Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse.
Vukusic S, Hutchinson M, Hours M, Moreau T, Cortinovis-Tourniaire P, Adeleine P, Confavreux C and the The Pregnancy In Multiple Sclerosis Group;
Commented by , 28 Jun 2004
Background
Multiple sclerosis (MS) is mainly affecting young females and counseling regarding pregnancy is therefore highly relevant. The PRIMS study (Confavreux et al., New Engl J Med 1998;339) showed that there is a decline in the relapse rate during pregnancy which is primarily observed in the third trimester, and a rebound increase in the first 3 months post partum. In the current study, the authors extended their observation of the same cohort of women for 2 years post partum.
Aim
To report the 2-year post-partum follow-up and to analyze factors predictive of relapse in the 3 months after delivery.
Methods
The authors studied 227 women who had full-term delivery of a live infant and who had MS for at least one year prior to conception. Kurtzke’s disability status scale (DSS) was assessed retrospectively 1 year prior to pregnancy, at the beginning of pregnancy and prospectively at entry to the study, at 36 weeks of gestation, and 3, 6, 12, 18 and 24 months post-partum. Paired two-sided t-test was used to compare relapse rate before, during and after pregnancy.
Univariate logistic regression was used to determine the effect of other clinical variables on relapse rate. 5 patients received disease modifying drugs in the 6-months period after delivery, and 11 patients in the following 6-months.
Results:
1. The reduction of relapse rate during pregnancy was most pronounced in the third trimester followed by an increase in the first trimester post partum (p<0,001).
2. From the second trimester post partum and onwards, the annualized relapse rate was not significantly different from the pre-pregnancy year.
3. 72% of the women did not experience a relapse in the first trimester post partum.
4. Confirmed disability progressed steadily during the whole study without any effect of pregnancy, delivery or postpartum period.
5. Factors that correlated significantly with a post-partum relapse were relapse in the pre-pregnancy year, relapse during pregnancy, and a high DSS.
6. The occurrence of a post partum relapse was not related to breast-feeding, epidural analgesia or other variables measured in the study.
7. A multivariate analysis predicted relapse in the first trimester after delivery in 72% of the women.
Discussion
The study confirms that pregnancy protects against MS relapses, most significantly in the last trimester of pregnancy, and that relapse rate increases in the first trimester post partum.
The study furthermore shows that relapse rate from the second trimester post-partum and onwards, is not significantly different from the pre-pregnancy relapse rate. This may encourage a more aggressive immunomodulatory intervention initiated right after delivery, possibly at the cost of interrupted breast-feeding.
Still, the authors conclude that confirmed disability increase is not determined by relapse rate during pregnancy, delivery or post-partum period, and only 28% of the women experience a relapse in the first trimester post partum despite the increased risk. These data suggest that development of disability is largely unaffected by relapses, and may argue for a more conservative and symptomatic therapeutic approach.
The authors were not able to predict relapses accurately post partum, although women with increased disability, and relapses before and during pregnancy had an increased risk.
A possible implication of the study is therefore an increased clinical attention and therapeutic intervention in this subgroup of patients. Whether treatment generally should be symptomatic or preventive in the post partum period is yet to be resolved in clinical trails.
References
Confavreux et al., New Engl J Med 1998;339