"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.
Many people living with the degenerative neurological disease multiple sclerosis (MS) are premenopausal women. This means clinicians will likely care for many patients with MS who are planning to be pregnant someday or are currently pregnant.
Historically, physicians discouraged women with MS from getting pregnant, but that changed with the publication of a landmark in 1998, which established that pregnancy does not worsen MS in the long term. Although many people with MS who are pregnant have a decrease in disease activity during pregnancy, they have an increased risk of relapse during the first 3 months postpartum.
In a 2022 , Ramón Villaverde-González, MD, of Hospital General Universitario José María Morales Meseguer in Murcia, Spain, noted that MS does not alter fertility and has no impact on fetal development, the course of pregnancy, or childbirth.
Best practices for management of women with MS call for regular, consistent communication with premenopausal patients about their fertility goals. Clinicians should keep up with evolving knowledge regarding the use of disease-modifying treatments (DMTs) before, during, and after pregnancy, and physicians who care for patients with MS may also want to develop a referral relationship with one or more trusted OB-GYN colleagues.
Establish Communication Early
A 2024 emphasized the importance of shared decision-making between clinician and patient. "Conversations about intent for family planning should happen at every visit and in the active decision-making phase should involve the patient's multidisciplinary team, including their neurologist, obstetric team, and primary physician," wrote Edith L. Graham, MD, of Northwestern University Feinberg School of Medicine in Chicago, and colleagues.
One thing to emphasize with patients with MS considering pregnancy is that most of today's DMTs are contraindicated during pregnancy and require a washout period due to their known and suspected teratogenic effects. It is important to educate patients on whether or not the specific DMT they are on is safe for use during pregnancy as some are not.
Many neurologists recommend that newly diagnosed patients receive a DMT immediately after diagnosis and that they should be stable on the drug for at least a year before attempting to conceive, based on evidence from the PRIMS study indicating that the level of disease activity in the year prior to pregnancy predicts the risk of postpartum relapse.
In conjunction with the widespread move from escalation therapy to early aggressive treatment, women who take a higher-efficacy treatment (HET) before conceiving may have less long-term disability: "Preconception use of DMTs whose pharmacodynamic effects outlast their pharmacokinetic effects (i.e., induction therapies and B-cell–depleting therapies) may reduce the incidence of relapses in the pre-pregnancy period while offering some protection from peripartum/postpartum relapses," Graham and co-authors said.
DMTs and Washout Periods
Exactly how long the washout period should be is still the subject of research. "HET seems to represent a particularly effective way of managing inflammatory activity before and after pregnancy," the team wrote. "It can therefore be expected that women with MS of childbearing potential will increasingly receive HETs as first-line therapy, and it is critical to educate clinicians about the safety of these medications during gestation and lactation."
Current FDA washout guidelines include the following:
- Monoclonal antibodies: alemtuzumab (Lemtrada), 4 months; ocrelizumab (Ocrevus), 6 months; ofatumumab (Kesimpta), 6 months; ublituximab (Briumvi), 6 months; and rituximab (MabThera; off label for MS), 12 months
- Sphingosine-1-phosphate (S1P) receptor modulators: ponesimod (Ponvory), 1 week; siponimod (Mayzent), 10 days; fingolimod (Gilenya), 2 months; ozanimod (Zeposia), 3 months
- Small molecules: oral cladribine (Mavenclad), 6 months; teriflunomide (Aubagio), until blood plasma concentration is <0.02 mg/L
- Large molecules: glatiramer acetate (Copaxone), none; and interferon beta, none
According to a , intravenous B-cell–depleting therapies may give prolonged protection against MS relapse for 6-9 months after administration of the last dose.
"When disease is highly active before initiation of B-cell–depleting therapy and it is necessary to minimize time off DMT, the patient may receive a B-cell–depleting therapy and then attempt pregnancy after 1 to 3 months," the authors wrote. "The rationale is that based on half-life, these therapies are eliminated 3.5 to 4.5 months after an infusion. Placental transfer of immunoglobulin G is minimal in the first trimester, so the risk of fetal exposure in the second trimester is low if conception occurs 3 to 6 months after the last dose of B-cell–depleting therapy."
B-cell–depleting monoclonal antibodies can also be used as bridge therapies to stabilize disease activity prepartum, peripartum, or postpartum for patients discontinuing fingolimod or natalizumab, the team added. "This underscores the importance of pregnancy planning discussions with patients throughout the MS management process."
Managing MS During Pregnancy
MS itself is not an indication that a pregnancy is high risk, but referral to or co-managing with a maternal-fetal medicine specialist can be important, especially since patients with MS may be on multiple medications for symptom management.
Folic acid and prenatal vitamins should be used as in all pregnancies, and vitamin D supplementation should be used in agreement with the patient's obstetrician. MRI during pregnancy after the first trimester is considered safe, but gadolinium enhancement should be avoided since it does cross the placenta.
The same vaccination schedule used for the general pregnant population applies here, said Villaverde-González. These vaccinations include inactivated influenza, inactivated diphtheria, tetanus, and acellular pertussis (Tdap), and mRNA COVID-19 vaccines.
People with MS are not limited to a specific type of obstetric anesthesia and no type is contraindicated due to the MS. Patients and obstetric providers should choose pain relief based on obstetric criteria.
The Possibility of Postpartum Relapse
Pregnancy does not appear to have long-term negative effects on the disease course of MS or its progression of disability, Villaverde-González said. "There is some evidence that pregnancy after MS onset could have a favorable long-term effect on the course of MS, as women who deliver one or more children after MS onset appear to have a slower disability progression than nulliparous women with MS."
"Whether pregnancy has a true protective effect on the MS course due to transient immunosuppression, or whether it represents a bias derived from female patients with milder MS being more inclined towards childbearing and causing those with more aggressive MS to avoid pregnancy, warrants further investigation," he wrote.
However, the short-term implications of pregnancy in MS are more complicated. Various studies have shown that about one-third of patients relapse in the first 3 months after delivery and about half do so in the first 6 months after delivery, although more recent studies have suggested a lower actual postpartum relapse risk.
Graham and colleagues said the main risk factors for postpartum relapse of MS include younger maternal age, higher number of relapses before and during pregnancy, higher preconception disability based on Expanded Disability Status Scale score, lack of preconception DMT use, and discontinuation of DMTs known to induce rebound disease activity.
Some clinicians administer IV corticosteroids or IV immunoglobulin to prevent postpartum disease relapses, although the clinical benefit remains unclear. Clinicians may want to consider postpartum physical therapy for pelvic floor rehabilitation in patients with MS and should closely monitor patients for postpartum depression, given that people with MS are more likely to experience depression than the general population.
A 2019 review in found a reduced rate of postpartum MS relapses among women who were breastfeeding compared with those who were not breastfeeding, and the benefit was stronger when women breastfed exclusively. The researchers concluded that breastfeeding was associated with a 43% lower rate of postpartum relapse, although they could not exclude the possibility of confounding factors.
Clinicians should not delay postpartum DMT resumption in women at elevated risk of active disease, Graham and colleagues emphasized.
"Women with MS may be able to breastfeed while on monoclonal antibody treatments, including ocrelizumab, natalizumab, and ofatumumab, with low risk to the infant. Monoclonal antibodies are detected at trace levels in milk and further are likely to be partially destroyed in the infant's gastrointestinal tract," the team wrote. "New data continue to support the use of anti-CD20 monoclonal antibodies during breastfeeding, with infants exposed to ocrelizumab and rituximab throughout breastfeeding showing normal growth and development with no unexpected severe or frequent infections."
Clinicians should consult the NIH's for detailed information about drugs and breastfeeding. The database includes information on the levels of drugs in breast milk and infant blood, and the possible adverse effects in nursing infants.
Read previous installments in this series:
Part 1: Early Diagnosis Can Mean Better Outcomes in Multiple Sclerosis
Part 2: How Does Multiple Sclerosis Start?
Part 3: The Deep and Multidimensional Connection Between Multiple Sclerosis and Depression
Part 4: Case Study: Sudden Blurred Vision in a Young Woman
Part 5: Early Aggressive Treatment May Work Best in Newly Diagnosed Multiple Sclerosis
Part 6: How Progressive Multiple Sclerosis Differs From Relapsing-Remitting MS
Part 7: The Challenge of Cognitive Changes in Multiple Sclerosis
Part 8: Case Study: What Is the Cause of This Right-Sided Numbness, Headache, and Blurred Vision?
Part 9: Improving Multiple Sclerosis Care for Black Patients