SBIR-STTR Award

The purpose of this project is to develop a diagnostic test to assess whether the umbilical cord can provide equivalent or superior information to meconium for the identification of fetal drug exposure. Maternal drug use causes numerous medical complications for both mother and child. While there are many success stories of effective intervention for newborns diagnosed with in utero drug exposure, many affected neonates are missed due to collection of the wrong specimen, or sample unavailability. In this project, we propose to determine the diagnostic viability of the umbilical cord, in comparison to the "gold standard" of meconium testing. The umbilical cord is available for analysis in all births, regardless of in utero distress or errors in urine and meconium collection. The ability to diagnose neonates at birth will increase their chances of receiving appropriate intervention; decrease overall healthcare costs dramatically and, with proper intervention greatly enhance the quality of life of a new family. Drugs of abuse are routinely detected in newborns using urine and/or meconium samples. Urine gives only a 2-3 day history of drug exposure, and meconium, while providing up to a 20-week history is not always present due to in utero distress. Therefore, in order to accurately diagnose as many exposed newborns as possible, a widely available specimen giving a good historical measurement of substance abuse is necessary. During Phase I, the analysis of paired meconium and umbilical cord samples for drugs of abuse is proposed in order to determine whether umbilical cord will provide the same information as meconium. If the analytical approach is feasible, the data produced will be able to determine whether the umbilical cord samples can be used to replace meconium and urine collections for the testing of all newborns potentially exposed to drugs. Further phases of the project will include extending the drug test panel and the analysis of alcohol bio-markers in the umbilical cord. Commercialization areas of the test involve primary care providers, who will be able to identify drug and alcohol exposure in all newborns using an easily collected, historically accurate, widely available sample type. The overall goal is to develop a diagnostic test to assess fetal drug and alcohol exposure based on the analysis of the umbilical cord.

Thesaurus Terms:
alcoholism /alcohol abuse, diagnosis design /evaluation, diagnosis quality /standard, drug abuse, drug detection, embryo /fetus toxicology, maternal behavior, newborn human (0-6 weeks), umbilical cord biomarker, feces, rapid diagnosis behavioral /social science research tag, clinical research, enzyme linked immunosorbent assay, human subject, immunologic assay /test, sample collection

The current "best practices" procedure for diagnosing the in utero drug exposure of fetuses is testing the newborn's meconium for the presence of drugs. Meconium is difficult to collect and in 8-20% of births in the U.S. the meconium is released into the amniotic fluid pre-birth due to some type of fetal distress. While drugs may have induced this fetal distress it is unlikely that these infants will be tested for drug exposure due to lack of available meconium for testing. Under Phase I funding we studied the feasibility of substituting umbilical cord for meconium in fetal drug testing. Umbilical cord is readily available at every birth event and is easily collected. During the Phase I study we screened 118 matched meconium/umbilical cord samples with immunoassays specific for amphetamines, opiates, cocaine metabolites, cannabinoids, and phencyclidine (PCP) (NIDA-5 panel). The meconium samples were tested and reported out as routine clinical samples. Umbilical cord extracts were prepared, screened for the same drugs, and the results compared to the screening data for the respective meconium samples. Cutoffs for the umbilical cord screening tests were determined by ROC analyses of the data. Agreement between meconium and umbilical cord for amphetamine screening was 96.6%; for opiates was 94.9%; for cocaine metabolites was 99.2%; for cannabinoids was 90.7%; and for PCP was 100% for negatives (no PCP positive samples were obtained). Having established feasibility of umbilical cord testing in these Phase I studies, we now propose to extend these studies in Phase II to optimize and develop for production testing the umbilical cord extraction and assay procedures. We will screen by drug group-specific immunoassays and analyze by gas chromatography/mass spectrometry (GC/MS), the gold standard in drug testing, a large sampling (1000) of umbilical cord specimens from potentially drug- exposed neonates obtained from various socio-economic and ethnic populations at several birthing sites in the U.S. The data obtained will be used to establish drug screening cutoffs having optimum sensitivity and specificity. The umbilical cord screening and gold standard GC/MS assays will be validated and a marketing plan will be developed to introduce these assays into the drug testing arena. Testing of umbilical cord specimens will simplify drug testing of newborns, will allow testing of those infants suffering fetal distress, and will provide the potential to intervene for a greater population of drug-exposed babies.

Project narrative:
The potential of using umbilical cord tissue as a drug testing matrix for determining neonatal exposure to drugs of abuse in utero offers several advantages over testing meconium, the current testing specimen of choice. The primary advantage is the ready availability of umbilical cord at each birthing event. This broadens the drug testing base to include those 8-20% of infants born exhibiting fetal distress that pass their meconium in utero and, though possibly exposed to illicit drugs, are never diagnosed