{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:47:22Z","timestamp":1792176442186,"version":"4.4.0"},"reference-count":57,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi221099-4\"><jats:title>Importance<\/jats:title><jats:p>The assessment of opioid withdrawal in the neonate, or neonatal opioid withdrawal syndrome (NOWS), is problematic because current assessment methods are based on subjective observer ratings. Crying is a distinctive component of NOWS assessment tools and can be measured objectively using acoustic analysis.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi221099-5\"><jats:title>Objective<\/jats:title><jats:p>To evaluate the feasibility of using newborn cry acoustics (acoustics referring to the physical properties of sound) as an objective biobehavioral marker of NOWS.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi221099-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This prospective controlled cohort study assessed whether acoustic analysis of neonate cries could predict which infants would receive pharmacological treatment for NOWS. A total of 177 full-term neonates exposed and not exposed to opioids were recruited from Women &amp;amp;amp; Infants Hospital of Rhode Island between August 8, 2016, and March 18, 2020. Cry recordings were processed for 118 neonates, and 65 neonates were included in the final analyses. Neonates exposed to opioids were monitored for signs of NOWS using the Finnegan Neonatal Abstinence Scoring Tool administered every 3 hours as part of a 5-day observation period during which audio was recorded continuously to capture crying. Crying of healthy neonates was recorded before hospital discharge during routine handling (eg, diaper changes).<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi221099-7\"><jats:title>Exposures<\/jats:title><jats:p>The primary exposure was prenatal opioid exposure as determined by maternal receipt of medication-assisted treatment with methadone or buprenorphine.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi221099-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Neonates were stratified by prenatal opioid exposure and receipt of pharmacological treatment for NOWS before discharge from the hospital. In total, 775 hours of audio were collected and trimmed into 2.5 hours of usable cries, then acoustically analyzed (using 2 separate acoustic analyzers). Cross-validated supervised machine learning methods (combining the Boruta algorithm and a random forest classifier) were used to identify relevant acoustic parameters and predict pharmacological treatment for NOWS.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi221099-9\"><jats:title>Results<\/jats:title><jats:p>Final analyses included 65 neonates (mean [SD] gestational age at birth, 36.6\u2009[1.1] weeks; 36 [55.4%] female; 50 [76.9%] White) with usable cry recordings. Of those, 19 neonates received pharmacological treatment for NOWS, 7 neonates were exposed to opioids but did not receive pharmacological treatment for NOWS, and 39 healthy neonates were not exposed to opioids. The mean of the predictions of random forest classifiers predicted receipt of pharmacological treatment for NOWS with high diagnostic accuracy (area under the curve, 0.90 [95% CI, 0.83-0.98]; accuracy, 0.85 [95% CI, 0.74-0.92]; sensitivity, 0.89 [95% CI, 0.67-0.99]; specificity, 0.83 [95% CI, 0.69-0.92]).<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi221099-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>In this study, newborn acoustic cry analysis had potential as an objective measure of opioid withdrawal. These findings suggest that acoustic cry analysis using machine learning could improve the assessment, diagnosis, and management of NOWS and facilitate standardized care for these infants.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2022.38783","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T15:08:36Z","timestamp":1666883316000},"page":"e2238783","source":"Crossref","is-referenced-by-count":12,"title":["Newborn Cry Acoustics in the Assessment of Neonatal Opioid Withdrawal Syndrome Using Machine Learning"],"prefix":"10.1001","volume":"5","author":[{"given":"Andrew W.","family":"Manigault","sequence":"first","affiliation":[{"name":"Brown Center for the Study of Children at Risk, Women & Infants Hospital of Rhode Island, Providence"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Sheinkopf","sequence":"additional","affiliation":[{"name":"Thompson Center for Autism and Neurodevelopmental Disorders, University of Missouri, Columbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey F.","family":"Silverman","sequence":"additional","affiliation":[{"name":"School of Engineering, Brown University, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry M.","family":"Lester","sequence":"additional","affiliation":[{"name":"Brown Center for the Study of Children at Risk, Women & Infants Hospital of Rhode Island, Providence"},{"name":"Department of Psychiatry, Alpert Medical School of Brown University, Providence, Rhode Island"},{"name":"Department of Pediatrics, Alpert Medical School of Brown University, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2022,10,27]]},"reference":[{"issue":"31","key":"zoi221099r1","doi-asserted-by":"publisher","first-page":"845","DOI":"10.15585\/mmwr.mm6731a1","article-title":"Opioid use disorder documented at delivery hospitalization\u2014United States, 1999-2014.","volume":"67","author":"Haight","year":"2018","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"1","key":"zoi221099r2","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1097\/AOG.0000000000002054","article-title":"Opioid use in pregnancy, neonatal abstinence syndrome, and childhood outcomes: executive summary of a joint workshop by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, American College of Obstetricians and Gynecologists, American Academy of Pediatrics, Society for Maternal-Fetal Medicine, Centers for Disease Control and Prevention, and the March of Dimes Foundation.","volume":"130","author":"Reddy","year":"2017","journal-title":"Obstet Gynecol"},{"issue":"2","key":"zoi221099r3","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1097\/MOP.0b013e32834fdc3a","article-title":"Neonatal abstinence syndrome.","volume":"24","author":"Jansson","year":"2012","journal-title":"Curr Opin Pediatr"},{"issue":"5","key":"zoi221099r4","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1377\/hlthaff.2019.00814","article-title":"Neonatal abstinence syndrome in the United States, 2004-16.","volume":"39","author":"Leech","year":"2020","journal-title":"Health Aff (Millwood)"},{"issue":"2","key":"zoi221099r5","doi-asserted-by":"publisher","first-page":"230","DOI":"10.2174\/138945012799201612","article-title":"Current research on opioid receptor function.","volume":"13","author":"Feng","year":"2012","journal-title":"Curr Drug Targets"},{"issue":"7","key":"zoi221099r6","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1053\/j.semperi.2015.08.013","article-title":"Opioids in pregnancy and neonatal abstinence syndrome.","volume":"39","author":"Stover","year":"2015","journal-title":"Semin Perinatol"},{"issue":"3","key":"zoi221099r7","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2019-0128","article-title":"Prenatal opioid exposure: neurodevelopmental consequences and future research priorities.","volume":"144","author":"Conradt","year":"2019","journal-title":"Pediatrics"},{"issue":"5","key":"zoi221099r8","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1016\/j.jpeds.2015.02.012","article-title":"Neonatal morphine exposure in very preterm infants\u2014cerebral development and outcomes.","volume":"166","author":"Steinhorn","year":"2015","journal-title":"J Pediatr"},{"issue":"7","key":"zoi221099r9","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1001\/jamapediatrics.2020.6364","article-title":"infant mortality associated with prenatal opioid exposure.","volume":"175","author":"Leyenaar","year":"2021","journal-title":"JAMA Pediatr"},{"issue":"4","key":"zoi221099r11","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1542\/hpeds.2012-0079","article-title":"Neonatal abstinence syndrome management from prenatal counseling to postdischarge follow-up care: results of a national survey.","volume":"3","author":"Mehta","year":"2013","journal-title":"Hosp Pediatr"},{"issue":"1","key":"zoi221099r12","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/sj.jp.7211427","article-title":"Management of neonatal abstinence syndrome in neonatal intensive care units: a national survey.","volume":"26","author":"Sarkar","year":"2006","journal-title":"J Perinatol"},{"issue":"24","key":"zoi221099r13","doi-asserted-by":"publisher","first-page":"2320","DOI":"10.1056\/NEJMoa1005359","article-title":"Neonatal abstinence syndrome after methadone or buprenorphine exposure.","volume":"363","author":"Jones","year":"2010","journal-title":"N Engl J Med"},{"issue":"1","key":"zoi221099r14","doi-asserted-by":"publisher","first-page":"47","DOI":"10.5055\/jom.2009.0006","article-title":"The opioid-exposed newborn: assessment and pharmacologic management.","volume":"5","author":"Jansson","year":"2009","journal-title":"J Opioid Manag"},{"issue":"6","key":"zoi221099r15","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1097\/ANC.0000000000000033","article-title":"Validation of the Finnegan Neonatal Abstinence Syndrome Tool\u2013short form.","volume":"13","author":"Maguire","year":"2013","journal-title":"Adv Neonatal Care"},{"issue":"1","key":"zoi221099r16","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1097\/ANC.0000000000000441","article-title":"A quality improvement initiative to increase scoring consistency and accuracy of the Finnegan tool: challenges in obtaining reliable assessments of drug withdrawal in neonatal abstinence syndrome.","volume":"18","author":"Timpson","year":"2018","journal-title":"Adv Neonatal Care"},{"issue":"3","key":"zoi221099r17","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2021.101218","article-title":"Escaping the Finnegan\u2014is it time?","volume":"26","author":"Singh","year":"2021","journal-title":"Semin Fetal Neonatal Med"},{"issue":"6","key":"zoi221099r18","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2016-3360","article-title":"An initiative to improve the quality of care of infants with neonatal abstinence syndrome.","volume":"139","author":"Grossman","year":"2017","journal-title":"Pediatrics"},{"issue":"1","key":"zoi221099r19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1542\/hpeds.2017-0128","article-title":"A novel approach to assessing infants with neonatal abstinence syndrome.","volume":"8","author":"Grossman","year":"2018","journal-title":"Hosp Pediatr"},{"issue":"1","key":"zoi221099r20","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41572-018-0045-0","article-title":"Neonatal abstinence syndrome.","volume":"4","author":"Coyle","year":"2018","journal-title":"Nat Rev Dis Primers"},{"issue":"4","key":"zoi221099r21","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.2275","article-title":"Association of a simplified Finnegan Neonatal Abstinence Scoring Tool with the need for pharmacologic treatment for neonatal abstinence syndrome.","volume":"3","author":"Devlin","year":"2020","journal-title":"JAMA Netw Open"},{"key":"zoi221099r22","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.jpeds.2021.12.021","article-title":"Standardizing the clinical definition of opioid withdrawal in the neonate.","volume":"243","author":"Jilani","year":"2022","journal-title":"J Pediatr"},{"key":"zoi221099r23","first-page":"167","article-title":"A biosocial model of infant crying.","volume":"3","author":"Lester","year":"1984","journal-title":"Advances in Infancy Research"},{"key":"zoi221099r24","doi-asserted-by":"publisher","first-page":"100","DOI":"10.3389\/fnbeh.2016.00100","article-title":"Methylation of the glucocorticoid receptor (NR3C1) in placenta is associated with infant cry acoustics.","volume":"10","author":"Sheinkopf","year":"2016","journal-title":"Front Behav Neurosci"},{"issue":"5","key":"zoi221099r25","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1044\/1092-4388(2013\/11-0298)","article-title":"A flexible analysis tool for the quantitative acoustic assessment of infant cry.","volume":"56","author":"Reggiannini","year":"2013","journal-title":"J Speech Lang Hear Res"},{"issue":"2","key":"zoi221099r26","doi-asserted-by":"publisher","first-page":"778","DOI":"10.3758\/s13428-018-1095-7","article-title":"Soundgen: an open-source tool for synthesizing nonverbal vocalizations.","volume":"51","author":"Anikin","year":"2019","journal-title":"Behav Res Methods"},{"issue":"5","key":"zoi221099r27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v028.i05","article-title":"Building predictive models in R using the caret package.","volume":"28","author":"Kuhn","year":"2008","journal-title":"J Stat Softw"},{"issue":"11","key":"zoi221099r29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0224365","article-title":"Machine learning algorithm validation with a limited sample size.","volume":"14","author":"Vabalas","year":"2019","journal-title":"PLoS One"},{"key":"zoi221099r30","doi-asserted-by":"crossref","article-title":"Stability of feature selection algorithm: a review.","author":"Khaire","DOI":"10.1016\/j.jksuci.2019.06.012"},{"issue":"11","key":"zoi221099r31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v036.i11","article-title":"Feature selection with the Boruta package.","volume":"36","author":"Kursa","year":"2010","journal-title":"J Stat Softw"},{"issue":"2","key":"zoi221099r32","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1093\/bib\/bbx124","article-title":"Evaluation of variable selection methods for random forests and omics data sets.","volume":"20","author":"Degenhardt","year":"2019","journal-title":"Brief Bioinform"},{"issue":"11","key":"zoi221099r33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v098.i11","article-title":"Cutpointr: improved estimation and validation of optimal cutpoints in R.","volume":"98","author":"Thiele","year":"2021","journal-title":"J Stat Softw"},{"issue":"4","key":"zoi221099r34","first-page":"203","article-title":"Measures of diagnostic accuracy: basic definitions.","volume":"19","author":"\u0160imundic","year":"2009","journal-title":"EJIFCC"},{"issue":"1","key":"zoi221099r36","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v077.i01","article-title":"Ranger: a fast implementation of random forests for high dimensional data in C++ and R.","volume":"77","author":"Wright","year":"2017","journal-title":"J Stat Softw"},{"issue":"1","key":"zoi221099r38","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2020-007393","article-title":"Evaluating definitions for neonatal abstinence syndrome.","volume":"147","author":"Doherty","year":"2021","journal-title":"Pediatrics"},{"issue":"2","key":"zoi221099r39","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1097\/ANC.0000000000000581","article-title":"Eat, Sleep, Console approach: a family-centered model for the treatment of neonatal abstinence syndrome.","volume":"19","author":"Grisham","year":"2019","journal-title":"Adv Neonatal Care"},{"issue":"7","key":"zoi221099r40","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1016\/0002-9378(71)90549-7","article-title":"Variations in birth cries of newborn infants from narcotic-addicted and normal mothers.","volume":"110","author":"Blinick","year":"1971","journal-title":"Am J Obstet Gynecol"},{"issue":"6","key":"zoi221099r41","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1542\/peds.110.6.1182","article-title":"The maternal lifestyle study: effects of substance exposure during pregnancy on neurodevelopmental outcome in 1-month-old infants.","volume":"110","author":"Lester","year":"2002","journal-title":"Pediatrics"},{"issue":"1","key":"zoi221099r42","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1002\/mrdd.v11:1","article-title":"Assessment of infant cry: acoustic cry analysis and parental perception.","volume":"11","author":"LaGasse","year":"2005","journal-title":"Ment Retard Dev Disabil Res Rev"},{"key":"zoi221099r43","doi-asserted-by":"publisher","DOI":"10.1002\/aur.v5.5"},{"issue":"7","key":"zoi221099r44","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.1038\/s41390-020-01172-0","article-title":"Epigenome-wide analysis identifies genes and pathways linked to acoustic cry variation in preterm infants.","volume":"89","author":"Aghagoli","year":"2021","journal-title":"Pediatr Res"},{"key":"zoi221099r45","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.pediatrneurol.2021.10.017","article-title":"Acoustic cry characteristics of infants as a marker of neurological dysfunction: a systematic review and meta-analysis.","volume":"129","author":"Lawford","year":"2022","journal-title":"Pediatr Neurol"},{"key":"zoi221099r46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvoice.2022.05.015","article-title":"Investigation of relation between hypoxic-ischemic encephalopathy and spectral features of infant cry audio.","author":"Satar","year":"2022","journal-title":"J Voice"},{"issue":"1","key":"zoi221099r47","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1111\/apa.2008.98.issue-1","article-title":"Acoustic cry characteristics of infants exposed to methadone during pregnancy.","volume":"98","author":"Quick","year":"2009","journal-title":"Acta Paediatr"},{"issue":"6 Pt 2","key":"zoi221099r48","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1542\/peds.89.6.1199","article-title":"Effects of in utero cocaine exposure on newborn acoustical cry characteristics.","volume":"89","author":"Corwin","year":"1992","journal-title":"Pediatrics"},{"issue":"4","key":"zoi221099r49","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1542\/peds.80.4.529","article-title":"Developmental outcome prediction from acoustic cry analysis in term and preterm infants.","volume":"80","author":"Lester","year":"1987","journal-title":"Pediatrics"},{"issue":"2","key":"zoi221099r50","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/S0022-3476(89)80090-3","article-title":"Abnormal brain-stem function (brain-stem auditory evoked response) correlates with acoustic cry features in term infants with hyperbilirubinemia.","volume":"115","author":"Vohr","year":"1989","journal-title":"J Pediatr"},{"issue":"4","key":"zoi221099r51","doi-asserted-by":"publisher","first-page":"694","DOI":"10.2307\/1131171","article-title":"Neurobehavioral syndromes in cocaine-exposed newborn infants.","volume":"62","author":"Lester","year":"1991","journal-title":"Child Dev"},{"issue":"4","key":"zoi221099r52","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.2307\/1131733","article-title":"The effects of maternal alcohol consumption and cigarette smoking during pregnancy on acoustic cry analysis.","volume":"67","author":"Nugent","year":"1996","journal-title":"Child Dev"},{"issue":"4","key":"zoi221099r53","first-page":"72A","article-title":"Prenatal methamphetamine exposure and neonatal cry acoustic analysis: preliminary results from the Infant Development, Environment, and Lifestyle Study (IDEAL).","volume":"55","author":"LaGasse","year":"2004","journal-title":"Pediatr Res"},{"issue":"12","key":"zoi221099r54","doi-asserted-by":"publisher","first-page":"2481","DOI":"10.1016\/j.sigpro.2003.07.018","article-title":"Novelty detection: a review\u2014part 1: statistical approaches.","volume":"83","author":"Markou","year":"2003","journal-title":"Signal Processing"},{"issue":"1","key":"zoi221099r55","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2020-008839","article-title":"Site-level variation in the characteristics and care of infants with neonatal opioid withdrawal.","volume":"147","author":"Young","year":"2021","journal-title":"Pediatrics"},{"issue":"1","key":"zoi221099r56","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1542\/hpeds.2017-0077","article-title":"Hospital variation in neonatal abstinence syndrome incidence, treatment modalities, resource use, and costs across pediatric hospitals in the United States, 2013 to 2016.","volume":"8","author":"Milliren","year":"2018","journal-title":"Hosp Pediatr"},{"issue":"4","key":"zoi221099r57","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.acap.2016.10.003","article-title":"Wide variation found in care of opioid-exposed newborns.","volume":"17","author":"Bogen","year":"2017","journal-title":"Acad Pediatr"},{"key":"zoi221099r10","author":"Finnegan","year":"1975"},{"key":"zoi221099r28","doi-asserted-by":"crossref","DOI":"10.1201\/9780367816377","volume-title":"Hands-On Machine Learning with R","author":"Boehmke","year":"2019"},{"key":"zoi221099r35","unstructured":"R Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing; 2020. Accessed September 27, 2022. https:\/\/www.R-project.org\/"},{"key":"zoi221099r37","unstructured":"Carstensen? B, Plummer? M, Laara? E, Hills? M. Epi: statistical analysis in epidemiology. Version 2.47. R Project. June 26, 2022. Accessed September 27, 2022. https:\/\/CRAN.R-project.org\/package=Epi"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2797784\/manigault_2022_oi_221099_1666195596.77548.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T15:08:48Z","timestamp":1666883328000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2797784"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,27]]},"references-count":57,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10,3]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2022.38783","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,27]]}}}