A proactive approach to reproductive planning that starts well before pregnancy and continues through to postpartum support can help women with multiple sclerosis (MS) achieve the family they want with the least impact on their disease.
“Where we’ve seen the field shift pretty dramatically is in trying to actually make recommendations for patients that are not based on fear, but that are based on evidence and shared decision-making,” said Riley Bove, MD, of the University of California San Francisco.
MS affects two to three times more women than men and usually strikes during the reproductive years, with diagnosis most common between the ages of 20 and 45.
Physicians no longer advise women with MS against having children out of concern for the potential effects of MS on their ability to conceive and care for a child as well as the impact pregnancy could have on their disease activity. The consensus now is that most women with MS can have safe pregnancies and healthy children.
“Pregnancy planning should not be an afterthought,” Bove said. “We want to encourage patients to have the families that they want and that they can have for other reasons. We really want to encourage active guidance and intentional, proactive conversations around how patients are feeling about childbearing and ideal timing for them, etc., and then to support this.”
Six months or a year of disease stability is ideal before pregnancy, making sure women are on prenatal vitamins, and have a plan in place before they become pregnant, she noted.
Pregnancy is a period of reduced MS activity, but risk of relapse spikes afterward. Cohort studies prior to 2004 had shown about one-third of women would relapse in the 3 months postpartum and up to half would have new MRI lesions, making it “the single highest risk time point over the course of MS,” Bove noted.
Risk of postpartum relapse has decreased over recent years to as low as 14% in modern cohorts, which a review by Bove and colleagues in the Lancet Neurology noted was “[p]ossibly due to improvements in sensitivity and earlier diagnosis of multiple sclerosis, and changing use of DMTs[disease-modifying therapies].”
Many women were, and still often are, taken off of DMTs due to a focus on possible teratogenicity, but it’s a tough balance to strike. While the S1P receptor modulators are contraindicated in pregnancy, for example, withdrawal of natalizumab (Tysabri), fingolimod (Gilenya), and possibly others in the class before or during pregnancy is associated with a particularly high risk of pregnancy-related relapse — more than 66% in one German study of natalizumab discontinuation.
“The biggest remaining issue is the use of immunotherapies during pregnancy, especially in women with an active disease course,” according to commentary on the review by Christoph Heesen, MD, of University Medical Center Hamburg Eppendorf, and Anne Christin Rahn, PhD, of the University of Lübeck, both in Germany.
“The only way to address these uncertainties and make preference-sensitive decisions is through shared decision-making,” they added. “Women with multiple sclerosis need to evaluate complex information, including the uncertainties concerning different options, and decisions need to be made based on their values, preferences, and attitudes towards risk.
That has been made even harder by a lack of information, Heesen and Rahn noted. “Typically, data on the use of immunotherapies in women who are pregnant are obtained by pharmaceutical companies and are often not systematically published.”
However, over the past 5 years, an increasing amount of safety data on drug exposure during both pregnancy and breastfeeding has been published. “Now, we have some nice data from several groups that really do show surprisingly little transfer … of medication into breast milk,” Bove said. “That work needs to continue.”
Exclusive breastfeeding has emerged as one way to reduce or delay postpartum relapses, Bove noted. Starting highly effective MS therapies early in the postpartum course is also very effective, she added.
The field “is really getting a better handle on how to manage MS before, during and after pregnancy,” Bove said. “The paradigm has shifted from risk avoidance to active treatment: informed and active treatment.”
Her group’s review paper suggested that proactive planning to reduce the risk of postpartum disease activity should ideally start before pregnancy, especially in women with active disease. “In these women, the preferred approach to reduce the risk of relapse both during pregnancy and postpartum is treatment with either depleting agents, such as monoclonal antibodies directed against CD20, or induction treatments, such as cladribine [Mavenclad] or alemtuzumab [Lemtrada] (with the caveat of alemtuzumab being considered by many as a third-line option due to risks) in advance of pregnancy, or continuing natalizumab through the third trimester.”
Bove emphasized that active management should encompass other non-medication aspects as well as support for pregnant persons with MS.
For example, women with MS should ideally be brought up to date on vaccinations, as certain MS therapies alter their effectiveness and make live vaccines contraindicated. Monitoring mood and energy is also important, Bove said, as women with MS face a higher risk of peripartum depression and fatigue.
In her practice, she sees patients in the seventh month of pregnancy to plan those needs — pre-ordering MRIs and labs, making sure insurance has approved their physical therapy and pelvic floor physical therapy, and arranging lactation support.
“It’s really, really, really challenging for them to do all the pieces they need to do postpartum because they’re dealing with a new baby,” she said. “Asking our MS community and our general neurology community to play an active role postpartum, making sure that patient’s needs are met, is really important.”