Pregnancy and neonatal outcomes in women with immune mediated inflammatory diseases exposed to anti-tumor necrosis factor-a during pregnancy: A systemic review and meta-analysis

Background: Anti-TNF alpha is increasingly used as treatment for immune mediated inflammatory diseases (IMID), such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and psoriasis (PS). However, the impact of anti-TNF alpha during pregnancy on mother and newborn is under debate. This requires a sound knowledge of the effects of this treatment on pregnancy and neonatal outcomes. Objectives: To assess pregnancy and neonatal outcomes after anti-TNF alpha therapy during pregnancy in women with IMID, specifically IBD, RA and PS. Methods: We performed a systematic review and meta-analysis of 39 studies assessing pregnancy and neonatal outcomes of women with IMID exposed to anti-TNF alpha agents during pregnancy. We used a random-effects model to determine pooled outcome measures. Results: An increased risk of preterm births (OR 1.45, 95% CI = 1.16 to 1.82, p = 0.001) and infections in newborns (OR 1.12, 95% CI = 1.00 to 1.27, p = 0.05)) was seen for women in the combined group of IMID exposed to anti-TNF alpha compared to diseased controls. Specifically for IBD patients exposed to anti-TNF alpha, the risk was increased for preterm birth (OR 1.66, 95% CI = 1.14 to 2.42, p = 0.009), and low birth weight (OR 1.49, 95% CI = 1.01 to 2.20, p = 0.047) compared to diseased controls. Combined data from studies of women with RA and PS, showed no increased risk for adverse pregnancy outcome after exposure to anti-TNF alpha. Most children of mothers with IMID received vaccination according to national vaccination schemes and only minor adverse events were reported. Conclusion: Exposure to anti-TNF alpha agents during pregnancy is associated with increased risk of preterm birth and infections in newborns of women with IMID compared to diseased controls. The risk of preterm birth and low birth weight was increased in women with IBD specifically. The increased risk of infections in newborns underlines the importance of vaccination, which seems to be safe in children exposed to anti-TNF alpha. Delay of vaccination is therefore unnecessary in these children. These data may aid in balancing the continuing anti-TNF alpha therapy versus the risk of adverse pregnancy outcomes.