{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:54:42Z","timestamp":1792191282447,"version":"4.4.0"},"reference-count":35,"publisher":"American Academy of Pediatrics (AAP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,6,1]]},"abstract":"<jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>Neonatal abstinence syndrome (NAS) is a postnatal opioid withdrawal syndrome. Factors associated with development of the syndrome are poorly understood; however, infant sex may influence the risk of NAS. Our objective was to determine if infant sex was associated with the development or severity of the syndrome in a large population-based cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>This retrospective cohort study used vital statistics and prescription, outpatient, and inpatient administrative data for mothers and infants enrolled in the Tennessee Medicaid program between 2009 and 2011. Multivariable logistic regression models were used to evaluate the association between male sex and diagnosis of NAS, accounting for potential demographic and clinical confounders. NAS severity, as evidenced by hospital length of stay, was modeled by using negative binomial regression.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>Of 102\u2009695 infants, 927 infants were diagnosed with NAS (484 male subjects and 443 female subjects). Adjustments were made for the following: maternal age, race, and education; maternal hepatitis C infection, anxiety, or depression; in utero exposure to selective serotonin reuptake inhibitors and cigarettes; infant birth weight, small for gestational age, and year; and the interaction between opioid type and opioid amount. Male infants were more likely than female infants to be diagnosed with NAS (adjusted odds ratio, 1.18 [95% confidence interval, 1.05\u20131.33]) and NAS requiring treatment (adjusted odds ratio, 1.24 [95% confidence interval, 1.04\u20131.47]). However, there was no sex-based difference in severity for those diagnosed with NAS.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>Treatment of NAS should be tailored to an infant\u2019s individual risk for the syndrome. Clinicians should be mindful that male sex is an important risk factor in the diagnosis of NAS.<\/jats:p><\/jats:sec>","DOI":"10.1542\/hpeds.2016-0218","type":"journal-article","created":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T08:35:19Z","timestamp":1496306119000},"page":"328-334","source":"Crossref","is-referenced-by-count":64,"title":["Male Sex Associated With Increased Risk of Neonatal Abstinence Syndrome"],"prefix":"10.1542","volume":"7","author":[{"given":"M. Katherine","family":"Charles","sequence":"first","affiliation":[{"name":"Vanderbilt University School of Medicine, Nashville, Tennessee;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William O.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine, Nashville, Tennessee;"},{"name":"Departments of Pediatrics,"},{"name":"Health Policy, and"},{"name":"Vanderbilt Center for Health Services Research, Nashville, Tennessee;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren M.","family":"Jansson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Dudley","sequence":"additional","affiliation":[{"name":"Health Policy, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Slaughter","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine, Nashville, Tennessee;"},{"name":"Biostatistics, Vanderbilt University, Nashville, Tennessee;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen W.","family":"Patrick","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine, Nashville, Tennessee;"},{"name":"Departments of Pediatrics,"},{"name":"Health Policy, and"},{"name":"Vanderbilt Center for Health Services Research, Nashville, Tennessee;"},{"name":"Mildred Stahlman Division of Neonatology, Vanderbilt University, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2017,6,1]]},"reference":[{"issue":"2","key":"2021120817234999100_B1","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2011-3212","article-title":"Neonatal drug withdrawal","volume":"129","author":"Hudak","year":"2012","journal-title":"Pediatrics"},{"issue":"2","key":"2021120817234999100_B2","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2013-3524","article-title":"Neonatal abstinence syndrome","volume":"134","author":"Kocherlakota","year":"2014","journal-title":"Pediatrics"},{"issue":"5","key":"2021120817234999100_B3","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1097\/AOG.0b013e31824ea276","article-title":"Maternal drug use and its effect on neonates: a population-based study in Washington state","volume":"119","author":"Creanga","year":"2012","journal-title":"Obstet Gynecol"},{"issue":"5","key":"2021120817234999100_B4","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1097\/AOG.0000000000000208","article-title":"Increase in prescription opioid use during pregnancy among Medicaid-enrolled women","volume":"123","author":"Desai","year":"2014","journal-title":"Obstet Gynecol"},{"issue":"8","key":"2021120817234999100_B5","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.annepidem.2013.05.017","article-title":"Increasing pregnancy-related use of prescribed opioid analgesics","volume":"23","author":"Epstein","year":"2013","journal-title":"Ann Epidemiol"},{"issue":"22","key":"2021120817234999100_B6","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1056\/NEJMsa1500439","article-title":"Increasing incidence of the neonatal abstinence syndrome in US neonatal ICUs","volume":"372","author":"Tolia","year":"2015","journal-title":"N Engl J Med"},{"issue":"18","key":"2021120817234999100_B7","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1001\/jama.2012.3951","article-title":"Neonatal abstinence syndrome and associated health care expenditures: United States, 2000-2009","volume":"307","author":"Patrick","year":"2012","journal-title":"JAMA"},{"issue":"8","key":"2021120817234999100_B8","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/jp.2015.36","article-title":"Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 2009 to 2012","volume":"35","author":"Patrick","year":"2015","journal-title":"J Perinatol"},{"issue":"3","key":"2021120817234999100_B9","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.drugalcdep.2004.03.012","article-title":"Neonatal abstinence syndrome in methadone-exposed infants is altered by level of prenatal tobacco exposure","volume":"75","author":"Choo","year":"2004","journal-title":"Drug Alcohol Depend"},{"issue":"5","key":"2021120817234999100_B10","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1515\/jpm-2012-0288","article-title":"Are there gender related differences in neonatal abstinence syndrome following exposure to buprenorphine during pregnancy?","volume":"41","author":"O\u2019Connor","year":"2013","journal-title":"J Perinat Med"},{"issue":"5","key":"2021120817234999100_B11","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1542\/peds.2014-3299","article-title":"Prescription opioid epidemic and infant outcomes","volume":"135","author":"Patrick","year":"2015","journal-title":"Pediatrics"},{"issue":"2","key":"2021120817234999100_B12","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1111\/j.1552-6909.2011.01330.x","article-title":"Opioid dependency in pregnancy and length of stay for neonatal abstinence syndrome","volume":"41","author":"Pritham","year":"2012","journal-title":"J Obstet Gynecol Neonatal Nurs"},{"issue":"9","key":"2021120817234999100_B13","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1080\/14767050701490327","article-title":"Maternal vagal tone change in response to methadone is associated with neonatal abstinence syndrome severity in exposed neonates","volume":"20","author":"Jansson","year":"2007","journal-title":"J Matern Fetal Neonatal Med"},{"issue":"1\u20133","key":"2021120817234999100_B14","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.drugalcdep.2010.01.004","article-title":"Infant autonomic functioning and neonatal abstinence syndrome","volume":"109","author":"Jansson","year":"2010","journal-title":"Drug Alcohol Depend"},{"issue":"1\u20132","key":"2021120817234999100_B15","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.drugalcdep.2010.05.015","article-title":"Gender and NAS: does sex matter?","volume":"112","author":"Holbrook","year":"2010","journal-title":"Drug Alcohol Depend"},{"issue":"6","key":"2021120817234999100_B16","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.genm.2011.10.001","article-title":"Are male neonates more vulnerable to neonatal abstinence syndrome than female neonates?","volume":"8","author":"Unger","year":"2011","journal-title":"Gend Med"},{"issue":"6","key":"2021120817234999100_B17","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1067\/mob.2002.127379","article-title":"Male predominance in fetal distress during labor","volume":"187","author":"Bekedam","year":"2002","journal-title":"Am J Obstet Gynecol"},{"issue":"5 pt 1","key":"2021120817234999100_B18","first-page":"747","article-title":"Clinical significance of fetal heart rate tracings during the second stage of labor","volume":"97","author":"Sheiner","year":"2001","journal-title":"Obstet Gynecol"},{"issue":"11","key":"2021120817234999100_B19","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1111\/tmi.12189","article-title":"Incidence of and risk factors for neonatal jaundice among newborns in southern Nepal","volume":"18","author":"Scrafford","year":"2013","journal-title":"Trop Med Int Health"},{"issue":"1","key":"2021120817234999100_B20","first-page":"41","article-title":"Gender-related physiologic differences in human neonates and the greater vulnerability of males to developmental brain disorders","volume":"4","author":"Nagy","year":"2001","journal-title":"J Gend Specif Med"},{"issue":"1","key":"2021120817234999100_B21","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1037\/0012-1649.35.1.175","article-title":"Gender differences in emotional expressivity and self-regulation during early infancy","volume":"35","author":"Weinberg","year":"1999","journal-title":"Dev Psychol"},{"issue":"20","key":"2021120817234999100_B22","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1056\/NEJMoa1110212","article-title":"ADHD drugs and serious cardiovascular events in children and young adults","volume":"365","author":"Cooper","year":"2011","journal-title":"N Engl J Med"},{"issue":"1","key":"2021120817234999100_B23","first-page":"101","article-title":"Prenatal prescription of macrolide antibiotics and infantile hypertrophic pyloric stenosis","volume":"100","author":"Cooper","year":"2002","journal-title":"Obstet Gynecol"},{"issue":"10","key":"2021120817234999100_B24","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1056\/NEJM198809083191006","article-title":"Risk of sudden infant death syndrome after immunization with the diphtheria-tetanus-pertussis vaccine","volume":"319","author":"Griffin","year":"1988","journal-title":"N Engl J Med"},{"issue":"1","key":"2021120817234999100_B25","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1097\/AOG.0000000000000345","article-title":"A revised birth weight reference for the United States","volume":"124","author":"Duryea","year":"2014","journal-title":"Obstet Gynecol"},{"key":"2021120817234999100_B26","unstructured":"Centers for Disease Control and Prevention, Centers for Medicare & Medicaid Services. ICD-9-CM International Classification of Diseases, Ninth Revision, Clinical Modification. Washington, DC: US Department of Health and Human Services, Centers for Disease Control and Prevention.\u2008Available at: http:\/\/purl.access.gpo.gov\/GPO\/LPS8749. Accessed February 15, 2016"},{"issue":"5","key":"2021120817234999100_B27","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.adnc.2005.06.003","article-title":"A retrospective study of length of hospital stay in infants treated for neonatal abstinence syndrome with methadone versus oral morphine preparations","volume":"5","author":"Lainwala","year":"2005","journal-title":"Adv Neonatal Care"},{"key":"2021120817234999100_B28","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4757-3462-1","volume-title":"Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis","author":"Harrell","year":"2001"},{"key":"2021120817234999100_B29","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.neuroscience.2015.07.068","article-title":"The gestational foundation of sex differences in development and vulnerability","volume":"342","author":"DiPietro","year":"2017","journal-title":"Neuroscience"},{"issue":"1\u20132","key":"2021120817234999100_B30","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.devbrainres.2004.05.002","article-title":"Differential effects of gestational buprenorphine, naloxone, and methadone on mesolimbic mu opioid and ORL1 receptor G protein coupling","volume":"151","author":"Hou","year":"2004","journal-title":"Brain Res Dev Brain Res"},{"issue":"8","key":"2021120817234999100_B31","first-page":"213","article-title":"Infant and maternal characteristics in neonatal abstinence syndrome\u2014selected hospitals in Florida, 2010-2011","volume":"64","author":"Lind","year":"2015","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"7500","key":"2021120817234999100_B32","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/509282a","article-title":"Policy: NIH to balance sex in cell and animal studies","volume":"509","author":"Clayton","year":"2014","journal-title":"Nature"},{"issue":"1\u20132","key":"2021120817234999100_B33","first-page":"141","article-title":"Neonatal abstinence syndrome: assessment and management","volume":"2","author":"Finnegan","year":"1975","journal-title":"Addict Dis"},{"issue":"6","key":"2021120817234999100_B34","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1177\/000992287501400613","article-title":"A proposed narcotic withdrawal score for use with newborn infants. A pragmatic evaluation of its efficacy","volume":"14","author":"Lipsitz","year":"1975","journal-title":"Clin Pediatr (Phila)"},{"issue":"2","key":"2021120817234999100_B35","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1097\/00004703-199804000-00005","article-title":"The neonatal withdrawal inventory: a simplified score of newborn withdrawal","volume":"19","author":"Zahorodny","year":"1998","journal-title":"J Dev Behav Pediatr"}],"container-title":["Hospital Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/hospitalpediatrics\/article-pdf\/7\/6\/328\/813671\/hpeds_2016-0218.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/hospitalpediatrics\/article-pdf\/7\/6\/328\/813671\/hpeds_2016-0218.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T13:47:16Z","timestamp":1719236836000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/hospitalpediatrics\/article\/7\/6\/328\/26477\/Male-Sex-Associated-With-Increased-Risk-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,1]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2017,6,1]]},"published-print":{"date-parts":[[2017,6,1]]}},"URL":"https:\/\/doi.org\/10.1542\/hpeds.2016-0218","relation":{},"ISSN":["2154-1663","2154-1671"],"issn-type":[{"value":"2154-1663","type":"print"},{"value":"2154-1671","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,1]]}}}