Obstetric management of a woman with limb-girdle muscular dystrophy type 2i and dilated cardiomyopathy

Short abstract

Limb-girdle muscular dystrophy describes a clinical phenotype with progressive weakness and atrophy of the muscles of the shoulders and hips. One of the more common types, limb-girdle muscular dystrophy type 2i, is associated with impaired cardiac function and restrictive lung disease, typically disproportionate to muscular disease. This condition presents a number of complex challenges in pregnancy and there are few case reports of its successful management. Here we discuss the course of the first pregnancy of a 20-year-old woman with limb-girdle muscular dystrophy type 2i.

Case report

Pre-pregnancy

A 20-year-old woman was referred to our unit for pre-pregnancy counselling. She had been diagnosed with limb-girdle muscular dystrophy type 2i (LGMD2i) by muscle biopsy at 15 years of age following investigation for leg weakness. Subsequent routine cardiac screening had demonstrated a reduced left ventricular ejection fraction (LVEF) of 45% with normal LV diastolic diameter (5.3 cm) and at this time she had no cardiac symptoms. She had been using a wheelchair for the three years preceding her pre-pregnancy counselling appointment as a result of increasing muscle weakness. Her body mass index was 34 kg/m². At the time of pre-pregnancy counselling, she remained asymptomatic with regard to her cardiac condition, but assessment of her functional class was precluded as a result of her limited mobility. She could stand at home for periods of up to 15 minutes but required standing aids and slings for transfer. She was taking 2.5 mg ramipril and 20 mg citalopram daily and was a current smoker (14–20 cigarettes per day). Assessment of her cardiac function at this time suggested a stable LVEF on echocardiogram with an incomplete right bundle branch block on electrocardiogram. Her cardiac disease in pregnancy (CARPREG) score was zero and thus her risk of cardiac complications was estimated to be 5% using this tool. In line with current guidelines, it was recommended that her angiotensin converting enzyme (ACE) inhibitor was stopped on the first positive pregnancy test and careful monitoring of cardiac function to be carried out. She was strongly encouraged to stop smoking.

Early pregnancy

Six months later, she became pregnant and stopped the ramipril after the positive pregnancy test. A Holter ECG recording demonstrated no rhythm disturbances. She had stopped smoking. She was taking folic acid (5 mg daily) and pregnancy multivitamins. She then started aspirin (75 mg daily) and dalteparin (5,000 units daily) at 7 weeks of gestation. She was referred to the manual handling team for review of her mobility, and the practical issues that might arise during her pregnancy and at delivery. Proximal muscle weakness of her upper limbs was felt to make manual assistance of transfer extremely difficult. At this time, it was felt there were no contraindications to a spontaneous vaginal delivery, as LGMD does not affect uterine smooth muscle. However, there was a low threshold for assistance in the second stage to limit maternal effort. The patient would be admitted at 38 weeks and four days of gestation (or a week earlier if signs of cervical ripening) to ensure appropriate equipment was available to facilitate delivery. The increased risk of emergency caesarean section was discussed, together with the possibility of a malignant hyperthermia developing, and she was referred to the obstetric anaesthetists. Due to the autosomal recessive nature of LGMD2i, paternal genetic testing was performed and was negative. An echocardiogram at seven weeks showed a stable LVEF (45%), and she had no cardiac symptoms. A BNP measurement was taken at 15 weeks for prognostic purposes (levels over 100 pg/ml have been associated with an increased risk of cardiac events in women with cardiac disease²). Although her level was mildly elevated at 188 pg/ml, she was tolerating her pregnancy well. She was managed jointly throughout her pregnancy by a maternal medicine specialist and cardiologist.

Late pregnancy

At 25 weeks of gestation, lung function testing was performed and a mild restrictive pattern was identified with a forced vital capacity (FVC) of 70%. At 28 weeks of gestation she developed exertional breathlessness and palpitations but an echocardiogram at this time showed her cardiac function to be stable (LVEF = 40%). Subsequently her breathlessness continued to deteriorate, and at 33 weeks of gestation, she attended the emergency department with new-onset chest pain that was central and aching in nature and accompanied by intermittent episodes of shortness of breath. In light of these symptoms she was reviewed in a tertiary unit combined obstetric cardiology clinic. A repeat echocardiogram there confirmed LVEF was stable at 40%. Her breathlessness was attributed to a combination of pain in the chest wall during movement, limited mobility, a third trimester pregnancy and her restrictive lung condition. She was reassured and plans for supportive care and delivery in her local consultant-led obstetric unit were pursued.

At 37 weeks and 6 days of gestation she was admitted electively to the antenatal ward to await spontaneous onset of labour. An elective admission meant that she was able to bring in the relevant equipment (wheelchair and transfer aids) which would not have been possible in an emergency ambulance transfer.

At 38 weeks and 6 days of gestation, a persistently suspicious cardiotocograph (CTG) trace with unprovoked decelerations was seen. This, in combination with reduced growth velocity reported on the fetal scans, (the fetus was below the 5th centile at 37 weeks) prompted a decision to perform an elective lower segment caesarean section (LSCS) in order to avoid the high probability of an emergency intrapartum LSCS for fetal distress. A combined spinal-epidural was inserted but was technically challenging and required three attempts. An uncomplicated LSCS was performed. Her infant was small for gestational age with birthweight 1960 g. APGAR score was 9 at both 1 and 5 min. Grade 2 meconium was noted with a small, ragged placenta. The infant required admission to the neonatal unit for 14 days. The mother’s recovery was complicated by an episode of pleuritic chest pain, which was not consistent with a coronary event (cardiac enzymes were negative), or resulting from her dilated cardiomyopathy. CT pulmonary angiogram was negative for a pulmonary embolus. However her temperature and CRP were raised and she received intravenous antibiotics. Blood cultures were subsequently reported as negative, and antibiotics were stopped. She remained an in-patient for 14 days, allowing for ongoing support to improve her mobility post-delivery and resolution of her chest pain. During her inpatient stay, she attempted to breastfeed but found this tiring, even with the use of a sling, and so decided to express instead. As she was breastfeeding she was restarted on 2.5 mg enalapril postnatally. Thromboprophylaxis was continued for six weeks post-partum. She was seen for follow-up at six weeks where both mother and baby were well, and she continued to receive support from occupational therapy regarding her ongoing mobility needs.

Discussion

A variety of mutations in proteins throughout the muscle fibre are found in LGMD. Mutations in the fukutin-related protein (FKRP gene) are responsible for LGMD2i and account between 25% and 40% of LGMD cases.³ LGMD2i typically presents in the second decade of life and is characterised by cardiac and respiratory dysfunction which may be disproportionate to the severity of muscular disease.⁴ Weakness and wasting of the proximal muscle group occurs – specifically the muscles of the shoulders, upper arms, pelvic area, and thighs. Cardiac dysfunction typically manifests as a dilated cardiomyopathy.⁵ A decline in FVC is also common. Calf hypertrophy and exaggerated lumbar lordosis are other phenotypic features highly associated with LGMD2i.

Pregnancy in women with LGMD therefore presents several challenges. Cardiovascular adaptations to pregnancy will place additional strain on the heart in order to provide sufficient blood to the placenta, which can cause a deterioration in the maternal condition if the ejection fraction is already compromised. Additionally, as the fetus grows and the uterus splints the diaphragm, a decline in respiratory capacity can be expected. This may necessitate pre-term caesarean section, contributing to the higher rates of caesarean sections seen in patients with muscular dystrophy.⁶

Operative delivery is also complicated by the condition. The lumbar lordosis, exaggerated further by pregnancy, makes the placement of epidural anaesthesia more challenging.⁷ Furthermore, patients with LGMD show an increased sensitivity to anaesthetic agents such as non-depolarising muscle relaxants, sedatives and analgesia. They also have an increased risk of malignant hyperthermia with succinylcholine or inhalational anaesthetics.⁸ The anaesthetic management of LGMD women at delivery is discussed extensively elsewhere.^8–10 In our case, the woman required delivery by caesarean section due to a persistently suspicious CTG tracing. However, vaginal delivery is possible and has been reported.^11,12

The largest study of obstetric outcomes in women with LGMD includes 22 patients who delivered 29 children. This study reported a high proportion of breech presentations in women with LGMD which was postulated to be related to mobility in pregnancy and wheelchair use.¹³ Increased breech presentation has also been reported in patients with Duchenne muscular dystrophy, again thought to be related to pelvic muscle weakness and decreased mobility.¹⁴ This, in part, might explain the increased rate of caesarean sections found in women with LGMD.¹³

The obstetric management of women with LGMD and cardiac complications has not been reported in the literature. In our patient, pregnancy was tolerated well with only a small decline in LVEF towards the end of pregnancy. The woman initially remained asymptomatic with regard to her cardiac disease and although she developed shortness of breath and chest pain later in her pregnancy, this was not thought to be due to a decline in cardiac function. Women with LGMD and pre-pregnancy cardiac disease require management by a multidisciplinary team, ideally in a joint obstetric and cardiology clinic. Where this is not possible, women should be managed by an obstetrician with a specialist interest in maternal medicine, with input from a cardiology consultant. Echocardiography should be performed in pre-pregnancy, early pregnancy and at least once in later pregnancy, depending on symptoms.

In addition, these women should have lung function tests performed in the second half of pregnancy. This is important for determining how the woman’s respiratory function is being affected by the increasing size of the gravid uterus and has implications for anaesthetic management around delivery.

Close fetal surveillance with serial ultrasound scans are important for monitoring fetal growth. Small-for-gestational-age infants have been reported in women with muscular dystrophy and this was also the case in our patient.^13,15 In addition, pregnancies complicated by compromised maternal cardiac function are at increased risk of uteroplacental insufficiency and resultant fetal growth restriction. In retrospect, earlier elective delivery could have been considered when the growth scan demonstrated reduced growth velocity at 37 weeks of gestation.¹⁶

We would suggest all women with LGMD, even those who remain stable during pregnancy, should be reviewed postnatally to assess for deterioration.^13,17 Women particularly at risk of worsening symptoms during pregnancy are those with early-onset disease and progressive myopathy.¹⁸ This has implications for both long-term management of the condition and future pregnancies.

Conclusion

Management of women with LGMD and cardiac involvement is challenging. A multidisciplinary approach is required to formulate a tailored labour and delivery plan with input from obstetrics, cardiology, respiratory, anaesthetics and manual handling teams. With regard to cardiac function, patients should be seen regularly by both a senior obstetrician and cardiologist, and there should be a low threshold for referral to a tertiary centre with development of new symptoms.

Contributorship

The manuscript was written and prepared by CB and AvG under the direction of SS. The final manuscript was edited by SS.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical approval

A statement of written consent for publication was signed by the patient.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Guarantor

SS