Pregnancy after solid organ transplantation is perfectly possible, but it is associated with an increased risk of major obstetrical complications including pre-eclampsia, foetal growth restriction and preterm birth.
Following liver and kidney grafting, the risk of complications is higher especially after kidney transplant, reflecting pre-existing hypertensive and vascular disease. In these patients, prevention should start before the onset of pregnancy through normalisation of hypertensive and vascular conditions.
Following heart and lung transplants, the risk of rejection during and after pregnancy remains significant and an adequate immunosuppression is imperative, especially after lung transplants because of their intrinsic high rate of rejection.
A likely explanation for the higher risk of pregnancy complication is an alteration of the ‘placental bed’, the decidua and the inner myometrium underlying the placenta, a zone encompassing the full length of the spiral arteries supplying maternal blood to the placenta. Unfortunately, this zone has not been investigated in pregnancy after solid organ transplantation.
Introduction
The first woman to receive a kidney from her identical twin sister conceived within 2 years of the transplantation and delivered twice, by caesarean section, two healthy babies after carrying both pregnancies to term . However, it is noteworthy that since the donor was an identical twin, immune suppression was not an issue and pregnancy was facilitated. Pregnancy is integral to expectations of women following vital organ transplantation. Unfortunately, despite thousands of successful pregnancies in solid organ transplant recipients, information regarding the outcome of these pregnancies remains limited . The available data to evaluate the risk of the major obstetrical syndromes after solid organ transplantation come from transplantation pregnancy registers, including the National Transplantation Pregnancy Registry (NTPR) , the United Kingdom Transplant Pregnancy Registry , the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) and the Australian National Perinatal Epidemiology and Statistics Unit (NPESU) . While today more data are available, studies on the pathophysiology of pregnancies in transplanted women are still lacking.
Major obstetrical syndromes include pre-eclampsia or pregnancy-induced hypertension, preterm birth and foetal growth restriction. In this contribution, we examine the incidence of major obstetrical syndromes following different solid organ transplantation, including kidney, liver, heart and lung. The critical uterine functions affected by solid organ transplantation and the risks associated with uterus transplantation are discussed. Improved understanding of the pathogenesis of the major obstetrical complications and early diagnosis will hopefully improve the outcome.
Major obstetrical syndromes in pregnant solid organ recipients
Successful pregnancy is possible after solid organ transplantation, but the risk of major obstetrical disorders, including pre-eclampsia, preterm birth and foetal growth restriction, is high.
Kidney and liver transplants
Systematic reviews and meta-analyses of articles have recently evaluated pregnancy outcomes in recipients of kidney and liver transplants. The Kidney Transfer Review reported on 4706 pregnancies in 3570 recipients ; the Liver Transfer Review included 450 pregnancies in 306 recipients . The comparison of pregnancy outcomes after kidney and liver transplantation in the United States shows a significant increase in the risk of major obstetrical complications, including pre-eclampsia, preterm delivery and low birth weight ( Table 1 ).
| Kidney a ( n = 4706) | Liver b ( n = 450) | Frequency in US population | |
|---|---|---|---|
| Pre-eclampsia | 27% | 21.9% | 3% |
| Preterm birth (<37 weeks) | 45.6% | 39.4% | 12.5% |
| Birth weight (mean) | 2420 g | 2866 g | ( p < 0.001) |
A recent population study, based on data from the ANZDATA and the NPESU, reported on 695 pregnancies in 447 kidney transplant recipients . The mean gestational age at birth was 35 ± 5 weeks in transplant recipients, significantly shorter than the national average of 39 weeks ( P < 0.0001). The mean live birth weight for transplant recipients was lower than the national average (2485 ± 783 vs. 3358 ± 2 g), a difference that remained significant after controlling for gestational age. The authors concluded that, although transplant pregnancies are generally successful, outcomes differ from the general population in terms of perinatal survival rate, indicating that these pregnancies remain high risk in spite of good allograft organ function.
Heart and lung transplantation
The first successful pregnancy after heart transplantation was reported in 1988 . The Heart Transfer Review by Cowan et al. included 103 pregnancies in 58 recipients whereas the Lung Transfer Review by Shaner et al. analysed 30 pregnancies with 32 outcomes (one triplet) in 21 female lung transplant recipients. Ten of the 21 recipients received a transplant because of cystic fibrosis and accounted for 12 pregnancy outcomes (seven live births, three spontaneous and two therapeutic abortions).
The risk of pre-eclampsia increases after cardiac transplantation. In the NTPR, the incidence of pre-eclampsia for cardiac recipients was 18% ( Table 2 ), lower than that seen in kidney transplant recipients, but higher than the 2–7% in healthy nulliparous women . Wu et al. reviewed the outcome of pregnancies after thoracic organ transplantation and concluded that the risk of rejection during and after pregnancy remains significant, rendering it necessary to maintain an adequate immunosuppression. This is especially true for lung transplants, which have a high rate of rejection independently of pregnancy status. As emphasised by the authors, with a 5-year mortality rate of 50%, it is paramount to counsel lung transplant patients regarding the impact of pregnancy on survival and their ability to participate in raising the child.
| Heart a ( n = 103) | Lung b ( n = 30) | |
|---|---|---|
| Pre-eclampsia | 18% | 3% |
| Preterm (<37 weeks) | 38% | 37% |
| Birth weight (mean) | 2600 g | 2206 g |
| Low birth weight (<2500 g) | 39% |
Co-morbidities
A number of associated factors, such as age, parity, chronic hypertension or renal disease, determine the risk of pregnancy complications, including miscarriage and gestational diabetes, in the solid organ recipient even more than the type of transplant. Chronic hypertension is a strongly unfavourable factor in all four groups of transplantation ( Table 3 ), and associated with early-onset pre-eclampsia, foetal growth retardation and foetal death . The high frequency of chronic hypertension in kidney recipients may explain the excess of severe obstetrical disorders in this population. In a retrospective study, Wielgos et al. compared maternal, neonatal and graft outcomes in pregnant women after kidney or liver transplantation. Complete data sets were collected in 38 pregnancies in 37 women. Pre-existing hypertension was present in 15 of 19 (79%) pregnant kidney recipients and in two of 19 (10.5%) pregnant women after liver transplantation ( P < 0.000X). The incidence of pre-eclampsia was also more prevalent in pregnant kidney recipients ( P 0.04). The mean gestational age at labour was lower in the kidney group (34.9 ± 3.56 vs. 37.5 ± 1.62, respectively; P < 0.000X). A similar relationship was observed with the incidence of preterm deliveries before 37 weeks of gestation (42% vs. 11%, respectively; P < 0.02) and small for gestational age (47% vs. 11%, respectively; P = 0.008). It can be concluded that pregnancies after solid organ transplantation, particularly those following kidney transplantation, carry a high risk of major obstetrical syndromes, which in many cases reflect the impact of the underlying hypertensive condition on the vascular remodelling associated with deep placentation .
| Kidney a ( n = 4706) | Liver b ( n = 450) | Lung c ( n = 30) | Heart d ( n = 103) | |
|---|---|---|---|---|
| Age (mean) | 29.0 years | 28.6 years | NA | NA |
| Miscarriage | 14.0% | 15.6% | 30.0% | 32.0% |
| Hypertension | 54.2% | 27.2% | 53.0% | 39.0% |
| Gestational diabetes | 8.0% | 5.1% | 23.0% | 2.0% |
Major obstetrical syndromes in pregnant solid organ recipients
Successful pregnancy is possible after solid organ transplantation, but the risk of major obstetrical disorders, including pre-eclampsia, preterm birth and foetal growth restriction, is high.
Kidney and liver transplants
Systematic reviews and meta-analyses of articles have recently evaluated pregnancy outcomes in recipients of kidney and liver transplants. The Kidney Transfer Review reported on 4706 pregnancies in 3570 recipients ; the Liver Transfer Review included 450 pregnancies in 306 recipients . The comparison of pregnancy outcomes after kidney and liver transplantation in the United States shows a significant increase in the risk of major obstetrical complications, including pre-eclampsia, preterm delivery and low birth weight ( Table 1 ).
| Kidney a ( n = 4706) | Liver b ( n = 450) | Frequency in US population | |
|---|---|---|---|
| Pre-eclampsia | 27% | 21.9% | 3% |
| Preterm birth (<37 weeks) | 45.6% | 39.4% | 12.5% |
| Birth weight (mean) | 2420 g | 2866 g | ( p < 0.001) |
A recent population study, based on data from the ANZDATA and the NPESU, reported on 695 pregnancies in 447 kidney transplant recipients . The mean gestational age at birth was 35 ± 5 weeks in transplant recipients, significantly shorter than the national average of 39 weeks ( P < 0.0001). The mean live birth weight for transplant recipients was lower than the national average (2485 ± 783 vs. 3358 ± 2 g), a difference that remained significant after controlling for gestational age. The authors concluded that, although transplant pregnancies are generally successful, outcomes differ from the general population in terms of perinatal survival rate, indicating that these pregnancies remain high risk in spite of good allograft organ function.
Heart and lung transplantation
The first successful pregnancy after heart transplantation was reported in 1988 . The Heart Transfer Review by Cowan et al. included 103 pregnancies in 58 recipients whereas the Lung Transfer Review by Shaner et al. analysed 30 pregnancies with 32 outcomes (one triplet) in 21 female lung transplant recipients. Ten of the 21 recipients received a transplant because of cystic fibrosis and accounted for 12 pregnancy outcomes (seven live births, three spontaneous and two therapeutic abortions).
The risk of pre-eclampsia increases after cardiac transplantation. In the NTPR, the incidence of pre-eclampsia for cardiac recipients was 18% ( Table 2 ), lower than that seen in kidney transplant recipients, but higher than the 2–7% in healthy nulliparous women . Wu et al. reviewed the outcome of pregnancies after thoracic organ transplantation and concluded that the risk of rejection during and after pregnancy remains significant, rendering it necessary to maintain an adequate immunosuppression. This is especially true for lung transplants, which have a high rate of rejection independently of pregnancy status. As emphasised by the authors, with a 5-year mortality rate of 50%, it is paramount to counsel lung transplant patients regarding the impact of pregnancy on survival and their ability to participate in raising the child.
| Heart a ( n = 103) | Lung b ( n = 30) | |
|---|---|---|
| Pre-eclampsia | 18% | 3% |
| Preterm (<37 weeks) | 38% | 37% |
| Birth weight (mean) | 2600 g | 2206 g |
| Low birth weight (<2500 g) | 39% |
Co-morbidities
A number of associated factors, such as age, parity, chronic hypertension or renal disease, determine the risk of pregnancy complications, including miscarriage and gestational diabetes, in the solid organ recipient even more than the type of transplant. Chronic hypertension is a strongly unfavourable factor in all four groups of transplantation ( Table 3 ), and associated with early-onset pre-eclampsia, foetal growth retardation and foetal death . The high frequency of chronic hypertension in kidney recipients may explain the excess of severe obstetrical disorders in this population. In a retrospective study, Wielgos et al. compared maternal, neonatal and graft outcomes in pregnant women after kidney or liver transplantation. Complete data sets were collected in 38 pregnancies in 37 women. Pre-existing hypertension was present in 15 of 19 (79%) pregnant kidney recipients and in two of 19 (10.5%) pregnant women after liver transplantation ( P < 0.000X). The incidence of pre-eclampsia was also more prevalent in pregnant kidney recipients ( P 0.04). The mean gestational age at labour was lower in the kidney group (34.9 ± 3.56 vs. 37.5 ± 1.62, respectively; P < 0.000X). A similar relationship was observed with the incidence of preterm deliveries before 37 weeks of gestation (42% vs. 11%, respectively; P < 0.02) and small for gestational age (47% vs. 11%, respectively; P = 0.008). It can be concluded that pregnancies after solid organ transplantation, particularly those following kidney transplantation, carry a high risk of major obstetrical syndromes, which in many cases reflect the impact of the underlying hypertensive condition on the vascular remodelling associated with deep placentation .
| Kidney a ( n = 4706) | Liver b ( n = 450) | Lung c ( n = 30) | Heart d ( n = 103) | |
|---|---|---|---|---|
| Age (mean) | 29.0 years | 28.6 years | NA | NA |
| Miscarriage | 14.0% | 15.6% | 30.0% | 32.0% |
| Hypertension | 54.2% | 27.2% | 53.0% | 39.0% |
| Gestational diabetes | 8.0% | 5.1% | 23.0% | 2.0% |
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