Of particular note were the findings on methotrexate, which the U.S. Food and Drug Administration identifies as a category X medication, meaning it can cause birth defects and fetal death. Yet the Vanderbilt researchers found that of 23 infants exposed to methotrexate in the first trimester, only one developed a birth defect, and it was a type not normally associated with the drug.

Dr. Cooper points out that most reports linking methotrexate with birth defects looked at higher doses, typically used in cancer treatment rather than the lower doses used to treat RA. Still, he stresses that his research doesn’t prove that methotrexate is safe.

One problem is the relatively small size of the study. Small studies often fail to find significant effects that a larger study would have detected. Yet Dr. Cooper believes the findings do provide “a critical piece of information to help guide women and their doctors.”

“Some of the medications in our study are recently approved and haven’t been extensively studied for use in pregnancy, although they are increasingly used and heavily marketed,” he says, referring to TNF inhibitors. “We thought it was important to take a look at them. …As we move forward, it will be important to do larger studies that provide more information.”

For now, he says each case is unique and women with autoimmune conditions should work closely with their health care providers to decide the best course of action to ensure optimal health outcomes for themselves and their babies. 

John M. Davis III, MD, a rheumatologist at Mayo Clinic in Rochester, Minn., adds a similar note of caution.

“Although it’s reassuring that the authors didn’t find evidence of a large increase in adverse fetal outcomes from first trimester exposure to immunosuppressive medications, the study had a low rate of events, which limits the power of this study to detect small but potentially meaningful increases in risk. As the authors acknowledge, further studies of a larger sample size are needed. But in the meantime, this information should be useful to women and their physicians in discussing the risks and benefits of immunosuppressive therapy before and during pregnancy.”

Alana Levine, MD, a rheumatologist with the Barbara Volcker Center for Women and Rheumatic Diseases at Hospital for Special Surgery in New York, is more optimistic, saying, “The results of this study are reassuring, particularly for those women who become inadvertently pregnant while taking these immunosuppressive medications. Now we may be able to allay the fear that early fetal exposure to some of these medications, particularly methotrexate, is as harmful as we currently believe.”