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Pregnancy Does Not Affect Long-Term Disability Accumulation in MS

Disease Spotlight | <b>Disease Spotlight: Multiple Sclerosis</b>

The cohort study was conducted using data from the Danish Multiple Sclerosis Registry for women with clinically isolated syndrome and relapsing remitting multiple sclerosis.

A recent cohort study using data from the Danish Multiple Sclerosis Registry (DMSR) found that pregnancy in women with clinically isolated syndrome (CIS) or relapsing remitting multiple sclerosis (RRMS) did not affect long-term disability accumulation.1

From the DMSR, investigators included a total of 1265 women. Within this group, 425 women became parous, tending to be younger and have a lower Expanded Disability Status Scale (EDSS) score at baseline, when compared with the 840 included women who remained nulliparous. 

Pregnancy was used as a time-dependent exposure, with data suggesting a nonsignificant association with time to reach an EDSS score of 4 (HR, 0.86 [95% CI, 0.61-1.20]; P = .39) and an EDSS score of 6 (HR, 0.70 [95% CI, 0.40-1.20]; P = .19) in a comparison of parous and nulliparous women. A slight change in HR was indicated by a dose-response association of having more than 1 child, but remained statistically insignificant (HR, 0.79 [95% CI, 0.48-1.29]; P = .35). Of the 425 parous women, 56 (13.2%) reached EDSS 4, compared to 179 (21.3%) of the 840 nulliparous women. Comparably, 20 parous women (4.5%) and 65 nulliparous women (7.9%) reached an EDSS score of 6. 

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“Our study is the first to present the association of parity and long-term disease accrual in women with MS using different statistical models to minimize bias,” first author Johanna Andersen, MSc, PhD student, DMSR, department of neurology, Copenhagen University Hospital, Denmark, et al wrote.1 “We found no evidence that parity influences the long-term disability accrual in women with MS.”

Investigators also evaluated a propensity score (PS) model, including the 425 parous women with a 1:1 matched cohort. Using this, no significant association was found with pregnancy on time to reach EDSS 4 (HR, 0.86 [95% CI, 0.57-1.31; P = .48) in the PS-matched cohort. Conventional Cox models were used to estimate HR for the EDSS 6 outcome, because 20 parous and 65 nulliparous women reached that score. 

Included patients were diagnosed with CIS or RRMS between January 1, 1997, and December 31, 2018, and all women without children at baseline, defined as date of diagnosis, were eligible for the study. Being between the age of 18-45 years at baseline, having and EDSS score less than 4 within 1 year of baseline date, a minimum of 2 follow-up EDSS records, and more than 1 year of follow-up time comprised the remainder of inclusion criteria. 

The study was limited in that only a small number of women (86 in total) reached EDSS 6. In addition, residual confounding from things such as comorbidities and smoking were advised not to be included. Limited available variables were included in the PS model, and EDSS presents limitations as an outcome due to inter and intra-rater reliability and sensitivity to change. Investigators noted that additional research is necessary to determine the association between disease development and immunological changes associated with pregnancy.

In another recent study performed in Italy, data from 2002 to 2008 were analyzed to determine the risk of long-term disability in 230 pregnant patients with MS and 102 non-pregnant patients with MS. Senior author Maria P. Amato, MD, director, Neurological Rehabilitation Unit, and professor of neurology, Careggi University Hospital, and colleagues found that over a follow-up period of 6.5 (±3.1) years, disability progression occurred in 87 women (26.2%) overall, 65 in the pregnant group (28.3%) and 22 in the control group (21.6%; P = .201). Investigators found that the risk of disability worsening was associated with relapse in pregnant women the year before conception (adjusted HR [aHR], 1.74 [95% CI, 1.06-2.84]; P = .027).2

In addition to previous relapses, disability worsening was associated with higher EDSS at baseline (aHR, 1.39 [95% CI, 1.12-1.74; P = .003), younger age (aHR, 0.95 [95% CI, 0.91-0.99]; P = .022) and shorter disease-modifying therapy (DMT) exposure over the follow-up period (P <.008). The risk of disability worsening for those in the pregnant group was also associated with the occurrence of relapses in the postpartum year (aHR, 1.85 [95% CI, 1.11-3.06]; P = .018), and, marginally, the occurrence of relapses in the year before conception (aHR, 1.61 [95% CI, 0.94-2.77]; P = .086). Investigators noted patients who had longer exposure to DMTs over the follow-up period had reduced risk of disability worsening (P <.010).

REFERENCES
1. Anderson JB, Wandall-Holm MF, Andersen PK, Sellebjerg F, Magyari M. Pregnancy in women with MS: Impact on long-term disability accrual in a nationwide Danish cohort. Mult Scler J. Published online November 18, 2021. doi:10.1177/13524585211057767
2. Portaccio E, Tudisco L, Pasto L, et al. Pregnancy in multiple sclerosis women with relapses in the year before conception increases the risk of long-term disability worsening. Mult Scler J. Published online June 16, 2021. doi:10.1177/13524585211023365