Myasthenia gravis affects a broad range of patients, among them women of reproductive age. Because women undergo significant physiological changes while pregnant, it is best practice for physicians to instruct women on what to expect with regards to their disease and treatment during the course of their pregnancy.
Epidemiological studies indicate that this autoimmune disorder has a prevalence of around 120 per million population among women of a childbrearing age in Europe alone. In the far east and China, myasthenia gravis is most commonly diagnosed in childhood and is more common in females compared to males.
Read more about myasthenia gravis etiology
Myasthenia gravis is driven by antibodies that pathologically bind to the postsynaptic membrane of the neuromuscular junction, causing muscular weakness. Most antibodies bind to acetylcholine receptors (AChR), followed by muscle-specific tyrosine kinase (MuSK), and occasionally lipoprotein-related peptide 4 (LRP4).
However, around 2 in 10 patients with myasthenia gravis do not have any detectable antibodies against the neuromuscular junction; this can be usually be reappraised via more sensitive and cell-based assays. Patients with seronegative myasthenia gravis tend to have a milder disease course.
Most women of a reproductive age have an oversized thymus with widespread germinal follicles. In around 1 in 10 patients, a thymoma is present, but this is less common among young females. Thymus pathology can give rise to the production of AChR antibodies, worsening disease presentation. Studies indicate that early thymectomy can significantly improve symptoms.
“For females in reproductive age with myasthenia gravis, one of their major concerns is potential consequences for fertility, pregnancy, giving birth, and lactation,” Dr Gilhus of the University of Bergen wrote in Frontiers in Neurology. “Any risks for the child as well as for themselves are of the highest importance.”
Pregnancy-Specific Care
All evidence points to myasthenia gravis as having no impact on fertility (although a combination of myasthenia gravis and other autoimmune comorbidities may change the equation). It is paramount that physicians stress that neither the disease, nor common drugs used to treat the condition, have any significant impact on fertility.
Women of a reproductive age should be assured that many pregnancies proceed uncomplicated. Nevertheless, it appears that many women remain unconvinced; in Germany, half of female patients interviewed said they abstained from having a child due to fears of complications, especially adverse drug effects.
Family planning is particularly important if a hereditary disease is involved. However, myasthenia gravis is not hereditary; no single gene causes this disorder. This is a point that should be emphasized to women who are thinking of becoming pregnant.
Even if a case can be made that myasthenia gravis negatively impacts the pregnancy experience, its effects are decidedly minimal. For example, patients who undergo a deterioration in their clinical condition may have a higher risk of experiencing the preterm rupture of amniotic membranes. Spontaneous abortions occur at a slightly higher frequency among women with myasthenia gravis. In terms of preeclampsia/eclampsia,—2 common disorders in pregnancy—they seem to occur with a similar frequency among women with or without myasthenia gravis.
Another major concern that women have is whether their drugs might impede the normal development of their child. Most women diagnosed with myasthenia gravis are on some form of immunosuppressive therapy; the question is whether any of them have teratogenic potential. Unfortunately, due to ethical considerations, it is impossible to perform randomized controlled studies on pregnant women, so this question can never be fully resolved via human studies.
However, prednisolone and azathioprine, long considered to be first-line medications for myasthenia gravis, are regarded as safe during pregnancy. For comparison, only 10% of prednisolone is found in the fetal circulation compared to the mother’s. Previous assertions that the use of prednisolone can cause cleft lip/palate have been thoroughly debunked.
Azathioprine has been used by pregnant women for decades; this has provided clinicians with experiential knowledge regarding any effects that the drug might have on a pregnant woman. Considerable data point to it as being a drug that is compatible for use in pregnancy; most disease signs and symptoms are manifestations of the disease itself (such as inflammatory bowel disease) and not adverse effects of the drug.
Read more about myasthenia gravis treatment
Like most women, pregnant women with myasthenia gravis are usually advised to give birth by vaginal delivery unless contraindicated. A cesarean section should be considered in the event that certain obstetric indications are met, such as the risk of prolonged labor and exhaustion.
“Myasthenia gravis women should continue with their standard drug treatment during the last part of pregnancy and during labor,” Dr. Gilhus wrote.
In terms of anesthetic drugs, most are safe in myasthenia gravis. Out of an abundance of caution, pregnant women with this condition are advised to give birth in a hospital setting, where emergency treatment can be offered if necessary. In addition, giving birth in a hospital gives the patient access to a multidisciplinary team of experts, including gynecologists, obstetricians, neonatologists, and neurologists.
“All aspects of pregnancy and giving birth should be discussed repeatedly with myasthenia gravis females in reproductive age,” Dr Gilhus wrote in Expert Review of Neurotherapeutics. “Most can be reassured that they can continue their treatment unchanged during their pregnancies and with no clinically relevant increased risk of complications or exacerbations apart from transient neonatal myasthenia.”
References
Gilhus NE. Treatment considerations in myasthenia gravis for the pregnant patient. Expert Rev Neurother. Published online February 20, 2023. doi:10.1080/14737175.2023.2178302
Gilhus NE. Myasthenia gravis can have consequences for pregnancy and the developing child. Front Neurol. Published June 12, 2020. doi:10.3389/fneur.2020.00554
