The Role of TNF-α and Anti-TNF-α Agents during Preconception, Pregnancy, and Breastfeeding

Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional Th1 cytokine and one of the most important inflammatory cytokines. In pregnancy, TNF-alpha influences hormone synthesis, placental architecture, and embryonic development. It was also shown that increased levels of TNF-alpha are associated with pregnancy loss and preeclampsia. Increased TNF-alpha levels in complicated pregnancy draw attention to trophoblast biology, especially migratory activity, syncytialisation, and endocrine function. Additionally, elevated TNF-alpha levels may affect the maternal-fetal relationship by altering the secretory profile of placental immunomodulatory factors, which in turn affects maternal immune cells. There is growing evidence that metabolic/pro-inflammatory cytokines can program early placental functions and growth in the first trimester of pregnancy. Furthermore, early pregnancy placenta has a direct impact on fetal development and maternal immune system diseases that release inflammatory (e.g., TNF-alpha) and immunomodulatory factors, such as chronic inflammatory rheumatic, gastroenterological, or dermatological diseases, and may result in an abnormal release of cytokines and chemokines in syncytiotrophoblasts. Pregnancy poses a challenge in the treatment of chronic disease in patients who plan to have children. The activity of the disease, the impact of pregnancy on the course of the disease, and the safety of pharmacotherapy, including anti-rheumatic agents, in pregnancy should be considered.

Automated summary

TNF-alpha plays a crucial role in influencing hormone synthesis, placental architecture, and embryonic development during pregnancy. Increased levels of TNF-alpha are associated with pregnancy loss and preeclampsia, and may also impact trophoblast biology and maternal immune cells. Additionally, the release of cytokines and chemokines in syncytiotrophoblasts may be affected by chronic inflammatory diseases in pregnancy.