Serra Allison E, Lemon Lara S, Mokhtari Neggin B, Parks W Tony, Catov Janet M, Venkataramanan Raman, Caritis Steve N
Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh Medical Center, Pittsburgh, PA.
School of Pharmacy, University of Pittsburgh, Pittsburgh, PA.
Am J Obstet Gynecol. 2017 Apr;216(4):418.e1-418.e5. doi: 10.1016/j.ajog.2016.12.016. Epub 2016 Dec 23.
Opioid use disorder among pregnant women is associated with adverse perinatal outcomes and is increasing in the United States. The standard of care for pregnant women with opioid use disorder is opioid maintenance therapy including either methadone or buprenorphine, which can be initiated at any time during pregnancy. These medications are known to cross the placenta but their placental and fetal effects have not been well characterized. Delayed villous maturation, a placental finding associated with stillbirth, was observed in placentas exposed to opioid maintenance therapy. Given the association of delayed villous maturation with stillbirth, and the possible relationship between opioid maintenance therapy and delayed villous maturation, this study was undertaken to explore the association between opioid maintenance therapy and this placental finding. Delayed villous maturation was not previously reported in placentas exposed to opioids or opioid maintenance therapy.
This study sought to compare risk of delayed villous maturation in term placentas exposed and unexposed to opioid maintenance therapy with buprenorphine or methadone.
This was a retrospective cohort study conducted between 2010 through 2012 at Magee-Womens Hospital comparing delayed villous maturation in placentas of women with opioid use disorder exposed to either buprenorphine (n = 86) or methadone (n = 268) versus women without opioid use disorder (n = 978). Potential covariates were assessed in univariate analyses with none significantly associated with delayed villous maturation. The final model used conditional logistic regression adjusting for smoking status alone.
Among women without opioid use disorder (and therefore not exposed to opioid maintenance therapy), delayed villous maturation was identified in 5.7% of placentas while the prevalence among women treated with buprenorphine or methadone was 8.1% and 10.8%. Overall, the crude odds of being diagnosed with delayed villous maturation were significantly greater in those exposed to opioid maintenance therapy compared to those not exposed (odds ratio, 1.86; 95% confidence interval, 1.20-2.89). When considered separately, women treated with methadone had significantly greater odds of having a placenta with delayed villous maturation than women without exposure to opioid maintenance therapy (odds ratio, 2.00; 95% confidence interval, 1.52-3.20). Women treated with buprenorphine did not have significantly greater odds of this placental diagnosis when compared to the women unexposed to opioid maintenance therapy (odds ratio, 1.46; 95% confidence interval, 0.64-3.31). Results were similar after accounting for smoking.
Delayed villous maturation was more common in the placentas of women exposed to opioid maintenance therapy. Further studies are required to characterize rates and extent of delayed villous maturation in the general population as well as to differentiate between possible effects of opioid exposure (eg, heroin, illicit use of prescription opioids) vs those of opioid maintenance therapy (buprenorphine and methadone).
美国孕妇阿片类药物使用障碍与不良围产期结局相关且呈上升趋势。患有阿片类药物使用障碍的孕妇的标准治疗方案是阿片类药物维持治疗，包括美沙酮或丁丙诺啡，可在孕期任何时间开始使用。已知这些药物可穿过胎盘，但它们对胎盘和胎儿的影响尚未得到充分描述。在接受阿片类药物维持治疗的胎盘组织中观察到绒毛成熟延迟，这是一种与死产相关的胎盘表现。鉴于绒毛成熟延迟与死产有关，以及阿片类药物维持治疗与绒毛成熟延迟之间可能存在的关系，本研究旨在探讨阿片类药物维持治疗与这种胎盘表现之间的关联。此前在暴露于阿片类药物或阿片类药物维持治疗的胎盘中未报告过绒毛成熟延迟。
本研究旨在比较足月胎盘暴露于丁丙诺啡或美沙酮进行阿片类药物维持治疗与未暴露于该治疗的情况下绒毛成熟延迟的风险。
这是一项回顾性队列研究，于2010年至2012年在梅杰妇女医院进行，比较了患有阿片类药物使用障碍且暴露于丁丙诺啡（n = 86）或美沙酮（n = 268）的妇女与未患有阿片类药物使用障碍的妇女（n = 978）的胎盘绒毛成熟延迟情况。在单因素分析中评估了潜在的协变量，未发现与绒毛成熟延迟有显著关联的因素。最终模型仅对吸烟状况进行条件逻辑回归调整。
在未患有阿片类药物使用障碍（因此未接受阿片类药物维持治疗）的妇女中，5.7%的胎盘出现绒毛成熟延迟，而接受丁丙诺啡或美沙酮治疗的妇女中这一比例分别为8.1%和10.8%。总体而言，与未暴露于阿片类药物维持治疗的妇女相比，暴露于该治疗的妇女被诊断为绒毛成熟延迟的粗比值显著更高（比值比，1.86；95%置信区间，1.20 - 2.89）。单独考虑时，与未暴露于阿片类药物维持治疗的妇女相比，接受美沙酮治疗的妇女胎盘出现绒毛成熟延迟的几率显著更高（比值比，2.00；95%置信区间，1.52 - 3.20）。与未暴露于阿片类药物维持治疗的妇女相比，接受丁丙诺啡治疗的妇女被诊断为这种胎盘表现的几率没有显著更高（比值比，1.46；95%置信区间，0.64 - 3.31）。考虑吸烟因素后结果相似。
绒毛成熟延迟在接受阿片类药物维持治疗的妇女的胎盘中更为常见。需要进一步研究以明确一般人群中绒毛成熟延迟的发生率和程度，并区分阿片类药物暴露（如海洛因、非法使用处方阿片类药物）与阿片类药物维持治疗（丁丙诺啡和美沙酮）可能产生的不同影响。
