Pregnancy in women with MS requires careful approach to care
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While we know women are threefold more likely than men to receive an MS diagnosis and they are usually diagnosed during their childbearing years, data on the impact of pregnancy on MS outcomes remain less clear.
Reproductive factors, such as sex steroid hormone production and pregnancy, have been shown to alter disease course in MS.
In a recent study published in JAMA Neurology, Nguyen and colleagues found that previous pregnancies and childbirths appeared to delay the onset of the first indicative symptoms of MS by 3.3 years compared with women who had never been pregnant. Moreover, women who had given birth also had delayed onset of symptoms by 3.4 years compared with women who had never given birth.
For women who have received an MS diagnosis and are pregnant, the risk for relapse during and after pregnancy varies.
“When women with MS are pregnant, it has been shown that relapse rates decrease and are lowest during the third trimester, which is particularly true for women with well-controlled or mild disease,” Vilija Jokubaitis, PhD, a senior research fellow in the department of neuroscience at Monash University in Melbourne, Australia, told Healio. “However, modern-day research has shown that approximately 14% of women with relapsing-remitting MS are at increased risk for postpartum relapse and the long-term impact of pregnancy on MS outcomes is unclear.”
Maternal, fetal outcomes
Although women with well-controlled or mild MS appear at lowest risk for relapse during pregnancy, this appears less true for women with more active MS, according to Ruth Dobson, PhD, a clinical senior lecturer in neurology at Queen Mary University of London.
“Women with with active relapsing disease prior to pregnancy have an approximate 12% higher risk for relapse during pregnancy and so these women need to be closely monitored by their neurology and obstetric teams,” Dobson told Healio. “After delivery, women with MS are at increased risk for postpartum relapse and this risk is greatest within the first 3 months after giving birth but may be mitigated by exclusive breastfeeding or rapid resumption of disease-modifying therapy.”
The effects of MS on maternal outcomes are both short- and long-term, according to Riley Bove, MD, assistant professor in the department of neurology at the University of California, San Francisco Weill Institute for Neurosciences.
“Short-term, MS does not impact much about the pregnancy itself, regarding risk for infertility, complications, cesarean sections or other outcomes,” Bove said. “There does appear to be an effect of the immunotolerant state of pregnancy on women’s risk for relapse, namely that during pregnancy and particularly the second and third trimesters, there is a decreased risk for relapse. Unfortunately, we do not always see this in women who are stopping certain medications, such as fingolimod or natalizumab, that carry risk for rebound relapse.”
The risk for MS relapse continues for several months after a woman gives birth.
“However, breastfeeding and rapidly restarting medications after delivery can help prevent relapse,” Bove said. “Some relapses, even if women recover from them in the short-term, could eventually result in more rapid worsening of function. But having children may somehow protect women from worsening MS, and from more relapses. Older studies were biased by the fact that women with worse MS might choose not to have children. Recently, studies have been able to account for this reverse causality.”
Regarding fetal outcomes, little evidence exists.
“Genetically, we counsel women with MS that there is about a 5% chance that their child could have MS, but most studies suggest that there is not an increased risk for premature, low-birthweight, or otherwise affected infant,” Bove said. “When looking at the wellness of children whose parents have MS, the factor that does seem to stand out is whether the parent with MS has untreated mood disorder.”
Treatment
There are several treatment options available for women with relapsing-remitting MS, but this may depend on their country of residence, according to Dobson.
“It has been shown that it is safe to continue taking interferon beta and glatiramer acetate until pregnancy has been confirmed,” Dobson said. “There is also no evidence of harm resulting from continuing these medications during pregnancy, and they can safely be continued during pregnancy. If women do choose to stop these medications, it is important to inform them that if they restart the same medication, it takes months for the medication to reach full efficacy. Therefore, starting post-partum will not prevent the ‘rebound’ in disease activity that may occur.”
Women treated with dimethyl fumarate should know that the agent has a very short wash out period — it leaves the body quickly when the medication is stopped, Dobson added.
“Whilst there have not been any clear signals of harm to babies when the mother takes dimethyl fumarate during pregnancy, there are still a relatively small number of pregnancies in which the medication has been continued throughout pregnancy and not just during the early stages,” Dobson said.
Recent research has also shown that the use of natalizumab for women with highly active MS is safe until the 34th week of pregnancy, at which time the medication should be stopped to avoid potential blood disorders in the baby, Jokubaitis noted.
“The dose of natalizumab can safely be spaced out during pregnancy so that it is given every 6 to 8 weeks to minimize the exposure to the baby. Natalizumab can be safely restarted very soon after childbirth to minimize the risk of post-partum rebound,” Jokubaitis said. “There is also the option of using long-acting therapies, such as B-cell therapies or alemtuzumab, so long as conception takes place approximately 6 months after the last infusion.”
This is what the labels say, but the drug is out of mom’s system in 3-4 months and doesn’t cross the placenta in the first trimester, so many people are recommending a shortened interval, with conception about 3-4 months after last infusion. When discontinuing natalizumab or fingolimod, a “bridge therapy,” such as rituximab or ocrelizumab, could be considered to prevent rebound relapses during pregnancy, Bove noted.
“Among women who are not continuing an MS therapy at all, those at high-risk for relapse may require steroids or IV immunoglobulin to prevent relapse,” Bove said. “These same steroids or immunoglobulins could be used should the woman experience a serious relapse during pregnancy, after conversation between the MS and obstetrical experts and the patient.”
Management
Experts with whom Healio spoke agreed that pregnant women with MS should be managed in a joint neuro-obstetric setting.
“Should a pregnant woman with MS have a relapse during pregnancy, she should be reviewed, and a joint decision made about the use of steroids to treat any relapse,” Dobson said. “This decision will depend on a number of factors including the severity of the relapse, the impact on her physical and mental state, and the possible impact to the infant exposed to steroids.”
Experts also recommend discussion about birth choices.
“Women should be informed that a diagnosis of MS does not necessarily mandate an instrumental delivery or caesarean section, and that birth choices should be based upon individual disability and other circumstances,” Dobson said. “Epidural or spinal anesthesia does not increase the risk for post-partum relapse — women should not be denied analgesia on this basis.”
Bove said there are four structured times in which physicians should evaluate, discuss and plan pregnancy in women with MS.
“First, we recommend that every time an MS physician sees a woman of childbearing potential that they assess her interest in and plans for childbearing in the coming few years,” Bove said. “If women are considering a pregnancy, then risks and benefits of various therapies can be discussed. If women are not considering a pregnancy, then effective contraception to prevent unintentional pregnancies should be discussed.”
Recommendations for women planning a pregnancy include a counseling visit before conception, followed by a visit around 7 months of pregnancy to plan the postpartum course and then a visit within a few months postpartum, Bove added.
“During the pre-conception visit, discussion topics should include routine prenatal care, whether and when to stop MS therapies, whether to consider a ‘bridge therapy’ if stopping certain therapies and how new symptoms will be handled during the pregnancy,” Bove said. “Certain pill medications must be stopped, and some can likely be continued, such as self-injectables. This is also a good time for the MS physician to initiate dialogue with the obstetrician to provide joint recommendations and care. During the pre-partum visit, counseling can focus on delivery planning. For example, ensuring that the obstetrical team is aware that obstetric, not MS-related, concerns generally guide the mode of delivery.”
Post-partum care should include scheduled MRIs, treatment, recommended physical therapy and other components of care. Bove added the mother should receive screening for peripartum mood disorders and health care teams should assess social support.
“In the United States, where maternity leave is notoriously short, these care elements should be lined up ahead of time to ensure that they can be scheduled and completed,” Bove said.
For more information:
Riley Bove, MD, can be reached at the University of California, San Francisco Weill Institute for Neurosciences, 675 Nelson Rising Lane, San Francisco, CA 94158; email: riley.bove@ucsf.edu.
Ruth Dobson, PhD, can be reached at Queen Mary University of London, Mile End Road, London E1 4NS; email: ruth.dobson@qmul.ac.uk.
Vilija Jokubaitis, PhD, can be reached at Monash University, Level 6, 99 Commercial Road, Melbourne, VIC 3004, Australia; email: vilijia.jokubaitis@monash.edu.