Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago Medicine, Chicago, USA.
Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, USA.
J Autoimmun. 2017 Jan;76:38-52. doi: 10.1016/j.jaut.2016.11.004. Epub 2016 Nov 30.
Immune mediated diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and inflammatory bowel disease (IBD) commonly affect young and adolescent females. Anti-tumor necrosis factor (TNF)-α agents are increasingly used to treat these conditions, but their safety during pregnancy remains unclear.
To evaluate the risk of pregnancy related outcomes in patients with various immune mediated diseases treated with anti-TNF-α agents.
Electronic databases were searched for studies assessing the outcome of pregnancy in female patients with various immune mediated diseases who were treated with anti-TNF-α agents. Direct and network meta-analyses were performed between anti-TNF-α users, non-users, and the general population.
Thirteen studies (including RA, IBD and various immune mediated diseases) were identified. Among the studies that compared the outcome between anti-TNF-α users and the general population, anti-TNF-α users had a non-significant trend towards reduced rate of live birth (odds ratio (OR) = 0.38 (P = 0.081), 95% confidence interval (CI) = 0.13-1.13) and were at significantly increased risk of preterm birth (OR = 2.62 (P < 0.0001), 95% CI = 2.12-3.23), spontaneous abortion (OR = 4.08 (P = 0.033), 95% CI = 1.12-14.89) and low birth weight (OR = 5.95 (P = 0.032), 95% CI = 1.17-30.38) compared to the general population. Risk of anomalies was not elevated (OR = 1.46 (P = 0.18), 95% CI = 0.84-2.56). Among the studies that compared the outcome between anti-TNF-α users and non-users, there were no significant differences in the rates of live birth and pregnancy related complications. Among the studies that compared the outcome between non-anti-TNF-α users and the general population, risk of spontaneous abortion was elevated (OR = 2.60 (P = 0.033), 95% CI = 1.08-6.27), but there were no significant differences in the rates of live birth and other pregnancy related complications. Network meta-analysis confirmed the rank order of all outcomes as general population, non-users and users of anti-TNF-α agents (ascending order based on safety).
Female patients with immune mediated diseases treated with anti-TNF-α agents were at significantly increased risks of preterm birth, spontaneous abortion and low birth weight compared to the general population, but had comparable outcomes with non-users. These results provide useful information for female patients in their reproductive age and raise awareness of the conditions that they are facing among clinicians managing their care.
类风湿关节炎（RA）、强直性脊柱炎（AS）和炎症性肠病（IBD）等免疫介导性疾病通常影响年轻和青春期女性。肿瘤坏死因子（TNF）-α 拮抗剂越来越多地用于治疗这些疾病，但它们在怀孕期间的安全性仍不清楚。
评估接受 TNF-α 拮抗剂治疗的各种免疫介导性疾病患者的妊娠相关结局风险。
检索评估接受 TNF-α 拮抗剂治疗的各种免疫介导性疾病女性患者妊娠结局的研究，评估接受 TNF-α 拮抗剂治疗的各种免疫介导性疾病女性患者的妊娠结局。对 TNF-α 拮抗剂使用者、非使用者和一般人群进行直接和网络荟萃分析。
确定了 13 项研究（包括 RA、IBD 和各种免疫介导性疾病）。在比较 TNF-α 拮抗剂使用者和一般人群之间结局的研究中，TNF-α 拮抗剂使用者的活产率呈下降趋势（比值比（OR）=0.38（P=0.081），95%置信区间（CI）=0.13-1.13），且早产（OR=2.62（P<0.0001），95%CI=2.12-3.23）、自然流产（OR=4.08（P=0.033），95%CI=1.12-14.89）和低出生体重（OR=5.95（P=0.032），95%CI=1.17-30.38）的风险显著增加与一般人群相比。异常风险没有升高（OR=1.46（P=0.18），95%CI=0.84-2.56）。在比较 TNF-α 拮抗剂使用者和非使用者之间结局的研究中，活产率和妊娠相关并发症无显著差异。在比较非 TNF-α 拮抗剂使用者和一般人群之间结局的研究中，自然流产的风险升高（OR=2.60（P=0.033），95%CI=1.08-6.27），但活产率和其他妊娠相关并发症无显著差异。网络荟萃分析证实了所有结局的等级顺序为一般人群、非使用者和 TNF-α 拮抗剂使用者（基于安全性递增顺序）。
与一般人群相比，接受 TNF-α 拮抗剂治疗的免疫介导性疾病女性患者早产、自然流产和低出生体重的风险显著增加，但与非使用者的结局相当。这些结果为处于生育年龄的女性患者提供了有用的信息，并提高了临床医生在管理其护理时对她们所面临的情况的认识。
