Reproductive Management in Multiple Sclerosis: Quick Takeaways for Your Practice

Multiple sclerosis (MS) affects approximately 3 times as many women as men, with the highest prevalence observed in women of reproductive age.¹ Counseling these patients about pregnancy-related concerns can be challenging due to the lack of consensus guidelines and the increase in MS treatment options in recent years.

While it is now well-established that having MS should not limit patients’ reproductive choices, this was not always the case. “At one time it was believed that having multiple pregnancies — or even one — could harm patients with MS, but this has not been found to be accurate,” Mary R. Rensel, MD, ABIHM, staff neurologist and director of wellness and pediatric programming at Cleveland Clinic’s Mellen Center for Multiple Sclerosis Treatment and Research in Ohio, told Neurology Advisor.

Several reviews have comprehensively addressed this topic, including one published in April 2018 in Neurology: Clinical Practice, which aimed to provide guidance to general neurologists regarding the specific needs of this population.² Evidence-based considerations relevant to each stage are highlighted below.

Pregnancy Planning

• MS does not appear to affect fertility or rates of spontaneous abortion, stillbirth, premature birth, Cesarean delivery, or birth defects.¹ Patients can also be assured that MS is not an inherited disease, although the risk for developing MS is slightly higher in individuals who have a first-degree relative with MS vs individuals who do not (0.13% vs 2% to 2.5%).¹
• In addition to basic counseling regarding the need for prenatal vitamins, adequate sleep and nutritional intake, and avoidance of alcohol and smoking, women with MS who are planning a pregnancy should be assessed for vitamin D deficiency and treated if indicated. A 2015 study found that women with MS had lower vitamin D levels during pregnancy and in the postpartum period.³
• Women should be counseled on contraceptive options prior to initiating disease-modifying therapy (DMT) as DMTs are generally considered not safe for use during pregnancy. Long-acting reversible contraceptive methods appear to have the highest efficacy and safety.⁴

“The main pre-pregnancy considerations for women with MS concern[s] starting and stopping medications — DMTs must be stopped for an appropriate period of time prior to a planned conception,” Barbara S. Giesser, MD, professor of neurology at the University of California, Los Angeles (UCLA), and clinical director of the MS program at UCLA, said in an interview with Neurology Advisor. “This is also true for most medications used for management of symptoms such as spasticity, pain, and bladder dysfunction.” She added that glatiramer acetate is an exception, which some neurologists allow their patients to use until pregnancy is confirmed.²

Pregnancy

• Pregnancy has not been shown to have a negative impact on long-term prognosis in patients with relapsing-remitting MS, who comprise the majority of pregnancies in patients with MS. Results of a 2012 study suggest that pregnancy may differentially affect patients with progressive MS.⁵ “For now, pregnant progressive MS patients should be managed like relapsing patients, and if possible entered into an ongoing pregnancy database,” wrote the author of a 2016 review.¹ In women with relapsing remitting MS, there is typically a decline in relapse rates during pregnancy, most notably in the third trimester.⁶ “Pregnancy tends to be a protective time for MS due to hormonal and immune system changes” such as increased estrogens, progesterone, and glucocorticoids, Dr Rensel explained.
• While magnetic resonance imaging (MRI) scans up to 3T have not conclusively been linked with fetal harm,⁷ imaging should be used judiciously during pregnancy. Gadolinium contrast should be avoided due to teratogenic effects demonstrated in animal studies.⁸
• A brief course of steroids may be considered for severe flares during pregnancy, although some evidence suggests that steroid exposure may cause cleft palate and transient neonatal immunosuppression during the first and third trimesters, respectively.⁹ “IV immunoglobulin (IVIg) is safe throughout pregnancy,” wrote Giesser and colleagues.² “Both steroids and IVIg can be used in place of DMT preconception and during pregnancy to prevent relapses.”
• Non-pharmacologic approaches should be used for symptom management, and vitamin D supplementation up to 2000 to 4000 IU daily can be continued during pregnancy.²
• When pharmacotherapy is deemed necessary, medication should be used at the minimum effective dose for the shortest possible duration.¹

Delivery and Postpartum

• MS status does not generally affect decisions regarding anesthetic options or delivery method. “Women with MS may safely have general or epidural anesthesia if needed,” Dr Giesser stated. “Some women with a sensory or motor deficit may need some mechanical assistance during labor and delivery.”
• There is an increased risk for relapse during the first 3 months postpartum, with the highest risk in women who had greater pre-pregnancy disease activity. The use of DMTs is not indicated during nursing and some patients may choose to forego breastfeeding or limit its duration so that they may start or restart DMT as soon as possible.
• MRI may safely be resumed following delivery.²

“Women with MS should not be discouraged from having a family if they so desire,” said Dr Giesser. “MS and the medications used to treat it can be managed appropriately before, during, and after pregnancy and delivery.”

References

1. Coyle PK. Management of women with multiple sclerosis through pregnancy and after childbirth. Ther Adv Neurol Disord. 2016; 9(3):198-210.
2. Kaisey M, Sicotte N, Giesser B. Multiple sclerosis management and reproductive changes: A guide for general neurologists. Neurol Clin Pract. 2018; 8(2):142-147.
3. Jalkanen A, Kauko T, Turpeinen U, Hämäläinen E, Airas L. Multiple sclerosis and vitamin D during pregnancy and lactation. Acta Neurol Scand. 2015; 131(1):64-67.
4. Committee on Gynecologic Practice. Committee Opinion No. 642: Increasing access to contraceptive implants and intrauterine devices to reduce unintended pregnancy. Obstet Gynecol. 2015; 126(4):e44-e48.
5. D’Hooghe M, Haentjens P, Nagels G, D’Hooghe T, Keyser J. Menarche, oral contraceptives, pregnancy and progression of disability in relapsing onset and progressive onset multiple sclerosis. J Neurol. 2012; 259(5):855-861.
6. Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T, Group tPiMS. Rate of pregnancy-related relapse in multiple sclerosis. N Engl J Med. 1998; 339(5):285-291.
7. Bove R, Klein J. Neuroradiology in women of childbearing age. Continuum. 2014; 20(1 Neurology of Pregnancy):23-41.
8. Chen MM, Coakley FV, Kaimal A, Laros RK, Jr. Guidelines for computed tomography and magnetic resonance imaging use during pregnancy and lactation. Obstet Gynecol. 2008; 112(2 Pt 1):333-340.
9. Houtchens MK, Kolb CM. Multiple sclerosis and pregnancy: therapeutic considerations.J Neurol. 2013; 260:1202-1214.