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Impact of pregnancy on the course of MS

Since the seminal study on pregnancy-related relapse rate in MS by the late Christian Confavreux and the PRIMS study group was published in 1998, several other studies on the impact of pregnancy on the disease on the course of MS have been carried out. The conclusions of these contemporary cohort studies have not changed significantly since then.

It has been well established that the relapse rate declines in the third pregnancy trimester, but increases during the first three months postpartum before returning to the pre-pregnancy rate.

In 2004 risk factors for postpartum relapse were identified in this PRIMS cohort. Disease activity in the year before pregnancy and during pregnancy were identified as risk factors for an increased postpartum relapse risk. However, despite the increased risk, almost three quarters of the women did not experience a clinical relapse postpartum.  

A recently conducted meta-analysis included 11 cohort studies including 2739 pregnancies, in order to assess the association between pregnancy and MS relapse activity.
A significantly increased relapse rate was demonstrated in the first 6 months postpartum in comparison with preconception rate. The incidence rate ratio (IRR) almost doubled in the first 3 months postpartum (1.87, 95% CI 1.40 to 2.50). Analysis of possible risk factors suggested that pre-conceptional Disease Modifying Therapies (DMTs) (IRR for highly effective DMTs 2.76, 95% CI 1.34 to 5.69) and exclusive breast feeding (risk ratio 0.39, 95% CI 0.18 to 0.86) significantly influenced postpartum relapse risk. 
Early studies did not include brain MRI as outcome. A recent study performed in the USA reported a significant association between active inflammation on MRI and disease activity.
Of seventy pregnancies with paired brain MRIs available, new T2 and/or Gd+ lesions postpartum occurred in 53%, compared with 32% pre-pregnancy (p < 0.001). Postpartum clinical relapses were associated with Gd+ lesions (p < 0.001). However, in 31% of patients without clinical disease activity postpartum, brain MRIs showed new T2 and/or Gd+ lesions.  

We can thus conclude that the higher postpartum relapse risk and increase in inflammatory disease activity on MRI has been clearly established. However, long-term effects of pregnancy on the disease on the course of MS remain more controversial. Indeed, earlier studies suggested a protective effect of pregnancy on MS, meaning that women who had at least one pregnancy demonstrated slower disability accumulation. However, these results have been challenged by recent studies. 

  Reassuringly, pregnancy does not influence long-term disease progression. 

In the context of the Barcelona CIS (clinically isolated syndrome) cohort, a cross-sectional survey was conducted to collect reproductive information of 501 female participants. In this cohort, menarche, pregnancies, and breastfeeding did not substantially modify the risk of developing clinically definite multiple sclerosis or disability accrual using a multivariable and time-dependent approach. The finding that pregnancy does not influence long-term disability accumulation was confirmed in the nationwide Danish MS registry, in which 425 parous women were compared with 840 nulliparous women. Time to reach EDSS 4 or 6 was not influenced by pregnancy. 

Contemporaneous cohort studies confirm the historical findings of increased relapse risk in the postpartum period. Reassuringly, pregnancy does not influence long term disease progression. This information can help to counsel women with MS who have a pregnancy wish. 

Dr. Barbara Willekens, UZA, Antwerp

The references of all the studies cited are available on request from the Belgian Charcot Foundation :
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