Pregnancy rates and outcomes in women with and without MS in the United States

Houtchens, Maria K.; Edwards, Natalie C; Schneider, G; Stern, Kevin; Phillips, Amy

doi:10.1212/wnl.0000000000006384

Cited by 83 publications

(96 citation statements)

References 30 publications

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“…Until just a few decades ago, women with MS were often advised to avoid pregnancy. In parallel with the introduction of more effective disease-modifying treatments (DMTs), earlier start of therapy due to revised diagnostic criteria using MRI (MRI), 1 and accumulated body of knowledge demonstrating no adverse effects in newborns of mothers with MS, pregnancy rates have been increasing in women with MS. 2 Still, the use of DMTs in pregnancy remains controversial, and the current guidelines are to discontinue DMTs before and during pregnancy unless the risk of disease worsening outweighs the risk to the fetus. 3 However, in practice, this is difficult to implement, given that comparative risk-benefit information concerning pregnancy for newer DMTs is lacking.…”

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confidence: 99%

Disease activity in pregnancy and postpartum in women with MS who suspended rituximab and natalizumab

Razaz

Piehl

Frisell

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo evaluate risks of disease reactivity during pregnancy and postpartum following rituximab (RTX) and natalizumab (NTZ) suspension in women with MS.MethodsAn observational cohort study of all women with MS disease onset before childbirth between 2006 and 2017. Women were identified through the Swedish MS Registry, a nationwide clinical register, with substratification into 3 groups: women who suspended RTX and NTZ within 6 months before conception and women who were not treated with any disease-modifying treatment (DMT) within 1 year of conception. The primary outcome was the annualized relapse rate (ARR) during pregnancy and 1 year postpartum.ResultsWe identified 2,386 women with MS onset before a live birth; of these, 76 women suspended RTX and 53 suspended NTZ, and 457 were untreated within 1 year before conception. In all women, regardless of the treatment type, the ARR declined from 0.05–0.04 prepregnancy to 0.03–0.02 during pregnancy, returning to prepregnancy rates at 3–6 months (0.05) postpartum. In the suspended cohort, 76% (98/129) of women resumed a DMT after delivery. The relapse rate 1 year postpartum was significantly higher in the suspended NTZ women compared with the suspended RTX women (adjusted rate ratio [aRR] 7.65, 95% CI 2.47–23.6) and was lower in the suspended RTX women compared with the untreated women (aRR 0.21, 95% CI 0.08–0.61).ConclusionDisease reactivity during the postpartum period was lower among women with MS who suspended RTX before pregnancy, relative to those who suspended NTZ and untreated women. These findings suggest that RTX may exert long-acting effects on MS disease activity that encompass pregnancy and postpartum periods.Classification of evidenceThis study provides Class IV evidence that in patients with MS who were on treatment before pregnancy, RTX reduces clinical disease activity compared with NTZ in the postpartum period.

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mentioning

confidence: 99%

Disease activity in pregnancy and postpartum in women with MS who suspended rituximab and natalizumab

Razaz

Piehl

Frisell

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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“… 3 , 4 Reproduction is an important consideration for women with MS, and over the past 20 years, pregnancy rates in patients with MS have been increasing. 5 Clinical disease activity is reduced in pregnancy, likely because of the immunotolerant state of pregnancy. 4 In the postpartum period, the clinical attack rate increases up to 3-fold, with up to one-third of women experiencing relapses.…”

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confidence: 99%

MRI activity in MS and completed pregnancy

Houtchens

Bove

Healy

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo evaluate postpartum MRI activity in patients with MS and a completed pregnancy and to compare these results to an age-matched untreated nonpregnant MS cohort.MethodsPatient with MS from a tertiary care MS center between 2006 and 2015, with prepartum and postpartum neurologic follow-ups and MRI scans were analyzed. Clinical activity and inflammatory brain MRI activity (new T2-hyperintense or gadolinium-enhancing [Gd+] lesions) were assessed peripartum. The results were compared with untreated reproductive-age patients with MS from the placebo arm of the clinical trials.ResultsA total of 123 pregnancies in 123 women (median Expanded Disability Status Scale 1.0) were analyzed. Approximately 7.2% relapsed during pregnancy and 48.7% relapsed postpartum. Of pregnancies with prepartum and postpartum gadolinium (Gd)-enhanced MRI (n = 112), 8% had Gd+ lesions prepartum and 33% had new Gd+ lesions postpartum. Overall, 54.4% had either new T2 or Gd+ lesions postpartum. Seventy-nine percent of subjects with postpartum relapse had new MRI activity compared with 37.1% without relapse (p < 0.001). Twenty-five percent had both clinical and radiographic activity and only 24.9% maintained no evidence of disease activity status postpartum. There was no association between postpartum MRI activity and disease-modifying treatments (DMTs) (p > 0.5). MRI and clinical outcomes were also assessed for 126 nonpregnant untreated female patients with MS. Comparing pregnancy and no pregnancy groups, there was no difference in MRI activity at follow-up.ConclusionsThere was a high level of inflammatory radiographic disease activity which was related to relapses in postpartum patients with MS. Further studies are needed to determine whether hormonal fluctuations vs extended time off DMTs may be the underlying cause of our observations.

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“…31 In contrast, other studies have found no differences in the risk of caesarean delivery, instrumental delivery or small neonates for their gestational age. 22,32 Previous studies have mainly focused on pregnancy outcomes related to a specific DMT, with some exceptions; a claims study by Houtchens et al found that women with MS had an increased rate of pregnancy compared with women without MS. 33 In contrast, we analysed the TFR, number of live births and rates of abortions and ectopic pregnancies using data from nationwide population-based registries with high validity and completeness. Some of the strengths of register-based studies are that the data are not dependent on memory or willingness to participate because all the data are mandatorily registered, thus avoiding selection and recall bias.…”

Section: Discussionmentioning

confidence: 99%

Reproductive history of the Danish multiple sclerosis population: A register-based study

et al. 2019

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Background: A diagnosis of multiple sclerosis (MS) may impact the choice of parenthood. Objective: To investigate the number of live births, abortions and ectopic pregnancies among persons with MS. Methods: From the Danish Multiple Sclerosis Registry, we extracted data from all persons diagnosed with MS from 1960 to 1996 and matched each MS person with four reference persons. We used a negative binomial regression model for the live births and Poisson regression model for abortions and ectopic pregnancies. The total fertility rate (TFR) during 1960–2016 and the annual number of live births in the MS population were analysed. Results: Persons with MS had fewer children than reference persons. Fewer women with MS had elective abortions after diagnosis (incidence rate ratio (IRR) = 0.88; 95% confidence interval (CI) = 0.78–1.00) than reference persons. There was no difference regarding the number of elective abortions, spontaneous abortions or ectopic pregnancies after onset. The TFR was lower for women with MS than for reference persons, and the number of annual live births by MS persons increased during 1960–2016. Conclusion: MS seems to considerably impact reproductive choices, especially after clinical diagnosis, resulting in the MS population having fewer children than the general population.

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Pregnancy rates and outcomes in women with and without MS in the United States

Cited by 83 publications

References 30 publications

Disease activity in pregnancy and postpartum in women with MS who suspended rituximab and natalizumab

Disease activity in pregnancy and postpartum in women with MS who suspended rituximab and natalizumab

MRI activity in MS and completed pregnancy

Reproductive history of the Danish multiple sclerosis population: A register-based study

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