Neonatal abstinence syndrome after methadone or buprenorphine exposure.
Neonatal abstinence syndrome after methadone or buprenorphine exposure.
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DOI：
10.1056/nejmoa1005359
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发表时间：
2010-12-09
期刊：
影响因子：
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通讯作者：
Fischer G
中科院分区：
文献类型：
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作者：
Jones HE;Kaltenbach K;Heil SH;Stine SM;Coyle MG;Arria AM;O'Grady KE;Selby P;Martin PR;Fischer G
美沙酮是一种完全的μ阿片类激动剂，是妊娠期间阿片类药物依赖的推荐治疗。然而，产前接触美沙酮与新生儿戒断综合征（NAS）有关，其特征是中枢神经系统过度兴奋和自主神经系统功能障碍，通常需要药物治疗和延长住院时间。丁丙诺啡是一种部分μ阿片类激动剂，是阿片类药物依赖的替代治疗，但尚未在妊娠期进行广泛研究。我们进行了一项双盲、双模拟、灵活给药、随机、对照研究，其中比较了丁丙诺啡和美沙酮在8个国际研究中心的175名阿片类药物依赖孕妇的综合护理中的使用。主要结果是需要治疗NAS的新生儿数量，NAS评分峰值，治疗NAS所需的吗啡总量，新生儿住院时间和新生儿头围。美沙酮组89名妇女中有16名（18%）和丁丙诺啡组86名妇女中有28名（33%）停止治疗。根据治疗组对母亲随访至妊娠结束的131例新生儿进行比较（58人暴露于丁丙诺啡，73人暴露于美沙酮）显示，前一组需要的吗啡明显较少。（平均剂量，1.1 mg vs. 10.4 mg; P<0.0091），住院时间明显缩短（10.0天vs.17.5天，P<0.0091），并且对新生儿戒断综合征的治疗持续时间显著缩短（4.1天对9.9天，P<0.003125）（根据预先设定的显著性阈值计算P值）。在其他主要或次要结局或母体或新生儿不良事件发生率方面，两组之间无显著差异。这些结果与使用丁丙诺啡作为妊娠女性阿片类药物依赖的可接受治疗一致。（由国家药物滥用研究所资助; ClinicalTrials.gov编号，NCT 00271219。
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. 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. 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, P<0.0091), and had a significantly shorter duration of treatment for the neonatal abstinence syndrome (4.1 days vs. 9.9 days, P<0.003125) (P values calculated in accordance with prespecified thresholds for significance). There were no significant differences between groups in other primary or secondary outcomes or in the rates of maternal or neonatal adverse events. These results are consistent with the use of buprenorphine as an acceptable treatment for opioid dependence in pregnant women. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00271219.)