Utility of Phosphatidylethanol for Identification of Fetal Alcohol Exposure

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DESCRIPTION (provided by applicant): Primary prevention of Fetal Alcohol Spectrum Disorders (FASD) is often problematic due to difficulties of early identification of alcohol use among pregnant women or women who might become pregnant. In addition, attempts to study Alcohol-related Neurodevelopmental Disorder (ARND) or the so-called "lesser affected" children, which are thought to make up a large majority of fetal alcohol-affected children, has been confounded by the diagnostic requirement of confirming a maternal history of drinking. Maternal self-report is unreliable and conventional ethanol biomarkers are not sensitive enough for a diagnosis of drinking in many pregnant women, especially moderate drinkers. Given the difficulties of confirming maternal drinking during pregnancy, as well as diagnosing less severe cases of FASD, the development of better biomarkers, either alone or in combination with other measures, would create opportunities for earlier interventions that may reduce long-term adverse outcomes associated with fetal alcohol exposure. We are currently conducting a ABMRF-supported prospective study of 150 pregnant women (moderate drinkers and light drinkers/abstainers) recruited from the University of New Mexico-affiliated clinic dedicated to pregnant women with a present or past history of substance abuse. Eligible patients participate in a baseline interview conducted by a trained study coordinator at the clinic. At the same visit, maternal biological samples (blood, urine, and hair) are collected. Subjects are followed up until labor and delivery when the second interview and collection of specimens take place. This SOAR application proposes to include the measure of a novel ethanol biomarker - phosphatidylethanol (PEth) in samples collected from our established cohort of pregnant women and their newborn children. PEth will be measured in banked maternal blood collected by venipuncture at the enrollment into the parent study. In newborns, PEth will be measured in dried blood spots (DBS) or Guthrie cards collected by heel-prick for routine genetic screening at birth. The analysis of PEth in this media could provide a sensitive and readily available tool to assess fetal alcohol exposure, given the availability of DBS samples from over 95% of newborns in the United States and the low cost of sample collection and processing. The sensitivity and specificity of PEth will be compared to traditional ethanol biomarkers (gamma glutamyltranspeptidase and carbohydrate-deficient transferrin), screening questionnaires, and other direct ethanol metabolites of the mother (i.e., urine ethyl glucuronide and ethyl sulfate) and the fetus (i.e., meconium fatty acid ethyl esters). To our knowledge this is the first study to examine validity of PEth in pregnant women and their offspring. Given the high sensitivity and specificity of PEth in non-pregnant populations, we expect that it will be an important addition to the biomarker profile for detecting more moderate levels of drinking and evaluating both maternal and fetal levels of exposure. PUBLIC HEALTH RELEVANCE: The proposed study is a first attempt to estimate validity of a novel and promising ethanol biomarker - Phosphatidylethanol (PEth), assessed both in the mother and newborn, for identification of prenatal alcohol exposure among pregnant women. The utility of biomarkers in the clinical practice, either alone or in combination with other measures, can facilitate primary and secondary prevention of Fetal Alcohol Spectrum Disorder.