Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure

作者：Hendrée E. Jones, Karol A. Kaltenbach, Sarah Hughes Heil, Susan M. Stine, Mara G. Coyle, Amelia M. Arria, Kevin E. O’Grady, Peter L. Selby, Peter Martin, Gabriele Fischer · 发表于：New England Journal of Medicine · 年份：2010 · DOI：10.1056/nejmoa1005359 · 被引用次数：992 · 研究领域：Prenatal Substance Exposure Effects、Opioid Use Disorder Treatment、Maternal Mental Health During Pregnancy and Postpartum

BACKGROUND: Methadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy. METHODS: We conducted a double-blind, double-dummy, flexible-dosing, randomized, controlled study in which buprenorphine and methadone were compared for use in the comprehensive care of 175 pregnant women with opioid dependency at eight international sites. Primary outcomes were the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, the length of the hospital stay for neonates, and neonatal head circumference. RESULTS: Treatment was discontinued by 16 of the 89 women in the methadone group (18%) and 28 of the 86 women in the buprenorphine group (33%). A comparison of the 131 neonates whose mothers were followed to the end of pregnancy according to treatment group (with 58 exposed to buprenorphine and 73 exposed to methadone) showed that the former group required significantly less morphine (mean dose, 1.1 mg vs. 10.4 mg; P<0.0091), had a significantly shorter hospital stay (10.0 days vs. 17.5 days, ...