpyrifos or propoxur (range 0.6-641 ng/m3) and diazinon levels were significantly associated with maternal self-reported pesticide use (p <0.05). In general, there was very little variability in indoor air levels among the individual women during the 2 months of the air monitoring (see Figure 1) and a highly significant degree of correlation was seen between the 2-week integrated indoor air levels for all three pesticides (r = 0.71-0.96, p <0.001, see Table 1). Of the remaining seven pesticides, three were not detected in any of the indoor air samples (malathion, methyl parathion, and carbofuran) and four (permethrin, piperonyl butoxide, carbaryl, and bendiocarb) were detected in less than 50 percent of samples (range 11-43 percent).

Figure 1. Two-Week Integrated Indoor Air Pesticide Levels for 38 Women Between the 32nd-40th Week of Pregnancy.


Table 1. Correlation Between 2-Week Integrated Indoor Air Pesticide Levels During the 32nd-40th Week Gestation.

  Chlorpyrifos Propoxur Diazinon
  32nd-34th 34th-36th 36th-38th 32nd-34th 34th-36th 36th-38th 32nd-34th 34th-36th 36th-38th
38th-40th r = 0.77* r = 0.81* r = 0.83* r = 0.71* r = 0.71* r = 0.95* r = 0.88* r = 0.92* r = 0.94*
36th-38th r = 0.82* r= 0.80*   r = 0.86* r = 0.83*   r = 0.89* r = 0.93*  
34th-36th r = 0.95*     r = 0.95*     r = 0.96*    

*p <0.001, Spearman's rank.

Dr. Dana Barr, from the Centers for Disease Control and Prevention, has completed analyses of the 6 common dialkylphosphate metabolites in 33 meconium samples collected from the newborns in the study for whom results on pesticide levels in indoor air also are available (see above). Diethylphosphate (DEP), a metabolite common to both diazinon and chlorpyrifos, was detected in 61 percent of samples (range ND-91 mg/g). However, DEP levels were not significantly associated with maternal self-reported pesticide use (p >0.05, Mann-Whitney U-test). They were not significantly correlated with indoor air levels of either chlorpyrifos or diazinon (p >0.2, Spearman's rank). The other dialkyl phosphate metabolites (diethylthiophosphate, diethyldithiophosphate, dimethylphosphate, dimethylthiophosphate and dimethyldithiophosphate) were detected less frequently (0-18 percent of samples).

In addition, Dr. Barr has completed the analysis of 3,5,6-trichloro-2-pyridinol (the chemical-specific metabolite of chlorpyrifos) and 2-isopropoxyphenol (the chemical specific metabolite of propoxur) in the same 33 meconium samples. 3,5,6-Trichloro-2-pyridinol was detected in 91 percent of samples (0.07-1.1 µg/g) and 2-isopropoxyphenol was detected in 34 percent of samples (range 0.6-40 ng/g). Levels of 3,5,6-trichloro-2-pyridinol and 2-isopropoxyphenol in meconium did not vary significantly with maternal self-reported pesticide use (p >0.05, Mann-Whitney U) and were not correlated with indoor air levels of chlorpyrifos or propoxur, respectiviely (p >0.2, Spearman's rank).

Future Activities:

We will continue to enroll and monitor women during pregnancy. We will collect questionnaire data and biologic samples, and analyze pesticide levels in the meconium and other biologic samples.


Journal Articles on this Report : 1 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)
R832141 (2007)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Supplemental Keywords:

    ambient air, newborn, developmental, insecticides, epidemiology., RFA, Health, Scientific Discipline, Toxics, Geographic Area, Toxicology, Environmental Chemistry, Health Risk Assessment, State, pesticides, Susceptibility/Sensitive Population/Genetic Susceptibility, Children's Health, genetic susceptability, Biology, health effects, pesticide exposure, risk assessment, sensitive populations, minority population, biomarkers, xenobiotics, postpartum meconium, prenatal exposure, validation study, exposure, children, neurodevelopmental, neurotoxicity, insecticides, pesticide residues, growth and development, environmental toxicant, neurobehavioral effects, biological markers, growth & development, developmental disorders, exposure assessment, organophosphate pesticides, New York (NY), maternal exposure

    Relevant Websites:

    http://cpmcnet.columbia.edu/dept/sph/ccceh/index.html Exit
    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:

    Original Abstract
  • 2001
  • 2003
  • 2004 Progress Report
  • Final Report