Pregnancy in heart transplant recipients – current perspectives

Figures & data

Box 1 Recommended (ISHLT) work-up prior to conception

ECG and echocardiogram Coronary angiography (if not in the last 6 months) Right heart catheter and endomyocardial biopsy (if clinically indicated) Review of liver and renal function (including urine analysis for proteinuria) Review of immunosuppressive and cardiac drugs for teratogenicity Vaccination review: influenza, pneumococcus, hepatitis B, tetanu should be vaccinated against (no live viruses

Note: Data from Costanzo et al.¹⁸

Abbreviations: ECG, electrocardiogram; ISHLT, International Society for Heart and Lung Transplantation.)

Table 1 Immunosuppression, FDA categories and potential adverse foetal effects

Drug	FDA category	ISHLT recommendation^Citation18	Potential foetal adverse effects^Citation4,Citation64–Citation72
Corticosteroids	B	Continue	Adrenal insufficiency, thymic hyperplasia, cleft palate
Mycophenolate Mofetil	D	Stop	Spontaneous abortion, facial abnormalities, distal limb, heart, oesophagus, kidneys and nervous system abnormalities
Azathioprine	D	Risk-benefit discussion	Skeletal and visceral malformations in mice; lymphopenia, pancytopenia and severe immunosuppression reported in infants
Cyclosporine	C	Continue	Gestational diabetes, hypertension, pre-eclampsia, low birth weight
Tacrolimus	C	Continue	Increased risk of miscarriage, pre-term delivery, low birth weight, birth defects and foetal distress, Transient neonatal hyperkalaemia
Everolimus	D	Does not comment	Abortions, maternal lethality in rabbits; reduction in body weight and survival in rats. Insufficient reports to inform drug associated risk of adverse developmental outcomes in humans
Sirolimus	C	Does not comment	Reduced foetal weight and fatality in rats. No teratogenesis. Inadequate evidence in humans
Antithymocyte globulin	Not assigned	Does not comment	No animal reproductive studies
Rituximab	C	Does not comment	B cell lymphocytopenia in infants exposed in utero, increased risk of infection
Basiliximab	B	Does not comment	No adequate controlled studies in humans. No maternal toxicity, embryopathy or teratogenicity in monkeys

Notes: Category B, animal studies have not shown any risk to the foetus, no studies in humans; Category C, animal studies have shown adverse effects on the foetus, no adequate or well controlled human studies but potential benefits may warrant use in pregnancy; Category D, evidence of human foetal risk based on adverse reaction data however the potential benefits may warrant use.

Abbreviations: FDA, Food and Drug Administration; ISHLT, International Society for Heart and Lung Transplantation.

Table 2 Summary of maternal and foetal outcomes in cardiac transplant recipients

Series	TPR data^Citation37 2018	Macera et al^Citation4 2018	D’Souza et al^Citation6 2018	Bhagra et al^Citation7 2016
Number of pregnancies (number of women)^*	162 (91)	17 (11)	17 (16)	22 (17)
Maternal complications (as % of pregnancies)
Hypertension	46	0	–	14
Pre-eclampsia	23	0	12	14
Diabetes mellitus	7	0	6	0
Graft loss	3	0	0	0
Rejection	9	0	12	5
Obstetric outcomes (as % of live births)
Live birth	68	71	76	91
Mean gestational	36	-	33	34
age (weeks)
Spontaneous miscarriage	25	-	6	9
Low birth weight (<2500g)	-	45	-	45
Premature (<37 weeks)	-	33	46	45
Caesarean delivery	-	83	46	55

Note:

* Some women may have had more than one pregnancy in each series.

Box 2 Recommendations for monitoring during pregnancy

Blood CNI levels should be monitored closely: ideally once a fortnight up to 36 weeks and then weekly Monthly urine culture Frequent blood pressure, urinalysis and blood sugar monitoring: surveillance for hypertension, pre-eclampsia and gestational diabetes mellitus Bloods including calcium and phosphate levels Surveillance for bacterial or viral infection (CMV, toxoplasmosis, hepatitis) Surveillance for rejection but fluoroscopy guided endomyocardial biopsy should be avoided; if required it should take place under echocardiographic guidance, or with lead draping Foetal ultrasound at 18–20 weeks’ gestation to assess growth, and for congenital malformations Serial foetal ultrasound every 4 weeks from the 24th week to monitor growth

Note: Data from Costanzo et al,¹⁸ Vos et al²⁴ and Durst and Rampersad.⁴³

Abbreviations: CNI, Calcineurin inhibitor; CMV, Cytomegalovirus.

Costanzo MR, Dipchand A, Starling R, et al. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010;29(8):914–956. doi:10.1016/j.healun.2010.05.034

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