vitamin D3 -

Opinion on how MS impacts pregnancy is based largely on data that predate the current era of active treatment and the newer generation of disease-modifying therapies (DMTs). In this section I have therefore addressed many of the important issues that women who are considering pregnancy need to understand, including:

the effect of pregnancy on the course of MS
how to manage relapse during pregnancy
the role of naturally occurring interferon-beta and its possible implications for women with MS taking therapeutic interferon-beta
management of MS symptoms and morning sickness during pregnancy
the crucial issue of DMT safety and possible teratogenic effects on the developing foetus.

Will pregnancy affect the course of my MS?

Yes, pregnancy effects on MS have been observed at a group level, though it is difficult to notice changes in individuals. It is well known that MS attack rates drop during the second and third trimesters of pregnancy and relapses rebound again in the first 6 months after delivery. However, only a minority of women with MS have post-partum relapses. Breastfeeding may blunt the post-partum rebound, but this is not absolute. Therefore, most neurologists now recommend starting or restarting DMTs soon after delivery to try and prevent post-partum relapses.

At a population level, the more children you have, the better your overall prognosis. This effect is small and is based on studies done in the pre-DMT era. It may be due to the immunological effects of pregnancy that work like a DMT in MS. Immunologists have tried to understand this phenomenon in the hope of developing treatments for MS that mimic the pregnancy state.

How is a relapse managed during pregnancy?

In the event of having a relapse during pregnancy, a short course of high-dose corticosteroids can be considered. However, I limit using steroids to disabling and/or severe relapses, especially early in the first trimester, as there is a small risk of orofacial abnormalities (cleft lip and palate) and reduced birth weight from exposure of the developing foetus to high-dose steroids. There is also a risk of precipitating gestational diabetes in women receiving high doses of steroids during pregnancy. In the rare situation of a severe relapse unresponsive to high-dose steroids, plasma exchange may need to be considered.

Could neutralising antibodies to therapeutic interferon-beta affect my baby?

Naturally occurring interferon-beta is a cytokine (cell-signalling agent) produced by the body to help fight infections. As there is only one human interferon-beta, antibodies to therapeutic interferon-beta (IFN-beta) will neutralise the body’s own natural interferon-beta. If you are taking IFN-beta for your MS, there is thus a theoretical risk that neutralising antibodies (NABs) to the DMT might cross the placenta and affect the role of human interferon-beta in foetal development.

Interferon-beta is important for innate immunity and neutralising your own interferon-beta may put you at risk of getting viral infections. Interferon-beta also plays a role in foetal bone development, but the placenta does not mature in relation to immunoglobulin transfer until near the end of the second trimester of pregnancy, so it is unlikely that sufficient NABs cross the blood ̶ placental barrier to affect foetal bone development. However, in the third trimester, NABs will cross over the placenta into the foetal circulation and may impact the baby’s innate immunity. Despite these theoretical concerns, there is no indication from published data to support these potential adverse effects of NABs on IFN-beta.

If I fall pregnant while on a DMT, will this affect the baby?

This depends on which DMT you are taking and what you mean by ‘affecting the baby’. We worry most about teratogenic effects, which describe congenital malformations. Teriflunomide, S1P modulators and cladribine are generally classified as drugs that may be teratogenic, and hence precautions need to be taken so as not to fall pregnant on these agents. Foetal malformations usually occur very early in foetal development, often before the woman knows she is pregnant; therefore, it is difficult to do anything about it once foetal exposure occurs. Despite this, even for women who are on these agents and fall pregnant, we don’t automatically recommend termination of pregnancy. We refer them to the high-risk pregnancy clinic to discuss the options with an obstetrician. Many women continue their pregnancies with an uneventful outcome and a normal baby. On the other hand, some women choose the option of terminating their pregnancy.

A large amount of data from MS pregnancy registries and post-marketing surveillance indicates no increased risk of major congenital anomalies or spontaneous abortions (miscarriages) after exposure to interferon-beta or glatiramer acetate. Most neurologists are, therefore, comfortable with their female patients falling pregnant on these agents, continuing the treatment through pregnancy and then breastfeeding their babies.

Fumarates (dimethyl fumarate [Tecfidera], diroximel fumarate [Vumerity]) are not teratogenic and are unlikely to have a negative impact on pregnancy outcomes. We need more data from registries and post-marketing surveillance before we can be confident that the fumarates are safe during pregnancy. However, these agents are prodrugs and converted to monomethyl fumarate, which is part of our metabolism, so it is very unlikely that the fumarates will cause problems. I don’t have an issue with women falling pregnant on the fumarates and continuing them through pregnancy, but there is conflicting advice about this.

Should I continue taking drugs for my MS symptoms during pregnancy?

Yes and no. It depends on what the medications are for and whether they are safe during pregnancy. Ideally, you should wean off any symptomatic therapies or at least change to alternative medications that are safe to take during pregnancy. It is important to try and plan your pregnancy and if necessary be referred to a special medical pregnancy clinic so that these issues can be addressed. Many women with MS find that their MS-related symptoms improve during pregnancy, and they can do without symptomatic therapies. However, unless you are prepared to wean yourself off symptomatic therapies you won’t know.

Physical therapies should be continued during pregnancy. One could argue that everyone with MS should be physically active and do pelvic floor exercises. Pregnancy and childbirth may impact bladder and bowel function, so it is important to see a pelvic floor therapist to start pelvic floor exercises. The latter are taught to women in antenatal classes.

How do you treat morning sickness or hyperemesis gravidarum during pregnancy?

Treating morning sickness or hyperemesis gravidarum is no different in women with MS than in the general population. It involves hydration, vitamin supplements (in particular, thiamine) and the judicious use of antiemetics (for example, cyclizine, prochlorperazine, promethazine, chlorpromazine, metoclopramide and domperidone). If the vomiting extends into the second trimester, ondansetron can be used. In very severe cases of morning sickness, steroids may be required; for example, hydrocortisone 100 mg twice daily can be converted to prednisolone 40 ̶ 50 mg daily by mouth, which can then be tapered to the lowest level that still controls symptoms. For patients taking a fumarate, try and take your medication later in the morning when you are less likely to vomit.

What dose of vitamin D do you advise during pregnancy?

During pregnancy vitamin D requirements are increased and I recommend doubling the dose for supplementation from 4,000 IU of vitamin D3 to 8,000 IU per day. At the same time, women who are pregnant should be on iron and folate supplements that should ideally be started before falling pregnant.

References

Krysko KM et al. Treatment of women with multiple sclerosis planning pregnancy. Curr Treat Options Neurol 2021;23:11.

Other articles in this series on Pregnancy and childbirth
Planning for pregnancy
Preparing to give birth
Breastfeeding if you are on a DMT
Concerns about parenting

Being disabled or unemployed because of MS does not mean you cannot be a good parent. Here I cover some of these practical considerations as well as the steps you can take to reduce the potential risk of your child developing MS.

Can I be a good parent if I become disabled from my MS?

This is difficult to answer and depends on how disabled you are, the nature of your disabilities and whether you have support. For example, some patients who are wheelchair users, or close to being wheelchair users, when they give birth manage to nurse and look after their children. On the other hand, some patients with cerebellar problems find it very difficult to bathe, change and feed their babies due to poor coordination and tremor. If you have advanced MS, the decision to start or extend your family needs to be discussed with your partner. If necessary, ask an occupational therapist to assess you and discuss all the issues relevant to you becoming a parent. Disability per se is not a reason not to have children, but it does raise important issues that need careful consideration. The decision to have children needs to be taken by you and not by your HCP.

If I become disabled or unemployed because of MS, will I be able to support my children?

This is another difficult question, and the answer depends on your circumstances. In the modern era having children and supporting them is expensive, but most high-income countries have social safety nets to protect you and your family in times of adversity. We now have effective DMTs that prevent or delay disability, so deciding to have children is easier than it was in the pre-DMT era.

What is the risk of my children getting MS?

MS is not a genetic disease in the Mendelian sense that you pass on to your children with a well-defined inheritance pattern. However, there are genetic factors that increase your risk of getting MS. In high-prevalence countries such as the UK, the lifetime chances of a woman developing MS is about 1 in 375 ̶ 400; for a man, it is close to 1 in 750 ̶ 800. However, for a daughter whose mother has MS, the risk is close to 1 in 40, and for a son, it is lower than 1 in 80. In some studies, the latter risk is no higher than the background rate. If the father has MS, the risk of his daughter developing MS is about half the risk of mother ̶ daughter pairing, i.e. 1 in 70. For a son of a father with MS, the risk is likely lower than this, but the results across studies are inconsistent.

Can I prevent my children from getting MS?

Based on the known and modifiable risk factors for MS, you should try and keep your children vitamin D replete. To do this, you will likely need to supplement your children’s vitamin D intake as follows:

for children less than 2 years of age, 600 IU per day
for children 2 ̶ 10 years of age 2,000 IU per day
for children above 10 years of age, 4,000 IU vitamin D3 per day (the same dose we recommend for adults).

Other modifiable risk factors are childhood and adolescent obesity and smoking. We estimate that about 15 ̶ 20% of new or incident new cases could potentially be prevented by eliminating obesity and smoking in the general population. I must stress that these suggested interventions are based on studies that show associations between the risk factors and MS but may not necessarily be cause and effect. I should also point out that most people with all the risk factors for MS will not get the disease. This implies that the development of MS involves other random factors, or bad luck, that can’t necessarily be modified.

The issues raised above show you how complex the management of MS has become, which is why there is a push for people with MS to be managed in specialist MS units.

References

Krysko KM et al. Treatment of women with multiple sclerosis planning pregnancy. Curr Treat Options Neurol 2021;23:11.

Other articles in this series on Pregnancy and childbirth
Planning for pregnancy
Managing MS during pregnancy
Preparing to give birth
Breastfeeding if you are on a DMT