Division of Clinical Pharmacy, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; Department of Pediatrics, Hadassah-Hebrew University Medical Centers, Jerusalem, Israel.
Department of Neonatology, Hadassah-Hebrew University Medical Centers, Jerusalem, Israel.
Am J Obstet Gynecol. 2019 Jan;220(1):57.e1-57.e13. doi: 10.1016/j.ajog.2018.08.030. Epub 2018 Aug 28.
There is a marked increase in the use of selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors in the last decade. Many newborns are likely to be exposed during pregnancy and labor.
We aimed to evaluate the association between exposure to selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors during pregnancy and the risk for persistent pulmonary hypertension of the newborn. We sought to compare the risk for persistent pulmonary hypertension of the newborn between specific selective serotonin reuptake inhibitor agents.
MEDLINE, Embase, and Cochrane were searched up to July 2017. No language restrictions were applied. Search key words included: "SSRI," "SNRI," "pregnancy," "risk," "new-born," and "pulmonary hypertension." Retrospective cohort studies and case-control studies reporting the risk for persistent pulmonary hypertension of the newborn in the offspring of women exposed to selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors during pregnancy, were extracted. Two independent researchers identified relevant data. Random effects meta-analysis was used to pool results. Odds ratios were calculated with subsequent 95% confidence intervals. Network meta-analysis was conducted, incorporating direct and indirect comparisons among different selective serotonin reuptake inhibitors. The primary outcome was risk for persistent pulmonary hypertension of the newborn after exposure to selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors during pregnancy.
A total of 11 studies were identified. A total of 156,978 women and their offspring were exposed to selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors during pregnancy. Persistent pulmonary hypertension of the newborn was detected among 452 exposed offspring, representing an incidence rate of 2.9 cases per 1000 live births and a number needed to harm of 1000. The risk for persistent pulmonary hypertension of the newborn was significantly increased in the analysis of exposure to selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor in any trimester (odds ratio, 1.82; 95% confidence interval, 1.31-2.54; I = 72%), as well as in analysis restricted to exposure week >20 (odds ratio, 2.08; 95% confidence interval, 1.44-3.01; I = 76%). In network meta-analysis, sertraline was ranked most likely to have the lowest risk for persistent pulmonary hypertension of the newborn among the different selective serotonin reuptake inhibitors (P = .83).
Exposure to selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors during pregnancy is associated with an increased risk for persistent pulmonary hypertension of the newborn. According to our findings, sertraline ranked as most likely to have the lowest risk for persistent pulmonary hypertension of the newborn compared to other selective serotonin reuptake inhibitors, suggesting it may have the best safety profile for use in pregnancy in this regard. Further studies are needed to fully establish these results.
在过去十年中，选择性 5-羟色胺再摄取抑制剂和 5-羟色胺-去甲肾上腺素再摄取抑制剂的使用明显增加。许多新生儿在怀孕期间和分娩时都可能接触到这些药物。
我们旨在评估怀孕期间接触选择性 5-羟色胺再摄取抑制剂和 5-羟色胺-去甲肾上腺素再摄取抑制剂与新生儿持续性肺动脉高压的风险之间的关联。我们试图比较特定选择性 5-羟色胺再摄取抑制剂之间新生儿持续性肺动脉高压的风险。
截至 2017 年 7 月，检索了 MEDLINE、Embase 和 Cochrane。未应用语言限制。搜索关键词包括：“SSRI”、“SNRI”、“pregnancy”、“risk”、“new-born”和“pulmonary hypertension”。提取了报告了怀孕期间接触选择性 5-羟色胺再摄取抑制剂或 5-羟色胺-去甲肾上腺素再摄取抑制剂的女性的后代中新生儿持续性肺动脉高压风险的回顾性队列研究和病例对照研究。两名独立研究人员确定了相关数据。使用随机效应荟萃分析来汇总结果。计算比值比及其随后的 95%置信区间。进行了网络荟萃分析，纳入了不同选择性 5-羟色胺再摄取抑制剂之间的直接和间接比较。主要结局是在怀孕期间接触选择性 5-羟色胺再摄取抑制剂或 5-羟色胺-去甲肾上腺素再摄取抑制剂后新生儿持续性肺动脉高压的风险。
确定了 11 项研究。共有 156978 名女性及其后代在怀孕期间接触了选择性 5-羟色胺再摄取抑制剂或 5-羟色胺-去甲肾上腺素再摄取抑制剂。在暴露于选择性 5-羟色胺再摄取抑制剂/5-羟色胺-去甲肾上腺素再摄取抑制剂的 452 名暴露后代中检测到新生儿持续性肺动脉高压，发生率为每 1000 例活产儿 2.9 例，危害人数为 1000 例。在任何孕期（比值比，1.82；95%置信区间，1.31-2.54；I=72%）和仅在孕期 20 周后（比值比，2.08；95%置信区间，1.44-3.01；I=76%）接触选择性 5-羟色胺再摄取抑制剂/5-羟色胺-去甲肾上腺素再摄取抑制剂的分析中，新生儿持续性肺动脉高压的风险显著增加。在网络荟萃分析中，舍曲林在不同的选择性 5-羟色胺再摄取抑制剂中最有可能具有最低的新生儿持续性肺动脉高压风险（P=.83）。
怀孕期间接触选择性 5-羟色胺再摄取抑制剂或 5-羟色胺-去甲肾上腺素再摄取抑制剂与新生儿持续性肺动脉高压的风险增加相关。根据我们的发现，与其他选择性 5-羟色胺再摄取抑制剂相比，舍曲林在治疗新生儿持续性肺动脉高压方面的风险最低，这表明它在这方面可能具有最佳的妊娠安全性。需要进一步的研究来充分证实这些结果。
