Birth outcomes in women who have taken adalimumab in pregnancy: A prospective cohort study
Birth outcomes in women who have taken adalimumab in pregnancy: A prospective cohort study
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DOI：
10.1371/journal.pone.0223603
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发表时间：
2019-10-18
期刊：
影响因子：
3.7
通讯作者：
Jones, Kenneth Lyons
中科院分区：
文献类型：
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作者：
Chambers, Christina D.;Johnson, Diana L.;Jones, Kenneth Lyons
背景需要有关阿达木单抗在妊娠期用于治疗某些自身免疫性疾病的安全性的信息。方法和结果在 2004 年至 2016 年间，加州大学圣地亚哥分校畸胎学信息专家研究中心组织对 602 名服用或未服用阿达木单抗的孕妇进行了一项前瞻性对照观察性队列研究。阿达木单抗暴露队列中的女性在妊娠前三个月接受过至少一剂该药物用于治疗类风湿性关节炎或克罗恩病 (N = 257)。疾病比较队列中的女性在怀孕期间未使用阿达木单抗 (N = 120)。健康对照队列中的女性没有风湿性或炎症性肠病 (N = 225)。通过产妇访谈、病历摘要和体检，对妇女及其婴儿进行跟踪直至产后一年。研究结果包括主要结构性出生缺陷、轻微缺陷、自然流产、早产、产前和产后生长缺陷、严重或机会性感染和恶性肿瘤。 42/602 (7.0%) 的妊娠失访。阿达木单抗暴露队列中 22/221 (10.0%) 的活产婴儿患有严重出生缺陷，而患病未暴露队列中这一比例为 8/106 (7.5%)（调整后比值比 1.10，95% 置信区间 [CI] 0.45 至 2.73）。与健康队列相比，阿达木单抗暴露队列中的女性更有可能早产（调整后风险比 [aHR] 2.59，95% CI 1.22 至 5.50），但与患病未暴露队列相比则不然（aHR 0.82，95% CI 0.66 至 7.20）。没有发现阿达木单抗暴露对任何其他研究结果的风险显着增加。结论与患病的未暴露妊娠相比，妊娠期阿达木单抗暴露与所检查的任何不良结果的风险增加无关。无论是否使用阿达木单抗，患有类风湿性关节炎或克罗恩病的女性早产的风险都会增加。
BackgroundInformation is needed on the safety of adalimumab when used in pregnancy for the treatment of certain autoimmune diseases.Methods and findingsBetween 2004 and 2016, the Organization of Teratology Information Specialists Research Center at the University of California San Diego conducted a prospective controlled observational cohort study in 602 pregnant women who had or had not taken adalimumab. Women in the adalimumab-exposed cohort had received at least one dose of the drug in the first trimester for the treatment of rheumatoid arthritis or Crohn's Disease (N = 257). Women in the disease comparison cohort had not used adalimumab in pregnancy (N = 120). Women in the healthy comparison cohort had no rheumatic or inflammatory bowel diseases (N = 225). Women and their infants were followed to one year postpartum with maternal interviews, medical records abstraction, and physical examinations. Study outcomes were major structural birth defects, minor defects, spontaneous abortion, preterm delivery, pre and post-natal growth deficiency, serious or opportunistic infections and malignancies. 42/602 (7.0%) of pregnancies were lost-to-follow-up. 22/221 (10.0%) in the adalimumabexposed cohort had a live born infant with a major birth defect compared to 8/106 (7.5%) in the diseased unexposed cohort (adjusted odds ratio 1.10, 95% confidence interval [CI] 0.45 to 2.73). Women in the adalimumab-exposed cohort were more likely to deliver preterm compared to the healthy cohort (adjusted hazard ratio [aHR] 2.59, 95% CI 1.22 to 5.50), but not compared to the diseased unexposed cohort (aHR 0.82, 95% CI 0.66 to 7.20). No significant increased risks were noted with adalimumab exposure for any other study outcomes.ConclusionsAdalimumab exposure in pregnancy compared to diseased unexposed pregnancies was not associated with an increased risk for any of the adverse outcomes examined. Women with rheumatoid arthritis or Crohn's Disease were at increased risk of preterm delivery, irrespective of adalimumab exposure.