Neuromuscular disorders that present during pregnancy

Bell palsy. Bell palsy is an abnormality of the facial nerve causing ipsilateral facial paralysis. It is a common condition occurring in both the general and pregnant population. Recovery usually occurs over weeks to months, but in some cases resolution of symptoms may take years or may never occur. A diagnostic workup is generally not indicated unless there are atypical features. For example, an insidious onset, progressive course, or association with other neurologic deficits would be atypical for idiopathic Bell palsy.

The prevalence of Bell palsy in the pregnant population is controversial. According to some authors, Bell palsy during pregnancy occurs in approximately 45 cases per 100,000 compared with 20 cases per 100,000 in the general population (38). However, Vrabec and colleagues published data showing that the number of Bell palsy cases is not considerably different in pregnant women compared to all women of childbearing age (106). A large Korean study also did not find an increased rate of Bell palsy among pregnant women versus controls (13). All of these studies agree that when Bell palsy occurs in pregnancy, it most commonly occurs during the third trimester or postpartum.

The treatment of Bell palsy has not been fully established in pregnancy. The medications used to treat Bell palsy in the general population have been used in pregnant patients. Prednisone, which is commonly used to aid in recovery from Bell palsy, is a category C medication. However, it is often used cautiously during pregnancy. There are data to support the use of steroids for Bell palsy in the general population, and several articles support its use in late stages of pregnancy or postpartum (106; 42). For example, a report demonstrated that complete recovery improved by 17% in all patients treated with steroids (79). Early treatment started within the first 3 days of symptoms with steroids can result in greater than 94% chance of recovered facial nerve function (97). The recommended dose of steroids is 1 mg/kg for 5 days followed by a taper. Hato and associates documented that treatment with both steroids and antivirals compared to steroids alone leads to a better outcome in the general population (37). However, another study found no benefit with the use of acyclovir given alone or in addition to steroids (97). The safety of both medications has been established. Both acyclovir and valacyclovir are category B medications and can be used in pregnancy and while breastfeeding according to the American Academy of Pediatrics.

The prognosis for recovery of Bell palsy in pregnancy is also debated. Bell palsy that occurs during late pregnancy or postpartum often has worse or more prolonged recovery (75). One retrospective review of 31 cases of complete facial paralysis in pregnancy found that only 52% had satisfactory recovery by 6 weeks compared to 77% to 88% recovery in the control nonpregnant group. However, all 17 of the patients with incomplete facial nerve palsy eventually had satisfactory resolution (31). Another review article boosted higher rates of recovery. Roughly 90% of their pregnant patients with Bell palsy had complete recovery within 80 days with mean duration of about 7 weeks (16). Predictors of bad prognosis include bilateral facial nerve palsy and recurrence in subsequent pregnancies (16).

There also seems to be an association between Bell palsy and preeclampsia. Preeclampsia is five times more common in patients with Bell palsy (92). Gestational hypertension or preeclampsia is present in 22.2% of pregnant women with Bell palsy, which is well above the national average of 5% (91). Chronic hypertension and obesity are also associated with the development of Bell palsy during pregnancy (47). Bell palsy can occur before preeclampsia is recognized, concurrently with preeclampsia, or it may occur in the postpartum period as preeclampsia is resolving (01).

Carpal tunnel syndrome. Carpal tunnel syndrome, also known as median mononeuropathy at the wrist, is very common during pregnancy. The patient-reported incidence of numbness and tingling affecting both hands during pregnancy is 34% (60). However, the incidence of electrodiagnostically confirmed carpal tunnel syndrome is lower with reported incidence of 17% to 19% (71; 49). Pregnant women who develop carpal tunnel are more likely to be older (101). Carpal tunnel syndrome is more likely to occur after 30 weeks’ gestation in patients with greater amounts of fluid retention (60).

Several reasons have been suggested to explain the increased prevalence of carpal tunnel syndrome in pregnancy. One idea is that during pregnancy fluid retention or relaxin-induced hypertrophy of the transverse carpal ligament causes compression of the median nerve (88). In fact, there does seem to be a correlation between large amounts of weight gain during pregnancy and the incidence of carpal tunnel syndrome. Turgut and coworkers found that women with carpal tunnel syndrome gained an average of 11.6 kg, whereas women who did not develop carpal tunnel syndrome gained an average of 8.5 kg (101).

The mainstays of treatment for carpal tunnel syndrome in pregnancy are conservative measures such as wrist splints, physical therapy, a low salt diet, antiinflammatory medications, and hydrocortisone injections. One example of a successful conservative approach is a study of 20 patients with electrophysiologically confirmed carpal tunnel syndrome who were treated with a local injection of 4 mg of dexamethasone. This resulted in significantly reduced pain levels (61). Surgical intervention is controversial because most patients improve with conservative measures alone. In cases where symptoms fail to resolve after pregnancy, surgical intervention may be warranted. This number may be higher than previously expected. A retrospective study suggested that symptoms continue in 50% of patients at 1 year after delivery and in about 30% of patients at 3 years (71).

Lumbosacral radiculopathy. Low back pain or pain over the lumbar region is extremely common in the general population and in the pregnant population. The incidence of low back pain was found to be 56% in a cohort of 200 pregnant women (25). In the same group of patients, the onset of the back pain occurred between the 5th and 7th month of pregnancy in 60.7% of mothers. However, a severe herniated disc causing significant symptoms is rare with a reported incidence of 1:10,000 pregnancies (53).

There are several factors that may influence the incidence of low back pain and radiculopathy during pregnancy, including lumbar lordosis, direct pressure from the gravid uterus, postural stress, and ligamentous laxity due to the hormone relaxin (88). Spinal anesthesia during delivery may also be a factor in developing back pain. Complications of epidural anesthesia are rare (0.1% or less), but may include epidural hematoma, abscess, chemical radiculitis or arachnoiditis, direct needle injury to a nerve root, or anterior spinal artery infarction (46). Rarely, a sacral fracture secondary to pregnancy-induced osteoporosis may occur and mimic radiculopathy (73; 94).

In the majority of patients, sacral and lumbar low back pain improves without intervention within 6 months after delivery (70). Conservative management including activity modification, analgesics, and physical therapy should be attempted first. In patients with exam findings indicating nerve root compression or myelopathy, MRI is considered the test of choice. The 2004 American College of Obstetrics and Gynecologists’ guidelines state that MRI is not associated with known adverse fetal defects, but contrast agents should be avoided unless medically necessary. Electromyography (EMG) is another diagnostic test that could be considered to determine which nerve root is involved. According to the American Association of Neuromuscular and Electrodiagnostic Medicine, EMG is safe in pregnancy as long as muscles near the developing fetus, such as the diaphragm, are avoided. Spinal surgery has been successfully completed during pregnancy in cases of severe disc herniation (02).

Other common mononeuropathies: meralgia paresthetica, femoral mononeuropathy, obturator mononeuropathy, sciatic mononeuropathy, and peroneal mononeuropathy. Multiple mononeuropathies can occur during pregnancy and postpartum, but all are relatively rare. One study found that the two most commonly injured peripheral nerves are the lateral femoral cutaneous nerve and the femoral nerve (109). The lateral femoral cutaneous nerve is frequently compressed near the attachment of the inguinal ligament to the anterior superior iliac spine. This syndrome of compression of the lateral femoral cutaneous nerve producing pain and paresthesias is called meralgia paresthetica. Femoral neuropathy may also occur during pregnancy. The femoral nerve can be injured by a retractor during cesarean delivery. It can also be compressed in the vicinity of the inguinal ligament during labor with thigh flexion, external rotation, or abduction (109). Less commonly, labor can result in damage to the obturator or sciatic nerves. The obturator nerve lies deep in the pelvis, but it can be compressed by the fetal head or forceps during delivery (109).

Postpartum neurologic complications after delivery occur in up to 1% of all deliveries (74). The factors associated with nerve injury include nulliparity and prolonged second stage of labor (109). Foot drop is often reported after delivery (100). This may result from a variety of lesions, including injury to the L5 root, lumbosacral plexus, sciatic nerve, or common peroneal nerve at the fibular head. The peroneal component of the sciatic nerve is often preferentially affected by compression of the fetal head or forceps, due to its proximity to the bony pelvis (109). The diagnosis can be made by EMG, but the diagnostic yield may be improved by waiting until 2 to 3 weeks after the injury to perform the initial study. In years past, peroneal mononeuropathy was more common. It is believed that peroneal mononeuropathy occurred more commonly in the past secondary to inappropriate leg positioning in stirrups during prolonged labor where pressure was applied to the lateral knee (109; 88). Peroneal neuropathy is also reported from compression of the distal posterior thigh by the patient’s dominant hand during labor in the setting of epidural anesthesia (78).

Overall, the prognosis for recovery of a compression mononeuropathy is good. Most patients have full recovery in 6 months. In a review article, the recovery was estimated to be between 3 to 6 months for demyelinating injuries or longer for axonal injury (88). Conservative measures such as physical therapy, bracing, and walking assist devices are commonly found helpful.

Demyelinating neuropathies (AIDP and CIDP). The incidence of acute inflammatory demyelinating polyradiculoneuropathy (AIDP), or Guillain-Barre syndrome, in both the general population and the pregnant population is 0.75 to 2 in 100,000 (81). However, an article puts the incidence of acute inflammatory demyelinating polyradiculoneuropathy to be even lower, at 2.4 cases per million (63). As in the general population, there is an association between vaccinations, bacterial and viral infection, and AIDP during pregnancy. In 2013 there was a report of a pregnant patient who developed AIDP 10 days after receiving the H1N1 vaccination (07). One patient with ZIKA viral infection was also reported with AIDP at 28 weeks gestation who subsequently recovered and delivered a healthy full-term baby (12). There are also multiple reports of AIDP during pregnancy or postpartum after COVID-19 infection (30; 99).

When AIDP does occur during pregnancy, the majority of reported cases occur in the third trimester or within the first 30 days postpartum (10). A similar observation was seen in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). One study of 16 women with CIDP had a significant increase in the number of relapses during pregnancy, especially during the third trimester or immediate postpartum period (59).

In general, most patients recover completely after AIDP, but about 10% have some residual disability. The mortality rate is 3% to 5%, with most deaths related to respiratory failure, aspiration, or complications of immobility (103). Most pregnant women with onset in the last trimester worsen until delivery, but then improve over weeks to months postpartum (65). Also, one third of women presenting with AIDP during pregnancy require respiratory support. Supportive care is essential including respiratory support and close cardiac monitoring. Precautions should be taken to prevent venous thrombosis.

The typical acute treatments for AIDP and CIDP include plasmapheresis and IVIG; both must be used cautiously during pregnancy (51; 110). The potential harmful side effects of plasmapheresis include volume status problems such as hypovolemia or hypervolemia, transfusion related infections, and transfusion reactions such as urticaria and anaphylaxis (107). Plasmapheresis is typically given every other day for a total of five transfusions. The main risk of IVIG in pregnancy is thromboembolism (88). Intravenous or oral corticosteroids have been shown to be beneficial for short-term treatment of CIDP but are not beneficial in AIDP (41; 56).

In regard to the delivery, AIDP does not seem to cause impairment of uterine contraction. Thus, it is not felt that AIDP is an indication for cesarean section (10). Epidural anesthesia is generally considered safe, but there have been some reports of worsening in neurologic symptoms in patients with AIDP who undergo regional anesthesia (10). However, if general anesthesia is used during pregnancy, caution should be taken with the use of succinylcholine, which has been shown to cause hyperkalemia in patients with AIDP. This is thought to occur because of the postsynaptic receptor proliferation that is seen with AIDP (26).

The effect of pregnancy and delivery on preexisting neuromuscular disorders

There are important considerations to be aware of in pregnant women with neuromuscular disorders such as hereditary neuropathies, myasthenia gravis, myopathy, and motor neuron disease. Women with hereditary neuromuscular conductions may experience worsening of their symptoms during pregnancy. Also, management may need to be modified during pregnancy.

Hereditary sensory and motor neuropathy. The effect of hereditary sensory and motor neuropathy, such as Charcot-Marie-Tooth on pregnancy and delivery, is variable. In a study, women who developed Charcot-Marie-Tooth type 1 in early childhood had a 50% risk of developing worsening symptoms during pregnancy. Progression of symptoms was temporary, occurring in about 33%, but continued deterioration occurred in 22% of pregnant women (03). Compared with healthy controls, patients with Charcot-Marie-Tooth had similar birth complications overall. Earlier publications did show an increased incidence of fetal presentation anomalies, forceps usage, cesarean section, and postpartum bleeding in patients with Charcot-Marie-Tooth (40), but this was not confirmed by more recent data (03).

The general care for patients with Charcot-Marie-Tooth is supportive. Prosthetic assist devices, walking assistance devices, and physical therapy are beneficial. At the time of delivery, if general anesthesia is needed, succinylcholine should be avoided because of risk of hyperkalemia (89).

Myasthenia gravis. Myasthenia gravis is an autoimmune disease that may develop for the first time during pregnancy or in the postpartum period. Myasthenia gravis occurs in 1:10,000 to 1:50,000 women of reproductive age (20).

Transient neonatal myasthenia gravis can occur in the newborn of myasthenia mothers in the first few hours to days after birth. Transient neonatal myasthenia gravis occurs in about 12% to 20% of infants of mothers with myasthenia gravis (62; 21). However, it is difficult to predict which infants will be affected by transient neonatal myasthenia gravis because there does not seem to be a clear correlation with severity of active disease in the mother and development of symptoms in the infant. High levels of acetylcholine receptor antibodies in the mother or infant do not necessarily correlate with more severe disease. Transient neonatal myasthenia can even occur in infants of myasthenic mothers who are in clinical remission. However, there does seem to be some correlation between the severity of transient neonatal disease and a high ratio of anti-fetal to anti-adult acetylcholine receptor antibodies (05). High levels of the anti-fetal acetylcholine receptor generated by the mother can rarely result in alteration in fetal muscle development leading to persistent facial and bulbar weakness or fetal arthrogryposis (104; 69). Antimuscle specific kinase (MuSK) can also cross the placenta and result in transient neonatal myasthenia (66). However, one retrospective publication of 14 MuSK myasthenic pregnancies all resulted in healthy infants (36).

The highest risk of exacerbation in a pregnant patient with myasthenia gravis appears to occur if pregnancy occurs within the first year of diagnosis, if an infection develops, or if the patient has an abnormal repetitive nerve stimulation test (20; 21). The clinical outcome of pregnant women with myasthenia is variable, with some patients remaining stable or improving and others worsening. Worsening of symptoms was most likely to occur in the first or second trimester or first month postpartum but can occur throughout pregnancy (05; 21). Worsening was more likely to occur in patients whose disease was not under good control at the time they became pregnant. Patients should be encouraged to plan their pregnancy in consultation with their treating obstetric and neurology physicians (67). However, pregnancy outcome can be favorable in patients who receive appropriate care.

Pyridostigmine, prednisone, plasmapheresis, and IVIG are generally considered to be safe for treating myasthenia gravis during pregnancy. There are multiple treatment options that have been successful in helping pregnant patients. The mainstay of symptomatic treatment for myasthenia gravis is oral pyridostigmine. Pyridostigmine should be started at three divided doses of 60 mg and increased as tolerated and as needed. Neostigmine can be administered intramuscularly during labor or if oral medications cannot be given. However, care must be taken to convert the pyridostigmine dose to neostigmine. Pyridostigmine 60 mg is equivalent to neostigmine 0.5 mg IV or 1.5 mg IM. Intravenous cholinesterase inhibitors should be avoided prior to onset of labor because they may result in premature labor. Prednisone and methylprednisolone are category C medications and are considered safe in moderate doses. They are often used to treat myasthenia gravis during pregnancy and should be used at the lowest possible effective dose. Oral prednisone is the recommended immunosuppressant during pregnancy (86). However, fetal adrenal suppression after delivery has been reported in mothers treated with long-term prednisone (52).

Plasmapheresis and IVIG can safely be used and are effective for more severe symptoms of myasthenia gravis as well as exacerbations of symptoms during pregnancy. The main risk of plasmapheresis is hypotension due to massive fluid shifts and coagulopathy. Although IVIG can cause hyperviscosity, volume overload, aseptic meningitis, and hypercoagulability, it is generally the preferred treatment because of its established safety profile during pregnancy in other neurologic diseases such as relapsing-remitting multiple sclerosis (22; 28). IVIG may even be used as IV monthly maintenance therapy (29).

Methotrexate is a folate inhibitor associated with congenital malformations and is absolutely contraindicated in pregnancy and breastfeeding. If used pre-pregnancy, a washout period of at least 3 months is recommended before conception. Other immunosuppressants such as azathioprine, cyclosporine, mycophenolate, methotrexate, cyclophosphamide, tacrolimus, rituximab, and eculizumab are used to treat myasthenia in the general nonpregnant population but may need to be avoided during pregnancy. However, azathioprine can be used with caution during pregnancy and breastfeeding, although it is a pregnancy class D medication (67; 86; 33). Lab work is required to monitor for leukopenia and liver toxicity while taking azathioprine. Azathioprine may cause sperm mutagenesis and should be stopped 3 months prior to conception in male partners (90). Cyclosporine does not appear to have any major risk for birth deformities and may also be considered for use during pregnancy. Mycophenolate is associated with miscarriage, premature birth, and birth defects and should be avoided during pregnancy. Methotrexate is a pregnancy category X medication and is associated with congenital malformations. There is also a publication of a pregnant Chinese patient with anti-MuSK antibody myasthenia who had improvement with rituximab in the postpartum period. Rituxan could be considered, although questions remain about the safety of rituximab during pregnancy and lactation (54). Only prednisone, pyridostigmine, IVIG, and azathioprine have safety data to support their use during breastfeeding (18; 04). Eculizumab may also be considered for use during pregnancy in refractory patients (87).

If a patient has been asymptomatic for more than a year prior to pregnancy, consideration should be given to reducing and stopping immunosuppressants at the beginning of the pregnancy or prior to contraception (preferably). Although there are no published guidelines regarding the discontinuation of medications, as a general rule, a taper can be attempted if a patient has achieved remission of myasthenic symptoms for 1 to 2 years. Per the MGFA class 1 definition, remission occurs when there is resolution of all muscle weakness and cranial nerve symptoms, except for mild eye closure weakness. The most successful tapers occur after the disease is under control or when it has been in remission for 4 to 5 years.

The rate at which myasthenic medications can be tapered differs depending on the medication. Close monitoring for recurrent symptoms once medications are discontinued is advised. About 30% to 50% of patients may experience a relapse after discontinuation of immunosuppressants (34; 68). Pyridostigmine can be tapered at 30 mg per week, although patients often tolerate faster tapering. Prednisone should be tapered more slowly, eg, by reducing the dose by 5 mg per month down to 20 mg per day and then reducing the dose in 2.5 mg intervals. A thymectomy may increase the chances of a successful taper of prednisone. Mycophenolate and azathioprine are often also tapered slowly. One author recommends reducing azathioprine by 25 mg every 6 months and mycophenolate by 500 mg every 6 months (24). In a study, about two thirds of patients treated with azathioprine were able to successfully taper down and discontinue azathioprine over 1 to 2 years (34). However, about a third of patients who were tapered off azathioprine relapsed within 1 year. In another study, two thirds of patients on mycophenolate were able to successfully taper and discontinue mycophenolate use after being treated for approximately 6 years, with an average dose of 2344 mg/day (39). The most successful tapers of mycophenolate occurred over about 5 years. Ideally, the reduction in dose should be slow, eg, by 500 mg per year. This type of slow taper may not be feasible prior to pregnancy unless the pregnancy is planned well in advance.

Table 1. Medications Commonly Used in Myasthenia Gravis: Safety During Pregnancy

Whether or not patients with myasthenia gravis have increased rates of pregnancy complications compared to the general population is debated. Myasthenia gravis does not affect uterine smooth muscle, but it may affect the striated muscles that are needed during voluntary pushing in the second stage of labor. However, the number of forceps deliveries or vacuum extractions needed during the second stage of labor is no greater than in the general population (108). Epidural anesthesia is preferred over general anesthesia for surgical delivery. Nondepolarizing muscle relaxants may cause prolonged or exaggerated reactions in myasthenic patients. Spontaneous abortion in the first trimester may improve myasthenic exacerbations, but elective cesarean section can cause worsening of myasthenic gravis (14). Magnesium sulfate used to treat preeclampsia can also worsen myasthenia by inhibiting acetylcholine release and should be avoided. Also, caution should be used when treating hypertension in myasthenic patients with a beta blocker as this can increase the risk of an exacerbation. Patients with myasthenia should be encouraged to proceed with vaginal delivery at term whenever possible as general anesthesia can lead to worsening disease (67; 21). Epidural anesthesia, combined spinal epidural anesthesia for caesarian section, and nitrous oxide are all considered safer methods of anesthesia in patients with myasthenia gravis.

Inflammatory myopathies. Inflammatory myopathies such as dermatomyositis and polymyositis are rare with only five cases per million (88) and only 14% of those occur in women who are of childbearing age (72). One case series of four pregnant patients with inflammatory myopathy found no increase in disease activity during pregnancy. This was confirmed in a cohort of 14 women, of which 11 had uncomplicated pregnancy and delivery (76). However, in a larger review, there was an increased risk of preterm delivery, low birthweight, and cesarian section in patients with inflammatory myopathy (11). However, there did seem to be an inverse relationship between more active disease and poor fetal outcome. Patients with active disease had a higher rate of spontaneous abortion or pregnancy loss (93). Patients with well-controlled inflammatory myopathies tend to have fewer complications (58) and may even have improvement during pregnancy (76). Hypertensive disorders such as preeclampsia and eclampsia may be more likely to occur in patients with dermatomyositis or polymyositis (50). Also reported was an increased risk of idiopathic inflammatory myositis beginning 1 to 3 months postpartum (96).

The first-line treatment for dermatomyositis and polymyositis is corticosteroids, which can be used with caution during pregnancy (class C). IVIG is also effective for steroid-resistant myositis (17). IVIG and corticosteroids have also been combined and used successfully to treat dermatomyositis in pregnancy (55). Uterine contractility is generally not affected by dermatomyositis or polymyositis, but these patients may need to be assisted with forceps or vacuum extraction if significant muscle weakness is present (88).

Muscular dystrophies. Myotonic dystrophy can have a variable course during pregnancy and likely depends on prepregnancy disease severity. Muscle weakness may be unchanged or may gradually worsen (44). However, women with myotonic dystrophy type 1 (DM1) have a higher risk of pregnancy complications such as ectopic pregnancies, urinary tract infections, placenta previa, spontaneous abortions, premature delivery, polyhydramnios, and neonatal death (44; 85; 88). Preeclampsia may also be more common. Late-term spontaneous abortions occur in 4% of pregnancies, and only 50% of pregnancies reach full term in patients symptomatic with myotonic dystrophy (85). Uterine smooth muscle can be affected by myotonic dystrophy, making assistance with forceps or vacuum extraction necessary. Rates of postpartum maternal hemorrhage are also higher in patients with myotonic dystrophy, which could necessitate emergent hysterectomy (88). The child may also have congenital myotonic dystrophy and present with respiratory distress, hypotonia, muscle weakness, and feeding difficulties. Polyhydramnios occurs in pregnancies with fetuses with congenital myotonic dystrophy (83). At the time of delivery, preparations should be taken to care for infants affected with congenital myotonic dystrophy. The role of the length of cytosine-thymine-guanine (CTG) expansion on pregnancy outcomes is not known. It is also not known if pregnancy complications are secondary to maternal or fetal muscle disease. Often mothers are not diagnosed until after their child is diagnosed with congenital myotonic dystrophy. Anticipation can occur with maternal transmission, which can result in larger repeat size in offspring.

However, women who carry the diagnosis of myotonic dystrophy type 1 have undergone successive preconception genetic testing and in vitro fertilization (102). DM1 patients who do undergo preimplantation genetic testing have lower success rates compared with healthy age-matched controls. DM1 patients also have lower ovarian reserve compared with age-matched controls (95).

Medications used during delivery can be associated with complications in patients with myotonic dystrophy. Respiratory depression can occur after use of depolarizing neuromuscular blockade. Whenever possible, general anesthesia should be avoided. Also, labor stimulants such as ritodrine, a beta-adrenergic agonist, may worsen myotonia and cause rhabdomyolysis (64). Care should also be taken with the use of magnesium sulfate for tocolysis because it may result in severe weakness and respiratory compromise in myotonic dystrophy type 1 (09). Recurrent episodes of myotonia associated with increased creatinine kinase have also been reported during pregnancy in patients with myotonic dystrophy (06).

Not as much is known about nondystrophic myotonias, such as myotonia congenita, during pregnancy. One study of pregnant patients with nondystrophic myotonia reported increased weakness and myotonia in just over half the patients during pregnancy, with the majority returning to their previous baseline within 3 months postpartum (98). Another small study of patients with nondystrophic myotonia and periodic paralysis reported similar decline during pregnancy (84).

Facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, and congenital myopathies do not have a higher risk of preterm labor compared with the general population (82). There are conflicting data regarding pregnancy outcomes in patients with facioscapulohumeral muscular dystrophy, as data suggest that the complication rate is similar to the general population (03). Some patients with facioscapulohumeral muscular dystrophy experience worsening muscle strength during pregnancy (15) and higher rate of low birth weight. Worsening strength during pregnancy is also reported in limb-girdle muscular dystrophy and congenital myopathies (82). There is an increased risk of abnormal fetal presentation in patients with muscular dystrophy, especially those who are wheelchair bound (03).

Metabolic and congenital myopathies. Familial hypokalemic periodic paralysis occurs in attacks triggered by stress and diet. Pregnant patients with familial hypokalemic periodic paralysis may need intravenous supplementation of potassium and close monitoring during delivery (105).

There are also a few reported cases of mitochondrial myopathy in pregnant females. The course of mitochondrial myopathies is variable. One case reported postpartum hemorrhage requiring emergent hysterectomy (19).

Patients with central core myopathy, mini-core myopathy, and some other congenital myopathies with cores and rods are at high risk for malignant hyperthermia with anesthesia (80). Care should be taken to either avoid operative delivery or avoid the use of medications that may lead to the development of malignant hyperthermia in these patients. The halothane caffeine test could be used to evaluate for a predisposition to malignant hyperthermia prior to pregnancy.

Cardiac dysfunction is known to occur in some patients with congenital muscle disorders, such as carriers of Duchene or Becker muscular dystrophy. However, there is a report of a pregnant Bethlem myopathy patient who had progressive cardiomyopathy during pregnancy. This was unusual, as Bethlem patients do not typically have cardiac dysfunction. She improved after giving birth (27).

There is little information available regarding pregnant women with metabolic myopathies, such as Pompe disease. However, there is a published cohort of pregnant women with Pompe who were able to successfully carry to term while on enzyme replacement (32).

Motor neuron disease. There are few reported cases of motor neuron disease in pregnancy. The most common motor neuron diseases are amyotrophic lateral sclerosis and spinal muscular atrophy. Patients with spinal muscular atrophy have successfully completed pregnancy and delivery (08). A questionnaire-based study of women with spinal muscular atrophy reported increased weakness during pregnancy and 42% reported continued weakness postpartum (23). However, the majority of mothers with spinal muscular atrophy in this study reported overall positive pregnancy outcomes. This data could be useful when counseling women, especially as gene therapy improves the health of women with spinal muscular atrophy, making it more likely they would consider pregnancy. Both nusinersen and risdiplam are not recommended during pregnancy because of concern for fetal harm in animal studies (45).

Amyotrophic lateral sclerosis (ALS) rarely occurs during pregnancy, as it typically affects older adults. However, there are multiple reports of women developing symptoms of amyotrophic lateral sclerosis during pregnancy. When it does occur, it is most likely to begin with limb rather than bulbar onset. One report is of a 33-year-old female with amyotrophic lateral sclerosis who delivered a healthy full-term baby but then had significant worsening strength and bulbar function by 6 weeks postpartum (77). Other reports suggest progression of amyotrophic lateral sclerosis can stop during pregnancy, leading to questions about how hormones can affect the course of amyotrophic lateral sclerosis (35).

An analysis of five patients who developed amyotrophic lateral sclerosis during pregnancy found an increased rate of pathologic mutations in the superoxide dismutase 1 gene and an association with a particular vascular endothelial growth factor haplotype (57). This publication, along with previous case reports, suggests that patients who develop amyotrophic lateral sclerosis during pregnancy are more likely to have a family history of amyotrophic lateral sclerosis, and have a genetic predisposition to develop the disease (43; 57). Riluzole has not been shown to cause complications when taken during pregnancy (48). There is little information on the use of edaravone in pregnancy.

Patients with motor neuron disease may deliver vaginally because uterine muscles are unaffected. However, caesarian section should be favored if respiratory compromise is present (88).

Clinical vignette

A 30-year-old, previously healthy female gave birth to a baby boy at 37 weeks. The pregnancy was complicated by polyhydramnios. The infant was born by vaginal delivery after prolonged labor. Forceps were used to aid in the delivery. The infant had low Apgars and respiratory distress at birth. He required respiratory support with blow-by oxygen. Examination of the infant showed low birth weight, hypotonia, and tented upper lip. The infant had inability to latch and suckle. Examination of the mother showed temporalis muscle wasting, weakness of finger flexors, and percussion myotonia at the thenar eminence in the hands.

The infant most likely has congenital myotonic dystrophy secondary to a maternally inherited expansion of the CTG repeat. The mother also has myotonic dystrophy, but her disease is much less severe. Often a mildly symptomatic parent is not discovered until after the birth of an infant with congenital myotonic dystrophy.