Grantee Research Project Results
2003 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, 2003 through April 1, 2004
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 overall 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). The specific objectives of this research project are 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, and their blood and hair will be obtained at the time of recruitment and at delivery. Cord blood, meconium, and neonatal hair also will be obtained at delivery. The samples will be analyzed by atomic absorption spectrometry for lead, mercury, and cadmium, and by gas chromatography/mass spectrometry for the following pesticides and their metabolites: propoxur, diazinon, transfluthrin, malathion, dichlorodiphenyltrichloroethane (DDT), chlorpyrifos, bioallethrin, pretilachlor, lindane, cyfluthrin, and cypermethrin.
Progress Summary:
Subject Enrollment
As of March 31, 2004, we have recruited into the study a total of 720 pregnant women at midgestation, which represents an increase of 393 enrollees since the previous progress report. Of the 720 enrollees, 577 have delivered, which included 5 sets of twins: 546 infants survived and 36 died during pregnancy (fetal death) or neonatal period. Of the surviving infants, 409 were born at the study site, the Bulacan Provincial Hospital; 407 of these infants (99.5 percent) were enrolled into the study. A total of 137 infants were born outside of the study site hospital, of which 81 (59 percent) were still successfully retrieved into the study because the research team was alerted by the mother of her delivery elsewhere. Overall, we have enrolled (from birth) a total of 488 mother/infant dyads into the study.
Demographics
The mean maternal age was 25.7 years. A majority of the mothers were married (75 percent) and had prenatal care. There were 35.5 percent who were gravida greater than 3, and 15.2 percent with parity greater than 3. There was high exposure to tobacco (70 percent), mostly from secondhand smoke at home. The mean gestation of the infants was 38.1 weeks, with a mean birth weight of 2,817 g. The infants were 54.7 percent male and 45.1 percent female. Neonatal problems included: hyaline membrane disease (3.9 percent), transient tachypnea (1.8 percent), meconium aspiration pneumonia (1.2 percent), and sepsis (11.9 percent).
Specimen Analysis
There is ongoing collection and analysis of specimens (maternal hair, maternal blood, cord blood, neonatal hair, and meconium) for parent pesticides and their metabolites and heavy metals. There has been further improvement in the methods to analyze the various matrices for parent pesticides and their metabolites leading to improved recovery, precision, and limits of detection. These procedures currently are used to analyze all of the samples. By meconium analysis, there was high fetal exposure to propoxur (39.18 percent, mean concentration = 0.81 µg/mL) and cypermethrin (3.51 percent, mean concentration = 2.21 µg/mL) and some exposure to pretilachlor (1.46 percent, mean concentration = 1.15 µg/mL), malathion (0.58 percent, mean concentration = 4.15 µg/mL), DDT (0.88 percent, mean concentration = 1.86 µg/mL ), bioallethrin (0.29 percent, mean conc = 1.79 µg/mL), and cyfluthrin (0.29 percent, mean concentration = 1.81 µg/mL ). Thus far, meconium seems to be the best matrix to detect fetal exposure to pesticides compared to infant hair or cord blood, although chlorpyrifos was found only in infant and maternal hair. In the mother, maternal hair seems to be the best index of maternal exposure to pesticides. Positive exposure was seen for propoxur (12.37 percent, mean concentration = 0.8 µg/mL ), bioallethrin (12.58 percent, mean concentration = 2.4 µg/mL), malathion (1.71 percent, mean concentration = 1.94 µg/mL ), chlorpyrifos (0.21 percent, mean concentration = 1.83 µg/mL), pretilachlor (0.21 percent, mean concentration = 1.07 µg/mL ), and DDT (0.43 percent, mean concentration = 0.41 µg/mL ). Hair samples taken at midgestation showed similar percentages of positivity for various pesticides compared to hair samples taken at delivery. Pesticide metabolites were seen in only a few of the matrices (maternal hair B, 0.57 percent for methyl methacrylate; maternal blood A = 2.47 percent for dichlorodiphenyldichloroethylene [DDE]; maternal blood B = 3.45 percent for 3-phenoxybenzoic acid and 0.57 percent for DDE).
Exposures to the heavy metals were only detected in maternal hair and blood. Maternal hair was 26.2 percent positive for lead (mean concentration = 10.65 µg/mL), 28.4 percent positive for mercury (mean concentration = 0.598 µg/mL), and 22.4 percent positive for arsenic (mean concentration = 0.303 µg/mL). Maternal blood was only positive for mercury (1.3 percent positive; mean concentration = 0.075 µg/mL). The positive maternal hair samples for heavy metals probably represent passive maternal exposure because maternal blood was either negative or low positive for these heavy metals. All fetal samples (neonatal hair, cord blood, and meconium) were negative for heavy metals.
Significance
Thus far, the best matrix to analyze for maternal exposure to pesticides is maternal hair, compared to maternal blood. This information is useful for monitoring the exposure of pregnant woman to pesticides during pregnancy. Overall, the best matrix to analyze for fetal exposure to pesticides is meconium. In particular, exposure to propoxur exceeds the detection rate using other matrices.
The detection of pesticide metabolites in any of the matrices has been very low. Thus, measurement of pesticide metabolites may be the least helpful for determining exposure. Exposure to heavy metals has been seen predominantly in maternal hair. This probably implies that exposure is passive in nature.
Relationship to the Goals of the Study
The results of our ongoing study provide further evidence as to the appropriate matrix to detect and analyze exposure in the mother and fetus to pesticides and heavy metals in the environment. For the first time, we are demonstrating that meconium analysis will detect far greater intrauterine exposure of the infant to pesticides compared to the analysis of cord blood or infant hair. Unfortunately, the latter matrices have been analyzed as indices of fetal exposure to pesticides in the past, and this approach may have to be reevaluated based on our current findings.
Relevance to the Protection of the Environment and Humans
We have found that the high fetal exposure rate to propoxur in the study population may be attributed to misuse of the pesticide spray, Baygon, as a result of inadequate labeling of the product. The principal ingredients of Baygon are propoxur and cyfluthrin, and our survey showed that the product is used in 47.1 percent of households and by pregnant woman in 42 percent of the cases. We are trying to correct this hazard by two measures:
1. We have brought to the attention of the manufacturer the inadequate labeling of their product so that they can be more explicit in warning about the hazards of the product and its appropriate use, particularly among pregnant women. SC Johnson, the manufacturer of Baygon in the United States and mother company of the subsidiary in the Philippines, has responded positively to our letter. We will have a meeting with the company’s representatives on June 21, 2004, to discuss this matter.
2. We also are educating the public, through health care givers, on the appropriate use of pesticides.
The Principal Investigator was invited to speak at a plenary session of the Annual Philippine Pediatric Society Convention in Manila on April 26, 2004, where he presented highlights of the study and made recommendations to the health care givers to educate their patients on the proper use of Baygon and other pesticides. The information was timely and well received.
Future Activities:
We will continue the study and enroll the projected 750 subjects. At our current enrollment rate, it is feasible to obtain this sample size within the study period of the grant. Because the first set of infants was born 6 months from the initial enrollment of the pregnant women into the study, we also plan to ask for a 6-month, no-cost extension to await the final births of the infants in the study and obtain their samples for analysis.
Journal Articles:
No journal articles submitted with this report: View all 20 publications for this projectSupplemental Keywords:
innovative technology, pesticides, heavy metals, health, physical aspects, sustainable industry, business, biology, chemistry, children's health, disease and cumulative effects, health risk assessment, new technologies, innovative technologies, physical processes, risk assessments, susceptibility, sensitive population, genetic susceptibility, toxicology, human health risk assessment, children, cord blood, detecting fecal matter, detection, diagnostic tool, environmental toxicant, exposure, exposure assessment, fetal exposure, fetus, human exposure, human health risk, infants, maternal exposure, meconium, meconium analysis, neonatal hair, pesticide exposure, pregnancy, pregnant women, hair, blood, intrauterine exposure., RFA, Scientific Discipline, Health, 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.