A Real-World Prospective Multiple Sclerosis Pregnancy Registry in the United States: PREG-MS.

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Abstract

Background and objectivesMultiple sclerosis (MS) affects more than 1 million people in the United States, including reproductive-age women. There has been a paucity of prospective, pregnancy registries based on MS disease rather than medication exposures. A prospective MS pregnancy registry (PREG-MS) was established in 2017 as a prospective, single-cohort, real-world MS pregnancy registry in New England States of the United States, with goals to evaluate (1) course of MS and disease-modifying therapies (DMT) use during conception attempts and in the peripartum period, (2) pregnancy outcomes in women with MS (WwMS), and (3) longer-term developmental outcomes in offspring of WwMS.MethodsBetween 2017 and 2020, PREG-MS recruited from 11 preselected academic and community MS centers and followed WwMS and their children from conception attempts and any pregnancy trimester, up to 3 years of postpartum. Comprehensive neurologic, obstetric, and pediatric development information was collected through telephone interviews and medical records.ResultsOne hundred forty-six patients were enrolled between 2017 and 2020; there were 122 pregnancies from 135 participants, and 105 infants were born on study. 24.6% pregnancies were unplanned; 14.1% had an infertility diagnosis. Assisted reproductive technologies were used by 12.6%. 54% of pregnancies were designated as "high-risk", and ∼40% had peripartum obstetrical complications with 17% adverse pregnancy outcomes. Mean baseline Expanded Disability Status Scale was 1.09 ± 0.84. ∼85% were treated with DMTs up to the time of conception. 19.7% had 1 or more relapses within prepregnancy year, correlating with increased duration of conception attempts (p < 0.0001). 12% had intrapartum, and 24.5% had postpartum relapses. Any fertility treatments predicted intrapartum relapses independent of DMT status (OR 5.18, 95% CI 1.58-17.02, p = 0.007). 33.6% were exposed to DMTs in pregnancy. Intrapartum relapses (p = 0.008) and high-risk pregnancy (p = 0.036) were associated with postpartum exacerbations.DiscussionOur real-world, prospective, nondisabled MS pregnancy cohort had a sizable proportion of participants with clinical disease activity in the prepartum and intrapartum period, despite high-DMT utilization prepartum. A greater-than-expected number of participants were considered to have high-risk pregnancies and reported peripartum complications. The use of any fertility treatments was independently predictive of intrapartum relapses, supporting hormonal-immune interactions as disease modulators in MS. Larger prospective, longitudinal registries are needed to confirm our findings.Trial registration informationClinical trial registration number: NCT03368157.
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Abstract

Background and Objectives Multiple sclerosis (MS) affects more than 1 million people in the United States, including reproductive-age women. There has been a paucity of prospective, pregnancy registries based on MS disease rather than medication exposures. A prospective MS pregnancy registry (PREG-MS) was established in 2017 as a prospective, single-cohort, real-world MS pregnancy registry in New England States of the United States, with goals to evaluate (1) course of MS and disease-modifying therapies (DMT) use during conception attempts and in the peripartum period, (2) pregnancy outcomes in women with MS (WwMS), and (3) longer-term developmental outcomes in offspring of WwMS.

Methods

Between 2017 and 2020, PREG-MS recruited from 11 preselected academic and community MS centers and followed WwMS and their children from conception attempts and any pregnancy trimester, up to 3 years of postpartum. Comprehensive neurologic, obstetric, and pediatric development information was collected through telephone interviews and medical records.

Results

One hundred forty-six patients were enrolled between 2017 and 2020; there were 122 pregnancies from 135 participants, and 105 infants were born on study. 24.6% pregnancies were unplanned; 14.1% had an infertility diagnosis. Assisted reproductive technologies were used by 12.6%. 54% of pregnancies were designated as “high-risk”, and ∼40% had peripartum obstetrical complications with 17% adverse pregnancy outcomes. Mean baseline Expanded Disability Status Scale was 1.09 ± 0.84. ∼85% were treated with DMTs up to the time of conception. 19.7% had 1 or more relapses within prepregnancy year, correlating with increased duration of conception attempts (p < 0.0001). 12% had intrapartum, and 24.5% had postpartum relapses. Any fertility treatments predicted intrapartum relapses independent of DMT status (OR 5.18, 95% CI 1.58–17.02, p = 0.007). 33.6% were exposed to DMTs in pregnancy. Intrapartum relapses (p = 0.008) and high-risk pregnancy (p = 0.036) were associated with postpartum exacerbations.

Discussion

Our real-world, prospective, nondisabled MS pregnancy cohort had a sizable proportion of participants with clinical disease activity in the prepartum and intrapartum period, despite high-DMT utilization prepartum. A greater-than-expected number of participants were considered to have high-risk pregnancies and reported peripartum complications. The use of any fertility treatments was independently predictive of intrapartum relapses, supporting hormonal-immune interactions as disease modulators in MS. Larger prospective, longitudinal registries are needed to confirm our findings. Trial Registration Information Clinical trial registration number: NCT03368157. Get full access to this article View all available purchase options and get full access to this article.

References

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Pregnancy, delivery, and birth outcome in women with multiple sclerosis. Neurology. 2005;65(12):1961-1963. Information & Authors Information Published In Neurology® Clinical Practice Volume 15 • Number 2 • April 2025 eLocator: e200425 Copyright © 2025 American Academy of Neurology. Publication History Received: April 3, 2024 Accepted: October 10, 2024 Published online: January 10, 2025 Published in issue: April 2025 Disclosure Disclosures will be provided separately, by each contributing author. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp. Study Funding Unrestricted Investigator-initiated grant from Sanofi Genzyme; Philanthropic donation by Michele LeMay Foundation. Authors Metrics & Citations Metrics Citation information is sourced from Crossref Cited-by service. Citations Download Citations If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download. Cited By - The Lithuanian multiple sclerosis registry: current framework and quality challenges, Frontiers in Neurology, 17, (2026).https://doi.org/10.3389/fneur.2026.1728596 - Multiple Sclerosis Relapse Treatment During Pregnancy and Offspring Functional and Structural Neurodevelopment, Neurology, 105, 9, (2025)./doi/10.1212/WNL.0000000000214217 - Four years on: Pregnancy and birth outcomes reported in the MSBase pregnancy, neonatal outcomes, and Women’s Health Registry (2020–2024), Multiple Sclerosis Journal, 31, 9, (1088-1101), (2025).https://doi.org/10.1177/13524585251349125 Loading... View Options Login options Check if you have access through your login credentials or your institution to get full access on this article. 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