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

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.