Advances in transplant surgery and immunosuppressive drug treatment have led to increasing numbers of women with transplanted organs choosing to embark on pregnancy. Pregnancy following renal transplantation is now almost commonplace, and successful pregnancy following liver, heart and heart-lung transplantation has been reported. The major considerations for the medical staff caring for the pregnant transplant recipient are the effects of immunosuppressive therapy, the alteration in physiological function of the transplanted organ and the impact of the physiological changes of pregnancy.
Problems and special considerations
Immunosuppressive therapy
All transplant patients are at risk of organ rejection and therefore require long-term immunosuppressive therapy. There is no evidence that pregnancy itself increases the risk of rejection, which, in the case of renal transplants, is about 10% in the first year and up to 40% after 5 years.
Infections, both bacterial and viral, are more common because of the immunosuppressed state, with urinary tract infections (already more common during pregnancy) the most frequent infectious complication. The immunosuppressed patient is at risk of infection with uncommon pathogens, and it is therefore important to take appropriate cultures before beginning treatment.
Immunosuppressive drugs include cyclosporin, azathioprine and corticosteroids. Frequent monitoring of drug levels is required because of the changing blood volume during pregnancy, weight gain and altered drug metabolism, although in some cases the dose requirement may be reduced rather than increased.
Cyclosporin is associated with systemic hypertension (caused by activation of the sympathetic nervous system), and women with transplanted organs also have an increased risk of developing pre-eclampsia - an incidence of 30% has been reported. Pre-eclampsia may be difficult to diagnose because of the pre-existing hypertension and proteinuria. There have also been reports of thrombotic complications occurring in patients receiving cyclosporin, leading to recommendations that prophylactic heparin should be considered during pregnancy.
Azathioprine is associated with abnormal liver function tests and thrombocytopenia.
The problems associated with long-term corticosteroid therapy are well known (see Chapter 150, Steroid therapy); of specific concern during pregnancy are hypertension and glucose intolerance. There is an increased incidence of hypertension and gestational diabetes post-transplantation, regardless of medication.
Immunosuppressive drugs are associated with a relatively low rate of fetal abnormality (cyclosporin is less teratogenic than azathioprine) but an increased rate of preterm delivery and fetal growth restriction.
Kidney transplant
Pre-pregnancy factors associated with a deterioration in renal function in renal transplant recipients are hypertension requiring medication, a raised serum creatinine level and proteinuria. In the absence of these factors, there is no evidence that pregnancy has an impact on graft outcome. It is important to monitor renal function closely throughout pregnancy; as with hypertension, there may be difficulty with differential diagnosis if preeclampsia develops.
Liver transplant
Alkaline phosphatase and serum transaminase levels increase during pregnancy; bilirubin and prothrombin time do not change and can be used to assess liver function during pregnancy. Liver function usually resolves quickly after transplantation, and concern about drug metabolism is usually not necessary in a well-functioning graft. The rate of caesarean delivery after liver transplant is about 50%; reasons suggested for this include the increased incidence of gestational diabetes and hypertensive disorders, and an increased tendency towards fetal distress.
Heart and heart-lung transplant
The transplanted heart is denervated, and thus there are no vagal influences acting upon it. Adequate cardiac output is dependent on maintenance of adequate preload. Heart rate can increase in response to hypovolaemia or vasodilatation, but this response is delayed compared with that of the normal pregnant woman; a high block may be particularly poorly tolerated. There is considerable controversy regarding the response of the denervated heart to adrenergic agonists, with reports of both extreme hypersensitivity and blunted response. Likewise there have been reports of bradycardia and even sinus arrest following administration of neostigmine, despite theoretical grounds for believing that the drug should not alter the rate of the denervated heart.
Afferent denervation of the heart prevents the patient from experiencing angina, but the anaesthetist and obstetrician should be aware that the woman with a cardiac transplant is at increased risk of coronary artery disease (20% by 1 year post-transplant and up to 50% by 5 years), which can only be reliably detected by cardiac catheterisation. Assessment of graft function includes pulmonary function tests, chest radiograph, arterial blood gas analysis, ECG, echocardiogram and cardiac catheterisation. There is some limited evidence from case series to suggest that graft failure may be higher in heart-lung transplantation than in other solid organ transplants after pregnancy.
Obstetric outcomes
Apart from the increased incidence of pre-eclampsia with cyclosporin, parturients who are recipients of transplanted organs have an increased risk of premature delivery, fetal growth restriction and the need for operative delivery. Surgery may be complicated by the previous transplant, and the risk of postoperative infection is also increased. There is also a risk of transplant rejection during pregnancy, possibly related to the physiological changes in pregnancy and alterations in drug metabolism.
Management options
Fertility is reduced in women with end-stage organ failure, because of hypothalamic- pituitary-gonadal dysfunction, but fertility tends to improve after 6 months with a wellfunctioning graft. Most women are advised not to become pregnant for 1-2 years after transplantation, in order to allow organ function and immunosuppressive therapy to stabilise. Pregnancy after organ transplantation may be considered high-risk and should be managed by a multidisciplinary team.
There are reports of successful vaginal delivery following kidney, heart, heart-lung and liver transplants. As a general rule, caesarean section is only indicated for obstetric complications, although each case must be considered individually. Anaesthetic priorities are to maintain adequate perfusion to the graft organ, but this should not differ from routine obstetric anaesthesia. A recent platelet count should be checked before neuraxial techniques, as it may be affected by pre-eclampsia, liver or kidney dysfunction, or immunosuppressive agents.
The woman with a well-functioning liver or kidney transplant can be treated as normal and may receive epidural analgesia and either regional or general anaesthesia. For renal patients, particular attention should be paid to venous access, keeping cannulae as peripheral as possible and preserving any sites for shunts and fistulae. Nephrotoxic agents are probably best avoided.
Epidural analgesia has been used for heart transplant recipients in labour, and regional anaesthesia (both epidural and spinal) has been used successfully for operative delivery; a combined spinal-epidural with a small spinal dose may be preferable to avoid a sudden and severe drop in blood pressure. Adrenaline is probably best avoided as an epidural additive, as an exaggerated tachycardia may be seen. If general anaesthesia is required, care should be taken with tracheal intubation in the presence of a tracheal-bronchial suture line. Airways may be more reactive after lung transplant, and agents that cause bronchospasm are best avoided. It is important to avoid dehydration and to use adequate preloading, but the risks of catheter-related sepsis probably outweigh the benefits of central venous pressure monitoring in these patients. Ephedrine has been used in normal doses, but it is wise to use small increments because of the risk of exaggerated response to the drug. If ineffective, a directly acting vasopressor such as noradrenaline or phenylephrine can be used; these drugs will cause vasoconstriction without a reflex bradycardia.
Infectious complications remain one of the major risks for all transplant recipients, and scrupulous attention to aseptic technique is therefore vital. There is an increased risk of red blood cell antibodies arising from transplanted organs; early discussion with the blood bank is advised to mitigate problems. Thromboembolism risk should be documented, as there is an increased incidence of thromboembolic disease.
An augmented dose of corticosteroids during delivery has been recommended to reduce the risk of graft rejection; this should be discussed with the transplant physician.
Key points
• Immunosuppressive drugs are used by all transplant recipients.
• Cyclosporin is associated with systemic hypertension and proteinuria.
• Transplanted hearts are denervated and cardiac output is primarily dependent on preload.
• Successful vaginal delivery with epidural analgesia has been reported following organ transplantation.
Further reading
Bramham K, Nelson-Piercy C, Gao H, et al. Pregnancy in renal transplant recipients: a UK national cohort study. Clin J Am Soc Nephrol 2013; 8: 290-8.
Chittka D, Hutchinson J. Pregnancy after renal transplantation. Transplantation 2017; 101: 675-8.
Moaveni DM, Cohn JH, Hoctor, KG, Longman RE, Ranasinghe JS. Anesthetic considerations for the parturient after solid organ transplantation. Anesth Analg 2016; 123: 402-10.
Mohamed-Ahmed O, Nelson-Piercy C, Bramham K, et al. Pregnancy outcomes in liver and cardiothoracic transplant recipients: a UK national cohort study. PLoS One 2014; 9 (2): e89151.
Vos R, Ruttens D, Verleden SE, et al. Pregnancy after heart and lung transplantation. Best Pract Res Clin Obstet Gynaecol 2014; 28: 1146-62.