Department of Pediatrics, The Floating Hospital for Children at Tufts Medical Center, Boston, Massachusetts.
Tufts Clinical and Translational Science Institute, Tufts University, Boston, Massachusetts.
JAMA Pediatr. 2018 Aug 1;172(8):741-748. doi: 10.1001/jamapediatrics.2018.1307.
Although opioids are used to treat neonatal abstinence syndrome (NAS), the best pharmacologic treatment has not been established.
To compare the safety and efficacy of methadone and morphine in NAS.
DESIGN, SETTING, AND PARTICIPANTS: In this randomized, double-blind, intention-to-treat trial, term infants from 8 US newborn units whose mothers received buprenorphine, methadone, or opioids for pain control during pregnancy were eligible. A total of 117 infants were randomized to receive methadone or morphine from February 9, 2014, to March 6, 2017. Mothers who declined randomization could consent to data collection and standard institutional treatment.
Infants were assessed with the Finnegan Neonatal Abstinence Scoring System every 4 hours and treated with methadone or placebo every 4 hours or morphine every 4 hours. Infants with persistently elevated Finnegan scores received dose increases. Infants who exceeded a predetermined opioid dose received phenobarbital. Dose reductions occurred every 12 to 48 hours when signs of NAS were controlled with therapy, stopping at 20% of the original dose.
The primary end point was length of hospital stay (LOS). The secondary end points were LOS attributable to NAS and length of drug treatment (LOT).
A total of 183 mothers consented to have their infants in the study; 117 infants required treatment. Because 1 parent withdrew consent, data were analyzed on 116 infants (mean [SD] gestational age, 39.1 [1.1] weeks; mean [SD] birth weight, 3157 [486] g; 58 [50%] male). Demographic variables and risk factors were similar except for more prenatal cigarette exposure in infants who received methadone. Adjusting for study site and maternal opioid type, methadone was associated with decreased mean number of days for LOS by 14% (relative number of days, 0.86; 95% CI, 0.74-1.00; P = .046), corresponding to a difference of 2.9 days; 14% reduction in LOS attributable to NAS (relative number of days, 0.86; 95% CI, 0.77-0.96; P = .01), corresponding to a difference of 2.7 days; and 16% reduction in LOT (relative number of days, 0.84; 95% CI, 0.73-0.97; P = .02), corresponding to a difference of 2.3 days. Methadone was also associated with reduced median LOS (16 vs 20 days, P = .005), LOS attributable to NAS (16 vs 19 days, P = .005), and LOT (11.5 vs 15 days, P = .009). Study infants had better short-term outcomes than 170 nonrandomized infants treated with morphine per standard institutional protocols.
With use of weight- and sign-based treatment for NAS, short-term outcomes were better in infants receiving methadone compared with morphine. Assessment of longer-term outcomes is ongoing.
ClinicalTrials.gov Identifier: NCT01958476.
尽管阿片类药物被用于治疗新生儿戒断综合征（NAS），但尚未确定最佳的药物治疗方法。
比较美沙酮和吗啡治疗 NAS 的安全性和疗效。
设计、地点和参与者：在这项随机、双盲、意向治疗试验中，来自美国 8 个新生儿单位的足月婴儿符合条件，其母亲在怀孕期间接受了丁丙诺啡、美沙酮或阿片类药物用于疼痛控制。共有 117 名婴儿于 2014 年 2 月 9 日至 2017 年 3 月 6 日随机分为接受美沙酮或吗啡治疗。拒绝随机分组的母亲可以同意进行数据收集和标准机构治疗。
婴儿每 4 小时用芬纳根新生儿戒断评分系统进行评估，并每 4 小时接受美沙酮或安慰剂或吗啡治疗。持续出现芬纳根评分升高的婴儿接受剂量增加。如果婴儿的芬纳根评分超过预定的阿片类药物剂量，则给予苯巴比妥。当 NAS 症状通过治疗得到控制时，每 12 至 48 小时减少剂量，减少到原始剂量的 20%。
主要终点是住院时间（LOS）。次要终点是由 NAS 引起的 LOS 长度和药物治疗时间（LOT）。
共有 183 位母亲同意让其婴儿参加研究；117 名婴儿需要治疗。由于 1 位家长撤回了同意，对 116 名婴儿的数据进行了分析（平均[SD]胎龄，39.1[1.1]周；平均[SD]出生体重，3157[486]g；58[50%]为男性）。除了接受美沙酮的婴儿在产前吸烟暴露更多外，人口统计学变量和危险因素相似。调整研究地点和母亲阿片类药物类型后，美沙酮与 LOS 平均天数减少 14%相关（相对天数，0.86；95%CI，0.74-1.00；P=0.046），相应的差异为 2.9 天；由 NAS 引起的 LOS 减少 14%（相对天数，0.86；95%CI，0.77-0.96；P=0.01），相应的差异为 2.7 天；LOT 减少 16%（相对天数，0.84；95%CI，0.73-0.97；P=0.02），相应的差异为 2.3 天。美沙酮还与缩短 LOS 中位数（16 天对 20 天，P=0.005）、由 NAS 引起的 LOS 中位数（16 天对 19 天，P=0.005）和 LOT 中位数（11.5 天对 15 天，P=0.009）相关。接受标准机构方案治疗的吗啡的 170 名非随机婴儿相比，研究婴儿的短期结局更好。正在评估长期结局。
使用基于体重和症状的 NAS 治疗方法，与接受吗啡的婴儿相比，接受美沙酮的婴儿的短期结局更好。正在评估长期结局。
ClinicalTrials.gov 标识符：NCT01958476。
