OBJECTIVE To evaluate the risk of adverse maternal and infant outcomes following in utero exposure to duloxetine. DESIGN Cohort study nested in the Medicaid Analytic eXtract for 2004-13. SETTING Publicly insured pregnancies in the United States. PARTICIPANTS Pregnant women 18 to 55 years of age and their liveborn infants. INTERVENTIONS Duloxetine exposure during the etiologically relevant time window, compared with no exposure to duloxetine, exposure to selective serotonin reuptake inhibitors, exposure to venlafaxine, and exposure to duloxetine before but not during pregnancy. MAIN OUTCOME MEASURES Congenital malformations overall, cardiac malformations, preterm birth, small for gestational age infant, pre-eclampsia, and postpartum hemorrhage. RESULTS Cohort sizes ranged from 1.3 to 4.1 million, depending on the outcome. The number of women exposed to duloxetine varied by cohort and exposure contrast and was around 2500-3000 for early pregnancy exposure and 900-950 for late pregnancy exposure. The base risk per 1000 unexposed women was 36.6 (95% confidence interval 36.3 to 36.9) for congenital malformations overall, 13.7 (13.5 to 13.9) for cardiovascular malformations, 107.8 (107.3 to 108.3) for preterm birth, 20.4 (20.1 to 20.6) for small for gestational age infant, 33.6 (33.3 to 33.9) for pre-eclampsia, and 23.3 (23.1 to 23.4) for postpartum hemorrhage. After adjustment for measured potential confounding variables, all baseline characteristics were well balanced for all exposure contrasts. In propensity score adjusted analyses versus unexposed pregnancies, the relative risk was 1.11 (95% confidence interval 0.93 to 1.33) for congenital malformations overall and 1.29 (0.99 to 1.68) for cardiovascular malformations. For preterm birth, the relative risk was 1.01 (0.92 to 1.10) for early exposure and 1.19 (1.04 to 1.37) for late exposure. For small for gestational age infants the relative risks were 1.14 (0.92 to 1.41) and 1.20 (0.83 to 1.72) for early and late pregnancy exposure, respectively, and for pre-eclampsia they were 1.12 (0.96 to 1.31) and 1.04 (0.80 to 1.35). The relative risk for postpartum hemorrhage was 1.53 (1.08 to 2.18). Results from sensitivity analyses were generally consistent with the findings from the main analyses. CONCLUSIONS On the basis of the evidence available to date, duloxetine is unlikely to be a major teratogen but may be associated with an increased risk of postpartum hemorrhage and a small increased risk of cardiac malformations. While continuing to monitor the safety of duloxetine as data accumulate over time, these potential small increases in risk of relatively uncommon outcomes must be weighed against the benefits of treating depression and pain during pregnancy in a given patient. TRIAL REGISTRATION EUPAS 15946.

中文翻译：

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孕期暴露于度洛西汀后的母婴结局：队列研究。

目的评估宫内暴露于度洛西汀后母婴不利结局的风险。DESIGN队列研究嵌套在2004-13年的Medicaid Analytic eXtract中。设置在美国有公共保险的怀孕。研究对象18至55岁的孕妇及其活婴。干预措施在病因相关的时间范围内，度洛西汀的暴露与未妊娠但未暴露于度洛西汀，选择性5-羟色胺再摄取抑制剂，暴露于文拉法辛和度洛西汀的暴露相比有所不同。主要观察指标总体上先天畸形，心脏畸形，早产，胎龄儿小，先兆子痫和产后出血。结果队列规模从130到410万不等，具体取决于结果。暴露于度洛西汀的妇女人数因队列和暴露对比而异，孕早期暴露为约2500-3000，孕晚期暴露为900-950。每1000名未暴露女性的基本风险是先天畸形总体为36.6（95％置信区间36.3至36.9），心血管畸形为13.7（13.5至13.9），早产为107.8（107.3至108.3），20.4（20.1至20.6）小于胎龄儿，子痫前期为33.6（33.3至33.9），产后出血为23.3（23.1至23.4）。在对测得的潜在混杂变量进行调整后，所有基线对比的所有基线特征都得到了很好的平衡。在倾向评分调整的分析与未暴露的妊娠中，相对风险为1.11（95％置信区间为0.93至1）。33）对于先天性畸形总体而言为1.29（0.99至1.68）对于心血管畸形。对于早产，早期暴露的相对风险为1.01（0.92至1.10），晚期暴露的相对风险为1.19（1.04至1.37）。对于胎龄小的婴儿，妊娠早期和晚期暴露的相对风险分别为1.14（0.92至1.41）和1.20（0.83至1.72），而对于子痫前期的相对风险分别为1.12（0.96至1.31）和1.04（0.80至0.80）。 1.35）。产后出血的相对风险为1.53（1.08至2.18）。敏感性分析的结果通常与主要分析的结果一致。结论根据迄今为止可获得的证据，度洛西汀不太可能是主要的致畸剂，但可能与产后出血的风险增加和心脏畸形的风险增加有关。随着数据的不断积累，在继续监测度洛西汀的安全性的同时，必须权衡这些潜在的相对不常见结局风险的小幅增加与给定患者怀孕期间治疗抑郁和疼痛的益处之间的权衡。EUPAS 15946试用注册。