Division of Maternal-Fetal Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH.
Vanderbilt University School of Medicine, Nashville, TN.
Am J Obstet Gynecol MFM. 2020 Feb;2(1):100075. doi: 10.1016/j.ajogmf.2019.100075. Epub 2019 Dec 10.
Data on the relationship between the dose of opioid replacement therapy in pregnancy and the risk and severity of neonatal opioid withdrawal syndrome are conflicting and have methodological limitations.
To assess the association of methadone and buprenorphine dose at delivery with neonatal opioid withdrawal syndrome in a large cohort.
We performed a retrospective cohort study using data from a comprehensive perinatal opioid dependency program from 2000 through 2016. Women with a history of opioid use disorder enrolled in a medication-assisted treatment program were included. Strict neonatal opioid withdrawal syndrome case definition and neonatal treatment guidelines were utilized throughout the study epoch. Comparisons were made between women on methadone and buprenorphine. The dose of opioid replacement at delivery and the risk and severity of neonatal opioid withdrawal syndrome were assessed with univariable analysis and multivariable logistic regression. In all analyses, methadone and buprenorphine dosing were evaluated as a continuous variable.
Four hundred eighty two of 709 women (68.0%) met inclusion criteria including 344 on methadone (71.4%) and 138 on buprenorphine (28.6%). Nonopioid polysubstance abuse, body mass index, medication-assisted treatment compliance, birthweight, and other characteristics were similar between groups. Overall, the frequency of neonatal opioid withdrawal syndrome was not significantly different between the methadone and buprenorphine groups (56.8% vs 52.0%, P = .35). Dose at delivery ranged at 0-165 mg for methadone and 0-30 mg for buprenorphine. In a univariable analysis, methadone dose at delivery was associated with neonatal opioid withdrawal syndrome (83.0 ± 34.2 mg vs 71.9 ± 35.8 mg for neonatal opioid withdrawal syndrome vs nonneonatal opioid withdrawal syndrome neonates, P < .001), but buprenorphine dose at delivery was not (8.4 ± 4.4 vs 7.6 ± 4.8 mg for neonatal opioid withdrawal syndrome vs nonneonatal opioid withdrawal syndrome neonates, P = .30). Peak neonatal opioid withdrawal syndrome score, duration of neonatal opioid withdrawal syndrome treatment, and cumulative neonatal morphine exposure were significantly associated with delivery methadone dose but not buprenorphine dose. The association between delivery methadone dose and neonatal opioid withdrawal syndrome persisted in multivariable regression.
The dose of methadone at the time of delivery is associated with the frequency and severity of neonatal opioid withdrawal syndrome, with higher doses associated with more severe neonatal opioid withdrawal syndrome when analyzed continuously. These data may inform future prospective studies on methadone dosing in pregnancy. While medication-assisted treatment agent and dose may have an impact on pertinent neonatal outcomes related to neonatal opioid withdrawal syndrome, the provision of medication-assisted treatment in pregnancy should reflect the goal of prevention of recidivism and maternal mortality and utilize an approach that balances fetal and maternal risk to optimize outcomes.
关于妊娠期间阿片类药物替代疗法剂量与新生儿阿片类戒断综合征风险和严重程度之间的关系，数据存在冲突，且具有方法学局限性。
在大型队列中评估分娩时美沙酮和丁丙诺啡剂量与新生儿阿片类戒断综合征的关系。
我们使用了 2000 年至 2016 年期间全面围产期阿片类药物依赖治疗计划的数据，进行了一项回顾性队列研究。纳入了参加药物辅助治疗计划的有阿片类药物使用障碍史的女性。在整个研究期间，均采用严格的新生儿阿片类戒断综合征病例定义和新生儿治疗指南。对使用美沙酮和丁丙诺啡的女性进行了比较。使用单变量分析和多变量逻辑回归评估分娩时阿片类药物替代治疗的剂量以及新生儿阿片类戒断综合征的风险和严重程度。在所有分析中，美沙酮和丁丙诺啡的剂量均作为连续变量进行评估。
共有 709 名女性中的 482 名（68.0%）符合纳入标准，包括 344 名美沙酮使用者（71.4%）和 138 名丁丙诺啡使用者（28.6%）。非阿片类药物多物质滥用、体重指数、药物辅助治疗依从性、出生体重和其他特征在两组之间相似。总体而言，美沙酮组和丁丙诺啡组的新生儿阿片类戒断综合征发生率无显著差异（56.8%比 52.0%，P=0.35）。分娩时美沙酮剂量范围为 0-165mg，丁丙诺啡剂量范围为 0-30mg。单变量分析显示，分娩时美沙酮剂量与新生儿阿片类戒断综合征相关（新生儿阿片类戒断综合征新生儿的美沙酮剂量为 83.0±34.2mg，而非新生儿阿片类戒断综合征新生儿的美沙酮剂量为 71.9±35.8mg，P<0.001），但分娩时丁丙诺啡剂量无此关联（新生儿阿片类戒断综合征新生儿的丁丙诺啡剂量为 8.4±4.4mg，而非新生儿阿片类戒断综合征新生儿的丁丙诺啡剂量为 7.6±4.8mg，P=0.30）。新生儿阿片类戒断综合征评分峰值、新生儿阿片类戒断综合征治疗持续时间和累积新生儿吗啡暴露量与分娩时美沙酮剂量显著相关，但与丁丙诺啡剂量无关。分娩时美沙酮剂量与新生儿阿片类戒断综合征之间的关联在多变量回归中仍然存在。
分娩时美沙酮的剂量与新生儿阿片类戒断综合征的频率和严重程度相关，剂量越高，新生儿阿片类戒断综合征越严重，且这种关联呈连续关系。这些数据可能为未来关于妊娠期间美沙酮剂量的前瞻性研究提供信息。虽然药物辅助治疗药物和剂量可能会对与新生儿阿片类戒断综合征相关的相关新生儿结局产生影响，但在妊娠期间提供药物辅助治疗应反映预防复发和产妇死亡的目标，并采用平衡胎儿和产妇风险的方法，以优化结局。
