Antiretroviral Drug and Ethanol Meconium Markers for In Utero Exposure Identification and Infant Toxicity Prediction

Abstract

With a longer detection window and collection easier than neonatal urine, drug quantification in meconium, the 1st neonatal feces, offers powerful insight into 3rd trimester fetal drug exposure. Meconium drug concentrations better represent fetal drug exposure compared to drug concentrations in maternal or neonatal plasma and urine, cord blood, and placenta that have much shorter (hours-weeks) detection windows. My research demonstrates the clinical impact of large multi-analyte meconium quantification methods and how these data can be utilized with maternal drug histories to explore relationships with infant developmental outcomes and better improve meconium result interpretation. The primary objectives investigated were 1) to develop novel liquid chromatography tandem mass spectrometry methods for sensitive and specific meconium quantification of a wide range of antiretroviral (ARV) drugs and alcohol markers, and 2) to assess these markers' ability to predict specific adverse infant growth and neurodevelopmental outcomes, and maternal ARV or alcohol history during pregnancy. This research showed meconium ARV concentrations can predict some infant outcomes, offering opportunities to intervene clinically with assistive services. Among infants exposed prenatally to atazanavir, higher meconium atazanavir concentrations were associated with lower late language emergence risk at 1 year. This information supports ATV exposure safety for infant language development. Continued meconium ARV testing research is needed to further develop our understanding of these markers' utility. This research also demonstrated the clinical value of meconium ethyl glucuronide (EtG) testing as a more accurate identification of maternal alcohol consumption in the latter half of pregnancy (at or beyond 19 weeks) compared to fatty acid ethyl ester (FAEE) testing, which is currently utilized by most in the meconium alcohol marker testing field. Implementation of meconium EtG testing in place of or in addition to current FAEE testing, would greatly improve clinicians' identification of prenatal alcohol exposure. In conclusion, this research demonstrates meconium drug quantification undoubtedly offers many advantages as an alternative matrix to identify in utero drug exposures. Predictions of infant outcomes from meconium drug concentrations offer opportunities to intervene in affected children's lives, provide mothers treatment, prevent adverse outcomes in future pregnancies, and confirm safety of therapeutic drugs administered during pregnancy.