Pregnancy in Multiple Sclerosis - Multiple Sclerosis Centers of Excellence
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Pregnancy in Multiple Sclerosis

Jacqueline Bernard, MD, FAAN -- Portland, OR

MS affects women nearly three times as often as men, and often presents during childbearing years, making pregnancy issues very important for people living with MS. Questions around pregnancy and MS are a common part of our patient-physician conversations.

Impact of Pregnancy on MS

Since MS is usually diagnosed in individuals between the ages of 20-40, the impact of pregnancy on MS is an important clinical concern. Fortunately, MS is typically least likely to relapse during pregnancy. Several reasons probably account for this, likely due to basic immunological mechanisms thought to be protective for a developing fetus. This is seen with some other autoimmune diseases such as psoriasis and rheumatoid arthritis. The hormonal changes accompanying pregnancy, such as increasing levels of estradiol and estriol, actually peak in the third trimester, and these correlate with decreased risk of MS activity during this time by as much as 70%.1 So, although these changes likely are meant to protect the developing baby, these changes are also protective for the mother.

Another consideration for women with MS planning pregnancy may include concerns about fatigue, a very common symptom for any expectant mother. Fatigue is also one of the most common symptoms of MS. In non-pregnant women with MS, numerous medications can be used to manage fatigue, but these are not considered safe during pregnancy. It is important to allow for adequate rest, and pay close attention to overall health during pregnancy, in order to combat fatigue. Watching for urinary tract infections as well as preventing pregnancy-associated anemia by taking prenatal vitamins with iron supplementation are some practical ways to reduce pregnancy-associated fatigue which may compound MS fatigue.

Over the longer-term, people with MS may wonder about the impact of the number of pregnancies on their MS progression. The studies thus far do not show general worsening of an individual’s overall MS course based on number of pregnancies. Additionally, one study showed that having one or more pregnancies was associated with a lower risk of developing MS than having no pregnancies at all. While this is only one study, this is encouraging for women with MS who are involved in family planning, but of course is not a sustainable treatment for MS and does not substitute for disease-modifying treatments (DMTs).

For those who do experience relapse during pregnancy, intravenous steroids (methylprednisolone ) or intravenous immunolobulin (IVIG) can be used. Coordination of care between the treating neurologist and OB/GYN is important should this occur.

Impact of MS on Pregnancy

The prevalence of impaired fertility in the US is approximately 10-15%, and the number is similar for people with MS. People with MS who do experience infertility may need to use assisted reproductive technology (ART), and these approaches can be associated with a slight, temporary increased risk of relapse.

People with MS do not have an increase in pregnancy complications due to MS, such as premature delivery. In general, there is no evidence of an association between maternal MS and adverse effects on fetal development. Some people with more progressive MS may experience sexual dysfunction which could lead to impaired fertility, and this may require more specific management with counseling and possibly physical therapy and/or medications.

Since unplanned pregnancies do occur, it is important for people with MS to also know that there is no evidence for any negative impact from use of contraceptives on MS disease course. For many, use of long-acting reversible contraceptives (LARC) such as IUDs are particularly helpful, since the risks of non-compliance are reduced and this results in fewer unintended pregnancies. In general, any form of contraception is safe for people with MS and is an important topic to be discussed with either a primary care provider or OB/Gyn.

Impact of Disease-Modifying Treatments (DMTs) on Pregnancy

Currently, there are over a dozen FDA-approved DMTs for MS in the US. These range from moderately to highly effective, each with unique potential adverse effects with regard to pregnancy and variable recommendations for stopping prior to attempts at conception due to mechanisms of action.2 Given the risk of unplanned pregnancy in the general population, discussions regarding choice of a DMT must be done in parallel with family planning discussions with both women and men with MS.

Pregnancy planning discussions should ideally start at least 6 months before attempts at conception so neurologic assessment of stability and specific recommendations for stopping DMTs can be made based on known risk guidelines. Previously, no DMTs were felt to be safe during pregnancy, based on FDA pregnancy and lactation risk designations. These include A): no evidence of fetal harm in human studies; B): no evidence of fetal harm in animal studies; C): evidence of fetal harm in animal studies or no data available; D): evidence of fetal harm in humans; and X): evidence of fetal harm in humans; not indicated for use in pregnancy.

Fortunately, at least one DMT is considered pregnancy category B (glatiramer acetate), and in fact the European Committee for Treatment and Research in MS (ECTRIMS) guidelines recommend use of glatiramer acetate (GA) or Interferon 1-B until pregnancy is confirmed. Additionally, all of the FDA approved DMTs maintain pregnancy registries, and data is available for review.

There are recent reports of MS relapses occurring during pregnancy after stopping highly-effective MS DMTs, such as fingolimod and natalizumab, adding to the complexity of making the right individual decision about DMT selection. Ultimately, the decision of which DMT to start, and then to either stop DMT or continue throughout pregnancy, needs to be made based on considerations of how active MS is in any particular individual in the context of risk vs benefit, both to mother and baby.

Having an appropriate vitamin D level likely reduces the risk of MS relapses in mothers with MS and the risk of developing MS in their offspring.3 A recent study showed that offspring of mothers with low vitamin D levels during their pregnancy had an increased risk of developing MS compared with children born to mothers with non-deficient levels.

Breast-Feeding and Post-Partum Considerations

Typically, the benefits of pregnancy with regard to the lower MS relapse rate rapidly diminishes postpartum, with risk of MS relapse peaking at around 3-6 months after delivery. There is not sufficient consistent evidence currently that supports not resuming DMT in that time frame in women with MS, particularly those with very active disease. Additionally, the FDA recommends not using DMT while breast feeding (see lactmed.org). Since DMTs are variable in how quickly a therapeutic benefit occurs after resuming these medications, patients and physicians should be prepared early by discussing how and when to restart medications before delivery.

Often, an MRI will help guide these discussions because MRI can provide information about how active MS disease is post-partum. Since gadolinium is contraindicated during pregnancy and lactation, non-contrast studies can be done. If a contrast study is desired post-partum, during lactation, women with MS need to “pump and waste” their breast milk for 24 hours after gadolinium exposure, to reduce any risk to the infant, although only a small amount of gadolinium would be measurable in breast milk. Timing of post-partum MRI should be based on clinical status of the mother, as well as breast-feeding and family planning goals, but would be urgently indicated if an acute relapse occurs.

References

  1. Voskuhl R, Momtazee C. Pregnancy: Effect on MS, Treatment Considerations, and Breastfeeding. Neurotherapeutics. 2017 Oct;14(4):974-984.
  2. Coyle PK, Oh J, Magyari M, Oreja-Guevara C, Houtchens M. Management strategies for female patients of reproductive potential with MS: An evidence-based review. Mult Scler Relat Disord. 3019 Apr 5;32:54-63.
  3. Munger KL, Åivo J, Hongell K, Soilu-Hänninen M, Surcel HM, Ascherio A. Vitamin D status during pregnancy and risk of MS in offspring of women in the Finnish maternity cohort. JAMA Neurol. 2016 May 1;73(5):515-9.

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