OBJECTIVE:To prospectively investigate the association of selective serotonin reuptake inhibitor (SSRI) exposure through critical windows of pregnancy establishment with fecundability and pregnancy loss. DESIGN:Prospective cohort study using longitudinal urine measurements of common SSRIs while women are actively trying to conceive. SETTING:Four clinical sites. PATIENT(S):A total of 1,228 women without uncontrolled depression/anxiety, attempting natural conception while participating in a randomized trial of preconception-initiated low-dose aspirin. INTERVENTIONS(S):Not applicable. MAIN OUTCOME MEASURE(S):Urinary SSRIs (fluoxetine, sertraline, escitalopram/citalopram) were measured while trying to conceive and, for women who became pregnant, at weeks 0, 4, and 8 of pregnancy. Fecundability odds ratios and incidence of pregnancy loss and live birth were estimated. RESULT(S):A total of 172 women (14%) were exposed to SSRIs while trying to conceive. SSRI exposure was associated with 24% reduced fecundability, and accordingly, a nonsignificant 9% lower live birth incidence, with significantly lower live birth in fluoxetine-exposed women. SSRI exposure was not associated with subsequent pregnancy loss, whether exposure was before conception or at 0, 4, or 8 weeks of gestation, although estimates varied by specific SSRI drug. CONCLUSION(S):Women using SSRIs may have more difficulty becoming pregnant, and although SSRI exposure overall was not associated with pregnancy loss, fluoxetine deserves caution and future study. CLINICAL TRIAL REGISTRATION NUMBER:NCT00467363.

译文

目的:前瞻性研究通过妊娠建立的关键窗口选择性血清素再摄取抑制剂(SSRI)暴露与生育能力和妊娠流失的关系。
设计:在女性积极尝试受孕的同时,对普通SSRIs进行纵向尿液测量的前瞻性队列研究。
地点:四个临床站点。
患者:共有1,228名没有失控的抑郁/焦虑症的妇女,在参加先孕前低剂量阿司匹林的随机试验时尝试自然受孕。
干预措施:不适用。
主要观察指标:在尝试怀孕时测量了尿液SSRI(氟西汀,舍曲林,依他普仑/西他普仑),对于怀孕的妇女,在怀孕的第0、4和8周进行了测量。估计可生育性比值比以及流产和流产的发生率。
结果:共有172名妇女(14%)在尝试受孕时接触了SSRI。 SSRI暴露会降低24%的生育能力,因此,氟西汀暴露的妇女的活产降低了9%,但无统计学意义。尽管估计值因特定的SSRI药物而异,但无论是在怀孕前还是在妊娠0、4或8周时,SSRI暴露都与随后的流产无关。
结论:使用SSRIs的妇女怀孕的困难可能更大,尽管SSRIs的总体暴露与流产无关,但氟西汀值得谨慎和今后的研究。
临床试验注册号:NCT00467363。

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