Multiple Sclerosis and Pregnancy
ABSTRACTS & COMMENTARY
Sources: Confavreux C, et al. Rate of pregnancy-related relapse in multiple sclerosis. N Engl J Med 1998;339:285-291; Whitaker JN. Effects of pregnancy and delivery on disease activity in multiple sclerosis. N Engl J Med 1998;339:339-340.
In this large, multi-center, prospective study by confavreux and colleagues, 254 women with multiple sclerosis (MS) in 12 European countries were monitored during 269 pregnancies and for 12 months post-partum. The rate of relapse per trimester and the score on the Kurtzke Expanded Disability Status Scale (EDSS) were determined and compared to the clinical attack rate the year before the pregnancy. The average age of patients was 30 years, 96% of whom were relapsing remitting MS patients with a baseline EDSS of 1.3 ± 1.4 (± SD) and rate of relapse before pregnancy of 0.7 ± 0.9. In comparison, the attack rate during the first trimester was 0.5 ± 1.3 (P = 0.03), 0.6 ± 1.6 in the second trimester (P = 0.17), and 0.2 ± 1.0 in the third trimester (P < 0.001). The relapse rate jumped significantly to 1.2 ± 2.0 in the initial three months post-partum (P < 0.001) and then returned to the prepregnancy rate. Although the EDSS worsened by 0.7 in 33 months of follow-up, there did not appear to be an acceleration in the post-partum period. Variables of breast-feeding and epidural analgesia did not have an adverse effect on the rate of relapse or progression of disability in MS.
COMMENTARY
Given the predominance of MS beginning in women of child-bearing age, the advice of the neurologist is frequently sought in decisions about pregnancy and childbirth. In the study by Confavreux et al, some helpful information may be obtained to counsel the patient. There was a highly significant reduction in the relapse rate during pregnancy-mainly in the third trimester. If the hormonal and immunologic mechanism(s) by which this occurs was understood (e.g., placental secretion of cytokines such as IL-10 that can down-regulate the immune response), it could have enormous therapeutic significance. Of concern in the post-partum period was a subsequent rebound increase in the relapse rate, which, for the patient, means a higher risk of an attack while she will be caring for the newborn.
Confavreux et al conclude that pregnancy did not accelerate the overall progression of the disease by increasing neurologic disability scores, which may be contrary to many clinicians anecdotal experiences. However, as Whitaker critically notes in his accompanying editorial, the 12-month, post-partum follow-up, with confirmed worsening at three months, are periods too short to be confident of an effect of pregnancy on disease progression. In addition, 78 patients required treatment with corticosteroids, cytotoxic immunosuppressives, or interferon-beta in the first six months post-partum, which is consistent with a more active disease process. This more aggressive therapeutic intervention might have forestalled an increase in the clinical disability scores for these patients. -BA
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