Grantee Research Project Results
2004 Progress Report: Meconium Analysis - A Promising Tool to Detect Fetal Exposure to Environmental Toxins
EPA Grant Number: R829395Title: Meconium Analysis - A Promising Tool to Detect Fetal Exposure to Environmental Toxins
Investigators: Ostrea, Enrique M. , Bielawski, Dawn , Villanueva-Uy, Esterlita , Ager, Joel
Institution: Wayne State University
EPA Project Officer: Aja, Hayley
Project Period: April 1, 2002 through April 1, 2006
Project Period Covered by this Report: April 1, 2004 through April 1, 2005
Project Amount: $726,411
RFA: Children's Vulnerability to Toxic Substances in the Environment (2001) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
The objective of this research project is to develop meconium analysis as a sensitive, diagnostic tool to detect fetal exposure to environmental toxins (heavy metals and pesticides). This study aims to: (1) compare the prevalence and amount of fetal exposure to environmental toxins through the analysis of meconium, cord blood, and neonatal hair and to determine the degree of agreement among these methods; and (2) determine the relationship between maternal exposure to environmental toxins during pregnancy, as determined by serial analyses of maternal hair and blood, and the positivity rate and concentrations of environmental toxins in meconium, cord blood, and neonatal hair.
Pregnant women (n = 750) will be recruited in midgestation from the Outpatient Prenatal Clinic of the Bulacan Provincial Hospital (BPH), and their blood and hair will be obtained at the time of recruitment and delivery. Cord blood, meconium, and neonatal hair also will be obtained at delivery. The samples will be analyzed by atomic absorption spectrometry (AAS) for lead, mercury, cadmium, and arsenic and by gas chromatography/mass spectrometry (GC/MS) for the following pesticides and some of their known metabolites: propoxur, diazinon, transfluthrin, malathion, DDT, chlorpyrifos, bioallethrin, pretilachlor, lindane, cyfluthrin, and cypermethrin.
Progress Summary:
Subject Enrollment
We have recruited into the study a total of 936 pregnant women at midgestation. From this recruited cohort, 25 opted to withdraw from the study, and the remaining 911 have delivered (which included 10 sets of twins): 875 infants survived, and 46 died during pregnancy (fetal death) or neonatal period. Of the surviving infants, 595 were born at the study site, BPH, and 593 (99.6%) were enrolled into the study. A total of 280 infants was born outside of the study site hospital, of which 200 (71.4%) still were retrieved successfully into the study because the research team was alerted by the mother of her delivery elsewhere. We have enrolled therefore a total of 793 mother/infant dyads into the study and achieved our goal of enrolling the projected sample size of 750 mothers/infant dyads. To compensate for potential losses of subjects from voluntary withdrawal from the study, fetal death, and delivery of the mother outside of the study site, a higher number of mothers (n = 936) was initially recruited, which resulted in a higher number of mother/infant dyads finally enrolled in the study.
Demographics
The mean maternal age was 25.8 years. Most mothers were married (73.3%) and had prenatal care. There were 36.1 percent who were gravida ≥ 3 and 16.4 percent with parity ≥ 3. There was high exposure to tobacco (72.3%), mostly from second-hand smoke at home. The mean gestation of the infants was 38.4 weeks, with mean birth weight of 2,839 g. There were 55 percent male and 45 percent female. For sociodemographic characteristics, the mean monthly income was 5,332 pesos ($100), the average number of people in the household was five persons, socioeconomic status scale was class D (low), makeshift homes were 7.5 percent, water seal type of toilet were in 80 percent, pests (flies, mosquitoes and roaches) at home were greater than 90 percent, and the use of home pesticides was 91 percent and in the farm, 3 percent.
Specimen Analysis
Maternal hair and blood at midgestation (A) and delivery (B), infant hair, umbilical cord blood, and meconium were collected from the 793 mother/infant dyads in the study. The majority of specimens have been analyzed for parent pesticides (propoxur, diazinon, transfluthrin, malathion, DDT, chlorpyrifos, bioallethrin, pretilachlor, lindane, cyfluthrin and cypermethrin) and a number of their known metabolites [2 isopropoxyphenol, cis-3- (2,2-dichlorovinyl) -2,2-dimethylcyclopropanecarboxylic acid, trans-3-(2,2-dichlorovinyl)-2,2-dimethyl cyclo propanecarboxylic acid, 3,5,6- trichloro-2-pyridinol. 4,4’ dichloro diphenyl dichloroethylene, malathion mono carboxylic acid] by GC/MS and for heavy metals (lead, mercury, cadmium, and arsenic) by AAS.
By meconium analysis, there was high fetal exposure to propoxur (27.62%, mean conc in the positive samples = 0.40 μg/g) and cypermethrin (2.17%, mean conc = 1.11 μg/g) and some exposure to pretilachlor (1.99%, mean conc = 0.42 μg/g), malathion (0.36%, mean conc = 2.15 μg/g), DDT (0.54%, mean conc = 0.93 μg/g ), bioallethrin (0.36%, mean conc = 0.64 μg/g), cyfluthrin (0.54%, mean conc = 2.10 μg/g ), and diazinon (0.18%, mean conc = 0.33 μg/g). Meconium has, so far, been the best matrix to detect fetal exposure to pesticides compared to infant hair or cord blood that were found to be positive only for propoxur (2.06% and 0.2%, respectively). For maternal exposure, maternal hair analysis has been the best index of exposure to pesticides compared to maternal blood. Maternal hair A (sample obtained at midgestation) and B (sample obtained at delivery) were positive for propoxur (9.89% and 13.32%, respectively), bioallethrin (8.99% and 8.36%, respectively), malathion (0.90%), chlorpyrifos (0.11% and 0.26%, respectively), pretilachlor (0.11% and 0.13%, respectively), and DDT (0.22% and 0.39%, respectively). Maternal blood A and B were positive only for propoxur (0.34% and 2.62%, respectively), and DDT (0.11% and 0.13%, respectively).
Pesticide metabolites rarely were detected in any of the matrices examined. In 489 meconium samples analyzed, DDE was seen in only one sample, and in cord blood, no metabolite was found. Because of the limited sample available, infant hair was tested only for the parent pesticides. In 666 maternal hair A samples, no metabolite was seen, and in 499 maternal hair B samples, DDE was detected only in one sample. Similarly, in 861 maternal blood A samples, 3-PBA was seen only in one sample, and in 521 maternal blood B samples, 3-PBA was found in two samples and DDE in one sample. It is, therefore, evident that pesticide metabolites rarely are detectable in the different matrices at the limits of sensitivity of the assay. Thus, further analysis of metabolites in the remaining samples is not warranted, considering the very low positive results and the labor intensiveness of the analysis.
Exposure to heavy metals was detected mostly in maternal hair. Maternal hair A was positive for lead (29.2%, conc range = 0-247.0 μg/mL), mercury (28.4%, conc range = 0-11.58 μg/mL), and arsenic (9.4%, conc range = 0-1.84 μg/mL). Maternal hair B was positive for lead (19.5%, conc range = 0-115.74 μg/mL), mercury (31.6%, conc range = 0-24.60 μg/mL), and arsenic (13.9%, conc range = 0-1.89 μg/mL). It is likely that the heavy metal exposure represents passive exposure, because maternal blood was either negative or low positive for these heavy metals. All fetal matrices (neonatal hair, cord blood, and meconium) were negative for heavy metals.
Significance
The analysis of all the matrices is ongoing; thus, statistical analysis comparing frequency and concentration among matrices is deferred until final results are available. From the present data, however, we continue to find that among the different matrices (maternal hair and blood, infant hair, cord blood, and meconium), meconium appears to be the best matrix to analyze for fetal exposure to pesticides. Eight of the 11 pesticides have been detected in meconium; in particular for propoxur, the positive rate in meconium (27.62%) far exceeds the positive rate seen in the other matrices, maternal hair A (9.8%), maternal hair B (13.3%), infant hair (0.2%), maternal blood A (0.34%), maternal blood B (2.62%), and cord blood (2.06%). For the detection of maternal exposure to pesticides, maternal hair appears to be the best matrix to analyze compared to maternal blood. The latter information is important, especially for monitoring concurrent exposure of pregnant woman to pesticides and the adoption of measures to prevent further exposure during pregnancy.
Pesticide metabolites were detected at a very low rate in any of the matrices examined. Thus, measurement of pesticide metabolites may be least helpful in determining pesticide exposure either in the mother or the fetus.
The exposure to heavy metals was seen predominantly in maternal hair and minimally in the other matrices and may therefore represent passive exposure to heavy metals in the mother.
Relationship to the Goals of the Study. This is the first time that evidence has been presented showing that the analysis of meconium is optimal for the detection of fetal exposure to pesticides compared to the analysis of cord blood, infant hair, maternal blood, or hair. The appropriate determination of exposure to pesticides is crucial in the study of potential adverse effects of these compounds, particularly on the infant.
Relevance to Protection of the Environment and Human. We have found that exposure to home pesticides, compared to farm pesticides, provided the highest risk of fetal exposure to pesticides. The high fetal exposure to propoxur was secondary to improper use of the pesticide spray, Baygon, because of inadequate product labeling and warning. Propoxur and cyfluthrin are the principal ingredients of Baygon, and our survey showed that Baygon was used in 91.3 percent of the households and by the pregnant woman in 42 percent of the cases. We are trying to correct this practice using three measures:
- We have brought to the attention of the manufacturer the inadequate labeling of their product, particularly regarding explicit warnings about hazards of their products and the potential harm if used by pregnant women. SC Johnson Company, the manufacturer of Baygon in the United States and parent company of the subsidiary in the Philippines, has conducted meetings with us regarding this matter.
- We continue to educate the mothers in our study on not using the pesticides when pregnant and offer training on the proper use of pesticides at home by others.
- We also have presented the results of our study in many scientific forums to provide information to the public and scientific community in the United States and the Philippines.
Future Activities:
We have completed enrollment of the total number of subjects for the study and plan to complete the analysis of the remaining samples for the parent pesticides. Because of the very low positive rate of pesticide metabolites in the samples so far analyzed, we do not feel it is warranted to continue the analysis of the remaining samples for the pesticide metabolites, particularly because the procedure is labor intensive. Statistical analysis of our results will be conducted when the results of all the pesticide analyses are completed.
Journal Articles on this Report : 2 Displayed | Download in RIS Format
Other project views: | All 20 publications | 4 publications in selected types | All 4 journal articles |
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Bielawski D, Ostrea Jr. E, Posecion Jr. N, Corrion M, Seagraves J. Detection of several classes of pesticides and metabolites in meconium by gas chromatography/mass spectrometry. Chromatographia 2005;62(11-12):623-629. |
R829395 (2004) R829395 (Final) R826408 (Final) |
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Corrion ML, Ostrea Jr. EM, Bielawski DM, Posecion Jr. NS, Seagraves JJ. Detection of prenatal exposure to several classes of environmental toxicants and their metabolites by gas chromatography/mass spectrometry in maternal and umbilical cord blood. Journal of Chromatography B 2005;822(1-2):211-229. |
R829395 (2004) R829395 (Final) |
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Supplemental Keywords:
pesticide, heavy metals, meconium, hair, maternal blood, maternal hair, cord blood, fetal exposure, intrauterine exposure,, RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Health Risk Assessment, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Disease & Cumulative Effects, Physical Processes, Children's Health, genetic susceptability, Biology, pesticide exposure, diagnostic tool, fetal exposure, infants, detection, cord blood, pesticides, exposure, children, fetus, Human Health Risk Assessment, meconcium, human exposure, meconium analysis, environmental toxicant, detecting fecal matter, pregnant women, pregnancy, toxicants, exposure assessment, maternal exposure, heavy metals, neonatal hairProgress and Final Reports:
Original AbstractThe 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.