Charcot-Marie-Tooth neuropathy and pregnancy: general and specific issues

Clinical picture of CMT

Women with CMT who plan to have a family are mostly affected by classical CMT disease. First symptoms usually occur in childhood or early adulthood with slowly progressive distal weakness and wasting. This leads to an abnormal gait, dropped foot and foot deformities. Weakness of hand muscles and deformities of fingers usually occur later in the course of the disease. CMT disease is most frequently autosomal dominantly inherited with a broad variability of age at onset, severity of symptoms and progression of disease. Despite the fact that many patients require special walking aids, only a small proportion of less than 5 % loses the ability to walk. However, there are many rare subtypes with atypical clinical findings and specific gestational implications [4].

Physiological changes in pregnancy

There are significant physiological changes occurring early in pregnancy and continuing throughout gestation [6]. The increase in plasma volume of 45–50 % has haematological effects such as a dilutional anaemia and a reduction in total plasma proteins. Thromboembolic risks are higher due to hormonal related increased clotting (and venous stasis). Maternal heart rate increases by about 20 %, and other cardiological changes include a rise in stroke volume and cardiac output by 30–50 %, while there are only minor changes in blood pressure. Respiratory changes include a rise in tidal volume and oxygen consumption starting in the second half of pregnancy, however routine spirometric tests remain essentially unchanged. There are immunological changes in pregnancy with infections being more common. Hormonal adaptations of the musculoskeletal system result in softening of ligaments, joints and smooth muscles but with no significant changes in skeletal muscles.

Due to the physiological adaptations and the increasing weight in pregnancy many patients with neuromuscular diseases experience a loss of mobility and strength during their second half of pregnancy which usually improves within weeks or months after delivery. The question of a lasting deterioration of muscle weakness caused by pregnancy and delivery is difficult to assess, since most hereditary disorders are progressive. The situation in pregnancy is more likely to remain unchanged if the patient has had long phases of clinical stability in her disease course.

Decisions when contemplating pregnancy

The process of decision making when contemplating pregnancy should start with the alternatives in the preconception planning phase [2]. Since CMT disease is most frequently autosomal dominantly inherited, there is often a 50 % recurrence risk to offspring. Prenatal or preimplantation genetic diagnosis may be discussed in the context of genetic counselling. Different pregnancy periods have to be considered in maternity care: the embryonic phase in the first trimester (miscarriage risk, teratogenicity of medication, prenatal testing), the foetal period in the second and third trimesters (foetal growth and development), delivery (presentation of foetus, spontaneous or operative delivery) and the postpartum period.

Course of pregnancy and delivery

Obstetric complications in both cohorts were not significantly different from a normal reference population (Table 1) [7]. Miscarriages occurred in 12.8 % of gestations. Only 2.2 % patients had gestosis/hypertensive disease in pregnancy, and there were no reports of polyhydramnios or placentation anomalies (placenta praevia or placenta accreta). Preterm delivery (below 37 weeks gestation) occurred in both cohorts with a slightly lower frequency than expected in the normal population. Presentation anomalies (breech or transverse presentation) were documented in 8.8 % and instrumental delivery (vacuum or forceps delivery) in 5.4 % of completed pregnancies (Table 1). The number of caesarean deliveries increased in the reference population during the study period from 15 % to 30 % and was within normal limits in our two study cohorts (11.1 % and 36.9 %). The proportion of primary and secondary caesarean sections was largely constant comprising about 50 % of each. In all caesarean sections, where details of anaesthesia were documented, spinal anaesthesia was administered in about 80 % and general anaesthesia in about 20 % of sections [4]. Generally, following Orphanet recommendations [8], regional anaesthesia is preferred over general anaesthesia in women with CMT neuropathy, however there is no clear rationale for this recommendation. In our study we did not find an adverse effect of general anaesthesia [4]. This is important information for patients who may have contraindications for epidural anaesthesia, e. g., patients with severe scoliosis or after spinal operation. In terms of analgesia or other medications, it has to be taken into account that neurotoxic substances should be avoided in CMT disease [8].

Newborn vitality

In both cohorts there was no increased neonatal morbidity and mortality as regards birth measurements, Apgar scores and clinical information. One newborn twin died of neonatal asphyxia in the context of prematurity being born at 29 weeks of gestation.

Influence on disease course

The severity of the disease – more progression rather than age at onset – influences the observation of any pregnancy related changes. The proportion of women who experienced a deterioration of symptoms in pregnancy was remarkably similar in both cohorts, comprising 37.8 % of pregnancies. After delivery worsening of neuropathy was reported in 31.1 % of gestations of the first cohort and in 37.5 % of the second cohort. However, in retrospect it was not possible to further evaluate an aggravating effect of gestation on the natural history of CMT disease. In the total cohort a deterioration was reported in pregnancy in 37.8 % (48 of 127) and after delivery in 34.6 % (44 of 127) of instances. Only in 2.4 % (3 of 127) of gestations an improvement in pregnancy or in 9.4 % (12 of 127) an improvement after delivery was noticed. For most patients deterioration had no significant impact on the handicap in everyday life. No adverse effects of anaesthesia were reported. While we found a correlation between age at onset and a negative influence of pregnancy on the disease course in the first cohort, this was not the case in the second cohort. Walking was maintained in nearly all patients who were still mobile at the beginning of pregnancy. There were four patients with a classical CMT disease who required walking aids at the time of delivery. One patient experienced significant worsening in and after pregnancy and was confined to a wheelchair and unable to rise from a sitting position following her first delivery (patient 2 from ref. [3]). Three patients were documented in the second cohort [4]. One patient with CMT2A used walking aids from early adulthood and did not report a change in mobility in her only pregnancy. Two patients with CMT1A were partly chairbound from youth and felt that there was no change or rather an improvement of motor functions in and after pregnancy.

Figure 2

Family picture of a study participant with CMTX who stressed the importance of medical advice and the awareness of challenges associated with pregnancy and who is active in her local self-support group.

Personal attitude and recommendations to other patients

The majority of participants stressed the value of a fulfilled family life and had a positive view of having children, despite being aware of the challenges associated with pregnancy (Fig. 2). Medical advice and expert opinion for specific medical interventions are recommended. Important issues are assistance and support in caring for the family. Women with a significant handicap will generally need help in the household and may have limited physical reserves for their tasks as a mother. Personal recommendations include a positive attitude and trust in own abilities. In the view of many mothers, children grow up in a different responsibility facing her mother’s handicap.