Management of Myasthenia Gravis in Pregnancy

Key points

Pathogenesis

Myasthenia is the Greek word for muscle weakness. It comes in several forms, including an acquired disorder (most common), a hereditary disorder, and transient neonatal myasthenia gravis, which affects infants born to mothers with the disease.³ Acquired myasthenia gravis is an autoimmune disorder in which antibodies block the receptor sites in striated muscle, preventing the transmission of impulses through the muscle that lead to contraction. The pathogenesis of myasthenia gravis involves both

Clinical presentation

Myasthenia gravis often presents with ocular symptoms with double vision, disconjugate gaze, and ptosis. Ptosis is enhanced with prolonged upward gaze and double vision is not present if 1 eye is closed; 85% of these individuals progress to involve limb muscles within 3 years of onset.1, 2, 7 Generalized symptoms involve proximal upper or lower extremity weakness, which worsens with repetitive activity. Patients may complain of difficulty climbing stairs or brushing their hair. Symptoms tend to

Thymectomy

Thymectomy can result in complete remission in disease in 40% to 50% of patients and has become the standard of care.³ Noncontrast chest CT is the is the preferred form of imaging in the general population. Iodinated contrast has been reported to trigger exacerbation of myasthenia gravis symptoms. Noncontrast MRI may be used safely in the pregnant population to assess for thymoma or thymic hyperplasia but does not visualize the anterior mediastinum as well as CT. Thymoma is uncommon in younger

Effects of pregnancy on myasthenia gravis

The effects of pregnancy on myasthenia gravis are variable from woman to woman and from pregnancy to pregnancy in the same individual. A large case series done in 1999 revealed that 41% of women had worsening of symptoms during pregnancy, 29% improved, and 30% remained unchanged.¹⁷ Disease exacerbation is more likely in the first trimester and the postpartum period. The physiologic changes of early pregnancy, including emesis, increased blood volume, and decreased gastrointestinal absorption,

Effects of myasthenia gravis on pregnancy and delivery

Myasthenia gravis does not increase the risk of miscarriage or preeclampsia/eclampsia. During pregnancy, the diaphragm becomes progressively elevated, increased participation by intercostal muscles to meet increase respiratory demands. Careful monitoring of respiratory status in pregnancy is necessary.³ Myasthenia gravis may be a factor in causing spontaneous preterm birth in the setting of congenital myasthenia, discussed later.

Effects of myasthenia gravis on the fetus

In pregnancy, maternal IgG antibodies cross the placenta and provide the newborn with a full host of immunity for the first weeks of life. In patients with myasthenia gravis, this transfer can result in transient neonatal myasthenia in 10% to 20% of newborns. Onset of symptoms may be delayed for 12 hours to several days in the offspring of women treated with water soluble anticholinesterase agents prior to delivery. Affected babies may develop decreased muscle tone, poor sucking, ptosis, and

Medical management of myasthenia gravis in pregnancy and delivery

Medical management aims to improve muscle function by increasing acetylcholine levels at the neuromuscular junction and by suppressing autoantibody production. When weakness is mild, no treatment may be needed. For symptomatic relief, pyridostigmine can be safely used in recommended doses during pregnancy. Changes in gastrointestinal absorption, emesis, and physiologic changes of pregnancy may necessitate adjustment of dosage. High doses of pyridostigmine have been reported to cause uterine

Management of myasthenia gravis in delivery

Myometrial muscle is composed of smooth muscle and function is not affected by myasthenia gravis. The first stage of labor may proceed without intervention and cesarean section should be reserved for obstetric considerations. In the second stage of labor, striated muscles are used to augment expulsion and use of forceps or vacuum for assisted delivery may be indicated. Medication should be administered throughout the delivery to optimize voluntary muscle function.

There is no contraindication to

Preeclampsia and eclampsia in the myasthenic patient

Use of magnesium in the treatment of preeclampsia and eclampsia should be avoided in the myasthenic patient if possible. Magnesium blocks calcium entry at the nerve terminal and inhibits acetylcholine release. This can lead to a dramatic increase in muscle weakness. To protect against seizure activity, intravenous levetiracetam may be given. Phenytoin can cause increased muscle weakness in patients with myasthenia gravis.

Myasthenia gravis in the postpartum patient

Symptoms of myasthenia gravis can acutely worsen in the postpartum period, and deterioration can be rapid and dramatic. It can occur despite a relatively symptom-free pregnancy and close monitoring of the mother’s neurologic and respiratory status is indicated. The care for a newborn can also carry challenges, including reduced sleep, frequent feedings, and the physical exertion of child care. Engagement of a support system should be encouraged.

Lactation

The American Academy of Pediatrics considers use of prednisone, prednisolone, and pyridostigmine to be safe during lactation.²² Cyclosporine, methotrexate, and azathioprine are considered contraindicated in lactation due to risk of immunosuppression, neutropenia, growth retardation, and potential for carcinogenesis. There are few data available to assess the safety of mycophenolate, mofetil and rituximab during lactation.

Contraception

There have been reported cases of exacerbation of myasthenia gravis symptoms during the cyclic withdrawal of oral contraceptives.23, 24 Continuous hormonal contraceptive in the form of implant, ring, or oral contraceptive may be preferable. An intrauterine device also is a reasonable and effective alternative.

Preconceptual counseling

Ideally, a patient with myasthenia gravis presents for counseling about her disease prior to conception. She should be advised that 40% of women have worsening symptoms during pregnancy and that 20% require ventilatory support, 30% of women have improvement in their symptoms during pregnancy, and 30% see no change. Exacerbations during pregnancy tend to occur in the first trimester and postpartum period. It is safe to use pyridostigmine during pregnancy, and steroids and IVIG are safe in