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taking SSZ have not shown a significant increase in birth defects (81, 82). There have been isolated reports of foetal anomalies including oral cleft, renal, and cardiac defects (83, 84). Folic acid should be continued throughout pregnancy. A small amount of SSZ is excreted into breast milk, but it is not thought to be at a level that would harm an infant. Although there is a theoretical risk that SSZ from breast milk could displace bilirubin, exacerbating jaundice, this has not been reported in human babies. TNFα antagonists (Category B). Etanercept, adalimumab, and infliximab are biological agents that inhibit TNFα, an inflammatory cytokine. Animal studies using etanercept in rats and rabbits at doses 60 to 100 times greater than the recommended human dose and an anti-TNFα monoclonal antibody similar to infliximab in mice have not shown adverse effects on pregnancy or foetal development (85, 86). For this reason, these medications have been classified as category B risk. The risk in humans has not been sufficiently documented. Initial reports from over 300 pregnancies exposed to anti-TNFα therapy during the first trimester appeared reassuring. In the Infliximab Safety Database, two infants of mothers with Crohn's disease had congenital anomalies: one with tetrology of fallot and the other with intestional malrotation. The occurrence of these abnormalities was not felt to be different from that seen in the general population (87). A review of the FDA database of reported adverse events with etanercept, infliximab, and adalimumab from 1999 to 2005 revealed 61 congenital anomalies in 41 children born to mothers on anti-TNFα therapy. Congenital anomalies included heart defects (most common), cystic kidney, pulmonary malformations, teratoma, tracheal stenosis, hypospadias, trisomy 21, and hydrocele (88). This last report is difficult to interpret for several reasons, including the fact that the number of exposed pregnancies is unknown (only 1500 pregnancies would be required to have 41 infants with malformations in the general population) and there is significant report bias for the elective reporting programme used. The types of congenital anomalies reported in the FDA database are similar in distribution to those found in the general population. Although this report suggests that further surveillance is needed, it should not lead to cessation of essential therapy in women with severe RA. Our current practice is to allow women to conceive on these medications, but discontinue them once a pregnancy is discovered. If a woman has a significant flare of arthritis during pregnancy, we will consider restarting the anti-TNFα therapy. Transfer of infliximab has been documented in the third trimester; avoidance of these drugs near the time of delivery may diminish the risk for infection in the infant (89–91). Although there are only a few cases reported, it does not appear that anti-TNFα medications pass into the breast milk of women who are actively lactating; however, more research into this area would be helpful (92). Azathioprine (Category D).Azathioprine is relatively safe in pregnancy, despite the warning category from the FDA. Although there are some early reports of immunosuppression in offspring, more recent studies have documented its relative safety. It is reported that the majority of azathioprine that crosses the placenta is in the inactive metabolite thiouric acid (93). Several case–control studies of pregnancies with and without azathioprine exposure found no significant increase in congenital abnormalities (93). In addition, there has been no identifiable pattern of congenital anomalies among these pregnancies (93). Mycophenolate mofetil (MMF; Category D). MMF has recently
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