Placental trophoblast transfer of opioids following exposures to individual or mixtures of opioids in vitro

Abstract

Infants born with neonatal abstinence syndrome increased 5-fold between 2000 and 2012. Prenatal exposure to opioids has been linked to altered brain development, congenital heart defects, neural tube defects, and clubfoot. In the study presented here, placental transfer rate of six opioids; morphine, heroin, fentanyl, methadone, oxycodone, and naloxone was compared in vitro using a human trophoblast cell monolayer model, BeWo b30. The rate and concentration of opioid translocation were investigated individually and in mixtures. The opioid transfer was quantified at 5, 15, 30, 60, and 120 min, using target liquid chromatography-mass spectrometry. The transfer was lowest for heroin (<1.2% of administered dose at 120 min; the permeability across the cells [P]: 0.21 × 10−5 cm/s) and highest for oxycodone (13.2% of administered dose at 120 min; P: 2.46 × 10−5 cm/s). As oxycodone is a preferred drug for both short- and long-term pain treatment, more knowledge is needed to understand the potential adverse impact on fetal development, growth, and well-being. Opioid exposure is likely to happen as mixtures, and we therefore investigated the transfer of selected mixtures. Permeability was significantly decreased for heroin when administered together with fentanyl. This study demonstrates that the transfer rate between individual opioids varies significantly and that some mixtures may impact the transfer of some individual opioids like heroin. Impact statement: Gaining knowledge about opioid exposure and placental transfer of opioids is an important part of providing clinicians with the necessary information for therapeutic strategies during pregnancy in the rising opioid epidemic. Opioids exposure often includes a mixture rather than an exposure to an individual opioid. We investigated placental trophoblast permeability to opioids in vitro for six individual opioids and selected mixtures. The rate and concentration of opioid translocation across placental trophoblast monolayer varied considerably between the six investigated opioids. Oxycodone had the highest level of translocation. We also found that the transfer of heroin decreased when administered together with fentanyl, while no change was observed for fentanyl transfer in the mixture. This suggests that opioid mixtures may decrease translocation of some opioids while others are unaffected.