关于除肿瘤坏死因子（TNF）抑制剂以外的生物制剂在妊娠期安全性方面的已发表数据有限。本研究旨在检测自身免疫性疾病孕妇使用生物制剂引起胎儿和新生儿不良药物反应（ADRs）的药物警戒信号。我们对世界卫生组织的VigiBase®药物警戒数据库进行了失调分析，时间跨越1968年至2021年6月1日。数据收集时间为2021年6月。我们使用《药物监管活动医学字典》不同层次的术语，筛选出以下胎儿或新生儿ADRs：死胎、早产、低出生体重、胎龄小、先天畸形。将感兴趣的生物制剂（阿达木单抗、英夫利昔单抗、戈露肽单抗、推拉昔单抗、恩特西普、阿那基拉、卡瑟珂单抗、托珠单抗、萨瑞珂单抗、乌斯替金单抗、古瑟库单抗、色库单抗、依西美注射液、贝利单抗和利妥昔单抗）与其他药物的所有其他报告的所有已识别ADRs的频率进行比较，并以报告比值（ROR）[95％的置信区间]进行引用。主要分析中，已知与致畸药物的同时使用的报告被排除。其他分析包括1968-2021年和2001-2021年治疗适 indication期间的ROR分层，以及排除激素使用报告后进行的分析。在主要分析中，使用阿那基拉（7.18 [3.50-14.73]），卡瑟珂单抗（19.54 [12.82-29.79]）和利妥昔单抗（5.09 [2.77-9.33]）与肌肉骨骼畸形以及卡瑟珂单抗（347.88 [217.9-555.50]）和利妥昔单抗（9.27 [2.95-29.15]）与免疫系统疾病相关的ROR特别高。排除激素使用报告后，贝利单抗（28.49 [5.75-141.25]）与新生儿感染的ROR显著。我们确定了某些不良胎儿和新生儿结局的可能关联，提示在妊娠期使用某些生物制剂时需要警惕。© 2022. 作者。

Published data on the safety of biologics other than tumor necrosis factor (TNF) inhibitors during pregnancy are limited.The aim was to detect pharmacovigilance signals for fetal and neonatal adverse drug reactions (ADRs) to biologics taken by pregnant women with autoimmune diseases.We performed a disproportionality analysis of the World Health Organization's VigiBase® pharmacovigilance database from 1968 to June 1, 2021. Data were collected in June 2021. By using terms for different hierarchical levels of the Medical Dictionary for Regulatory Activities, we selected the following fetal or neonatal ADRs: stillbirth, premature birth, low birth weight, small for gestational age, and congenital malformations. The frequency of all identified ADRs for biologics of interest (adalimumab, infliximab, golimumab, certolizumab, etanercept, anakinra, canakinumab, tocilizumab, sarilumab, ustekinumab, guselkumab, secukinumab, ixekizumab, belimumab, abatacept, and rituximab) was compared with that of all other reports for all other drugs and quoted as the reporting odds ratio (ROR) [95% confidence interval]. Reports with known concomitant use of teratogenic drugs were excluded from the main analysis. Other analyses included ROR stratifications by therapeutic indication in the periods 1968-2021 and 2001-2021, and an analysis after excluding reports with steroids.In the main analysis, the RORs were particularly high for musculoskeletal malformations with anakinra (7.18 [3.50-14.73]), canakinumab (19.54 [12.82-29.79]), and abatacept (5.09 [2.77-9.33]), and for immune system disorders with canakinumab (347.88 [217.9-555.50]) and rituximab (9.27 [2.95-29.15]). After the exclusion of reports with steroids, the ROR was significant for neonatal infections with belimumab (28.49 [5.75-141.25]).We identified possible associations with some adverse fetal and neonatal outcomes, suggesting that vigilance is required when prescribing certain biologics during pregnancy.© 2022. The Author(s).