Improving Outcomes of Lupus Pregnancies
- Intravenous immunoglobulin therapy in pregnant patients affected with systemic lupus erythematosus and recurrent spontaneous abortion
Rheumatology, Volume 47, Number 5, May 2008, pp. 646-651
What is the topic?
Although most women with lupus will have successful pregnancies, serious complications can occur in some cases, perhaps none more devastating than the loss of the baby. In fact, some women with lupus have consecutive miscarriages, a condition known as recurrent spontaneous abortion (RSA).
Immunglobulins (Ig) are antibody proteins that circulate in the blood. Intravenous immunoglobulin infusion (IVIg) is a medical treatment in which immunoglobulin is administered intravenously. It has been approved as a treatment for several autoimmune diseases, and has been used off-label as a treatment for lupus, as well as for high-risk pregnancies.
What did the researchers hope to learn?
Despite the successful use of IVIg for both autoimmune diseases and high-risk pregnancies, there were no reports of IVIg use for women with lupus who had a history of RSA. A research team in Rome designed this study to learn about the potential benefits and risks of IVIg for those women -- if it improved their chances of successfully completing their pregnancy, and how it affected the lupus disease activity.
Who was studied?
The researchers followed 24 pregnant women with lupus, all of whom had at least three consecutive pregnancies that resulted in miscarriage, thus meeting the definition of RSA. All of the women were Caucasian, and their average age was just under 35 years old. By the time of their pregnancies the women had a history of a variety of lupus symptoms and organ involvement (i.e., arthritis, fever, malar rash, blood disorders, neurological involvement, kidney disease, antiphospholipid antibodies); however, none of them were experiencing a disease flare at the time they enrolled in the study. The women all were taking some medication, either steroids or NSAIDs (non-steroidal anti-inflammatory drugs); one patient also was being treated with azathioprine (AZA), an immunosuppressant.
How was the study conducted?
The 24 patients were divided into two groups of 12, who were similar in their lupus symptoms and disease activity. Once their pregnancies were confirmed, one group of 12 women received IVIg treatments every three weeks up until the 33rd week; they were not given any other medications during their pregnancy. Participants in the second group were treated with prednisone or aspirin, which was halted at the 34th week of pregnancy; one woman in this second group who had been taking AZA before the study began had the AZA therapy resumed during her pregnancy owing to flares. Four of the women in the group receiving IVIg treatment also were diagnosed with APS, antiphospholipid syndrome.
Lupus disease activity scores were recorded at the beginning of each pregnancy, before the first IVIg treatment, and then after each IVIg infusion. Blood tests, urine samples, and other lab measures were taken at the beginning and end of the study, and at 12-week intervals during the pregnancy for each of the patients; these tests included measurements of different antibodies and complement factors associated with lupus.
What did the researchers find?
IVIg therapy was found to be both safe and effective for this group of women who had lupus and RSA. All 12 of the women receiving IVIg therapy successfully completed their pregnancies. Nine of the pregnancies in this group were full-term (at least 36 weeks). Eleven of the 12 babies were delivered via Caesarian section. Their average weight was 7 lb., 3 oz., and no sign of illness or disease was noted in any of the newborns. The women in this group also showed reductions in their lupus symptoms from the beginning to the end of their pregnancies, and these reductions were reflected in improved disease activity scores after IVIg therapy. Antibody levels (anti-dsDNA, anti Ro/SS-A, ANA, anticardiolipin) also tended to improve, except for lupus anticoagulant (LAC), which remained unchanged. One woman receiving IVIg treatment developed mild hypertension, which did not interfere with the pregnancy; the researchers attributed the hypertension to the woman’s obesity, not to the study medication.
In contrast, among the 12 women who were treated with prednisone or aspirin, three spontaneous abortions occurred, at weeks 7, 11, and 23. Of the nine pregnancies that resulted in live births, four were full-term. Six of the deliveries were via Caesarian section, three as a result of spontaneous delivery. Average weight of the nine babies born in this group was 7 lb., 1.5 oz., and none of the newborns in this group showed signs of illness. Clinical improvements in lupus symptoms and antibody levels were significantly less than those shown in the IVIg group; one of the women had to receive additional treatment for flares. Lupus disease activity scores in this group were not significantly reduced, and in three cases the scores were poorer at the end of the pregnancy than at the beginning.
What were the limitations of the studies?
The primary limitations of this study were its size (only 24 patients) and the fact that all of the women were Caucasian (and probably Italian). Larger studies involving women with lupus from a variety of ethnic and racial groups need to be conducted to further validate these encouraging findings about IVIg as a safe and effective treatment for women with lupus who have been unable to sustain pregnancies. Larger studies could also help determine if there are clinical or demographic characteristics that affect the response to IVIg; for instance, does IVIg work equally well for African American women with lupus nephritis as for Caucasian women with lupus arthritis, or for women who were diagnosed with lupus during childhood or adolescence than for those diagnosed later as adults?
What do the results mean for you?
For women with lupus who become pregnant or intend to, the improvements noted with IVIg therapy in this study are very promising. For those who have experienced multiple miscarriages, IVIg may help increase their odds of having a successful pregnancy and delivering a healthy baby. Encouraging as these findings are, however, it should be noted that IVIg is both expensive and in very short supply. At current production levels, it may not be easy to provide IVIg therapy to all of those who might benefit from its use.
Also of note, even most of those with the conservative treatment were able to deliver babies, so having had RSA previously does not necessarily mean the next pregnancy will fail.