Multiple sclerosis (MS) is a lifelong neurologic disease affecting the central nervous system and resulting in demyelination and axonal loss over time. Symptoms are widely variable and often involve motor and sensory impairment, vision loss, gait disturbance, cognitive dysfunction, and fatigue. Furthermore, MS is a disease common to women of childbearing age, with 70% of patients being women and with 90% of patients presenting between the ages of 15 and 50.1 Family planning must be taken into account at time of diagnosis and when discussing which disease modifying agent to employ. Accurate knowledge and understanding of family planning issues is important for best outcomes.
The relationship between pregnancy and relapse outcomes is complex and might not be fully understood by many patients. Many studies have shown that pregnancy can have a protective effect against MS relapses, although the mechanisms underlying this phenomenon are still being studied. The Pregnancy in Multiple Sclerosis (PRIMS) study evaluated 227 women with MS from 1 year prior to pregnancy until 2 years after delivery and found that the risk for relapse decreased by about 70% during the third trimester but increased by twofold in the 3 months postpartum compared with the risk for relapse during the prepregnancy year.2,3 Furthermore, the long-term favorable effects of pregnancy on patients with relapsing-remitting MS have been established by several studies, demonstrating a lower risk for reaching an Expanded Disability Status Scale of 6.0 and thus a decreased possibility of needing an ambulatory device.4
Education about peripartum concerns is also paramount. In a study of 461 women with MS, there was a higher rate of caesarian section; however, these findings represented a concurrently higher rate of planned, rather than emergency, caesarian sections,5 a finding that might reflect an overly cautious approach. Previous practice advocated for caesarian sections to avoid pelvic floor trauma and thus exacerbation of preexisting urinary frequency and bladder control issues; however, it was shown in a study of 273 women in 2006 that urinary incontinence postpartum was more related to duration and severity of MS and not method of delivery.6
Similarly, accurate knowledge about environmental and genetic influences on MS is crucial for informed family planning considerations. Overall, MS is not considered a principally hereditary illness, and the risk for MS in the general population is approximately 0.1% compared with the risk in children of an affected parent, which is approximately 3%. For dizygotic twins, the risk for the second twin developing MS is about 4%, and for monozygotic twins the risk is about 30% over their lifetime.7,8 In terms of environmental risks, there was previous concern over use of oral contraceptives, which has been dispelled by studies showing both no effect and even possible association with a milder MS course. It is also important that women with MS and their offspring are not dissuaded from using oral contraceptives over concerns of developing MS.9,10
Furthermore, familiarity with pregnancy risks with MS disease-modifying therapies (DMTs) can lead to safe family planning practices. Current safety data is only based on animal studies and/or human observational cohorts and registries. Of the 13 approved medications, glatiramer acetate has shown no evidence to date of any danger to fetuses, but there is possible evidence for toxic effects with the other medications in animal and/or human studies, including known harm with teriflunomide in animal studies for which there is an absolute contraindication during pregnancy.11 Patients on certain DMTs must be aware that they might need to undergo a washout period prior to becoming pregnant. Moreover, it is equally important for women to know that it is safe to receive intravenous methylprednisolone (IVMP) for treatment of MS exacerbations during the second and third trimesters, and with caution during the first trimester. For breastfeeding women it is recommended to “pump and dump” for four hours after IVMP treatment.1,5,12
Use of DMTs then necessitates education about consistent contraception and safety while breastfeeding. For example, while there is no evidence that glatiramer acetate is absorbed into a newborn’s gastrointestinal tract to any significant degree, safety has not been established. There was one study of interferons and breast milk that showed that it is present in extremely small amounts,13 and natalizumab is detectable in breast milk but might not be absorbed by an infant. All three oral MS medications (fingolimod, dimethyl fumarate, teriflunomide) are known to be detectable in animal breast milk.11 In terms of relapse risk, the decision to breastfeed versus restarting MS therapy after delivery is complex, as patients must weigh increased risk for postpartum relapse off of therapy with the putative protective benefits of breastfeeding. However, exclusive breastfeeding typically requires a patient to remain off of DMTs, and thus the risks and benefits of these highly personal decisions must be made on an individual basis.14