Outcome of pregnancy and neonatal complications with anti-tumor necrosis factor-α use in females with immune mediated diseases; a systematic review and meta-analysis

Abstract

Background: 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.

Objectives: To evaluate the risk of pregnancy related outcomes in patients with various immune mediated diseases treated with anti-TNF-α agents.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: Anti-TNF-α; Immune mediated disease; Meta-analysis; Pregnancy related complications; Systematic review.