Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Rubin reports no financial relationships relevant to this field of study.

SYNOPSIS: Myasthenia gravis increases both maternal and fetal complications and mortality during pregnancy, but the MuSK-antibody variant appears less morbid, based on this small retrospective series of 17 patients.

SOURCE: Santos E, Braga A, Gabriel D, et al. MuSK Myasthenia gravis and pregnancy. Neuromuscul Disord 2017; Nov. 28. https://doi.org/10.1016/j.nmd.2017.11.014. [Epub ahead of print].

Pregnancy is not contraindicated in women with myasthenia gravis (MG), but carries a 40% risk of exacerbation during pregnancy, an additional 30% risk in the puerperium, maternal mortality of 40/1,000 live births, and perinatal mortality 68/1,000 births.¹ How safe is pregnancy for prospective mothers with muscle-specific tyrosine kinase (MuSK) antibody-positive MG?

In this retrospective, multicenter, cohort study, 17 MuSK-MG pregnant women, 13 with more than one pregnancy, were identified among seven hospitals in northern Portugal. Diagnosis of MuSK-MG was based on clinical presentation, electrodiagnostic testing, and positive antibody titers, with clinical status, including refractory MG, based on Myasthenia Gravis Foundation of America guidelines. Following informed consent, data were collected on all patients. Age of MG onset was 34.5 years, of which 46.2% were refractory. Other autoimmune conditions were present in 23%, including thyroid disease, sacroiliitis, and anti-phospholipid syndrome. MG occurred either before (n = 4) or after (n = 23) pregnancy, with no instance of MG-onset during or within the six-month postpartum period.

Among patients who became pregnant after MG onset (n = 4), none experienced myasthenic crisis during pregnancy, none suffered a miscarriage, and there were no cases of fetal akinesia, hydramnios, or intrauterine growth retardation. Two patients delivered preterm, at 35 and 37 weeks, respectively, due to membrane rupture, and two underwent cesarean delivery, one by choice and one for obstetric reasons. Among patients who became pregnant before MG onset (n = 23), there were similarly no instances of fetal akinesia, hydramnios, or intrauterine growth retardation, but three ended in miscarriage, two in one patient with anti-phospholipid syndrome and one of unknown cause. Neither group experienced pre-eclampsia, stillbirths, or birth defects, and none fulfilled criteria for low neonatal birth weight, although compared to babies born to mothers before MG onset, those born to mothers after MG onset had lower birth weight. Among the neonates, there was one case of neonatal MG lasting three weeks in a full-term baby with an Apgar of 9/10, delivered by cesarean delivery under general anesthesia. In the 12-month postpartum period, all babies developed normally.

Pregnancy does not precipitate MuSK-MG, nor does MuSK-MG negatively affect pregnancy. Newborn weight may be lower than expected, but does not fulfill criteria for low birth weight.

COMMENTARY

When choosing immunosuppressive agents for women of childbearing age with myasthenia gravis (MG), always discuss the possibility of pregnancy. Oral pyridostigmine is safe but not intravenously, as it may precipitate uterine contractions. Where immunosuppression is warranted, corticosteroids at the lowest effective dose are the agent of choice. Although retrospective studies suggest they increase the incidence of cleft palate when used during the first trimester, recent studies show no such increase, although they may increase the risk of gestational diabetes, infection, and preterm deliveries. IVIG and PLEX frequently have been used during pregnancy for a variety of autoimmune conditions and generally are well tolerated. Hence, they may be used for MG crisis or severe MG during pregnancy, but the risks and benefits to mother and fetus must be weighed carefully. Immunosuppression other than corticosteroids is best avoided during pregnancy, although recent international consensus guidelines propose that azathioprine and cyclosporine are relatively safe in pregnancy for MG when corticosteroids do not adequately control symptoms or are not tolerated. If a pregnancy is incidentally discovered while a patient is taking nonsteroidal immunosuppression, one must consider the possibility that drug withdrawal may be too late to avoid teratogenesis.²

REFERENCES

1. Plauche WC. Myasthenia gravis in mothers and their newborns. Clin Obstet Gynecol 1991;34:82-99.
2. Edmundson C, Guidon AC. Neuromuscular disorders in pregnancy. Semin Neurol 2017:37:643-652.