Myasthenia Gravis Can Have Consequences for Pregnancy and the Developing Child

Abstract

Myasthenia gravis (MG) with onset below 50 years, thymic hyperplasia and acetylcholine receptor (AChR) antibodies is more common in females than in males. For a relatively large group of MG patients, pregnancy represents therefore an important question. The muscle weakness, the circulating autoantibodies, the hyperplastic thymus, the MG drug treatment, and any autoimmune comorbidity may all influence both mother and child health during pregnancy and also during breastfeeding in the postpartum period. Mother's MG remains stable in most patients during pregnancy. Pyridostigmine, prednisolone, and azathioprine are regarded as safe during pregnancy. Mycophenolate, methotrexate and cyclophosphamide are teratogenic and should not be used by women with the potential to become pregnant. Rituximab should not be given during the last few months before conception and not during pregnancy. Intravenous immunoglobulin and plasma exchange can be used for exacerbations or when need for intensified therapy. Pregnancies in MG women are usually without complications. Their fertility is near normal. Vaginal delivery is recommended. MG patients have an increased rate of Cesarean section, partly due to their muscle weakness and to avoid exhaustion, partly as a precaution that is often unnecessary. Around 10% of the newborn develop neonatal myasthenia during the first few days after birth. This is transient and usually mild with some sucking and swallowing difficulties. In rare cases, transplacental transfer of AChR antibodies leads to permanent muscle weakness in the child, and arthrogryposis with joint contractures. Repeated spontaneous abortions have been described due to AChR antibodies. MG women should always give birth at hospitals with experience in newborn intensive care. MG does not represent a reason for not having children, and the patients should be supported in their wish of becoming pregnant.

Benefits and Risks of IgG Transplacental Transfer

“…This neuromuscular disease is characterized by autoantibodies directed against the acetylcholine receptors (AChR) found at the neuromuscular junction of the skeletal muscles. Myasthenia gravis affects between 1 in 10,000 and 1 in 30,000 pregnant women, depending on the geographic area [ 91 ], and transplacental passage of AChR antibodies or anti-MuSK (anti-muscle-specific kinase) from the affected mother to the fetus can produce transient neonatal myasthenia gravis in 15% [ 92 ] of cases or a more severe condition, arthrogryposis multiplex congenita, in about 2% of cases [ 93 ]. Two types of autoantibodies against Ach receptors have been described: the adult type, which seem to be involved in maternal and transient neonatal MG, and the fetal type, which are found in the fetal neuromuscular junction up to 33–35 weeks of gestation and may be more frequently involved in fetal arthrogryposis congenita [ 94 ].…”

“…This condition can be prenatally diagnosed by ultrasound, and it is characterized by polyhydramnios, lack of movement and abnormal position with fixed flexion or extension deformities in fetal joints [95] (Figure 4). can produce transient neonatal myasthenia gravis in 15% [92] of cases or a more severe condition, arthrogryposis multiplex congenita, in about 2% of cases [93]. Two types of autoantibodies against Ach receptors have been described: the adult type, which seem to be involved in maternal and transient neonatal MG, and the fetal type, which are found in the fetal neuromuscular junction up to 33-35 weeks of gestation and may be more frequently involved in fetal arthrogryposis congenita [94].…”

Fetal Surveillance in Pregnancies with Myasthenia Gravis

“…Myasthenia gravis is not directly causing infertility, but many affected women of reproductive age postpone or avoid pregnancy. Concerns of possible consequences of their disease or its treatment on pregnancy outcomes, fear of potential worsening of MG due to pregnancy, the uncertainty regarding breastfeeding are the main triggers for anxiety linked to MG and pregnancy [12]. Women with MG should be encouraged to conceive if they wish so.…”

Myasthenia gravis: do not forget the patient perspective

“…This probably explains the infrequent use of MG medication in pregnancy [50] , despite the fact that the most commonly used drugs such as pyridostigmine, prednisolone and azathioprine are regarded as safe for the developing child [51 , 52] . Intravenous immunoglobulin (IVIg) is safe during pregnancy and should be used for exacerbations of muscle weakness [53] . Such treatment will also counteract antibody-mediated neonatal myasthenia in the child.…”

“…Such treatment will also counteract antibody-mediated neonatal myasthenia in the child. Onethird of MG patients experience worsening of their symptoms when pregnant while most remain stable [53] . Some MG patients experience arm weakness, which makes taking care of a baby challenging.…”