The analysis of drugs in neonates using an ad hoc oral fluid collection device to develop a prediction model for neonatal abstinence syndrome and provide maternal support

Abstract

To use oral fluid specimens collected in an ad hoc device to test for opioid exposure and to help assess the risk of withdrawal in potential neonatal abstinence syndrome (NAS) cases. Testing for Neonatal drug exposure typical uses meconium, urine, blood, hair, or umbilical cord tissue/blood specimens. Due to the invasiveness, challenges, and limitations of collection, and/or analytical difficulties of these matrices, oral fluid may be a more desirable specimen when testing for opioid exposure and assessing the risk of neonatal abstinence syndrome (NAS). Traditional oral fluid collection devices are not viable options for neonatal specimen collection due to their large size and potential chemicals additives that induce salivation. Unstimulated and stimulated infant oral fluid samples have been used for therapeutic drug monitoring as an alternative matrix to blood. Oral fluid samples were collected under Virginia Commonwealth University's Institutional Review Board from ten neonates born to mothers in methadone or buprenorphine treatment programs. Oral fluid samples were collected by rolling three foam-tipped swabs along the mouth, inner cheeks, and tongue until saturated. The three swabs containing approximately 300 μL oral fluid were placed in 2.0 mL of phosphate-buffered saline, centrifuged, and analyzed by ultra-high-pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for 26 drugs and/or metabolites after solid phase extraction (SPE) with OFXQ columns. Results were compared to maternal and the neonatal medical history. The following analytes were detected in the neonatal oral fluid: 2-Ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP), 2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), 6-acetylmorphine, amphetamine, benzoylecgonine, cocaine, cotinine, ethyl sulfate, methadone, methamphetamine, morphine, nicotine, and norfentanyl. Maternal history and infant medications were available for 9 of 10 neonates. The detection of norfentanyl was consistent with epidurals given during birth. The following analytes detected were inconsistent with patient histories; 6-acetylmorphine, amphetamines, benzoylecgonine, ethyl sulfate, and nicotine. Three of the ten neonates were treated for withdrawal symptoms by an oral suspension of methadone given twice daily. These neonates were released from the hospital on day of life 18, 20, or 24. Prior to treatment, four to eleven drugs and/or metabolites were identified in the three neonates, including 6-acetlymorphine, amphetamine, benzoylecgonine, cocaine, cotinine, EDDP, EMDP, ethyl sulfate, methadone, morphine, nicotine, and/or norfentanyl. In two neonates, methadone oral fluid concentrations increased in the first few days of life then significantly decreased in concentration prior to treatment. No methadone was detected in the third neonate, but a variety of other drugs were identified. None of the other neonates presented symptoms of withdrawal and were released from the hospital on day 3 or 4 of life, except for one neonate born pre-term (35 weeks gestation) was not released until day of life 9. An easy-to-use collection device for neonatal oral fluid must be developed. Identifying trends between neonates who demonstrate withdrawal symptoms and those who do not could be vital to developing a predictive model for the determination of NAS. When analyzing neonatal samples, complete clinical histories of mother and neonate are necessary to prevent the misinterpretation of data, which could lead to unwarranted criminal or legal complications.