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 (TNE)-alpha 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-alpha 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-alpha agents. Direct and network meta-analyses were performed between anti-TNF-alpha 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-alpha users and the general population, anti-TNF-alpha 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 L13) 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-alpha 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-alpha 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-alpha agents (ascending order based on safety). Conclusions: Female patients with immune mediated diseases treated with anti-TNF-alpha 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. (C) 2016 Elsevier Ltd. All rights reserved.