From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine (E.A.S., K.F.H., L.S., H.M.), and the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology (K.J.G.), Brigham and Women's Hospital, the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine (E.A.S., K.F.H., L.S., H.M.), and the Department of Psychiatry (H.S.C.), Harvard Medical School, the Department of Epidemiology, Harvard T.H. Chan School of Public Health (S.H.-D.), and the Department of Pediatrics, Tufts Medical Center and the Tufts Clinical and Translational Science Institute (J.M.D.), Boston, and the Division of Alcohol, Drugs, and Addiction, McLean Hospital, Belmont (H.S.C.) - all in Massachusetts; UNC Horizons and the Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill (H.E.J.); the Center for the Study of Children at Risk, Departments of Psychiatry and Pediatrics, Warren Alpert Medical School of Brown University, and Women and Infants Hospital - both in Providence, RI (B.L.); Friends Research Institute, Baltimore (M.T.); and the Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of Medicine, Stanford, CA (B.T.B.).
N Engl J Med. 2022 Dec 1;387(22):2033-2044. doi: 10.1056/NEJMoa2203318.
Opioid agonist therapy is strongly recommended for pregnant persons with opioid use disorder. Buprenorphine may be associated with more favorable neonatal and maternal outcomes than methadone, but existing data are limited.
We conducted a cohort study involving pregnant persons who were enrolled in public insurance programs in the United States during the period from 2000 through 2018 in which we examined outcomes among those who received buprenorphine as compared with those who received methadone. Exposure to the two medications was assessed in early pregnancy (through gestational week 19), late pregnancy (gestational week 20 through the day before delivery), and the 30 days before delivery. Risk ratios for neonatal and maternal outcomes were adjusted for confounders with the use of propensity-score overlap weights.
The data source for the study consisted of 2,548,372 pregnancies that ended in live births. In early pregnancy, 10,704 pregnant persons were exposed to buprenorphine and 4387 to methadone. In late pregnancy, 11,272 were exposed to buprenorphine and 5056 to methadone (9976 and 4597, respectively, in the 30 days before delivery). Neonatal abstinence syndrome occurred in 52.0% of the infants who were exposed to buprenorphine in the 30 days before delivery as compared with 69.2% of those exposed to methadone (adjusted relative risk, 0.73; 95% confidence interval [CI], 0.71 to 0.75). Preterm birth occurred in 14.4% of infants exposed to buprenorphine in early pregnancy and in 24.9% of those exposed to methadone (adjusted relative risk, 0.58; 95% CI, 0.53 to 0.62); small size for gestational age in 12.1% and 15.3%, respectively (adjusted relative risk, 0.72; 95% CI, 0.66 to 0.80); and low birth weight in 8.3% and 14.9% (adjusted relative risk, 0.56; 95% CI, 0.50 to 0.63). Delivery by cesarean section occurred in 33.6% of pregnant persons exposed to buprenorphine in early pregnancy and 33.1% of those exposed to methadone (adjusted relative risk, 1.02; 95% CI, 0.97 to 1.08), and severe maternal complications developed in 3.3% and 3.5%, respectively (adjusted relative risk, 0.91; 95% CI, 0.74 to 1.13). Results of exposure in late pregnancy were consistent with results of exposure in early pregnancy.
The use of buprenorphine in pregnancy was associated with a lower risk of adverse neonatal outcomes than methadone use; however, the risk of adverse maternal outcomes was similar among persons who received buprenorphine and those who received methadone. (Funded by the National Institute on Drug Abuse.).
阿片类激动剂疗法强烈推荐用于患有阿片类药物使用障碍的孕妇。与美沙酮相比,丁丙诺啡可能与更有利的新生儿和产妇结局相关,但现有数据有限。
我们进行了一项队列研究,纳入了美国公共保险计划中 2000 年至 2018 年期间分娩的孕妇,研究比较了接受丁丙诺啡和接受美沙酮的孕妇的结局。在妊娠早期(妊娠第 19 周之前)、妊娠晚期(妊娠第 20 周到分娩前一天)和分娩前 30 天评估两种药物的暴露情况。使用倾向评分重叠权重调整混杂因素的新生儿和产妇结局的风险比。
研究的数据来源包括 2548372 例以活产结束的妊娠。妊娠早期,10704 名孕妇接触丁丙诺啡,4387 名孕妇接触美沙酮。妊娠晚期,11272 名孕妇接触丁丙诺啡,5056 名孕妇接触美沙酮(分娩前 30 天分别为 9976 人和 4597 人)。暴露于丁丙诺啡的婴儿在分娩前 30 天出现新生儿戒断综合征的比例为 52.0%,而暴露于美沙酮的婴儿为 69.2%(调整后的相对风险,0.73;95%置信区间[CI],0.71 至 0.75)。暴露于丁丙诺啡的婴儿早产的比例为 14.4%,而暴露于美沙酮的婴儿为 24.9%(调整后的相对风险,0.58;95%CI,0.53 至 0.62);小胎龄儿的比例分别为 12.1%和 15.3%(调整后的相对风险,0.72;95%CI,0.66 至 0.80);低出生体重儿的比例分别为 8.3%和 14.9%(调整后的相对风险,0.56;95%CI,0.50 至 0.63)。妊娠早期暴露于丁丙诺啡的孕妇中,33.6%行剖宫产分娩,而暴露于美沙酮的孕妇中,33.1%行剖宫产分娩(调整后的相对风险,1.02;95%CI,0.97 至 1.08),严重产妇并发症的发生率分别为 3.3%和 3.5%(调整后的相对风险,0.91;95%CI,0.74 至 1.13)。妊娠晚期的暴露结果与妊娠早期的暴露结果一致。
与美沙酮相比,妊娠期间使用丁丙诺啡与新生儿不良结局风险降低相关;然而,接受丁丙诺啡和接受美沙酮的产妇不良结局风险相似。(由国家药物滥用研究所资助)。