{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:35:06Z","timestamp":1761093306274,"version":"build-2065373602"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T00:00:00Z","timestamp":1692748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Study Objective<\/jats:title><jats:p>Neonatal opioid withdrawal syndrome (NOWS) is a condition that often occurs in neonates born to mothers who received methadone treatment for opioid use disorder during pregnancy. Early identification and treatment of infants at risk of NOWS may improve clinical outcomes. The purpose of this study was to evaluate whether maternal and umbilical cord plasma concentrations of methadone and its metabolite, 2\u2010ethylidene\u20101,5\u2010dimethyl\u20103,3\u2010diphenylpyrrolidine (EDDP), could predict the need for NOWS treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Single\u2010center prospective study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>University of Michigan Neonatal Intensive Care Unit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>The study included 11 opioid\u2010dependent mother\u2013infant dyads, where the mothers were treated with methadone at 34\u2009weeks' gestation or later.<\/jats:p><\/jats:sec><jats:sec><jats:title>Intervention<\/jats:title><jats:p>Maternal and cord blood samples were collected from the study participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements and Main Results<\/jats:title><jats:p>Maternal and cord plasma concentrations of methadone and EDDP were determined. Six out of the 11 infants required treatment for NOWS. Maternal methadone plasma concentrations were comparable between infants requiring and not requiring NOWS treatment (329.1\u2009\u00b1\u2009229.7\u2009ng\/mL vs. 413.2\u2009\u00b1\u2009329.8\u2009ng\/mL). However, the average cord plasma methadone concentration in infants who did not require NOWS treatment was 2.9\u2010fold higher than in those who required the treatment (120.0\u2009\u00b1\u200988.6\u2009ng\/mL vs. 40.9\u2009\u00b1\u200924.4\u2009ng\/mL), although the difference was not statistically significant. The ratios of maternal\u2010to\u2010cord methadone plasma concentrations were significantly higher in patients who required treatment for NOWS compared with those who did not (7.7\u2009\u00b1\u20091.9 vs. 3.5\u2009\u00b1\u20091.6, <jats:italic>p<\/jats:italic>\u2009=\u20090.003). Maternal and cord plasma EDDP concentrations and the maternal\u2010to\u2010cord plasma EDDP concentration ratios did not differ between patients who required and did not require treatment for NOWS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results suggest that methadone permeability across the blood\u2013placental barrier may affect in utero exposure to methadone, and the maternal\u2010to\u2010cord methadone plasma concentration ratio could be a potential biomarker for predicting the need for NOWS treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2863","type":"journal-article","created":{"date-parts":[[2023,8,13]],"date-time":"2023-08-13T23:10:06Z","timestamp":1691968206000},"page":"22-27","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transplacental methadone exposure and risk of Neonatal Opioid Withdrawal Syndrome"],"prefix":"10.1002","volume":"44","author":[{"given":"Varsha","family":"Bhatt\u2010Mehta","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyue","family":"Jing","sequence":"additional","affiliation":[{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Northeast Ohio Medical University  Rootstown Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2248-4419","authenticated-orcid":false,"given":"Hao\u2010Jie","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, 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