Rate of Pregnancy-Related Relapse in Multiple Sclerosis
Confavreux C, Hutchinson M, Hours MM, et al. NEJM. 1998;339(5):285–291
MS affects women of childbearing age. Prior to this study, it was suspected that there was a decreased rate of relapse during pregnancy and an increase in the postpartum period; however, these prior studies were small and some had reached different conclusions. This was the first large-scale prospective study to assess the effects of pregnancy on the natural history of MS.
This study aimed to investigate the natural history of MS in pregnant women. Specifically, the study was designed to determine the effect of pregnancy and the postpartum state on the course of the disease, along with that of breast-feeding and epidural analgesia.
Multicenter, prospective, observational study with recruitment from 1993 through 1995.
254 women (246 with relapsing MS) and 269 pregnancies. Each patient’s first pregnancy leading to a live birth was included for analysis, for a total of 227 pregnancies.
Patients were followed for at least 12 months postpartum. Women were followed during their pregnancies and for up to 12 months after delivery to determine the rate of relapse per trimester and the score on the Kurtzke Expanded Disability Status Scale (EDSS)
(range 0 to 10, with higher scores indicating more severe disability).
Outcomes measured included degree of disability and rate of relapse.
- The mean (±SD) rate of relapse was 0.7 ± 0.9 per woman per year in the year before pregnancy, it was 0.5 ± 1.3 during the first trimester (p = 0.03 for the comparison with the rate before pregnancy), 0.6 ± 1.6 during the second trimester (p = 0.17), and 0.2 ± 1.0 during the third trimester (p < 0.001).
- The rate significantly increased to 1.2 ± 2.0 during the first 3 months postpartum and then returned to the prepregnancy rate.
- Overall, compared to prepregnancy, annualized relapse rate fell by 70% during the third trimester.
- Neither epidural analgesia nor breast-feeding increased the risk of relapse or of worsening disability in the postpartum period. However, women who breast-fed their infants had a significantly lower rate of relapse than women who did not.
In women with MS, the rate of relapse declines during pregnancy, especially in the third trimester, and increases during the first 3 months postpartum before returning to the prepregnancy rate. The overall rate of disability progression does not change over the period studied.
At the time of publication, this was the largest prospective analysis on the natural history of pregnancy in MS published. Prior to this study, the influence of pregnancy on the course of MS was controversial, and many women with MS were discouraged from having children out of fear that pregnancy would worsen their disease course. After the publication of this study, the way in which women with MS were counseled about pregnancy changed dramatically.
The significant decrease in clinical attacks in later pregnancy has been confirmed in several prospective clinical trials. Since this trial, the 3-month period of increased risk postpartum has been a consistent observation. The most consistently identified markers associated with postpartum activity are high relapse rate in the year before pregnancy, higher disability level before pregnancy, and relapse during pregnancy.