Managing Myasthenia Gravis During Pregnancy

Managing generalized myasthenia gravis (MG) during pregnancy involves addressing various obstetric factors, such as deciding the appropriate site for delivery and planning for postpartum care for both mother and child.

“Neurologists should be comfortable discussing and optimizing MG treatment in patients of childbearing potential or who are pregnant,” wrote Vern Juel, MD, of Duke University Medical Center in Durham, North Carolina, in a review article in Continuum.

A recent commercial claims analysis in Muscle & Nerve that compared 900 pregnancies of MG patients and 5.2 million pregnancies of women without MG found that “pregnancy in MG can carry real risks for both the mother and the baby,” co-author Ashley Anderson, MD, MPH, of Houston Methodist Hospital, told MedPage Today.

“We observed increased rates of preeclampsia, C-section, preterm birth, and small-for-gestational-age infants in women with MG compared to age-matched peers in the general population,” she said.

An important motivation for planning is to avoid preventable, long-term maternal disability, noted Kerstin Hellwig, MD, of Ruhr-University Bochum in Germany, and co-authors in Lancet Neurology. “Patients with MG who are not pregnant but plan to be benefit from planning,” they observed, adding that MG is among diseases that “frequently affect women in their reproductive years and require careful treatment planning around pregnancy.”

Pregnancy Planning

Ideally, women who plan to become pregnant would achieve minimal disease manifestation while maintaining a stable treatment plan with minimal potential fetal risk, Juel noted.

For women with acetylcholine receptor-positive generalized MG, “thymectomy, ideally at least 1 year before pregnancy, can minimize immunotherapy requirement,” he wrote. “Thymectomy reduces the risk of MG exacerbation during pregnancy and of transient neonatal MG.”

For women with muscle-specific tyrosine kinase (MuSK) MG, “rituximab may be considered before pregnancy to achieve minimal manifestation status,” he added.

Also, since an increased risk of complications at delivery has been reported, high-risk obstetric care and a delivery site with neonatal intensive care services are appropriate.

Both pregnancy and the postpartum period can precipitate MG exacerbations, as can thymectomy, the abrupt cessation of immunosuppressive therapy, or excessive cholinesterase inhibitor use.

“MG exacerbations are more common during the first or third trimesters or postpartum, but myasthenic crisis is very rare,” Juel wrote.

Evidence for rates of other MG pregnancy concerns has been varied. A systematic review of 824 pregnancies with MG estimated an overall risk of MG exacerbation of 33.8%. The risk of crisis was 6.4% in pregnancy and 8.2% postpartum, and the risk of transient neonatal MG was 13%.

A Swedish population study concluded that there was no increased risk of pregnancy complications in women with MG, though they presented evidence for less frequent spontaneous onset of labor than in women without MG, higher labor induction rates, and higher rates of elective cesarean section deliveries. Infants of women with MG were born 2 days earlier on average but without evidence of higher rates of low APGAR, small for gestational age, or congenital malformation.

A North American survey that compared outcomes in 56 planned versus 34 unplanned pregnancies in women with MG reported more exacerbations, more hospitalizations, and more ICU admissions with unplanned pregnancies.

Treatment Considerations

In 2016, the American Academy of Neurology (AAN) published international consensus guidelines for MG management, including a section on pregnancy.

The AAN guidance advised that mycophenolate mofetil and methotrexate were contraindicated during pregnancy due to teratogenicity; that IV magnesium should be avoided in eclampsia due to the risk for increased myasthenic weakness, and IV cholinesterase inhibitors be avoided due to the risk for uterine contractions; that prednisone is the immunosuppressive agent of choice during pregnancy; and that azathioprine and cyclosporine are relatively safe in those not controlled with or intolerant of corticosteroids.

Although the statement on azathioprine achieved consensus, guideline authors noted, “there was a strong minority opinion against the use of azathioprine in pregnancy.”

Other guidance suggested that plasma exchange or IV immunoglobulin (IVIG) may be useful if a quick, though temporary, response is urgently needed during pregnancy, and noted that spontaneous vaginal delivery is reasonable and should be actively encouraged. Guidance also recommended all infants born to myasthenic mothers be examined for transient myasthenic weakness with rapid access to neonatal intensive care.

Neonatal Concerns

MG-specific neonatal concerns revolve around how maternal transfers of substances including treatments or antibodies via placenta or breast milk can cause harm. “Physiological transfer includes pathogenic antibodies, therapeutic monoclonal antibodies, and vaccination antibodies,” Hellwig and colleagues wrote.

Transient neonatal MG, due to placental transfer of maternal MG antibodies, is temporary and expected to resolve in weeks to months. Affected infants are not thought to have an increased risk for developing MG later in life.

Hellwig and co-authors noted that while pregnancy safety data for newer MG treatments like complement inhibitors or neonatal fragment crystallizable receptor (FcRn)-blocking agents are limited, “preliminary data suggest that selected therapies could be continued during pregnancy to maintain disease stability and are compatible with breastfeeding.”

Since MG is associated with a risk of postpartum worsening, “effective treatment should not be postponed because of breastfeeding,” they wrote.

“Exposure of newborns to immunotherapy taken by mothers with autoimmune diseases raises questions over the timing and safety of vaccination in the newborns,” Hellwig and colleagues added. Vaccination is an area with important evidence gaps and uncertainty, they noted.

Uncertainties around pregnancy and breastfeeding in MG have clinical consequences. Claims data showed that most women received no treatment for MG during pregnancy, and of those who did, many experienced treatment changes, Anderson pointed out.

“Women with MG face a greater risk of serious pregnancy complications compared to the general population,” she said. “Understanding that risk underscores the urgent need for better clinical guidance, improved preconception counseling, and safe and effective treatment options that providers and patients can confidently use.”