Final 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 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 was to validate a new biomarker of cumulative prenatal exposure to organophosphates and other nonpersistent pesticides. Specifically, the study sought 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 evaluation of health impacts associated with exposures during pregnancy, given the widespread residential use of these pesticides. Evidence suggests significant trapping of xenobiotics in meconium , with measured levels reflecting months of exposure.

Summary/Accomplishments (Outputs/Outcomes):

Enrollment, Indoor Air Monitoring, and Biologic Sample Collection

Enrollment into the study began in February 2001and was completed by July, 2004. The study included 102 women for an average of 7.0 ± 2.3 weeks, from the initial visit during the 32nd-34th week of gestation through delivery. Levels of 10 pesticides and an adjuvant were measured in 2-week integrated indoor air samples collected over the final 2 months of pregnancy (total 354 air samples). Personal air samples also were collected from 96 of the women over 48 hours during the 32nd-34th week of gestation. Biologic samples were collected from the mother during pregnancy and from the mother and newborn at delivery and included: 253 repeat spot urine samples collected from the mothers during pregnancy; urine samples collected from the mothers (n = 74) and newborns (n = 69) after delivery; maternal blood (n = 95) and umbilical cord blood (n = 69) collected after delivery; and postpartum meconium (n = 85).

Results on Pest Sightings and Self-Reported Pesticide Use

Ninety (91%) of the women reported that pests were sighted in the home during the study period. Cockroaches were the pest sighted most frequently, with 80 percent of the women reporting that cockroaches were sighted at some point during the study period and 49 percent reporting that cockroaches were sighted 4-7 times per week. Sixty women (61%) reported using some form of pest control during the final two months of pregnancy. Of these, 53 percent reported using lower toxicity methods only (sticky traps, bait traps, and gels), and 47 percent reported using one or more of the higher toxicity methods (can spays, sprays by exterminators, and pest bombs) with or without the other methods. There was no significant difference in the proportion of women using any form of pest control or in the proportion using the higher and lower toxicity pest control methods by year of enrollment (2001 through 2004, chi-square = 2, p = 0.9), nor was there any significant difference in pesticide use habits between African Americans and Dominicans (chi-square = 1.4, p = 0.5).

Results on Pesticide Levels in Indoor and Personal Air Samples. II.C

The insecticides chlorpyrifos, diazinon, and propoxur were detected in 99.6 percent to 100 percent of the indoor air samples and piperonyl butoxide (an adjuvant to pyrethroid insecticides) was detected in more than 45 percent of samples. The remaining insecticides either were not detected (malathion, methyl parathion, carbofuran) or were detected in 20 percent or less of the samples (carbaryl, bendiocarb, cis-permethrin, and trans-permethrin). Similar results were seen for insecticide levels in personal air samples. Average indoor air levels of chlorpyrifos and diazinon decreased significantly (approximately 5-fold) between homes monitored in 2001 compared to homes monitored in 2004. A verage indoor air levels of diazinon and piperonyl butoxide were significantly associated with maternal self-reported pesticide use. There was relatively little within-home variability in most of homes in indoor air concentrations of the insecticides detected frequently. Between-home variability accounted for 92 percent of the variance in chlorpyrifos levels, 94 percent in diazinon, 87.7 percent in propoxur, and 62.1 percent in piperonyl butoxide levels (p < 0.001 mixed effects model). There was no significant difference in average indoor air insecticide levels between homes of African Americans compared to homes of Dominicans. The correlation between levels of chlorpyrifos, diazinon, and propoxur in personal air compared to those in indoor air samples was highly significant (r-values ranged from 0.74 to 0.87, p < 0.001, Spearman’s rank). A somewhat weaker correlation was seen between personal and indoor air levels of piperonyl butoxide (r-values ranged from 0.36 to 0.56) but the association was still generally highly statistically significant (p < 0.05). These high correlations between personal and indoor air levels in the cohort support the use of indoor air levels as a measure of inhalation exposure.

Results on Pesticide Levels in Urine Samples Collected From the Mother During Pregnancy and From the Mother and Newborn at Delivery

We measured 12 insecticide metabolites in the urine samples, corresponding to the parent insecticidal compounds measured in air samples. The metabolites detected most frequently in maternal urine samples during pregnancy and at delivery were the pyrethroid metabolites 3-phenoxyphenoic acid (3-PBA), 4-fluro-3-phenoxybenzoic acid (4F3PBA) and trans-3-(2,2-dichlorovinyl)2,2-dimethylcyclopropane-1-carboxylic acid (TDCA) (detected in 32%-48% of samples); the organophosphate metabolites 3,5,6-trichloro-2-pyridinol (TCPY), malathion dicaboxylic acid (MDA), and 4-nitrophenol (detected in 39% to 77% of samples); and 1-naphthol, which is a metabolite of both the carbamate carbaryl and of naphthalene (detected in > 70% of samples).

The metabolites were detected much less frequently in the infant urine samples collected the day after delivery than in the maternal urine samples collected either during pregnancy or the day after delivery. The metabolites that were detected most frequently in the maternal urine samples, however, also were the ones detected most frequently in the infant urine samples. A generally positive and often highly significant correlation was seen between the pyrethroid metabolites 3PBA and 4F3PBA in the repeat maternal urine samples. These results suggest that exposures to the pyrethroid insecticides may remain fairly constant during pregnancy. In addition, a positive correlation that was often significant was seen between levels of chlorpyrifos metabolite TCPY in the repeat maternal urine samples.

Prior to adjusting either the urine of the mother or infant for creatinine, a significant and positive correlation was seen in levels of 3PBA (r = 0.38, p = 0.006, n = 51) and 4F3PBA (r = 0.5, p = 0.001, n = 39) in maternal and newborn urine samples collected after delivery. TCPY levels in maternal urine samples decreased significantly among those enrolled in 2002 (p = 0.04), 2003 (p < 0.001), and 2004 (p = 0.005) compared to 2001 levels. By contrast, ranks of the pyrethroid metabolites, 3PBA and 4F3BPA, increased significantly in 2002 and 2003 compared to 2001. They then decreased again in 2004, although caution is needed in interpreting these latter results because of the smaller number of subjects included in 2004 compared to the earlier years. A similar pattern was seen for the pyrethroid trans-DCCA; however, no results were available for subjects enrolled in 2004. Ranks of 4-nitrophenol also initially increased in 2002 compared to 2001 (p = 004) and then decreased, while mean ranks of MDA were significantly greater in 2003 and 2004 compared to 2001 levels (p < 0.001).

We also have evaluated the correlation between insecticide levels in 2-week integrated indoor air samples and the corresponding metabolite levels in maternal urine samples. A positive correlation was seen between levels of chlorpyrifos in the 2-week integrated indoor air samples and levels of TCPY in the maternal spot urine samples that was significant at each time point and when we compared average indoor air to average urine levels. The correlation between average chlorpyrifos levels in indoor air and average TCPY in maternal urine was significant among the women enrolled in both 2001 (r = 0.48, p = 0.005, n = 32) and 2002 (r = 0.5, p = 0.01, n = 25) but not among women after 2002 (all r-values < 0.01,p > 0.3). These results indicate that indoor air levels initially explained about 25 percent of the variance in maternal urinary TCPY levels but explained much less of the variance once levels of chlorpyrifos in indoor air had dropped.

A significant positive correlation also was seen between average diazinon levels in indoor air samples during the 6-10 weeks of sampling and average levels of IMPY in spot maternal samples collected over the same time period; however correlations were weaker than for chlorpyrifos. When we restricted analyses by year of enrollment, among women enrolled in 2001 (n = 32), a highly significant correlation was seen between average diazinon levels in the indoor air samples and average IMPY in maternal spot urine samples (r = 0.50, p = 0.004). The correlation was not significant among women enrolled later in the study.

Results on Pesticide Levels in Blood Samples From the Mother and Newborn at Delivery

Sixteen insecticides or metabolites were measured in the blood samples. The insecticides detected most frequently were the pyrethroid permethrin and the organophosphates chlorpyrifos and diazinon; however, all were found in less than 50 percent of samples. Maternal and umbilical levels of these insecticides were highly correlated. There was a significant decrease in levels of chlorpyrifos and diazinon in both the maternal and newborn blood samples between subjects enrolled in 2001 and 2004. By 2004, neither insecticide was detected in either maternal or umbilical cord blood samples.

The insecticides in blood samples were not correlated significantly to those in indoor air and, although there were some occasional significant associations with urinary levels, most correlations were weak and not significant and no clear trends were apparent.

Results on Pesticide Levels in Meconium Samples Collected From the Newborn After Delivery

Eleven insecticide metabolites were measured in meconium. Those detected most frequently were carbofuranphenol (detected in 94% of samples), 1-naphthol (detected in 91%), 4-nitrophenol (detected in 39%), 2-isopropoxyphenol (detected in 36%), and TCPY (detected in 28%). TCPY levels in postpartum meconium decreased by year of enrollment. TCPY levels in meconium were correlated positively but generally not significantly with chlorpyrifos in the indoor air samples and were correlated positively and generally significantly with TCPY levels in the prenatal maternal urine samples, both before and after adjusting for creatinine (r-values ranged from 0.3-0.57, p-values ranged from 0.06 to <0.001). TCPY in meconium also was correlated significantly with chlorpyrifos levels in both the maternal blood (r = 0.35, p = 0.001, n = 80) and umbilical cord blood (r = 0.44, p = 0.001, n = 56) samples collected after delivery.

Conclusions:

We had hypothesized that measurements of insecticides in meconium would provide a dosimeter of fetal prenatal exposure. Our results for chlorpyrifos described above indicate that this hypothesis is correct. Chlorpyrifos or its chemical-specific metabolite, TCPY, was the only compound that was detected consistently across all environmental and biologic matrices in the current study. Although we saw only weak correlation between chlorpyrifos levels in indoor air samples and TCPY levels in meconium, a consistent and often highly significant correlation was seen between TCPY in meconium and TCPY levels in repeat maternal urine samples during pregnancy as well as with chlorpyrifos levels in maternal and umbilical cord blood collected after delivery. Thus, the measurements of TCPY levels in meconium appear to provide a valuable internal dosimeter for chlorpyrifos exposure during pregnancy.


Journal Articles on this Report : 5 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 Bradman A, Whyatt RM. Characterizing exposures to nonpersistent pesticides during pregnancy and early childhood in the National Children's Study: a review of monitoring and measurement methodologies. Environmental Health Perspectives 2005;113(8):1092-1099. R828609 (Final)
R827027 (2002)
R831710 (2004)
R831710 (2005)
R831710 (Final)
R832141 (2006)
R832141 (2007)
R832141 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Journal Article Fenske RA, Bradman A, Whyatt RM, Wolff MS, Barr DB. Lessons learned for the assessment of children's pesticide exposure: critical sampling and analytical issues for future studies. Environmental Health Perspectives 2005;113(10):1455-1462. R828609 (Final)
    R827027 (2002)
    R831709 (2005)
    R831709 (2007)
    R831710 (2004)
    R831710 (2005)
    R831710 (Final)
    R831711 (2004)
    R831711 (2005)
    R831711 (2006)
    R831711 (2007)
    R831711 (Final)
    R831711C001 (2006)
    R831711C002 (2006)
    R831711C003 (2006)
    R832141 (2006)
    R832141 (2007)
    R832141 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • 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
  • Journal Article Whyatt 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)
    R832141 (2007)
    R832141 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • 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)
    R832141 (2007)
    R832141 (Final)
  • Abstract from PubMed
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  • Supplemental Keywords:

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

    Relevant Websites:

    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
  • 2002 Progress Report
  • 2003
  • 2004 Progress Report