A safety assessment of tumor necrosis factor antagonists during pregnancy

Disease modifying antirheumatic drugs are being increasingly utilized in the treatment of many autoimmune disorders. TNF-alpha antagonists have become the standard of care in treating many of these autoimmune diseases. Because these autoimmune disorders often affect women in their childbearing years, the safety of anti-TNF therapy in pregnancy becomes important.

We critically review the current literature on anti-TNF therapy safety in pregnancy. The available data regarding the anti-TNFs in the setting of pregnancy from 1999 to the present are reviewed.

Case reports and small case series have produced conflicting results, yet their results should only be viewed with cautious interest. Two database reviews suggest little to no risk of congenital anomalies, whereas a much larger independent review of the FDA database reveals congenital anomalies born to mothers who were exposed to anti-TNFs during pregnancy. An ongoing prospective registry (Organization of Teratology Information Services) suggests that about 7 - 10% of children born to mothers taking a TNF antagonist during pregnancy are born with congenital anomalies.

Whether or not these data represent a significant increase, or if a definitive pattern of birth defects exists, remains in question. All these sources have limitations, which are discussed. Further studies are needed to definitively determine the safety and role of anti-TNFs in pregnancy.