{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:47:25Z","timestamp":1792176445302,"version":"4.4.0"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:00:00Z","timestamp":1690761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:p>Infants with neonatal opioid withdrawal syndrome commonly receive morphine treatment to manage their withdrawal signs. However, the effectiveness of this pharmacotherapy in managing the infants' withdrawal signs vary widely. We sought to understand how information available early in infant monitoring can anticipate this treatment response, focusing on early modified Finnegan Neonatal Abstinence Scoring System (FNASS) scores, polygenic risk for opioid dependence (polygenic risk score (PRS)), and drug exposure. Using k\u2010means clustering, we divided the 213 infants in our cohort into 3 groups based on their FNASS scores in the 12\u2009hours before and after the initiation of pharmacotherapy. We found that these groups were pairwise significantly different for risk factors, including methadone exposure, and for in\u2010hospital outcomes, including total morphine received, length of stay, and highest FNASS score. Whereas PRS was not predictive of receipt of treatment, PRS was pairwise significantly different between a subset of the groups. Using tree\u2010based machine learning methods, we then constructed network graphs of the relationships among these groups, FNASS scores, PRS, drug exposures, and in\u2010hospital outcomes. The resulting networks also showed meaningful connection between early FNASS scores and PRS, as well as between both of those and later in\u2010hospital outcomes. These analyses present clinicians with the opportunity to better anticipate infant withdrawal progression and prepare accordingly, whether with expedited morphine treatment or non\u2010pharmacotherapeutic alternative treatments.<\/jats:p>","DOI":"10.1002\/cpt.3007","type":"journal-article","created":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T08:29:32Z","timestamp":1689841772000},"page":"1015-1022","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Predicting Heterogeneity in Patient Response to Morphine Treatment for Neonatal Opioid Withdrawal Syndrome"],"prefix":"10.1111","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3860-2181","authenticated-orcid":false,"given":"Daniel","family":"Smolyak","sequence":"first","affiliation":[{"name":"Department of Computer Science University of Maryland  College Park Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Humphries","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences University of Maryland School of Medicine  Baltimore Maryland USA"},{"name":"Program in Molecular Epidemiology University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhinav","family":"Parikh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics New York Presbyterian Brooklyn Methodist Hospital  Brooklyn New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2881-9870","authenticated-orcid":false,"given":"Mathangi","family":"Gopalakrishnan","sequence":"additional","affiliation":[{"name":"Department of Practice, Science, and Health Outcomes Research University of Maryland School of Pharmacy  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulden","family":"Aycan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margr\u00e9t","family":"Bjarnad\u00f3ttir","sequence":"additional","affiliation":[{"name":"Robert H. Smith School of Business, University of Maryland  College Park Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth A.","family":"Ament","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences University of Maryland School of Medicine  Baltimore Maryland USA"},{"name":"Department of Psychiatry University of Maryland School of Medicine  Baltimore Maryland USA"},{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Nutrition and Program for Personalized and Genomic Medicine University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"El\u2010Metwally","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Beitelshees","sequence":"additional","affiliation":[{"name":"University of Maryland \u2013 Medicine Institute for Neuroscience Discovery (UM\u2010MIND)  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritu","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Carey Business School, Center for Digital Health and Artificial Intelligence Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,31]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1377\/hlthaff.2019.00814"},{"key":"e_1_2_8_2_1","first-page":"141","article-title":"Neonatal abstinence syndrome: assessment and management","volume":"2","author":"Finnegan L.P.","year":"1975","journal-title":"Addict. 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