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With planning, pregnancy and breastfeeding are safe for women with RA
Lisa R. Sammaritano, MD, is an associate attending physician at the Hospital for Special Surgery and an associate professor of clinical medicine at Weill Cornell Medical College. She is particularly interested in reproductive issues, such as contraception and pregnancy, among patients with rheumatic diseases, including rheumatoid arthritis. She spoke with Healio about how pregnancy affects the disease course of RA, treatment options during pregnancy and breastfeeding and unmet needs in the management of these patients.
What are the potential complications of pregnancy and childbirth for women with RA?
Women with RA have a greater risk for pregnancy complications than women in the general population, but the risks are, fortunately, still relatively low and less of a concern than the risks for women with other connective tissue diseases such as systemic lupus erythematosus or antiphospholipid syndrome.
In terms of disease activity, about 50% of women will have some degree of pregnancy-induced remission. Many of these women are able to discontinue their RA medications. Although it is far less common now than in past years, some women with severe cervical spine or hip involvement may require special attention or altered procedures during delivery because of limited range of motion in these areas. Active disease during pregnancy should be controlled with pregnancy-compatible medications such as hydroxychloroquine, sulfasalazine, and TNF inhibitors because active disease increases the risk of pre-term and small for gestational age babies. We try to avoid high-dose steroid therapy because of the associated risks for diabetes and hypertension in the mother.
A small proportion of women, roughly 15%, may have anti-Ro/SSA and/or anti-La/SSB antibodies (so-called Sjögren’s antibodies), which are present in 70% of patients with primary Sjögren syndrome. These antibodies may cross the placenta after the first trimester and lead to reversible rash, liver function test abnormalities or low blood counts in the baby in 15% to 25% of cases and, very rarely, irreversible heart block requiring pacemaker placement in 2% of cases. Recent data suggest hydroxychloroquine may lower these risks, so antibody-positive women may benefit from taking this drug before and during pregnancy. Monitoring with fetal echocardiograms is also recommended for these women.
How does pharmacologic treatment for RA affect women during and after pregnancy?
Medications used to treat RA vary widely in terms of their established safety in pregnancy. Methotrexate causes significant birth defects and should be stopped 1 to 3 months before conception. Leflunomide may also cause birth defects, although the data are less clear. Because of the long half-life of this drug, women who take it within 2 years of becoming pregnant should be treated with cholestyramine “washout” therapy and have their levels of this drug checked afterwards.
TNF inhibitors are biologic medications that do not cross the placenta during the first trimester. However, levels of the drug are present in the newborn when TNF inhibitor therapy is continued throughout the pregnancy. The exception is certolizumab pegol (Cimzia, UCB), which does not cross the placenta. In general, except for certolizumab, we recommend stopping TNF inhibitors at the start of the third trimester if possible.
Is there any evidence of negative outcomes for babies born to mothers who are treated for RA during pregnancy?
There is, for drugs that are known or suspected to be teratogenic, such as methotrexate or leflunomide.
There does not appear to be an increase in the rate of major birth defects for babies born to women treated with TNF inhibitors. The major concern with these drugs is the risk for neonatal immunosuppression if mothers are treated throughout pregnancy, although this concern is largely theoretical. One baby born to a mother treated with a TNF inhibitor through pregnancy died after being immunized with the bacille Calmette-Guerin vaccine, a tuberculosis vaccine given in countries outside the U.S. For this reason, children of mothers treated with TNF inhibitors in the third trimester of pregnancy should not receive any live vaccines for the first 6 months of life.
There are few data on the use of other non-TNF inhibitor biologic drugs in pregnancy and so these agents are not recommended. New small-molecule drugs have no data on use in pregnancy and are not recommended; in addition, the small molecular size of these drugs suggests that they will easily cross the placenta.
What are the most significant unmet needs regarding pregnancy and childbirth among women with RA?
The most important unmet need at this time is education for both physicians and patients. We have disease-modifying antirheumatic drugs that we can use with very low risk through much of pregnancy, yet many women refuse therapy (or physicians do not prescribe therapy) due to fear of adverse fetal effects. In fact, uncontrolled RA disease is more likely to cause problems, in terms of increased risk for preterm birth and small for gestational age babies. Many physicians and patients feel more comfortable using prednisone rather than DMARD therapy, but, again, this drug can also cause problems in pregnancy when used chronically at higher doses, including hypertension, diabetes and premature rupture of membranes.
What should clinicians ensure that new mothers know about disease activity after delivery?
Most women with RA who have a remission during pregnancy will have a post-partum flare anywhere from several weeks to several months after delivery. Patients should be aware of this and prepared for it. Active arthritis after delivery can make an already stressful time – caring for a newborn – even more challenging. Hydroxychloroquine, sulfasalazine and TNF inhibitors are compatible with breast-feeding; other biologic medications may also be used. It is reasonable to restart pregnancy-compatible medications after delivery or, if it is more reassuring to the patient, at the first sign of flare.
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