Successful Pregnancy with Lupus Requires Careful Monitoring, Study Reports

Pregnancy in patients suffering from systemic lupus erythematosus (SLE) can be complicated by a range of factors affecting both the mother and the fetus, and women with the disease were often advised against becoming pregnant. A research review from Yokohama City University Medical Center researchers, however, shows that optimal monitoring and treatment can improve the odds of a successful pregnancy.

The review, “Systemic lupus erythematosus: strategies to improve pregnancy outcomes,“ published in the International Journal of Women’s Health, explored evidence supporting optimal strategies during pregnancy for women with lupus who wish to conceive.

Even though lupus can impact the ovarian tubes, women with lupus are as fertile as anyone else. But studies have shown that disease activity at the time of conception largely determines how much complications during pregnancy a woman can expect. The more disease activity, the more problems, and doctors recommend that women should wait for six months of stable disease before attempting to become pregnant.

Complications during pregnancy affect both the mother and the fetus, and sometimes even the child after birth. Women with lupus are known to experience preeclampsia, fetal growth retardation, premature birth, and fetal loss more often than healthy women. Although the exact reasons for these complication elude scientists, it is clear that immune activation in the placenta, as well as antibodies against phospholipids, are likely contributors.

Considering the general hesitation of using drugs during pregnancy, it is natural that women with lupus often wish to stop using all drugs during a pregnancy. This is, however, not necessarily a good strategy, since the disease’s activation is even more likely to cause pregnancy complications. The balance physicians face when trying to maintain the health of the mother, while not exposing the fetus to toxic substances, is not an easy task.

Generally, non-steroid anti-inflammatory drugs (NSAIDS) are considered safe until the third trimester, when such drugs can trigger the premature closure of a blood vessel needed before the baby starts breathing air. Low-dose aspirin, often used to keep preeclampsia at bay, is also seen as safe, as are the antihypertensive drugs nifedipine, methyldopa, and hydralazine. But drugs blocking the angiotensin-converting enzyme and angiotensin II receptor blockers, also used to treat high blood pressure and kidney disease, can cause complications and birth defects, and should not be used.

The antimalarial drug Plaquenil (hydroxychloroquine) is encouraged throughout pregnancy, both for keeping lupus symptoms in check and because of its good safety profile. Glucocorticoids might increase the risk for lip cleft, growth retardation, and a premature rupture of membranes.

Most immunosuppressant drugs, including methotrexate and mycophenolate, can give rise to birth defects and are not allowed during pregnancy. Azathioprine is considered safer, but recent reports have suggested that the drug might be linked to developmental problems later in a child’s life. Also, drugs such as tacrolimus (brand names Prograf, Advagraf, Protopic)  and cyclosporine (Gengraf, Neoral, Sandimmune) seem to be acceptable. Biological drugs targeting TNF-alpha might be used in early pregnancy, but should be stopped before the third trimester.

What about the actual complications? Studies that explored disease activity during pregnancy tend to reach widely varying conclusions. This is likely caused, at least in part, by the fact that it might be difficult for a physician to see the difference between a lupus flare and preeclampsia, a  common complication characterized by high blood pressure.

Women who suffer lupus-related kidney disease are known to be at greater risk for complications both regarding their own health and that of their unborn child. These women are still recommended to avoid pregnancy until their disease has been in remission for at least six months, particularly since it might be difficult to distinguish between worsening lupus-related kidney disease and preeclampsia, making it more likely the wrong treatment is given. Most importantly, worsening kidney disease during pregnancy can lead to irreversible kidney damage.

Antiphospholipid syndrome is a common complication among pregnant women with lupus. The condition is characterized by blood clots, and often give rise to miscarriages and premature births. The condition can be treated with low-dose aspirin, and studies show that adding heparin might be even more beneficial. But all studies of the condition looked only at the syndrome, and did not include women with lupus.

The risk for complications does not end once the baby is born, as there is a greater risk for lupus flares soon after birth. Babies born to lupus mother also risk developing neonatal lupus, with symptoms of rash and heart block. Although this is a rare condition, affecting up to 2 percent of all children born to lupus mothers, women who had one child with the condition are more likely to other children likewise affected.

In babies, the rash usually resolves within a few weeks, but heart problems that might be found are more severe, leading to death in about 17 percent of all cases. Among surviving children, 70 percent will need a pacemaker before age 10. Such outcomes can be prevented to some degree. Heart block in the fetus can be diagnosed between 18 and 24 weeks of pregnancy, and drugs such as fluorinated steroids can reverse its development, preventing the child from acquiring the most severe form of the disease. Plaquenil was also recently shown to prevent heart block in women who previously had an affected child.

Overall, the review presents an argument that successful pregnancy is possible for women with lupus. However, controlling the disease activity, and making sure a woman is closely monitored by both a rheumatologist and an experienced obstetrician greatly improves the chances of an uneventful pregnancy, as does access to neonatal care in the event of complications affecting the newborn.