Project 2: Validation of Meconium Markers of Fetal Neurotoxicant Exposures
Investigator: Cynthia F. Bearer, MD, PhD
Project Period: 10-1-2001 through 6-30-2006
Objectives/Hypothesis
Environmental toxicants have been implicated in a number of developmental disorders. Unfortunately, the health effects subscribed to these exposures occur long after the actual exposure. For fetuses, exposure estimates are particularly difficult to quantify due to the problem of obtaining tissue for analysis. Biological markers for low to moderate exposure to environmental toxicants, as well as biological markers for adverse neurodevelopmental effects of these exposures, would allow earlier identification and intervention for affected infants, allow recognition of women at risk for exposure, and facilitate research on dose-response relationships between environmental exposures to mixtures of toxicants and to other known developmental neurotoxicants (ethanol and nicotine) and neurodevelopmental outcome.
Meconium, the first stool passed by a newborn, has been used to establish exposure to drugs of abuse. The presence of environmental toxicants in meconium has been reported. Research in our laboratory has shown a significant association between maternal self-reported low to moderate levels of drinking during pregnancy and the presence of metabolites of ethanol in their infants' meconium. (Bearer C.F., Lee S., Salvator A.E., Minnes S., Swick A., Yamashita T., Singer L.T. Ethyl linoleate in meconium: a biomarker for prenatal ethanol exposure. Alcohol Clin Exp Res 1999;23:487-493). Infants whose meconium contained more metabolites than that found in meconium of infants from abstaining women performed more poorly on the Bayley Scales of Infant Development. We propose that environmental toxicants as well as nicotine and ethanol metabolites in meconium are useful biological markers for exposure to developmental neurotoxicants and may indicate infants at risk for poor neurodevelopment.
Characterization of the quantity of each toxicant in meconium and the neurodevelopmental outcome of the infant is clearly relevant to validating meconium as a biological marker. The patient cohort and environmental measures described in Project 1 will be used to address the following specific objectives:
- We seek to test the hypothesis that meconium samples can be used for simultaneous analysis of several different environmental toxicants.
- We seek to test the hypothesis that an association exists between the presence of environmental toxicants in meconium and maternal / infant / environmental measures of toxicant exposure.
Approach
A technique will be developed to quantitatively analyze cotinine, lead, methyl mercury, organophosphate metabolites, pyrethrins, and ethanol metabolites in a single sample of meconium. Concentrations of toxicants and their metabolites in meconium will be compared to maternal and infant measures to determine the relationship between these markers and meconium markers.
Expected Results
These studies will provide preliminary data on the feasibility and utility of meconium analysis to gauge the influence of environmental neurotoxicants on human fetuses.
