Commentary

Managing Lupus in Pregnancy Draws on Evidence, Judgment


 

Outcomes of pregnancy in women with systemic lupus erythematosus have improved over the past 50 years, with dramatic reductions in rates of pregnancy loss and preterm delivery. These gains are due in large part to better management of lupus before and during pregnancy, a challenge that requires applying both evidence and clinical judgment on a case-by-case basis.

Prepregnancy Evaluation

All women with lupus should have a rheumatologic evaluation before conceiving to assess the likely safety of pregnancy. This evaluation includes clinical assessment with consideration of factors such as minor and major organ manifestations, comorbidities, medications, time since last flare, and current health.

By Dr. Carl A. Laskin

It also includes careful assessment of renal status and updating of routine lab work. Serology should include testing for anti-Ro and anti-La antibodies, and for antiphospholipid antibodies – both lupus anticoagulant and anticardiolipin antibodies. Accumulating data suggest that lupus anticoagulant is by far the more important antiphospholipid antibody.

The presence of anti-Ro and/or anti-La antibodies always changes pregnancy management, prompting fetal echocardiographic monitoring because of the potential for congenital heart block. In contrast, the presence of antiphospholipid antibodies typically warrants aspirin therapy only if a woman has had clinical manifestations; otherwise, it may just be an antibody looking for a problem.

The medications assessed include any taken to treat lupus and any taken to manage complications of the disease, such as calcium channel blockers and angiotensin-converting enzyme inhibitors. Some medications may require discontinuation, depending on their teratogenicity profile.

Fortunately, most of the mainstay drugs used to treat lupus are safe in pregnancy. For example, prednisone can be continued, although women must be counseled about the small increased risk to the fetus of cleft lip and palate that may be related to dose. Similarly, hydroxychloroquine (Plaquenil) has a great safety track record in pregnancy and should be left in place. The risk of a flare when these drugs are stopped is far greater than any risk of toxicity.

Ideally, patients with lupus should be stable for at least 6 months on minimal medication before conceiving. The main risk factors for poor outcomes in women considering pregnancy are active disease, proteinuria exceeding 0.5 g/day, hypertension, thrombocytopenia, antiphospholipid antibodies, and certain medications.

Impact of Renal Disease

Any major organ involvement in lupus is a concern during pregnancy, but renal disease is the most common and is also a strong prognostic indicator.

Proteinuria before pregnancy is worrisome because it will almost certainly worsen in the first trimester. Women who conceive with proteinuria of 2 g/day or higher often develop a preeclampsia-like condition that can rapidly lead not only to fetal death, but also to maternal death. This is a group who should avoid pregnancy.

Another group we worry about are women who have needed dialysis and have been able to stop, but still have an elevated serum creatinine level (150-200 micromol/L). We know that their creatinine will worsen considerably during pregnancy. Such patients are good candidates for in vitro fertilization with use of a gestational carrier.

On the other hand, women who have undergone kidney transplantation and have good renal function and are doing well otherwise can usually safely undertake pregnancy. Most antirejection drugs can be continued during the pregnancy, but mycophenolate mofetil (CellCept) is a notable exception.

Communication and Counseling

A critical aspect of caring for women of childbearing age who have lupus is maintaining a good open line of communication. Patients who think that their rheumatologist will discourage pregnancy often proceed anyway and may conceal information, sometimes with bad consequences. By seeing patients regularly and keeping communication channels open, you minimize the risk of women conceiving nonelectively or before they are healthy enough, and outcomes are better.

Two counseling strategies may be helpful here. The first is use of a simple traffic light metaphor in describing the likely safety of pregnancy. A green light means there is no reason why a woman can’t go through a pregnancy. A yellow light means that you have concerns but are going to work with her to achieve the best possible outcome; this is by far the most difficult area, and you have to decide whether you are comfortable dealing with it. A red light means the woman is not ready to conceive, and if she is pregnant, she should be counseled about termination.

The second strategy is use of a "light at the end of the tunnel" approach. With this approach, you work and bargain with the patient over time with the goal of eventually improving her health status to the point at which she can safely undertake pregnancy. This strategy requires you to maintain continued follow-up to ensure that the patient perceives that you are working with her to reach a stage where it is safe to undertake a pregnancy.

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