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Despite Best Safety Evidence, Some Women with Neurologic Disorders Delay Pregnancy
Early Family Planning Discussions Are Critical, Neurologists Say

Article In Brief

Many women with migraine experience a temporary break from their headaches while pregnant, yet many delay their pregnancy due to concerns about the safety of their medications. Neurologists who treat migraine as well as multiple sclerosis and myasthenia gravis say earlier discussion about the array of safe therapeutic options are needed.

Most women with migraine experience a temporary break from their headaches while pregnant, according to research studies. But a recent survey suggests patients may not be getting this message.

In an observational study, one in five women with migraine surveyed said they avoided becoming pregnant because of their migraines, according to a report published online in Mayo Clinic Proceedings on September 15. Of these women, 72.5 percent said they avoided becoming pregnant because their migraines would get worse during pregnancy, and 68 percent said disability caused by migraine would make pregnancy difficult.

“What I took away from the findings of the study is that we don't always know what our patients are thinking and they don't know what we think about what happens to migraine during pregnancy,” said Rebecca Burch, MD, FAHS, director of the headache fellowship offered through Brigham and Women's Health, Massachusetts General Hospital, and Harvard Medical School, who was not involved with the study.

Indeed, neurologists who specialize in women's health said these findings are not specific to migraine. The last few decades have brought about an unprecedented amount of research related to pregnancy and neurologic conditions, as well as new therapeutics that have given women more options than ever, several neurologists told Neurology Today.

But they said more research is needed on better management of patients who are pregnancy; indeed, some said it was challenging to get some institutional review boards to approve studies involving pregnant women. But, they said, as the current survey suggests, neurologists and their patients need to have more (and earlier) discussions about family planning—not only in regard to migraine but for multiple sclerosis (MS) and myasthenia gravis (MG) as well.

“The half-life of the medicines we use to control MS is variable, but not very long, on average. This allows us to plan treatment discontinuation so that in pregnancy, the drug is no longer circulating in the patient's body, but the biologic effects, the positive, favorable effects that they have on MS will remain throughout early pregnancy. The beneficial hormonal state of second and third pregnancy trimesters can be thought of as treatment in itself. Overall, most of our patients do very well with pregnancy and in the postpartum period.”

—DR. MARIA K. HOUTCHENS

Dispelling Migraine Misinformation

The women in the Mayo Clinic study—who had been seen at headache clinics—completed questionnaires as part of the American Registry for Migraine Research: 607 women completed the family planning section of the questionnaire between February 2016 and September 2019.

Among the findings, 19.9 percent said they avoided pregnancy because of migraine. The women who responded this way also expressed concern about the effects of migraine on their baby: 76 percent said migraine medications could negatively affect their child's development, and 14 percent said migraine would cause the baby to have abnormalities at birth.

“In our study, we found that those who indicated intent to avoid pregnancy were predominantly young, more likely to have menstrual migraine, and more likely to have never been pregnant since the onset of migraine,” said lead author Ryotaro Ishii, MD, PhD, visiting scientist at Mayo Clinic in Phoenix, AZ. “I recommend that clinicians talk about pregnancy plans with their patients as early as possible.”

Several migraine specialists said they do just that. Dr. Burch said she reviews contraception status with female patients at every visit. She tells patients that if they are planning to become pregnant, they should let her know so they can review the preventative medication plan to see if it is safe to continue during pregnancy. She said she will also discuss an acute treatment plan for early pregnancy “so they have a clear treatment plan for when they are not feeling well.” When patients become pregnant, Dr. Burch schedules frequent follow up visits to make sure the plans are working.

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“I have seen patients who have been discouraged from having a pregnancy by a former neurologist—that is thankfully happening less and less—but we still see a lot of patients who have not been adequately counseled about medication choice in the setting of childbearing.”—DR. RILEY BOVE

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“Over the last few decades, a lot of observational studies, including a registry from industry, have shown that sumatriptan seems to be quite safe in pregnancy with occasional use.”—DR. MATTHEW ROBBINS

Matthew Robbins, MD, FAAN, FAHS, neurology residency program director and associate professor of neurology at Weill Cornell Medicine/New York Presbyterian Hospital, said many of his female patients worry that if they become pregnant and have a major migraine attack, their only options would be drugs that might affect the baby's development.

“I think the most problematic misconception is that there are no safe treatments for migraine during pregnancy,” Dr. Burch said.

Drs. Robbins and Burch said patients and providers should know that triptan medications can be used for most women with uncomplicated pregnancies. “Over the last few decades, a lot of observational studies, including a registry from industry, have shown that sumatriptan seems to be quite safe in pregnancy with occasional use,” Dr. Robbins said.

Talking to patients about lifestyle changes they can make prior to pregnancy, such as understanding triggers or embracing behavioral techniques including biofeedback, progressive muscle relaxation, and mindfulness, can also help, Dr. Robbins said. To manage pregnant patients, he tends to rely on acetaminophen, dopamine-blockers, lidocaine nasal spray, and occasionally, neuro-stimulation devices. For prolonged attacks that do not respond to other treatments or short-term preventive treatment, Dr. Robbins recommends nerve blocks.

Dr. Burch said she often sees patients who have erroneously been told they can't take migraine medications while breastfeeding. “I do think that there's a lot of misinformation out there about medication safety during lactation. We need more provider education. If providers are aware of databases like LactMed, that will help to inform better decisions for patients,” she said.

Multiple Sclerosis: No Need to Fear Pregnancy

Many women with multiple sclerosis are also often told that pregnancy or breastfeeding are not good options for them, even as the science says otherwise, said Riley Bove, MD, MMSc, assistant professor of neurology at the University of California, San Francisco.

“I have seen patients who have been discouraged from having a pregnancy by a former neurologist—that is thankfully happening less and less—but we still see a lot of patients who have not been adequately counseled about medication choice in the setting of childbearing,” she said.

Part of the issue stems from the fact that neurologists do not receive much training on such topics as teratogenicity, placental transfer, breastmilk composition, or the efficacy of various forms of hormonal contraceptives, Dr. Bove said. The good news is that over the last five years there seems to be more of an interest on the part of general neurologists to understand women's neurology, she added.

Maria K. Houtchens, MD, MMS, clinical director of the Brigham Multiple Sclerosis Center in Boston, said the standard of “negative thinking” about pregnancy and MS began to evolve with the 1998 publication of a natural history study in the New England Journal of Medicine showing that the relapse rate decreases significantly in MS patients during pregnancy and may increase in some patients in the post-partum period.

“Ever since that time, we've tried to study and understand this phenomenon even better, and every year we learn more. As we do, we share this knowledge with our patients and the community of neurologists at large,” she said.

Ideally, patients will tell their neurologists when they are interested in starting a family. The goal is to get their MS managed before they get pregnant so that their disease is as stable as possible going into pregnancy, Dr. Houtchens said.

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“In our study, we found that those who indicated intent to avoid pregnancy were predominantly young, more likely to have menstrual migraine, and more likely to have never been pregnant since the onset of migraine. I recommend that clinicians talk about pregnancy plans with their patients as early as possible.”—DR. RYOTARO ISHII

Figure

“What I took away from the findings of the study is that we dont always know what our patients are thinking, and they dont know what we think about what happens to migraine during pregnancy.”—DR. REBECCA BURCH

Figure

“As more neurologists become comfortable treating pregnant women with neurologic disease, the health of the mother and her offspring is likely to benefit.”—DR. JANET WATERS

“The half-life of the medicines we use to control MS is variable, but not very long, on average,” she explained. “This allows us to plan treatment discontinuation so that in pregnancy, the drug is no longer circulating in the patient's body, but the biologic effects, the positive, favorable effects that they have on MS will remain throughout early pregnancy. The beneficial hormonal state of second and third pregnancy trimesters can be thought of as treatment in itself. Overall, most of our patients do very well with pregnancy and in the postpartum period.”

Annette Langer-Gould, MD, PhD, regional lead for clinical and translational neuroscience at Southern California Permanente Medical Group, said many small molecules will cross the placenta so for pregnant women with active disease, she recommends rituximab or a low dose of an alternative B-cell depleting treatment. For non-pregnant women on drugs with proven teratogenic effects, Dr. Langer-Gould writes six-month prescriptions and checks in with them when that time is up to make sure they are still on a reliable form of contraception.

“I would say women with MS can have babies and breastfeed as per their wishes and can do that safely. There are medication options, so there are no reasons for them to delay or to forgo having children or to forgo exclusive breastfeeding in order to keep their disease under control,” she said.

Dr. Bove said that if their MS is stable before pregnancy, many women don't need to be on MS therapy while they are pregnant outside the setting of certain specific medication exposures. She encouraged neurologists to discuss family planning with patients regularly.

“Simply asking about a woman's goals doesn't mean you'll be stuck giving answers you're not comfortable giving,” she said. “It just means being able to appropriately triage women. When a patient is planning a pregnancy or is pregnant or considering whether or not to breastfeed, you can refer patients to experts if you don't have the expertise.”

Myasthenia Gravis Patients Have Options

As with migraine and MS, patients with myasthenia gravis also need to be asked about family plans long before they become pregnant, said Janet Waters, MD, chief of the division of women's neurology at Magee Women's Hospital in Pittsburgh. Dr. Waters said she initiates the conversation with patients as young as 12.

“I think if you introduce it very early, as soon as the woman reaches child-bearing age, you are more likely to have a good outcome. That way, you can plan things,” she said.

Roughly one-third of women with myasthenia gravis will get better in pregnancy, one-third will stay the same, and one-third will worsen, according to Dr. Waters, who is the author of a review paper about managing myasthenia gravis in pregnancy.

Of those who worsen, half end up on a ventilator. In about 20 percent of mothers with myasthenia gravis, their immunoglobulin G antibodies will cross the placenta and cause temporary myasthenia gravis in the baby. The newborn may experience eyelid weakness, respiration, or sucking difficulty, but symptoms tend to resolve within two to three weeks.

Dr. Waters advises women with myasthenia gravis who are interested in having children to wait two years after diagnosis to conceive, to ensure that their condition is stable. Since some patients experience complete remission after having their thymus removed, Dr. Waters encourages her patients to have the surgery before they get pregnant. For women who need it, myasthenia gravis medications, including pyridostigmine, can be safely taken in pregnancy, while patients with severe exacerbations can be given intravenous immunoglobulin, she said. Prednisone and pyridostigmine can be used by breastfeeding mothers as well. In the long-term, pregnancy does not have a negative effect on patients with myasthenia gravis; the disease risk is the same for women who have given birth as it is for those who have not, she noted.

The most important points are for women to know they do not need to avoid pregnancy, and for neurologists to become more educated on issues affecting women of reproductive age, Dr. Waters said. “As more neurologists become comfortable treating pregnant women with neurologic disease, the health of the mother and her offspring is likely to benefit,” she added.

Dr. Burch said that any treatment decisions should be made with the patient in mind regardless of their neurologic condition.

“People's risk decision-making occurs on a spectrum. There are people who feel strongly they want to treat their pain and others who feel strongly they don't want to take any medications during pregnancy and would rather cope with the pain. What's important is that it is the patient's choice, that we, as providers, are responding to what the patient feels is right for her, not imposing our own values or judgments on treatment,” she said.

Disclosures

Dr. Burch's spouse is an employee of CarePort Health/Allscripts, and receives salary and stock options. He focuses on discharge planning software. Dr. Houtchens receives consulting income and research support from Biogen, Sanofi, Roche, and Serono. Drs. Ishii, Langer-Gould, Robbins, and Waters had no relevant disclosures. Dr. Bove has received research support from Akili Interactive and Roche Genentech. Dr. Bove has also received personal compensation for consulting from Alexion, Biogen, EMD Serono, Novartis, Sanofi Genzyme, Roche Genentech, and Pear Therapeutics.

More Research on Pregnant Women is Overdue, Neurologists Say

Additional research would help us better understand which treatments are safe during pregnancy and the postpartum period, neurologists who specialize in the care of women say.

The problem is it is incredibly difficult to get institutional review board approval to conduct research on pregnant women, said Janet F. Waters, MD, chief of the division of women's neurology at Magee Women's Hospital in Pittsburgh. “When you are doing it retrospectively or as a patient improvement type of study, then it's a lot easier to get approval, but prospective studies are very tough,” she said.

With little data, physicians tend to take an overly cautious approach that can put women at a disadvantage, Dr. Waters said. As an example, Dr. Waters explained that limited evidence has caused many physicians to recommend that women with Chiari I malformation deliver via cesarean section of concern about the increase in intracranial pressure that occurs in the second stage of labor.

But Dr. Waters and Dr. Angela O'Neal published a case series in 2018 in the journal Obstetrics and Gynecology, which retrospectively reviewed deliveries in 92 women with Chiari I malformation. None of the women had neurologic deterioration regardless of whether they were delivered by vaginal delivery or cesarean section. No neurologic complications occurred in women who received epidural or spinal anesthesia.

Matthew S. Robbins, MD, FAAN, FAHS, neurology residency program director and associate professor of neurology at Weill Cornell Medicine/New York Presbyterian Hospital, said more data can sometimes bring reassurance about using treatments in pregnant women. He noted, for example, that pregnant women with migraine who receive onabotulinumtoxinA (Botox) injections don't seem to experience fetal effects, according to data presented at the American Headache Society virtual annual scientific meeting.

“There is a tremendous amount of unexamined gender bias in neurology and the way we approach pregnancy and breastfeeding across diseases is a symptom of this problem,” said Annette Langer-Gould, MD, PhD, regional lead for clinical and translational neuroscience at Southern California Permanente Medical Group. “There is this fear of allowing women to take certain medications during pregnancy or nursing even when the biological possibility of risk is extremely low.”

Link Up for More Information

• Ishii R, Schwedt TJ, Kim SK, et al. Effect of migraine on pregnancy planning: Insights from the American Registry for Migraine Research https://www.mayoclinicproceedings.org/article/S0025-6196(20)30820-X/fulltext. Mayo Clin Proc 2020; Epub 2020 Sept 15.
    • Confavreux C, Hutchinson M, Hours MM, et al; for the Pregnancy in Multiple Sclerosis Group. Rate of pregnancy-related relapse in multiple sclerosis https://www.nejm.org/doi/full/10.1056/nejm199807303390501#:~:text=Results,third%20(P%3C0.001). New Engl J Med 1998; 339: 285–289.
    • Waters J. Management of myasthenia gravis in pregnancy https://www.neurologic.theclinics.com/article/S0733-8619(18)31252-0/abstract. Neurol Clin 2019;37:113–120.
    • Langer-Gould AM. Pregnancy and family planning in multiple sclerosis https://journals.lww.com/continuum/Abstract/2019/06000/Pregnancy_and_Family_Planning_in_Multiple.13.aspx. Continuum 2019;25(3):773–792.
      • Massey JM, De Jesus-Acosta C. Pregnancy and myasthenia gravis https://journals.lww.com/continuum/Abstract/2014/02000/Pregnancy_and_Myasthenia_Gravis.14.aspx. Continuum 2014;20(1):115–127.
        • Robbins MS. Headache in pregnancy https://journals.lww.com/continuum/Abstract/2018/08000/Headache_in_Pregnancy.10.aspx. Continuum 2018; 24(4):1092–1107.
          • National Library of Medicine Drugs and Lactation Database (LactMed). https://www.ncbi.nlm.nih.gov/books/NBK501922/. Accessed Oct. 1, 2020.
            • Waters JF, O'Neal MA, Pilato M, et al. Management of anesthesia and delivery in women with Chiari 1 malformations https://journals.lww.com/greenjournal/Fulltext/2018/11000/Management_of_Anesthesia_and_Delivery_in_Women.14.aspx. Obstet Gynecol 2018;132(5):1180–1184.