Wherever possible, pregnancy must be anticipated in women with Gaucher disease, as pregnancy can worsen signs of the disease. For example, worsening of thrombocytopaenia and coagulation disorders could lead to post-partum haemorrhage and induce bone pain.1 Skeletal manifestations can also be exacerbated in pregnant patients with Gaucher disease.2 Moreover, the signs and symptoms of Gaucher disease may have an impact on pregnancy and birth. Hepatosplenomegaly may be massive and could affect the normal growth of the pregnancy, and bleeding tendency could become critical during and after birth. Bone involvement in Gaucher disease, such as avascular necrosis of the hip joints, may also affect the choices of mode of delivery.3 However, women with Gaucher disease should generally not be discouraged from considering pregnancy, unless there are clear contraindications, such as moderate-to-severe pulmonary hypertension, which is rare in Gaucher disease, or comorbidities that are unrelated to the disease.4,5
What are the recommendations for managing pregnant patients with Gaucher disease?
As outlined in Granovsky-Grisaru et al. Eur J Obstet Gynecol Reprod Biol 2011, a group of experts in Gaucher disease reviewed current practices in the management of pregnancy in women with the disease. The experts agreed upon recommendations with the aim of helping clinicians to optimise the care of patients with Gaucher disease during pregnancy and delivery.5
Pregnancy and delivery
Firstly, the possible complications of pregnancy should be explained to patients with Gaucher disease, and, if possible, patients should be assessed in centres experienced in the management of the disease. Patients with Gaucher disease who have comorbidities should be individually assessed, and guidelines for that specific comorbidity should be followed; all medications should also be reviewed to assess compatibility with pregnancy. The genetic inheritance of Gaucher disease should be explained, in addition to carrier testing and prenatal screening, and genetic counselling should be made available.5
A multidisciplinary approach to pregnancy management is recommended; an anaesthetist, haematologist, obstetrician and orthopaedic specialist may need to contribute to the birth plan, alongside the Gaucher disease expert, who should be in regular contact with the patient. It is recommended that for patients who do not attend a major Gaucher disease centre, access to such a centre should be given. There is no additional requirement for routine antenatal monitoring of the foetus during pregnancy compared with non-Gaucher disease pregnancies.5
During the first antenatal appointment, a comprehensive assessment of the patient and a drafting of the birth plan should be discussed. Factors to consider in the birth plan include5:
- Preferred location of delivery
- Mode of delivery (including the possibility of an emergency caesarean section delivery)
- Pain-relief options (with specific discussion on epidural analgesia)
- Any limitations that may affect delivery.
It is not recommended that women with Gaucher disease have a home birth, even if they are asymptomatic, as they must have immediate access to blood transfusions from medical centres.5
Unless otherwise indicated, assessments during the second trimester should be conducted in accordance with local standard-of-care policies. The medication and nutritional status of the patient should be reviewed, and a dietary consultation before mid-pregnancy is advised; calcium, folic acid, iron and vitamin B12 supplementation is recommended if needed.5
Ideally, the third trimester assessment should take place in a centre with experience in the management of Gaucher disease. However, if this is not possible, then the assessment may be carried out locally, with the results communicated to a Gaucher disease centre. During this assessment, standard tests should be conducted, in addition to a risk-of-bleeding assessment (blood counts, coagulation profile and platelet-function tests). If blood clotting parameters are normal, it is recommended that the obstetrician may continue to follow-up with the patient. However, if these parameters are abnormal, follow-ups should include an expert in Gaucher disease, or a haematologist. It may also be beneficial for the patient’s obstetrician and Gaucher disease expert to discuss specific aspects of the delivery in the context of the disease, with recommendations included in the birth plan.5
It is advised that blood parameters are measured before delivery, unless results are available from the previous 14 days, as these may have changed. If mild thrombocytopaenia is detected for the first time in an otherwise uncomplicated pregnancy, this is unlikely to require special obstetric intervention, other than hospital delivery. Skeletal imaging should ideally be delayed until after delivery; however, symptomatic bone pain can be treated intensively with pain medications appropriate for pregnancy. If skeletal imaging does become immediately necessary, magnetic resonance imaging is preferred; however, X-ray imaging of the pelvis may be considered towards the end of pregnancy, if indicated for immediate orthopaedic rescue of the hip. If an increase in organ size is suspected during pregnancy, ultrasound monitoring of the liver and spleen may be necessary.5
Most deliveries can occur in local hospitals, assuming there is immediate access to a blood bank and blood products. There is no specific indication for caesarean delivery in patients with Gaucher disease, but if necessary, a midline longitudinal incision should be avoided in patients with hepatomegaly and/or splenomegaly unless there is an obstetrical indication. Epidural anaesthesia is generally not contraindicated in Gaucher disease, unless platelet counts are <70 x 109/L or not functioning normally. Care should also be taken not to place pressure on the abdomen during labour or caesarean delivery if the organs are enlarged.5
Patients who have experienced uncomplicated vaginal deliveries may be monitored post-partum as inpatients, according to local healthcare policies. It is recommended that patients who have had a caesarean delivery should be monitored as inpatients for 24‒48 hours in the event of potential bleeding complications. The disease status and individual patient risk will dictate any other monitoring immediately after delivery, and additional supportive care. It is suggested that all women are reviewed 6 weeks post-partum by a Gaucher disease specialist, and particular attention should be given to bone disease parameters. The frequency of follow-up visits should be determined through collaboration between the attending physician and the Gaucher disease specialist.5
All medications should be reviewed during this stage for compatibility with breast feeding, and mineral and vitamin supplementations may be recommended, particularly calcium and vitamin D, to promote bone health.5 As a result of the potential risk of bone complications with reduced bone mineral density, breast feeding may not be recommended in patients with Gaucher disease for periods longer than 6 months.4,5 Therefore, breast feeding may be supplemented with formula, even in stable patients at risk of exacerbated bone disease and those receiving therapy for their Gaucher disease.5
Can patients with Gaucher disease receive therapy during pregnancy?
A study from the Gaucher Outcome Survey, an international Gaucher disease-specific registry (sponsored by Shire, now part of Takeda) established in 2010, indicated that the proportion of normal outcomes (live birth delivered at term with no congenital abnormalities) was comparable in enzyme replacement therapy-treated* (n=117; 68 patients) and untreated (n=336; 143 patients) pregnancies (91.4% vs 92.9%; p=0.6830). There were also no significant differences in the proportion of spontaneous abortions during treated and untreated pregnancies (6.9% vs 3.6%; p=0.1866). Of the women included in this study, 99.5% had Gaucher disease Type 1 (one patient had Gaucher disease Type 3); 57.4% of patients were homozygous for the N370S (c.1226A>G; p.Asp409Ser) mutation. These findings suggest that continuation of enzyme replacement therapy during pregnancy may be appropriate for women with Gaucher disease.6
*Of the 117 treated pregnancies, 63 were treated with imiglucerase, 36 with velaglucerase alfa, 6 with alglucerase and 6 with taliglucerase alfa; in 6 pregnancies, the treatment type was not specified6
C-ANPROM/INT//7568; Date of preparation: September 2020
- Haute Autorité de Santé. Gaucher disease: national diagnosis and treatment protocol. January 2007. Available at https://www.has-sante.fr/upload/docs/application/pdf/ven_gaucher_web.pdf. Accessed September 2020.
- Granovsky-Grisaru S, Aboulafia Y, Diamant YZ, et al. Gynecologic and obstetric aspects of Gaucher's disease: a survey of 53 patients. Am J Obstet Gynecol 1995; 172: 1284-1290.
- Elstein Y, Eisenberg V, Granovsky-Grisaru S, et al. Pregnancies in Gaucher disease: a 5-year study. Am J Obstet Gynecol 2004; 190: 435-441.
- Zimran A, Morris E, Mengel E, et al. The female Gaucher patient: the impact of enzyme replacement therapy around key reproductive events (menstruation, pregnancy and menopause). Blood Cells Mol Dis 2009; 43: 264-288.
- Granovsky-Grisaru S, Belmatoug N, vom Dahl S, et al. The management of pregnancy in Gaucher disease. Eur J Obstet Gynecol Reprod Biol 2011; 156: 3-8.
- Lau H, Belmatoug N, Deegan P, et al. Reported outcomes of 453 pregnancies in patients with Gaucher disease: an analysis from the Gaucher Outcome Survey. Blood Cells Mol Dis 2018; 68: 226-231.