Article

Ethical Considerations Related to Pregnancy

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Abstract

In deciding whether to pursue pregnancy, transplant recipients need to know what they can expect for their own health and for that of their potential children. This article considers how physicians can ethically address fertility issues with female transplant recipients.

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... However, "voluntary risk taking" in the form of pregnancy should not result in disqualification for retransplantation, especially since not all pregnancies are intentional (Leyser-Whalen et al. 2014). Ross (2006) argues that transplant recipients considering pregnancy should take into account their potential reduced life expectancy and the impact on the future child, but this risk is not prohibitive and can be mediated by appropriate planning; likewise, the impact of immunosuppression and prematurity should also be considered from the perspective of offspring health but does not preclude pregnancy. Pregnancy offers transplant recipients clear social, psychological, and experiential benefits which cannot be summarily ignored (Leyser-Whalen et al. 2014). ...
... For women who express a desire to pursue pregnancy, discussions should also include options to overcome potential infertility or avoid passing on hereditary conditions, such as referral to a reproductive endocrinologist and infertility specialist (DePinho and Sauer 2014). Alternative paths to motherhood through adoption or gestational surrogacy should be discussed, acknowledging that these alternatives might not be available to all patients due to personal objections, cost, legal restrictions on surrogacy, or policies that prevent adoption by persons with serious health conditions (Ross 2006;Tong et al. 2015a). ...
... Information about breastfeeding and parenting as a transplant recipient, who must balance caring for her child with simultaneously managing her own chronic illness and health needs, is highly relevant (Leyser-Whalen et al. 2014). Likewise, transplant recipients and their partners should be specifically counselled regarding the importance of planning for a child's future, given at least one parent is facing premature death; however, as noted by others, such planning is prudent for all parents as longevity is guaranteed to no one (Leyser-Whalen et al. 2014;Ross 2006;McKay and Josephson 2005). ...
Article
Survival after solid-organ transplantation has improved significantly, and many contemporary transplant recipients are of childbearing potential. There are limited data to guide decision-making surrounding pregnancy after transplantation, variations in clinical practice, and significant knowledge gaps, all of which raise significant ethical issues. Post-transplant pregnancy is associated with an increased risk of maternal and fetal complications. Shared decision-making is a central aspect of patient counselling but is complicated by significant knowledge gaps. Stakeholder interests can be in conflict; exploring these tensions can help patients to evaluate their options and inform their deliberations. We argue that uniform, evidence-based recommendations for pregnancy after solid organ transplantation are needed. Conducting research, including patient-engaged studies, in this area should be priority for the transplant community.
... A 1975 editorial in the Lancet encouraged physicians to collaborate to care for women with kidney disease who wanted to pursue pregnancy (Pregnancy and Renal Disease, 1975). Nephrologists specifically are often called upon to provide reproductive counseling to women with CKD, including women awaiting kidney transplantation (Burgner & Hladunewich, 2019;Davison, 2007;Jesudason & Tong, 2019;McKay & Josephson, 2008;Ross, 2006). Yet, many women with kidney disease still are discouraged, explicitly or implicitly (e.g., through silence), by their physicians or other healthcare professionals from becoming pregnant, and others report being criticized for having children (Beanlands et al., 2020;Tong et al., 2015a;van Ek et al., 2017). ...
... In transplant recipients, the possibility that pregnancy might harm the allograft raises concerns about protecting a scarce resource and respecting/honoring the gift received, since graft loss would necessitate re-transplantation (Holley & Reddy, 2015;Leyser-Whalen et al., 2014;Ross, 2006;Tong et al., 2015b). In the interim, women experiencing graft loss would require dialysis. ...
... Some may object to putting a scarce resource at risk for the sake of procreation, while others see pursuing pregnancy as helping a transplant recipient lead a fulfilling life, which is among the goals of transplantation. Timing pregnancy so that it occurs only when the transplanted kidney is stable may mitigate this risk (Ross, 2006;Davison, 2007;Wiles & Oliveira, 2019). However, because of limited evidence, disagreement persists about optimal timing (Burgner & Hladunewich, 2019;Jesudason & Tong, 2019;Shah et al., 2019;Oliverio & Hladunewich 2020;Wiles & Oliveira, 2019). ...
Article
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The bioethics literature has paid little attention to matters of informed reproductive decision-making among women of childbearing age who have chronic kidney disease (CKD), including women who are on dialysis or women who have had a kidney transplant. Women with CKD receive inconsistent and, sometimes, inadequate reproductive counseling, particularly with respect to information about pursuing pregnancy. We identify four factors that might contribute to inadequate and inconsistent reproductive counseling. We argue that women with CKD should receive comprehensive reproductive counseling, including information about the possibility of pursuing pregnancy, and that more rigorous research on pregnancy in women with CKD, including women on dialysis or who have received a kidney transplant, is warranted to improve informed reproductive decision making in this population.
... 16,22 The patient does have a moral duty to protect their fetus if possible, but they cannot be compelled to do so. 15,28 This may make the prescribing physician uncomfortable, as they are implicated in the potential harm to the fetus. Faced with the decision whether or not to continue prescribing a medication that may be teratogenic, the physician may prefer to prescribe a safer, but less effective option instead. ...
... However, the ultimate choice depends on the patient's values and whether they would opt for a potentially inferior medication for their own health in order to protect the fetus. 28 which, by reducing the impact of the power differential in the relationship, has been helpful for counselling pregnant patients with substance use disorder. 19,29 Pregnancy in the face of a shortened lifespan J o u r n a l P r e -p r o o f Davison, and Ross) acknowledge that some physicians believe that women with a chronic medical illness should not have children due to the mother's shortened expected lifespan. ...
... 19,29 Pregnancy in the face of a shortened lifespan J o u r n a l P r e -p r o o f Davison, and Ross) acknowledge that some physicians believe that women with a chronic medical illness should not have children due to the mother's shortened expected lifespan. 15,21,28 Does a physician facilitate a negative outcome for the fetus simply by aiding such a pregnancy that could lead to an eventually motherless child? ...
Article
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Problem Pregnancy planning in patients with chronic kidney disease can result in ethical conflicts due to the potential for adverse outcomes. Traditionally, many nephrologists have advised their patients to avoid pregnancy altogether; however this approach is paternalistic and not patient-centered. An ethical framework could guide joint decision-making between physicians and their patients, but does not currently exist. Methods We performed a literature search to identify the ethical considerations associated with this patient population. We searched for articles published between 1975 and 2019 using the terms “Ethics” and “High risk Pregnancy” along with 29 chronic disease-specific MeSH terms. Subsequently, we performed a critical evaluation using established ethical theories and adapted anonymized clinical cases from the pregnancy in kidney disease clinic (PreKid Clinic) at our institution to guide the discussion. Results We identified 968 articles and excluded 947 based on their title or abstract. 12 full text articles were included, representing discussions, case reports, and literature reviews on the ethics of pregnancy in 8 chronic diseases. The extracted data were applied to 5 clinical cases to guide the discussion. Conclusions This clinical review focuses on three main ethical themes: duty to patient, duty to the fetus and duty to society, to help physicians explore common scenarios that may arise when counselling patients around pregnancy. Primarily, physicians have an duty to facilitate autonomous decision-making and informed consent. Secondarily, they have a duty to protect the fetus and use resources judiciously as long as it does not impact the care of their patients.
... Achieving parenthood for women with chronic kidney disease (CKD) is challenging because as the severity of CKD progresses, sexual function and fertility declines, and the risk of adverse fetal and maternal outcomes (fetal loss, pre-eclampsia, premature birth) substantially increases [1][2][3][4][5][6][7][8]. Advice by clinicians to these women when contemplating pregnancy is also inherently complex because of the conflict between potentially serious (even life-threatening) complications of pregnancy versus the innate desire of many women to bear children [9]. Fully-informed pre-pregnancy counseling is essential, and if pregnancy occurs, intensive antenatal monitoring and management is critical [1,8]. ...
... Much more is known about pregnancy outcomes in kidney transplant recipients, with pregnancy generally accepted as being safe, even though there remains a high risk of prematurity and low birth weight in the babies [12][13][14]. Guidelines suggest that women wait 1-2 years post-transplantation before becoming pregnant [47,48] and that patients be informed about the benefits and risks of immunosuppressive agents [9]. However, it is noted that while short-term outcomes (including live birth rates) have improved, there is less evidence about the long-term outcomes [5,12]. ...
... However, it is noted that while short-term outcomes (including live birth rates) have improved, there is less evidence about the long-term outcomes [5,12]. Physicians have also been encouraged to discuss fertility issues proactively with kidney transplant recipients and to facilitate access to reproductive services, and refer patients to obstetricians with expertise in managing high-risk pregnancies [1,9,48]. A multidisciplinary approach is recommended and valuable to ensuring best outcomes. ...
Article
Full-text available
Achieving parenthood in women with chronic kidney disease (CKD) is challenging due to reduced fertility and the risk of adverse outcomes. We aimed to describe women's perspectives of pregnancy in CKD. Electronic databases were searched to April 2014. Studies were synthesized thematically. From 15 studies (n = 257) we identified seven themes. 'Pursuing motherhood' was fulfilling an innate or social desire to have a child. 'Failure to fulfill social norms' of being unable to conceive diminished their self-worth. 'Fear of birth defects' was attributed to the potential side effects of immunosuppression. 'Decisional insecurity and conflict' encompassed uncertainties of prioritizing pregnancy as sacrifices had to be made in family life and work to minimize their risk of complications. Transplant recipients were concerned about the increased likelihood of graft loss. The possibility of genetic transmission of kidney disease influenced decisions about childbearing. 'Withholding emotional investment' was a way of protecting against the devastation of inability to conceive, miscarriage or stillbirth. 'Control and determination' reflected their capacity to choose to accept the risks of pregnancy. Some felt traumatized when their physician unduly warned against pregnancy. 'Exacerbating disease' due to pregnancy was also of concern to women. For women with CKD, pregnancy decisions can be emotionally complicated by health risks, family burden and the perceived risk of fetal malformation. Proactive counseling, shared decision-making about family planning and managing pregnancy in CKD that addresses patient preferences, and multidisciplinary care involving nephrologists, reproductive and obstetrics specialists, and psychological support may improve management of pregnancy issues in CKD. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
... The themes of beneficence and non-maleficence, in both the internal medicine and transplantation journals, included an evaluation of risks and benefits. Two articles from the internal medicine journal sample also addressed the specific issue of pregnancy after renal transplantation (risks for the mother, graft and fetus) [32,41] and three articles discussed transplantation from high infectious risk donors [29,42,43]. Otherwise, risks and benefits were discussed in terms of: (i) predictable and individualized methods of risk assessment before registration on the waiting list [44,45]; (ii) risks and benefits of the transplantation [46][47][48]; (iii) choice of immunosuppressive drugs [49,50]; and (iv) transplants on patients with HIV [51,52]. ...
... Risks vs. benefits: assessment methods, pregnancy (only in IM journals), transplantation with marginal donor, choice of medication, HIV patients "Physicians should discuss the risks and benefits of the various immunosuppressive regimens with respect to pregnancy and the fetus with their female patients and make decisions collaboratively" [32]. ...
... Personal responsibilities and organ transplantation "Even though the issue of personal responsibility for organ failure is usually raised in the literature with regard to whether patients who abuse alcohol should be given a lower priority for an organ, a similar argument could be made that a woman who wittingly chooses to get pregnant when her graft is unstable (and who therefore has an increased risk of graft loss) should be given a lower priority for retransplantation" [32]. ...
Article
Full-text available
In their book Spare Parts, published in 1992, Fox and Swazey criticized various aspects of organ transplantation, including the routinization of the procedure, ignorance regarding its inherent uncertainties, and the ethos of transplant professionals. Using this work as a frame of reference, we analyzed articles on organ transplantation published in internal medicine and transplantation journals between 1995 and 2008 to see whether Fox and Swazey's critiques of organ transplantation were still relevant. Using the PubMed database, we retrieved 1,120 articles from the top ten internal medicine journals and 4,644 articles from the two main transplantation journals (Transplantation and American Journal of Transplantation). Out of the internal medicine journal articles, we analyzed those in which organ transplantation was the main topic (349 articles). A total of 349 articles were randomly selected from the transplantation journals for content analysis. In our sample, organ transplantation was described in positive terms and was presented as a routine treatment. Few articles addressed ethical issues, patients' experiences and uncertainties related to organ transplantation. The internal medicine journals reported on more ethical issues than the transplantation journals. The most important ethical issues discussed were related to the justice principle: organ allocation, differential access to transplantation, and the organ shortage. Our study provides insight into representations of organ transplantation in the transplant and general medical communities, as reflected in medical journals. The various portrayals of organ transplantation in our sample of articles suggest that Fox and Swazey's critiques of the procedure are still relevant.
... I n 1954, the first successful solid organ transplantation was performed in a set of male twins. [1][2][3] Two years later a set of female twins underwent successful renal transplantation. Six months after transplant, the recipient twin resumed menstrual cycling, and three months later she conceived and subsequently delivered a healthy term baby. ...
... 1 The fetus has an increased risk of prematurity, intrauterine growth restriction, birth defects, and potential long-term or lateonset consequences of exposure to potential teratogenic medications including immunosuppressants. [1][2][3] During the past 10 years in British Columbia, over 500 women have received solid organ transplants, and many of these women have been of child-bearing age. British Columbia Transplant, the provincial agency that is responsible for all organ transplant services in British Columbia, has noted that there still is misinformation and confusion surrounding local women's attempts to pursue pregnancy post transplantation. ...
... Therefore, it is important to counsel women regarding potential pregnancy before they undergo transplantation. 3,8 As our demographics revealed, most of the surveyed women were educated, most had not yet started a family, and many wished to have children regardless of their transplant. Counselling on the timing of the transplant is suggested to optimize the success of the pregnancy. ...
Article
Since 1954, over 14 000 women have given birth after having had an organ transplantation. Unfortunately, some women and physicians remain misinformed about the feasibility and outcomes of pregnancy post transplantation. Our primary objective was to assess their perceptions and difficulties with regard to becoming pregnant. Our secondary objectives were to determine the incidence of pregnancies among transplant recipients in British Columbia and any maternal, graft, or fetal complications. From 1997 to 2007 in British Columbia, there were over 500 female recipients of solid organ transplants. We surveyed recipients in this group who were of child-bearing age. One hundred forty of 295 (47%) eligible recipients responded: 44 of these women had attempted pregnancy after transplant, and 31 women gave birth to 47 children. One half of the respondents planned to have children post transplant; 108 of 140 (77%) had no children before transplant. One quarter of the respondents were advised against pregnancy by their physician, and 33% of these women found a new physician to support their pregnancy. Rates of miscarriage (27%), rejection (21%), and prematurity (65%) were higher than expected. Infections were rare, and no birth defects or noteworthy health problems in the offspring were reported. Overall, pregnancy appears to be safe following solid organ transplantation, but careful monitoring and counselling are recommended.
... The main reported fetal outcomes are preterm delivery, restricted intrauterine growth, and low birth weight 11,25,26 . The risk of malformations, except those linked to genetic diseases, is not increased if teratogenic drugs were discontinued at least six weeks before conception 6,25 . ...
... The main reported fetal outcomes are preterm delivery, restricted intrauterine growth, and low birth weight 11,25,26 . The risk of malformations, except those linked to genetic diseases, is not increased if teratogenic drugs were discontinued at least six weeks before conception 6,25 . ...
Article
Full-text available
Background: Kidney transplantation (KT) improves quality of life, including fertility recovery. Objective: to describe outcomes of post-KT pregnancy and long-term patient and graft survival compared to a matched control group of female KT recipients who did not conceive. Methods: retrospective single-center case-control study with female KT recipients from 1977 to 2016, followed-up until 2019. Results: there were 1,253 female KT patients of childbearing age in the study period: 78 (6.2%) pregnant women (cases), with a total of 97 gestations. The median time from KT to conception was 53.0 (21.5 – 91.0) months. Abortion rate was 41% (spontaneous 21.6%, therapeutic 19.6%), preterm delivery, 32%, and at term delivery, 24%. Pre-eclampsia (PE) occurred in 42% of pregnancies that reached at least 20 weeks. The presence of 2 or more risk factors for poor pregnancy outcomes was significantly associated with abortions [OR 3.33 (95%CI 1.43 – 7.75), p = 0.007] and with kidney graft loss in 2 years. The matched control group of 78 female KT patients was comparable on baseline creatinine [1.2 (1.0 – 1.5) mg/dL in both groups, p = 0.95] and urine protein-to-creatinine ratio (UPCR) [0.27 (0.15 – 0.44) vs. 0.24 (0.02 – 0.30), p = 0.06]. Graft survival was higher in cases than in controls in 5 years (85.6% vs 71.5%, p = 0.012) and 10 years (71.9% vs 55.0%, p = 0.012) of follow-up. Conclusion: pregnancy can be successful after KT, but there are high rates of abortions and preterm deliveries. Pre-conception counseling is necessary, and should include ethical aspects.
... Os principais desfechos fetais relatados são parto prematuro, crescimento intrauterino restrito e baixo peso ao nascer 11,25,26 . O risco de malformações, exceto aquelas ligadas a doenças genéticas, não aumenta se os medicamentos teratogênicos forem descontinuados pelo menos seis semanas antes da concepção 6,25 . ...
... Os principais desfechos fetais relatados são parto prematuro, crescimento intrauterino restrito e baixo peso ao nascer 11,25,26 . O risco de malformações, exceto aquelas ligadas a doenças genéticas, não aumenta se os medicamentos teratogênicos forem descontinuados pelo menos seis semanas antes da concepção 6,25 . ...
Article
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Resumo Histórico: Transplante renal (TR) melhora qualidade de vida, incluindo recuperação da fertilidade. Objetivo: descrever desfechos gestacionais pós-TR e sobrevida de longo prazo da paciente e do enxerto renal comparada a um grupo controle pareado de receptoras de TR que não conceberam. Métodos: estudo retrospectivo caso-controle com receptoras de TR de 1977 a 2016, acompanhadas até 2019. Resultados: foram identificadas 1.253 receptoras de TR em idade fértil no período do estudo: 78 (6,2%) gestantes (casos), total de 97 gestações. Tempo mediano entre TR até concepção foi 53,0 (21,5 – 91,0) meses. Taxa de aborto foi 41% (espontâneo 21,6%, terapêutico 19,6%), parto prematuro, 32%, e a termo, 24%. Pré-eclâmpsia (PE) ocorreu em 42% das gestações que alcançaram pelo menos 20 semanas. Presença de 2 ou mais fatores de risco para desfechos gestacionais desfavoráveis foi significativamente associada a abortos [OR 3,33 (IC95% 1,43 – 7,75), p = 0,007] e perda de enxerto renal em 2 anos. O grupo controle de 78 mulheres com TR foi comparável na creatinina basal [1,2 (1,0 – 1,5) mg/dL nos dois grupos, p = 0,95] e na relação proteína/creatinina urinária (RPCU) [0,27 (0,15 – 0,44) vs. 0,24 (0,02 – 0,30), p = 0,06]. Sobrevida do enxerto foi maior nos casos que nos controles em 5 anos (85,6% vs. 71,5%, p = 0,012) e 10 anos (71,9% vs. 55,0%, p = 0,012) de acompanhamento. Conclusão: a gestação pode ser bem-sucedida após TR, mas existem altas taxas de abortos e partos prematuros. Aconselhamento pré-concepção é necessário e deve incluir aspectos éticos.
... The high frequency of a previous history of pre-eclampsia in kidney recipients [17][18][19] and the knowledge of a short life expectancy in lung recipients affected by cystic fibrosis might explain this fear. Consistent with many published studies [9,20,21], the importance of multidisciplinary counseling for SOT patients planning pregnancy cannot be over-emphasized and was performed on more than 70% of the pregnancies in our survey. ...
... Achieving pregnancy and delivering a child after SOT raises several ethical questions [21]. Having children is a strong life goal for many, and the societal "exclusion" caused by a disease requiring SOT is reinforced further by being childless. ...
Article
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In recent years, solid organ transplantations, such as kidney or lung grafts, have been performed worldwide with an improvement of quality of life under immunosuppressive therapy and an increase in life expectancy, allowing young women to consider childbearing. In the current study, we conduct a retrospective study in two French centers for kidney and lung transplantations to evaluate the rate and outcomes of pregnancies, contraception and gynecological monitoring for women under 40 years old who underwent solid organ transplantation. Among 210 women, progestin was the most widely used contraceptive method. Of the 210 women, 24 (11.4%) conceived 33 pregnancies of which 25 (75.8%) were planned with an immunosuppressant therapy switch. Of the 33 pregnancies, 7 miscarried (21.2%) and 21 (63.7%) resulted in a live birth with a high rate of pre-eclampsia (50%). No graft rejections were observed during pregnancies. Among the deliveries, 19 were premature (90.5%, mostly due to induced delivery) and the C-section rate was high (52.4%). No particular pathology was identified among newborns. We conclude that pregnancies following solid organ transplantation are feasible, and while they are at an increased risk of pre-eclampsia and prematurity, they should still be permitted with close surveillance by a multidisciplinary care team.
... On the other hand, the environment of HTx is evolving with an increasing proportion of female [10] and a shift toward younger recipients [11], as patients with complex congenital heart diseases are now surviving into adulthood and are being increasingly referred for HTx [12]. As a result, an increasing number of women are considering maternity after HTx, half being unplanned [13] despite recommendation for preconception counseling to potentially reduce the complications. Therefore, the HTx team has to provide accurate information to help their patients make an enlightened decision. ...
... All patients were followed by a high-risk pregnancy obstetrician and the HTx clinic, with 8.4 (5-11) and 6.2 (3-10) visits, respectively (Table 2). Among all 18 pregnancies, 56% were unplanned, with announcement to the HTx teams at 10.8 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) weeks. The pregnancy complications include hypertension (38.5%), preeclampsia (15.4%), and diabetes (15.4%). ...
Article
Background: Despite reports of successful pregnancies in heart transplant (HTx) recipients, many centers recommend their patients against maternity. Methods: We reviewed our provincial experience of pregnancy in HTx recipient by performing charts review of all known gestations following HTx in the province of Quebec (Canada), stratified between planned and unplanned pregnancies. Long-term survival was compared to HTx recipient women of childbearing age who didn't become pregnant. Results: Eighteen pregnancies, 56% unplanned, occurred in eight patients, 10.1(2.6-27.0) years after HTx. Immunosuppression was CNI-based, with a mean dose increase of 48.3% (tacrolimus) and 26.5% (cyclosporine), without rejection. Cardiometabolic complications were high compared to the general Canadian population, including preeclampsia (15.4%vs 5.5%), hypertension (38.5%vs4.6%) and diabetes (15.4%vs 5.6%). Mean gestational age was 35.1(23.4-39.6) weeks (72.2% live births; 53.8% prematurity). Mean birth weight was 2418 (660-3612)g. Serum creatinine increased during pregnancy, becoming significant after delivery(p=0.0239), and returning to preconception level in all but three patients within a year. After 4.6(1.2-17.2) years of follow-up, two rejection episodes occurred in one patient. Long-term mortality was similar to overall HTx women (Kaplan Meier;p=0.8071). Conclusions: Pregnancy in HTx carries high cardiometabolic complications and decreased kidney function, but is feasible with acceptable outcomes and no impact on mother's survival. This article is protected by copyright. All rights reserved.
... 14,15 Women with kidney disease report feelings of guilt, failure, and grief, concerns about loss of control over decisions, and defending their choices to health professionals. 15, 16 The question "Should I have a baby?" raises ethical issues 7,22 that may conflict with the clinician's values, creating tensions between clinician duty to the patient, fetus, health system, and society. Navigating this requires shared decision-making and trusting relationships between clinician and patient. ...
Article
Full-text available
Achieving parenthood can be an important priority for women and men with kidney failure. In recent decades, the paradigm has shifted towards greater support of parenthood, with advances in our understanding of risks related to pregnancy and improvements in obstetric and perinatal care. This review, co-designed by people with personal experience of kidney disease, provides guidance for nephrologists on how to answer the questions most asked by patients when planning for parenthood. We focus on important issues that arise in preconception counselling for women receiving dialysis and post-kidney transplant. We summarise recent studies reflecting pregnancy outcomes in the modern era of nephrology, obstetric and perinatal care in developed countries. We present visual aids to help clinicians and women navigate pregnancy planning and risk assessment. Key principles of pregnancy management are outlined. Finally, we explore outcomes of fatherhood in males with kidney failure.
... In counseling transplanted women concerning pregnancy an open and frank discussion is necessary [54]. It is known that pre-pregnancy renal function should be "good", however, the lower limit usually is not given. ...
Article
Full-text available
Background: After kidney transplantation, pregnancy and graft function may have a reciprocal interaction. We evaluated the influence of graft function on the course of pregnancy and vice versa. Methods: We performed a retrospective observational study of 92 pregnancies beyond the first trimester in 67 women after renal transplantation from 1972 to 2019. Pre-pregnancy eGFR was correlated with outcome parameters; graft function was evaluated by Kaplan Meier analysis. The course of graft function in 28 women who became pregnant after kidney transplantation with an eGFR of < 50 mL/min/1.73m2 was compared to a control group of 79 non-pregnant women after kidney transplantation during a comparable time period and with a matched basal graft function. Results: Live births were 90.5% (fetal death n = 9). Maternal complications of pregnancy were preeclampsia 24% (graft loss 1, fetal death 3), graft rejection 5.4% (graft loss 1), hemolytic uremic syndrome 2% (graft loss 1, fetal death 1), maternal hemorrhage 2% (fetal death 1), urinary obstruction 10%, and cesarian section. (76%). Fetal complications were low gestational age (34.44 ± 5.02 weeks) and low birth weight (2322.26 ± 781.98 g). Mean pre-pregnancy eGFR was 59.39 ± 17.62 mL/min/1.73m2 (15% of cases < 40 mL/min/1.73m2). Pre-pregnancy eGFR correlated with gestation week at delivery (R = 0.393, p = 0.01) and with percent eGFR decline during pregnancy (R = 0.243, p = 0.04). Pregnancy-related eGFR decline was inversely correlated with the time from end of pregnancy to chronic graft failure or maternal death (R = -0.47, p = 0.001). Kaplan Meier curves comparing women with pre-pregnancy eGFR of ≥ 50 to < 50 mL/min showed a significantly longer post-pregnancy graft survival in the higher eGFR group (p = 0.04). Women after kidney transplantation who became pregnant with a low eGFR of > 25 to < 50 mL/min/1.73m2 had a marked decline of renal function compared to a matched non-pregnant control group (eGFR decline in percent of basal eGFR 19.34 ± 22.10%, n = 28, versus 2.61 ± 10.95%, n = 79, p < 0.0001). Conclusions: After renal transplantation, pre-pregnancy graft function has a key role for pregnancy outcomes and graft function. In women with a low pre-pregnancy eGFR, pregnancy per se has a deleterious influence on graft function. Trial registration: Since this was a retrospective observational case series and written consent of the patients was obtained for publication, according to our ethics' board the analysis was exempt from IRB approval. Clinical Trial Registration was not done. The study protocol was approved by the Ethics Committee of Hannover Medical School, Chairman Prof. Dr. H. D. Troeger, Hannover, December 12, 2015 (IRB No. 2995-2015).
... Impact of pregnancy on the kidney allograft, premature delivery, pre-eclampsia, and the longterm effects of immunosuppressive medications on the offspring remains some challenges in this group. Counseling about pregnancy should start in the pre-transplant period, continued following transplantation, and reliable contraception is recommended until patient is ready to embark on a planned pregnancy (89)(90)(91). The optimal timing of pregnancy after transplantation is considered to be 1 to 2 years. ...
... Limited studies on the pediatric outcomes of children born to transplant recipients suggest the anthropometric and developmental outcomes of these children are not different from those of non-transplant recipients, 10,11 though there is still a paucity of longitudinal data. 12 ...
Article
Full-text available
Recipients of solid organ transplants who become pregnant represent an obstetrically high‐risk population. Preconception planning and effective contraception tailored to the individual patient are critical in this group. Planned pregnancies improve both maternal and neonatal outcomes and provide a window of opportunity to mitigate risk and improve lifelong health. Optimal management of these pregnancies is not well defined. Common pregnancy complications after transplantation include hypertension, preterm birth, infection, and metabolic disease. Multidisciplinary preconception and prepartum management, and counseling decrease complications and benefit the maternal‐neonatal dyad.
... However, lung transplant recipients remain at higher risk for maternal and fetal complications compared to the general population [6•]. Pregnancy in solid organ recipients poses ethical concerns as they have a limited life span and are at risk for serious medical complications [7]. Herein, we review the available literature regarding the impact of pregnancy on lung transplant recipients and discuss recommendations for management. ...
Article
Full-text available
Purpose of Review In this article, we review the impact of pregnancy in lung transplant recipients. Specifically, we discuss maternal, fetal, and allograft outcomes. Furthermore, we highlight important considerations for management of pregnancy in these patients. Recent Findings Improved survival after lung transplantation means more women of childbearing age; many of them with cystic fibrosis may be able to consider pregnancy. Despite the high number of live births, these pregnancies remain at risk for hypertensive disorders, graft rejection, postpartum graft loss, preterm birth, maternal, and neonatal mortality. Furthermore, data on the fetal effects of standard immunosuppressive regimens used in lung transplant recipients is lacking. A detailed discussion regarding these complications and gaps in knowledge is critical during pre-pregnancy counseling. Despite these hurdles, carefully planned pregnancies with close monitoring and management by multidisciplinary teams can be successful. Summary In selected patients, planned pregnancy after lung transplantation, albeit high risk for maternal and fetal complications, is feasible.
... Furthermore, 40% of the women who had received a transplant were back on dialysis before their child attended elementary school. Ross (45) spoke to the issue of expected life span of recipients of transplants, arguing that, although there are never guarantees that any prospective parents will remain healthy until their children reach adulthood, "the greater likelihood of a lower maternal life expectancy is morally relevant in that physicians have an obligation to encourage women to consider their reproductive decisions both from their own perspective and from that of the child-to-be." ...
Article
Placed in a historic context, this overview focuses on post-transpant pregnancy, fatherhood, and contraception in women and men. The critical importance of early reproductive counseling because of improved sexual function and the early return of ovulation and menses post-transplant is emphasized. We explain the decision making regarding contraception choices. The available data on the safety of immunosuppressive drugs in pregnancy, and for men desiring fatherhood, are detailed. The risk of maternal ingestion of mycophenolate products on the in utero fetus is considered and contrasted with the lack of concern for their use by men fathering children. Pregnancy risks to the allograft, baby, and mother are discussed. An infant’s exposure to specific immunosuppressant medications through breastfeeding is reviewed. The ethics and realities of post-transplant parenthood are explored.
... Approximately half of all pregnancies are unintended, and this has also been shown in the transplant population despite recommendations for preconception counseling. 9,18 Multiple characteristics including respondent sex, age, specialty, volume of transplant center, and prior experience with pregnancy were not predictors of beliefs surrounding pregnancy after HT. One might anticipate that centers with prior pregnancy experience might have supported pregnancy after transplant, though it is possible that experience with posttransplant pregnancy complications prevented respondents from encouraging future pregnancies in transplant recipients. ...
Article
Background Pregnancy after heart transplantation (HT) is a concern for many female recipients. The International Society for Heart and Lung Transplantation has guidelines regarding reproductive health, but limited data exist regarding providers’ attitudes and practices surrounding pregnancy post-HT. Methods We conducted an independent, confidential, voluntary, web-based survey sent electronically to 1643 United States heart transplant providers between June and August 2019. Results There were 122 responses, the majority from cardiologists (n=85, 70%) and nurse or transplant coordinators (n=22, 18%). Thirty-one percent (n=37) of respondents indicated that pregnancy should be avoided in all HT recipients, and only 43% (n=52) reported that their center had a formal policy regarding pregnancy following HT. The most commonly reported contraindications included nonadherence (n=109, 89%), reduced left ventricular ejection fraction (n=104, 85%), coronary allograft vasculopathy (n=86, 70%), prior rejection (n=76, 62%), presence of donor-specific antibodies (n=69, 57%), and prior peripartum cardiomyopathy pretransplant (n=57, 47%). Respondent sex, specialty, transplant volume, or prior experience with pregnancy after HT were not associated with recommendations to avoid posttransplant pregnancy. Conclusions Transplant providers’ attitudes regarding posttransplant pregnancy vary widely. Despite International Society for Heart and Lung Transplantation guidelines, a significant proportion indicates that pregnancy is contraindicated in all recipients and the majority of programs have no center-specific policy to manage such pregnancies. While the low response rate limits the generalizability of the findings, they do suggest that education on the feasibility of pregnancy post-HT is indicated as many recipients are of, or survive to, childbearing age.
... At its best, controlling complications and ensuring a stable clinical condition has made it possible to allow women with solid organ transplants to undertake pregnancies. However, there are still ethical questions [2]. The largest studies available relate to women with renal transplants, and describe an increased risk of pregnancy-induced hypertension, pre-eclampsia, gestational diabetes and premature childbirth [3][4][5]. ...
Article
Full-text available
Pregnancy after lung and heart–lung transplantation remains rare. This French study deals with change in lung function after a pregnancy and the maternal and newborn outcomes. We retrospectively included 39 pregnancies in 35 women aged >20 years. Data on patients, course of pregnancies and newborns were collected from nine transplantation centres. Mean age at time of pregnancy was 28 years. Cystic fibrosis affected 71% of patients. Mean± sd time between transplantation and pregnancy was 63±44 months. 26 births occurred (67%) with a mean term of 36 weeks of amenorrhoea and a mean birthweight of 2409 g. Prematurity was observed in 11 cases (43%). Forced expiratory volume in 1 s was 83.9% of predicted before pregnancy and 77.3% of predicted 1 year after the end of pregnancy (p=0.04). 10 patients developed chronic lung allograft dysfunction after delivery. Nine patients died at a mean± sd time after transplantation of 8.2±7 years and a mean± sd time after pregnancy of 4.6±6.5 years. These data show that pregnancy remains feasible in lung and heart–lung transplant recipients, with more frequent maternal and newborn complications than in the general population. Survival in this cohort appears to be similar to the global survival observed in lung transplant recipients. Planned pregnancy and multidisciplinary follow-up are crucial.
... Conversely, in Englishspeaking countries, where the patient's self-determination is seen as paramount, autonomy comes first, and it is felt that it should be respected after ensuring that the patient has comprehended and accepted the risks her decision involves. The practice, observed in some transplant centres, of asking the patients to avoid pregnancy, as a way to optimize the social advantage of a successful transplantation, considers justice to be the leading principle [60][61][62][63][64][65][66][67][68]. ...
Article
Full-text available
Kidney transplantation (KT) is often considered to be the method best able to restore fertility in a woman with chronic kidney disease (CKD). However, pregnancies in KT are not devoid of risks (in particular prematurity, small for gestational age babies, and the hypertensive disorders of pregnancy). An ideal profile of the potential KT mother includes “normal” or “good” kidney function (usually defined as glomerular filtration rate, GFR ≥ 60 ml/min), scant or no proteinuria (usually defined as below 500 mg/dl), normal or well controlled blood pressure (one drug only and no sign of end-organ damage), no recent acute rejection, good compliance and low-dose immunosuppression, without the use of potentially teratogen drugs (mycophenolic acid and m-Tor inhibitors) and an interval of at least 1–2 years after transplantation. In this setting, there is little if any risk of worsening of the kidney function. Less is known about how to manage “non-ideal” situations, such as a pregnancy a short time after KT, or one in the context of hypertension or a failing kidney. The aim of this position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology is to review the literature and discuss what is known about the clinical management of CKD after KT, with particular attention to women who start a pregnancy in non-ideal conditions. While the experience in such cases is limited, the risks of worsening the renal function are probably higher in cases with markedly reduced kidney function, and in the presence of proteinuria. Well-controlled hypertension alone seems less relevant for outcomes, even if its effect is probably multiplicative if combined with low GFR and proteinuria. As in other settings of kidney disease, superimposed preeclampsia (PE) is differently defined and this impairs calculating its real incidence. No specific difference between non-teratogen immunosuppressive drugs has been shown, but calcineurin inhibitors have been associated with foetal growth restriction and low birth weight. The clinical choices in cases at high risk for malformations or kidney function impairment (pregnancies under mycophenolic acid or with severe kidney-function impairment) require merging clinical and ethical approaches in which, beside the mother and child dyad, the grafted kidney is a crucial “third element”.
... It has been stated that counseling must be given to post-transplanted women who are considering getting pregnant to explain the possible risks and special care required [25]. ...
Article
Full-text available
Objective: The number of successful pregnancies in kidney transplant (KT) recipients has increased in recent years. Little evidence is available about the risk of in utero immunosuppressive exposure for long-term cognitive consequences. The aim of this study was to evaluate the impact of immunosuppression during pregnancy on intellectual performance of children born to KT recipients. Methods: Using a cross-sectional design, women who had undergone KT and their children (aged 4+ years) were recruited at the outpatient follow-up in five transplant centers. Women who did not receive immunosuppression during pregnancy with similar distributions of socioeconomic status and length of gestation and their children were also recruited. Children were assessed with Wechsler Intelligence Scales. Results: The study sample included 50 exposed and 50 unexposed children. No differences between groups in all the proposed confounding factors were found. Full-scale IQ did not differ significantly between both groups. Also, significant differences in any index or subscale score were not observed, with the exception of time required to complete the Wechsler preschool and primary scale of intelligence (WPPSI) Zoo locations subtest, which was done quicker in the unexposed group (p = .007). Exposure to immunosuppression during pregnancy was not a significant predictor of low IQ in logistic regression after adjustment for other factors. Conclusions: Immunosuppression therapy during pregnancy of KT women did not affect global intellectual performance of their offspring, except maybe for visuospatial working memory in preschool children.
... Multiple pregnancies are rarer [12]. Pregnancy must be planned since risk factors increase of 75% the maternal and/or fetal complications [6,13,14,15]. ...
... 4,10,28,31 Lung transplant candidates, recipients, and the team of transplant personnel caring for them face major ethical issues. 33 Transplant recipients with cystic fibrosis who are considering pregnancy should be offered genetic counseling, and the woman's partner should undergo complete analysis of the cystic fibrosis transmembranous regulator gene by sequencing. 34 Careful consideration and appropriate counseling about termination, preterm birth, and possible arrangements in the event of morbidity or maternal mortality, or alternatives such as adoption, should be discussed before pregnancy. ...
... Multiple pregnancies are rarer (Nicovani et al., 2009). Pregnancy must be planned since risk factors increase to 75% of the maternal and/or fetal complications (Davison 2006;Davison 1995;Fitoussi et al., 1990 ;Ross 2006). ...
Article
هدفت هذه الدراسة إلى استخدام نموذج ميلر (Miller) للكشف عن ممارسات المحاسبة الإبداعية في الشركات المساهمة المسعرة ببورصة لندن وبورصة باريس، وتوصلت الدراسة إلى أن العينة المدروسة من الشركات المسعرة المقيدة في سوق الأوراق المالية (بورصة لندن وبورصة باريس) تمارس المحاسبة الإبداعية بدرجات متفاوتة، فبعض الشركات تمارس المحاسبة الإبداعية باتجاه ايجابي عن طريق التعظيم المتعمد لأرباحها، وشركات أخرى تمارس المحاسبة الإبداعية باتجاه سلبي عن طريق التخفيض المتعمد في أرباحها.
... [20][21][22] Ethical issues are also changing; in a setting of shared decisions, kidney biopsy may be considered in specific situations, such as a systemic lupus erythematosus flare-up or rapid kidney function impairment in the presence of favourable fetal parameters, if it might help to identify therapies that will allow continuation of the pregnancy to a relatively safe stage in terms of fetal outcomes. [23][24][25] Despite there being a great deal of theoretical interest in this issue, no systematic review has addressed kidney biopsy and pregnancy in the last few decades. ...
Article
Kidney diseases, which have a prevalence of 3% in women of childbearing age, are increasingly encountered in pregnancy. Glomerulonephritis may develop or flare up in pregnancy, and a differential diagnosis with pre-eclampsia may be impossible on clinical grounds. Use of kidney biopsy is controversial, but a systematic review has not been carried out to date. To review the literature on kidney biopsy in pregnancy, with a focus on indications, risks and timing. Medline, Embase, CHINAL and the Cochrane Library were searched in September 2012, with ‘pregnancy’ and ‘kidney biopsy’ used as MESH and free terms, for the period 1980–2012. Results were filtered for ‘human’ if this option was available. Biopsies during pregnancy and within 2 months after delivery. Case reports (fewer than five cases) and kidney grafts were excluded. Paper selection was performed in duplicate. Data were extracted in duplicate. The high heterogeneity in study design necessitated that the review be narrative, except for data on adverse events, which were analysed with regard to the timing of kidney biopsy. Of 949 references, 39 were selected, providing data on 243 biopsies in pregnancy and 1236 after delivery (timing was unclear in 106 women). The main aims of the studies were to define morphology in pre-eclampsia (23 studies), to carry out a risk–benefit analysis of kidney biopsy (11 studies), and to investigate pregnancy-related acute kidney injury (five studies). Four cases of major bleeding complications occurred at 23–26 weeks of gestation. Relevant complications were observed in 7% of women during pregnancy and 1% after delivery (P = 0.001). Kidney biopsy performed for the diagnosis of glomerulonephritis or pre-eclampsia led to therapeutic changes in 66% of cases. The evidence on kidney biopsy in pregnancy is heterogeneous, but a significantly higher risk of complications (relative to postpartum biopsy) was found, with a possible peak at around 25 gestational weeks.
... 4,10,28,31 Lung transplant candidates, recipients, and the team of transplant personnel caring for them face major ethical issues. 33 Transplant recipients with cystic fibrosis who are considering pregnancy should be offered genetic counseling, and the woman's partner should undergo complete analysis of the cystic fibrosis transmembranous regulator gene by sequencing. 34 Careful consideration and appropriate counseling about termination, preterm birth, and possible arrangements in the event of morbidity or maternal mortality, or alternatives such as adoption, should be discussed before pregnancy. ...
Article
Full-text available
The purpose of this study was to analyze pregnancy outcomes in female lung transplant recipients. Data were collected from the National Transplantation Pregnancy Registry via questionnaires, interviews, and hospital records. Twenty-one female lung recipients reported 30 pregnancies with 32 outcomes (1 triplet pregnancy). Outcomes included 18 live births, 5 therapeutic abortions, and 9 spontaneous abortions. No stillbirths or ectopic pregnancies were reported. Mean (SD) interval from transplant to conception was 3.6 (3.3) years (range, 0.1-11.3 years). Comorbid conditions during pregnancy included hypertension in 16, infections in 7, diabetes in 7, preeclampsia in 1, and rejection in 5 women. Ten of the 21 recipients received a transplant because of cystic fibrosis and accounted for 12 pregnancy outcomes (7 live births, 3 spontaneous abortions, and 2 therapeutic abortions). At last recipient contact, 13 had adequate function, 2 had reduced function, 5 recipients had died (2 with cystic fibrosis), and 1 recipient had a nonfunctioning transplant. Mean gestational age of the newborn was 33.9 (SD, 5.2) weeks, and 11 were born preterm (<37 weeks). Mean birthweight was 2206 (SD, 936) g and 11 were low birthweight (<2500 g). Two neonatal deaths were associated with a triplet pregnancy; one fetus spontaneously aborted at 14 weeks and 2 died after preterm birth at 22 weeks. At last follow-up, all 16 surviving children were reported healthy and developing well. Successful pregnancy is possible after lung transplant, even among recipients with a diagnosis of cystic fibrosis.
... Ethical issues have been raised about the wisdom of pregnancy in transplant recipients who might have a limited life span or in whom serious medical complications might develop. 48 However, for many women the benefi ts of pregnancy outweigh known risks and they opt to proceed. ...
Article
Pregnancy after transplantation is common, particularly for women with kidney transplants. Several potential complications need to be considered in counseling women who wish to resume their reproductive life after transplantation; complications can occur that impact both the mother and the fetus. This manuscript reviews the common potential problems associated with pregnancy in maternal renal transplant recipients and discusses current information about fetal outcomes after in utero exposure to immunosuppressive agents. It is important to impart the potential risks and complications of pregnancy in renal transplant recipients to both the mother and her partner before embarking upon pregnancy, and pre-conception counseling is recommended to begin at the time of pre-transplant evaluation.
Article
Introduction: Many women who are solid organ transplant (SOT) recipients wish to have children after transplantation. Contraception is an important component of post-transplant planning and care, given the increased risk associated with post-transplant pregnancies. We sought to understand patient attitudes and concerns about post-transplant contraception and pregnancy. Methods: Following a comprehensive literature review, our team developed a survey that was administered to female SOT recipients of childbearing age. We used descriptive and inferential statistics to characterize participant views. Results: 243 transplant recipients completed the survey (80.7% response rate). The mean age of respondents was 37.5 years (±8.1 years), 66.7% were kidney recipients, and 40.7% were within the first year after transplant. The most common concerns among respondents included fetal and maternal health complications. Participants generally did not agree that transplant recipients should be advised to avoid pregnancy. There was strong support for shared decision making about pregnancy after transplantation. Conclusion: Understanding patient perspectives can help transplant providers make better care recommendations and support patient autonomy in reproductive decisions post-transplant. Given that there are some differences in views by transplant type, individualized conversations between patients and providers are needed. This article is protected by copyright. All rights reserved.
Article
A combined kidney and pancreas transplant is a therapeutic option for patients with type 1 diabetes and end-stage renal disease. After successful transplantation, fertility is rapidly restored, allowing women of childbearing age to have spontaneous pregnancies and men to father pregnancies. These pregnancies are at increased risk for maternal and neonatal adverse outcomes due to immunosuppressive therapy, comorbidities, previous type 1 diabetes and previous transplant surgery, although the majority ends with the birth of a live and healthy offspring. Hypertension, miscarriages, diabetes, infections, graft rejections, preterm delivery and low birth weight may complicate pregnancies after pancreas-kidney transplantation. Since not all immunosuppressive drugs can be safely used in pregnancy, it is important to review immunosuppressive treatment before conception. Adequate pre-conception counseling is important to inform women and their partners about potential risks for the pregnancy and the grafts and the advantages of pregnancy planning. These pregnancies should be managed within a multidisciplinary team, comprising a transplant physician, an endocrinologist, a nephrologist, an obstetrician and a neonatologist. Last but not least, it is very important to continue collecting data on the pregnancies in pancreas-kidney transplantation with the aim to improve knowledge and to generate evidence-based guidelines for the care of women after pancreas-kidney transplants who are considering a pregnancy.
Chapter
The issue of antenatal ultrasound examination has become a routine component for the care of a pregnant woman. Congenital anomalies of the kidney and urinary tract (CAKUT) are among the most frequent organ malformations and constitute the most common cause of chronic renal failure in children. In this chapter we introduce the tools of assessment, describe the spectrum of fetal phenotypes and discuss the various approaches taken in the clinical management of prenatally diagnosed disorders of the kidneys and urinary tract. Based on this body of information, we outline rational antenatal and postnatal investigation strategies.
Article
The patient was admitted to the Boston Lying-in Hospital to await delivery. To avoid any possible trauma to the transplanted kidney as the vertex engaged, it was decided to deliver the patient by cesarean section. This was performed under spinal anesthesia on March 10, 1958, a time arbitrarily regarded as the 41st week of gestation. A normal male infant weighing approximately 3300 grams was delivered.
Article
Women with cardiomyopathy are at risk for complications during and after pregnancy if they are unable to adapt to the hemodynamic changes of pregnancy. The hemodynamic challenges of pregnancy, labor, and delivery pose unique risks to this group of patients which can result in clinical decompensation with overt heart failure, arrhythmias, and even maternal death. A multidisciplinary approach and a controlled delivery are crucial to adequate management of patients with underlying heart disease. Preconception planning, proper counseling, and accurate risk assessment are essential and should be offered to women of childbearing age. In this chapter, the risk assessment of pregnancy in women with cardiomyopathy will be reviewed. In addition, the management of pregnant women with cardiomyopathies and heart failure will be discussed including consideration of issues at the time of labor and delivery.
Chapter
What the patient wants to knowWhat the clinician needs to know about normal pregnancyWhat the clinician needs to know about chronic renal diseaseWhat the clinician needs to know about dialysis patientsWhat the clinician needs to know about kidney allograft recipients
Article
Advances in solid-organ transplantation have allowed many women to reach reproductive potential, and pregnancy is no longer a rarity for these women. To identify (1) potential complications to allograft function posed by pregnancy, (2) expected perinatal outcomes in women with solid-organ transplants, (3) risks of potential immunosuppressant regimens, (4) safety of lactation, and (5) contraceptive options for women with solid-organ transplants. Single-center, registry data, and previous systematic reviews were evaluated in women with solid-organ transplants to identify the objectives of this review. In addition, recommendations from public health organizations were examined in regard to safety of medications and contraceptive methods. Women with solid-organ transplants are at risk for premature birth, low birth weight, cesarean delivery, and hypertensive disorders of pregnancy. Most immunosuppressant regimens are safe; however, mycophenolate mofetil should be avoided. Lactation with tacrolimus, cyclosporine, azathioprine, and prednisone appears safe. Long-acting reversible contraceptive methods are safe and effective for transplant recipients. Many successful pregnancies have been achieved in women following transplantation; however, optimal perinatal outcomes require stable allograft function. As more women are becoming pregnant after organ transplantation, a review of obstetric recommendations and perinatal outcome is warranted.
Article
Kidney transplantation (KT) increases fertility in patients with chronic kidney disease (CKD); their pregnancies are considered of high risk because of higher incidence of complications. The objective of this study was to propose, based on current concepts, an algorithm for preconception and perinatal care of KT recipients with a desire for parity. We searched for literature published within the last 10 years related to pregnancy and KT. Based on the results, we developed an algorithm for the approach to preconception/perinatal care of these patients. Preconception care begins with pre-KT study of women of childbearing age, continues with contraception, and ends with the proper selection of candidates; an exhaustive study of health condition, function of renal graft, and infections that may affect the fetus is required; fetotoxic drugs must be suspended, immunosuppression must be based in corticosteroids, azathioprine, and tacrolimus or cyclosporine. Once conception is achieved, prenatal care should be done by a multidisciplinary team; follow-up of graft function and maternal-fetal health must be strict. Pregnancy has no deleterious effect on graft function; pelvic localization of graft does not contraindicate vaginal delivery; breastfeeding is indicated if immunosuppressive levels in the newborn are low. KT returns the possibility of motherhood to women with CKD. Proper selection and optimal care of patients determines success in maternal, fetal, and graft results.
Article
Study question: What is the child morbidity after IVF in women who have received a kidney transplant? Summary answer: Overall, obstetric outcome and morbidity in children of women who had undergone renal transplantation and IVF treatment were favourable. What is known already: There are several studies of the obstetric outcome in women with spontaneous conception after solid organ transplantation as well as studies of obstetric outcome after IVF in general. There are only a few case reports of women with kidney or pancreas-kidney transplantation and deliveries after IVF treatment. Study design, size, duration: A population-based retrospective register study was carried out in Sweden including all women with solid organ transplantation and deliveries after IVF; however, only women with kidney transplants were recruited. It also included information on all singleton deliveries after kidney transplantation and spontaneous conception between 1973 and 2012. Participants/materials, setting and methods: We cross-linked the IVF registers with the Medical Birth Register, the Patient Register and the Cause of Death Register. Study group 1 consisted of women with kidney transplantation and deliveries after IVF treatment. Study group 2 consisted of women with kidney transplantation and singleton deliveries after spontaneous conception. Group 3 (control group to singletons in study group 1) consisted of women without organ transplantation and with singleton deliveries after IVF, matched for maternal age, parity and date of birth. Group 4 (control group to study group 2) consisted of women without organ transplantation and with singleton deliveries after spontaneous conception, matched for maternal age, parity and year of birth. Main results and the role of chance: Seven singletons and one set of twins were born after organ transplantation and IVF. All women in this group had renal transplants. Among singletons, two (28.6%) were preterm births (PTB), one (14.3%) had very low birthweight (VLBW) (672 g) and one (14.3%) was small for gestational age (SGA). Two infants had minor birth defects. One woman developed pre-eclampsia (14.3%). Mean age at follow-up of the children was 9.7 years (SD 4.2). Two children were diagnosed with hyperactivity disorders. There were 199 singletons born after renal transplantation and spontaneous conception. The rates of pre-eclampsia (23.6%), PTB (48.5%), LBW (43.7%) and SGA (21.2%) were significantly higher in pregnancies of women with renal transplants who had conceived spontaneously than in pregnancies where there was no transplantation and conception was spontaneous. Neonatal morbidity, early neonatal and infant mortality were all significantly higher. No increase in birth defects was seen. Mean age at follow-up of the children was 14.7 years (SD 9.4). Acute bronchitis, systemic lupus erythematosus and hyperactivity disorders were more common in children delivered to women with renal transplantation than in children delivered to women with no transplanted organs. Otherwise, long-term child morbidity was comparable. Limitations, reasons for caution: The women who had received renal transplants and who had given birth after IVF were a small group and may represent a selected group of comparatively healthy women. Wider implications of the findings: The results are important to transplant recipients with infertility problems. Neonatal outcomes after maternal renal transplantation and spontaneous conception were in agreement with the literature. Long-term follow-up of this group of children has long been asked for and findings are included in this report. Study funding/competing interests: No conflict of interest was reported. The study was supported by grants from Swedish Association of Local Authorities and Regions and by grants from the University of Gothenburg/Sahlgrenska University hospital (LUA/ALF 70940).
Article
Organ transplantation (OT) has improved the long-term survival of patients facing specific organ failure and has refocused management to a chronic condition, with emphasis on enhancing life quality, including respecting a patient's autonomy to have children. Transplant patients are often faced with subfertility, frequently a consequence of gonadotoxic medical therapy. For some patients, successful OT management, reproductive conservation measures and the use of assisted reproductive technologies (ART) may help preserve fertility. There is a growing literature on the use of ART in these patients. The main objective of ART in OT recipients is attaining a healthy pregnancy, while minimizing potential complications that would jeopardize both the maternal health status and offspring. The purpose of this article is to address the distinctive medical, ethical and psychosocial concerns surrounding the fertility management of OT recipients.
Article
Pregnancy after lung transplantation has been described, but pregnancy after living donor lobar lung transplantation (LDLT) has not been reported. The aim of this study was to evaluate outcomes after pregnancy with LDLT and discuss current recommendations regarding pregnancy and lung transplantation. A total of four LDLT patients and five pregnancies were identified, all from our institution. No patient has developed worsening pulmonary function or acute or chronic rejection. The complications of pulmonary hypertension and rejection may be overestimated in this population, and recommendations for preventive sterilization at transplantation or abortion at the time of conception are likely unwarranted and unnecessary.
Article
The clinical literature notes that pregnancy has become an expected benefit of solid organ transplant. Establishing “best practices” in the management of this particular transplant population requires careful consideration of the ethical dimensions, broadly speaking, of post-transplant pregnancies and these women’s lived experiences. In this article we present the current clinical and social science post-transplant pregnancy research. We specifically address the psycho-social and ethical issues surrounding pre-conception counselling and post-transplant health quality of life and mothering and suggest areas for future research.
Article
Should surgeons offer uterus transplants to women who want to become pregnant but do not have a functioning uterus? The debate reminds us that society often neglects the interests of the infertile. Only a handful of uterus transplants have been reported worldwide—including two this past September—but advances in technique may make the transplants available more widely. Some women are born without a functioning uterus; others have hysterectomies for cancer, postpartum hemorrhage, or other reasons. Many of these women want to become mothers and carry their own pregnancies. However, the prospect of uterus transplantation has elicited sharp criticism. According to ethics professor Rebecca Kukla, the surgery is not, “in any traditional sense, therapeutic.”
Article
Pre-pregnancy planning in chronic renal patients has relied mainly on information gleaned from case reports, small series and variable registries. Nevertheless, guidelines have emerged to help clinicians in the care of their patients, so that as with other chronic medical conditions, it is becoming recognised as part of the traditional organisation of care associated with pregnancy. Nevertheless, most chronic renal patients do not plan their pregnancies with their health care team, and this complex behaviour is affected by the quality of the relationship with the team and by the woman’s attitude to her health and beliefs. The basic components of pre-pregnancy counselling should be analysis of risks, provision of health education and advice, and then making specific helpful interventions. Such ‘active preparation for pregnancy’ should be individualised to each woman’s needs and involve her partner. The ethical controversies associated with the need to understand the psychology of women who pursue parenthood, despite substantial risk to their own health and that of their unborn baby, should not be underestimated.
Article
The first successful pregnancy after heart transplantation was reported in 1988. Worldwide experience with heart and heart/lung transplanted (H-HLTx) pregnant women is limited. To expand this knowledge the collaborating Nordic thoracic transplant centers wanted to collect information on all such pregnancies from their centers. Information was retrospectively collected on all H-HLTx pregnancies in the Nordic countries. A total of 25 women have had 42 pregnancies and all survived the gestation. Minor complications were increasing incidence of proteinuria, hypertension and diabetes. Major problems were two rejections (early post partum), two severe renal failures, seven pre-eclampsias and 17 abortions. Five women died two to 12 years after delivery. Of 25 live born children, one was born with cancer and one died early after inheriting the mother's cardiomyopathy. Pregnancy after H-HLTx can be successful for both mother and child. There are, however, many obstacles which should be addressed. Respecting the couple's desire for children the attitude should be carefully, not too optimistic, after proper pre-pregnant information and counseling. Delivery should preferably take place at the transplant center.
Article
Pregnancy in the context of chronic kidney disease (CKD) is a daunting clinical scenario for both health-care providers and patients and raises ethical and social questions that have important implications for health policy and funding. Despite potential problems, women with CKD will continue to conceive and deliver babies, and nephrologists will be faced with the challenge of caring for them. This paper discusses ethical issues regarding pregnancy in CKD and highlights the controversies surrounding parental, fetal, and societal rights.
Article
Pregnancy, although rare in the patient with end-stage renal disease, is not uncommon in the transplant recipient. Physicians taking care of transplant recipients must be able to inform patients about the potential risks of pregnancy in this setting. The patient and her partner must know that the risks associated with pregnancy increase with worsening kidney function and hypertension. Current consensus opinion is that pregnancy can be relatively safely undertaken by 1 year after transplant if the patient has had no rejections during the year, allograft function is adequate, there are no infections that could affect the fetus, the patient is not taking teratogenic medications, and immunosuppressive medication dosing is stable. Consideration must be given to immunosuppression during pregnancy both with respect to the specific agents as well as the level of dosing. None of the medications are FDA category A; all are B or higher. Part of planning for pregnancy should include an evaluation of immunosuppression medication and a plan to modify the regimen prior to conception if its use may be risky for the developing fetus. Rejection can occur during a kidney transplant, so maintaining adequate immunosuppression is important. Other issues that need to be managed when caring for a pregnant transplant patient include: potential for infection (urinary tract infections are very common), hypertension, and anemia. The type of delivery, posttransplant contraception, and breast-feeding also need to be addressed.
Article
Full-text available
The circumstances of liver transplantation are unique among organ transplantation because of the dire, absolute scarcity of donor livers and the predominance of one disease--alcohol-related end-stage liver disease--as the principal cause of liver failure. We propose that patients who develop end-stage liver disease through no fault of their own should have higher priority for receiving a liver transplant than those whose end-stage liver disease results from failure to obtain treatment for alcoholism. We base our proposal on considerations of fairness and on whether public support for liver transplantation can be maintained if, as a result of a first-come, first-served approach, patients with alcohol-related end-stage liver disease receive more than half the available donor livers. We conclude that since not all can live, priorities must be established for the use of scarce health care resources. KIE In 1990, the Health Care Financing Administration recommended that Medicare coverage for liver transplantation be offered to patients with alcoholic cirrhosis who are abstinent, and that the same eligibility criteria be used for patients with alcohol-related end-stage liver disease (ARESLD) as for patients with other causes of end-stage liver disease (ESLD). Moss and Siegler argue against this policy, proposing that patients who develop ESLD through no fault of their own have a higher priority for receiving a transplant than patients whose ESLD results from a failure to obtain treatment for alcoholism. They base their proposal on considerations of fairness and on whether public support for liver transplantation can be maintained if over half the available donor livers, which are in scarce supply, go to patients with ARESLD.
Article
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To identify incidence of school and behaviour problems at age 7 years in children born between 32 and 35 weeks gestation, and investigate perinatal risk factors. The study population consisted of all children born at 32-35 weeks gestation to mothers resident in Oxfordshire in 1990. General practitioners, parents, and teachers were asked about health, behaviour, and education by postal questionnaire. Teachers rated children on level of function in six areas using a five point scale. They also completed the Strengths and Difficulties behaviour questionnaire. Perinatal risk factors were identified for children with poor school performance using a univariate and multivariate analysis. Teacher responses were obtained for 117 (66%) of the 176 children in the cohort. Twenty nine (25%) required support from a non-teaching assistant, five (4%) had required a statement of special educational needs, and three (3%) were at special school. Poor outcome was reported for 32% in writing, 31% in fine motor skills, 29% in mathematics, 19% in speaking, 21% in reading, and 12% in physical education. On the behaviour questionnaire, 19% of the cohort achieved an abnormal hyperactivity score (population norm 10%). Multivariate analysis showed perinatal variables that remained significant, independent of other variables; they were discharge from the special care baby unit > 36 weeks postconceptional age (odds ratio 4.15; 95% confidence interval 1.43 to 12.05) and male sex (odds ratio 3.88; 95% confidence interval 1.42 to 10.6). Up to a third of children born between 32 and 35 weeks gestation may have school problems. As there are larger numbers in this gestational category compared with smaller babies, this finding has implications for educational services.
Article
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Background: The success in performing organ transplantations and prevention of rejection has resulted not only in a substantial increase in life expectancy, but also improvement in the patients' quality of life. Thus, women who underwent organ transplantation are now reaching puberty and the age of reproduction. This has presented new challenges regarding the teratogenicity and the long-term effect of immunosuppressive medications used by these patients. Previous studies have shown that pregnancies after renal transplantation are associated with an increased risk for both the mother and the fetus. There is, however, very little information available on neonatal and long-term pediatric follow-up of babies born to mothers who have undergone renal transplantation and have been exposed to immunosuppressive medications, compared to controls. We report the experience of our center, the largest in Canada, regarding the prenatal and long-term postnatal outcome of pregnancies after renal transplantation. Methods: This is a retrospective case series reporting the outcome of 44 consecutive pregnancies followed by the Toronto Renal Transplant Program. Follow-up data were gathered on the 32 live born children by either a return visit to the clinic or by telephone interview. Medical, as well as developmental information, was gathered on all children and the study group was compared to controls, matched for maternal age (+/-2 years) and smoking status, obtained through the Motherisk Program. Results: Of the 44 pregnancies followed by us, there were 32 live-born children delivered by 26 mothers and 12 stillborn/abortuses. Twenty-six pregnancies were treated with cyclosporine, azathioprine and prednisone, 13 with azathioprine and prednisone and five with cyclosporine and prednisone. The mean gestational age at delivery in the study group was 36.5 +/- 2.7 weeks compared to 40.2 +/- 1.6 weeks in the control group (P < 0.001). The mean birthweight in the study group was 2.54 +/- 0.67 kg, compared to 3.59 +/- 0.53 kg in the control group (P < 0.0001). In the study group there was one child with multiple anomalies and four stillbirths compared to zero in the control group. There were also six spontaneous abortions and two therapeutic abortions in the study group. On follow-up (from 3 months to 11 years of age) there was one child with insulin-dependent diabetes mellitus, two children with asthma and one child with recurrent otitis media. Developmental follow-up revealed one child with moderate to severe sensorineural hearing loss, one child with a learning disability and one child with pervasive developmental disorder. In none of these cases were there signs of perinatal asphyxia. Conclusion: There are significantly more stillbirths, preterm deliveries and increased incidence of low birth weight in the transplant group. Most pregnancies in the study group went well, however, and their offspring had normal postnatal growth and development. Further studies with long-term pediatric follow-up are needed to delineate their outcome and rule out possible long term effects of the immunosuppressive medication on their growth, development, reproduction and general health.
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The cognitive and behavioral outcomes of school-aged children who were born preterm have been reported extensively. Many of these studies have methodological flaws that preclude an accurate estimate of the long-term outcomes of prematurity. To estimate the effect of preterm birth on cognition and behavior in school-aged children. MEDLINE search (1980 to November 2001) for English-language articles, supplemented by a manual search of personal files maintained by 2 of the authors. We included case-control studies reporting cognitive and/or behavioral data of children who were born preterm and who were evaluated after their fifth birthday if the attrition rate was less than 30%. From the 227 reviewed studies, cognitive data from 15 studies and behavioral data from 16 studies were selected. Data on population demographics, study characteristics, and cognitive and behavioral outcomes were extracted from each study, entered in a customized database, and reviewed twice to minimize error. Differences between the mean cognitive scores of cases and controls were pooled. Homogeneity across studies was formally tested using a general variance-based method and graphically using Galbraith plots. Linear meta-analysis regression models were fitted to explore the impact of birth weight and gestational age on cognitive outcomes. Study-specific relative risks (RRs) were calculated for the incidence of attention-deficit/hyperactivity disorder (ADHD) and pooled. Quality assessment of the studies was performed based on a 10-point scale. Publication bias was examined using Begg modified funnel plots and formally tested using the Egger weighted-linear regression method. Among 1556 cases and 1720 controls, controls had significantly higher cognitive scores compared with children who were born preterm (weighted mean difference, 10.9; 95% confidence interval [CI], 9.2-12.5). The mean cognitive scores of preterm-born cases and term-born controls were directly proportional to their birth weight (R(2) = 0.51; P<.001) and gestational age (R(2) = 0.49; P<.001). Age at evaluation had no significant correlation with mean difference in cognitive scores (R(2) = 0.12; P =.20). Preterm-born children showed increases in externalizing and internalizing behaviors in 81% of studies and had more than twice the RR for developing ADHD (pooled RR, 2.64; 95% CI, 1.85-3.78). No differences were noted in cognition and behaviors based on the quality of the study. Children who were born preterm are at risk for reduced cognitive test scores and their immaturity at birth is directly proportional to the mean cognitive scores at school age. Preterm-born children also show an increased incidence of ADHD and other behaviors.
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From the first reports of pregnancy in each of the organ groups to the present, concerns varied and were specific to the type of transplant. Organ-specific issues still require additional attention and analyses. Lung recipients appear at greatest risk for poorer pregnancy outcomes. Given these ongoing concerns and the constant advent of new developments, clinicians are responsible for providing pregnancy counseling in all pre- and posttransplant recipients of childbearing age. As individual physicians and centers accrue experience with these major therapeutic decisions, it is critical that both positive and negative outcomes be reported in appropriate settings-symposia, meetings, publications, and registries. Future analyses from the NTPR are directed at potential effects of newer immunosuppressive regimens, not only from immediate exposure, but also from continued exposures such as may occur from breastfeeding. As the registry study design allows for contact between registry staff and recipients and their health care providers, efforts are ongoing to analyze long-term outcomes of parent and child. Continued close collaboration among specialists will help to identify potential pregnancy risks in these populations, particularly as new immunosuppressive agents are developed. Therefore, centers are encouraged to report all pregnancy exposures in transplant recipients to the NTPR. The 50th anniversary of the first posttransplant pregnancy (reported by Joseph Murray, et al. (11)) was in March 2008. With this important landmark event and with ongoing pregnancy issues concerning posttransplant pregnancy safety, this is an ideal time to raise the awareness of the need for continued worldwide cooperation for data collection. Enhanced assessment of pregnancy safety is essential to the development of guidelines for counseling and management of pregnancy in the transplant population.
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Chronic liver disease often leads to amenorrhea in women of childbearing age. There are several reports of successful pregnancy after liver transplantation (LTx) with cyclosporine A immunosuppression. Tacrolimus has been increasingly used in solid-organ transplantation, and the effect of the drug on pregnancy is still of interest to clinicians. This study updates our single-center experience. All pregnancies after LTx with tacrolimus immunosuppression were followed prospectively. Patients' clinical courses during pregnancy and labor along with gestational period and birth weight were catalogued. Changes in liver function, renal function, and immunosuppression also were recorded. The birth weight percentile was calculated on the basis of the gestational period using a standard chart. Thirty-seven mothers delivered 49 babies. Three mothers delivered three times, and six mothers delivered two times. Thirty-six mothers (97%) survived the pregnancy, and 36 allografts (97%) survived. The one death and graft loss was in a patient who demonstrated infra-aortic arterial graft, which clotted by the gravid uterus during labor. The patient developed a gangrenous liver and died before she could undergo retransplantation. The mean gestational period was 36.4+/-3.2 weeks, excluding two premature deliveries at 23 and 24 weeks gestation. Twenty-two babies (46.9%) were delivered by cesarean section, and the other babies were delivered vaginally. In addition to the two premature babies, one baby, who was born to a mother with Alagille syndrome, died from congenital birth defects. The rest of the newborns survived. The mean birth weight was 2,797+/-775 g, with 38 babies (78%) weighing more than 2,000 g. The mean birth weight percentile to gestational period was 54+/-23. Four babies (8.5%) had a birth weight percentile of less than 25, and 28 babies (59.6%) had a birth weight percentile greater than 50. Twelve patients demonstrated an increase in hepatic enzymes without jaundice during the pregnancy. All of them responded to augmentation of immunosuppression. The present report reconfirms the safety of tacrolimus during pregnancy after LTx. Preterm delivery and low birth weight seem to be a persistent problem in all solid-organ transplantation under any form of immunosuppression. However, toxemia of pregnancy and new onset of hypertension seem to be have a low occurrence with the use of tacrolimus.
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The ideal of equality constitutes a criterion for assessing current practice through attention to differences among individuals and groups. Inequality occurs when irrelevant differences are invoked in order to secure power or advantages over others. This book examines health care issues from an egalitarian perspective, focusing particularly on those that affect the lives of women and children. These are some of the most hotly debated, controversial, yet genuinely humanitarian issues of our time. They include gender stereotypes in medicine and in adolescent socialization, fertility curtailment and enhancement, coercive treatment during pregnancy, fetal tissue transplantation, decisions regarding newborns, decision-making by minors, the feminization of poverty and its impact on women’s and children’s health, and the meaning and role of “family” in health care decisions. The book describes a case-based or “feminine” model of reasoning as appropriate to the health care setting, but also as a possible rationale for exploitation of women. Different versions of feminism are clearly explained and specifically related to care-based reasoning. To overcome the pitfalls of paternalism and excessive stress on patient autonomy, a concept of “parentalism” is defended. An egalitarian perspective, the author claims, involves use of one’s power to empower others. Because of the timeliness of the topics discussed, and the depth of detail, this book will be necessary reading for all bioethicists, health-care analysts and policy-makers, and women’s studies researchers.
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Women and Children in Health Care should be required reading, along with Susan Sherwin's No Longer Patient, for those who are uneasy about the moral environment of contemporary medical practice. Both books show how serious inequality permeates the health care establishment, and both authors encourage their readers to do something about the problem.Mahowald's book ranges from the theoretical to the practical. She starts with a useful critique of contemporary ethical theory and lays out a model for an egalitarian approach to moral problem solving. Although her initial discussion of the seven guidelines she proposes is schematic, her subsequent treatment of specific issues develops them more fully. Mahowald pays special attention to the sex-role stereotypes and power differentials that permeate medical practice. Her remedy is what she calls a "parentalist" model of relationships that empowers others by promoting both autonomy and health needs. Parentalism requires collaborative decision making and awareness
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In most discussions of the ethics of fertility treatment it is claimed that the interests of the potential child are of major if not paramount importance. The practical significance of this consideration has been grossly overestimated. Contrary to conventional wisdom, the interests of the potential child hardly ever constitute an adequate reason for withholding fertility treatment.Modern fertility treatments became the focus of much media attention in 1993 after the widely publicised case in which a 59 year old woman was enabled to give birth to twins by means of in vitro fertilisation with donated eggs and her partner's sperm. Fertility treatments raise a wide range of ethical and social issues. We focus on one specific issue: the interests and welfare of the potential child. These factors are often cited as important reasons for withholding fertility treatment. We contend that they are almost never relevant, and moreover, we support a wider provision of fertility treatment.The Human Fertilisation and Embryology Act 1991 states that “centres considering treatment must take into account the welfare of any child who may be born.” Robert Winston, professor of fertility studies at the Hammersmith Hospital, argued that it is wrong to offer in vitro fertilisation to most postmenopausal women.1 One of his reasons concerned the potential child. Hugh Whittall of the Human Embryology and Fertilisation Authority said that although there was no upper age limit for …
Article
The National Transplantation Pregnancy Registry (NTPR) was established in 1991 to study the outcomes of pregnancies in female transplant recipients and pregnancies fathered by male transplant recipients. Data from the NTPR have helped to endorse the reassurances from publications of smaller experiences that successful pregnancies are possible in the transplant population. In our last review for this journal (2000), we noted that important future issues would include the reassessment of prepregnancy guidelines, gestational and organ-specific problems, the role of new immunosuppressive drugs, and the long-term effects of pregnancy on both graft and child. Data collected by the NTPR over the last 7 years have addressed these issues, thus providing additional information for health care providers of transplant recipients of childbearing age. There has been some refinement of prepregnancy guidelines, but there is a need for additional data collection so that organ-specific outcomes and risks can further be identified. To date, the outcomes of the children followed have been encouraging, and specific remote effects have not been identified, but continued surveillance is still vital. Of special concern are the new immunosuppressive drugs, specifically for mycophenolate mofetil (CellCept, Roche Laboratories Inc., Nutley, New Jersey), where data reported to the NTPR and through postmarketing surveillance have shown an increased incidence of nonviable outcomes and a specific pattern and increased incidence of malformation in the newborn, which has resulted in a pregnancy category change. Newer information points to an increased need for vigilance among centers and continued monitoring of pregnancy outcomes in this population. As the first reported pregnancy after transplantation occurred in a kidney recipient 50 years ago, in March 1958, this review also highlights the first reported pregnancies in other solid organ recipients.
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As the numbers of women infected with HIV continue to increase, there are more calls for women who are HIV-infected not to have children, or for policies to be created that limit or try to influence the reproductive choices of HIV-infected women. Although motivated by legitimate concerns, such potential policies may be problematic in terms of their threats to the autonomy of women and considerations of justice. An alternative counseling approach is proposed that advocates encouraging HIV-infected women to make reasoned and considered decisions concerning childbearing. Such an approach would require providers to discuss with women not only the medical facts relevant to vertical transmission, but also many of the psychosocial issues relevant to the woman's interest in bearing a child. Moreover, the encounter would be contextualized to include discussion of issues unique to the woman's situation and other family considerations.
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The causes of infertility can be divided into seven categories. In older couples, valuable time can be lost if evaluation is delayed. An orderly diagnostic approach assures that no diagnosis is overlooked. Many of the causes of infertility are amenable to therapy.
Article
Because of a shortage of transplantable livers and hearts, the transplant community has had to decide--by who gets an organ--who lives or dies. Despite this shortage, whether one has previously received a transplant is not used as a criterion to distribute organs. The existing allocation system distributes 10% to 20% of available hearts and livers to retransplant patients. This article examines three differences between primary transplantation and retransplantation that may affect the priority that retransplant candidates should receive in vying for organs: (1) the special obligations that transplant teams have not to abandon patients on whom they have already performed a transplant, (2) the fairness of allowing individuals to get multiple transplants while some die awaiting their first, and (3) the difference in efficacy between primary transplantation and retransplantation. Only this last difference holds up to critical analysis. Our moral duty to direct scarce, lifesaving resources to those likely to benefit from them, suggests that, all other things equal, primary transplant candidates should receive priority because their mortality after transplantation is lower. Consistency also demands that previous transplant history be taken into account, as we already allocate organs according to ABO blood group matching, a factor that affects transplant outcome approximately the same amount as a previous transplantation. We therefore conclude that the system should be revised so that primary transplant candidates have a better chance of receiving organs than retransplant candidates.
Article
The are two common replies to the question of whether carriers of genetic disorder should have children. The first simply ends any argument by claiming that everyone has an inalienable right to have children. In many ways this view is quite attractive. The right is said to be universal as well as inalienable. It avoids odious comparisons and applies to everyone, including those whom society has deemed unfit for the flimsiest reasons. In the United Kingdom, for example, a High Court judge recently upheld the decision by Sheffield Health Authority to refuse IVF treatment to Julie Seale, who was then 36, on the grounds of her advanced age. This latest salvo in what one writer has called “the fertility war” follows on from the Grand Peninsular Campaign against IVF treatment for post-menopausal women and the recurrent guerilla battle over enforced sterilisation. As this author remarks, “What has happened without our really noticing it is that, with every new skirmish in the fertility war, we are becoming more and more comfortable with the idea that some people deserve to be parents more than others” [1]. And in an age of what is essentially payment by results, there is a great temptation for healthcare providers to think that those who deserve to be parents are those with the best clinical chances.
Article
The literature contains reports of 2,309 pregnancies in some 1,600 women who have undergone renal transplantation. Certain pre-pregnancy factors, especially hypertension, renal graft dysfunction and short interval between transplant and pregnancy, appear to increase the neonatal risks. We describe the outcome of 42 pregnancies in 27 allograft recipients at Beilinson Medical Center in Israel during the last 8 years. All were treated with combination immunosuppression regimens. The average interval from time of transplantation to conception was 3.7 +/- 0.4 years (2 months to 9 years). Rejection episodes occurred in 37% prior to pregnancy but in none during or immediately after pregnancy. Of the 42 pregnancies 28% ended in therapeutic or spontaneous abortions, and 29 of the 30 deliveries ended in a life birth. The prematurity rate (65%) was similar to that described in the literature. Renal deterioration was evident in seven women (26%) within 2 years after delivery. Despite this significant success rate, pregnancy in organ transplant patients should still be considered high risk.
Article
SINCE 1973, renal transplantation have been performed in children and adolescents in our department. Of the 345 female patients of this series, 33 pregnancies occured in 20 young women of childbearing age, leading to 25 births, while 5 ended in early spontaneous abortion, and 3 in therapeutic abortions. The mean age was 12 years at dialysis onset, 15 at renal transplantation, and menarch occured at the mean age of 15 years. The delay between renal transplantation and first pregnancy was 9.25 years (1.5 to 12.5 years), and between first and second pregnancy, 2.5 years (0.8 to 4 years). Nine patients received double immunosuppressive therapy (Azathioprine + Prednisone), and 11 triple therapy (Azathioprine + Prednisone + Cyclosporine). Azathioprine is decreased to 1 mg/kg/d at the fourth month. Mean serum creatinine level during the year before pregnancy was 119 μmol/L, raising to 133 at delivery. Age at the first delivery was 23.7 years (22.7 to 29 years), and 26.5 for the five who had a second pregnancy. Postpartum mean creatinine level was 139 to 3 months, 126 at 6 months, and 135 μmol/L at 12 months. Three kidneys were lost: two after the first pregnancy, with baseline serum creatinine levels at 140 and 183 mmol/L at start, and one after the second despite a normal baseline serum creatinine level (101 mmol/L). No change in renal function was observed in the 17 other patients. Twelve patients received hypotensive drugs: 10 had this treatment before, and two developed mild hypertension during pregnancy (triple therapy); toxemia gravidis occured in one not receiving cyclosporine. Cesarian delivery was performed in 12 of the 25 pregnancies. Mean duration of gestation was 36 weeks and 4 days and sex ratio was 68% female babies (17 girls/8 boys). The the average birth weight was 2460 g (2398 for male, 2525 for female). Five babies were critically ill birth (four of them due to prematurity, and one because of side effects of maternal therapy; Amitryptilin-Laroxyl). No side effects of immunosuppressive drugs have been detected in children. By December 31, 1995, all of these, aged 8 months to 18 years, were known to be in good condition. Despite the late age of menarch onset (15 years), our patients recovered regular ovarian function after renal transplantation. Half of them had oral contraception. Most of the pregnancies were planned. All have been carefully followed by obstetricians and nephrologists. The recorded data about pregnancies in women who underwent renal transplantation at the end of childhood period are not different from those recorded in adults.
Article
Current debates on how to reduce the high U.S. abortion rate often fail to take into account the role of unintended pregnancy, an important determinant of abortion. Data from the 1982, 1988 and 1995 cycles of the National Survey of Family Growth, supplemented by data from other sources, are used to estimate 1994 rates and percentages of unintended birth and pregnancy and the proportion of women who have experienced an unintended birth, an abortion or both. In addition, estimates are made of the proportion of women who will have had an abortion by age 45. Excluding miscarriages, 49% of the pregnancies concluding in 1994 were unintended; 54% of these ended in abortion. Forty-eight percent of women aged 15-44 in 1994 had had at least one unplanned pregnancy sometime in their lives; 28% had had one or more unplanned births, 30% had had one or more abortions and 11% had had both. At 1994 rates, women can expect to have 1.42 unintended pregnancies by the time they are 45, and at 1992 rates, 43% of women will have had an abortion. Between 1987 and 1994, the unintended pregnancy rate declined by 16%, from 54 to 45 per 1,000 women of reproductive age. The proportion of unplanned pregnancies that ended in abortion increased among women aged 20 and older, but decreased among teenagers, who are now more likely than older women to continue their unplanned pregnancies. The unintended pregnancy rate was highest among women who were aged 18-24, unmarried, low-income, black or Hispanic. Rates of unintended pregnancy have declined, probably as a result of higher contraceptive prevalence and use of more effective methods. Efforts to achieve further decreases should focus on reducing risky behavior, promoting the use of effective contraceptive methods and improving the effectiveness with which all methods are used.
Article
Many believe that it is morally wrong to give lower priority for a liver transplant to alcoholics with end-stage liver disease than to patients whose disease is not alcohol-related. Presumably, alcoholism is a disease that results from factors beyond one's control and therefore one cannot be causally or morally responsible for alcoholism or the liver failure that results from it. Moreover, giving lower priority to alcoholics unfairly singles them out for the moral vice of heavy drinking. I argue that the etiology of alcoholism may involve enough control for the alcoholic to be responsible for his condition and accordingly have a weaker claim to receive a new liver than someone who acquires the disease through no fault of his own. In addition, I show why it is more plausible to reframe the question of priority in terms of control and responsibility rather than virtue and vice. Given that medical resources like livers are scarce, some people may justifiably be given lower priority than others in receiving these resources.
Article
Successful pregnancy outcomes are possible after solid organ transplantation. While there are risks to mother and fetus, there has not been an increased incidence of malformations noted in the newborn of the transplant recipient. It is essential that there is closely coordinated care that involves the transplant team and an obstetrician in order to obtain a favourable outcome. Current data from the literature, as well as from reports from the National Transplantation Pregnancy Registry (NTPR), support the concept that immuno suppression be maintained at appropriate levels during pregnancy. At present, most immunosuppressive maintenance regimens include combination therapy, usually cyclosporin or tacrolimus based. Most female transplant recipients will be receiving maintenance therapy prior to and during pregnancy. For some agents, including monoclonal antibodies and mycophenolate mofetil, there is either no animal reproductive information or there are concerns about reproductive safety. The optimal (lowest risk) transplant recipient can be defined by pre-conception criteria which include good transplant graft function, no evidence of rejection, minimum 1 to 2 years post-transplant and no or well controlled hypertension. For these women pregnancy generally proceeds without significant adverse effects on mother and child. It is of note that the epidemiological data available to date on azathioprine-based regimens are favourable in the setting of a category D agent (i.e. one that can cause fetal harm). Thus, there is still much to learn regarding potential toxicities of immunosuppressive agents. The effect of improved immunosuppressive regimens which use newer or more potent (and potentially more toxic) agents will require further study.
Article
Female solid organ recipients with good graft function generally tolerate pregnancy well. However, the combination of mother, fetus, transplanted organ, and immunosuppressive and other medications increases the complexity of management and raises the specter of adverse outcomes. For the mother, considerations include the nature of the original disease (i.e. genetic risk of transmission), co-morbid conditions which increase pregnancy risk (i.e. hypertension, diabetes, renal insufficiency), and long-term maternal prognosis. For the fetus, questions include the adequacy of maternal physiology (cardiac, renal, glycernic control, etc.), exposure to medications, and exposure to infectious agents. The transplanted organ must accommodate the increased workload of pregnancy and the needs of the fetus. The delicate balance between immunosuppression and rejection may be altered by the pregnancy. The impact of pregnancy on recurrent disease can also be an issue. Medication issues include changes in drug pharmacokinetics and the potential for adverse effects on the fetus. These effects could include chromosomal aberrations, structural malformations, organ-specific toxicity, intrauterine growth retardation, and immune system development. For female kidney recipients there are sufficient data to demonstrate a direct relationship between creatinine levels before and during pregnancy and risk of graft loss in the postpartum period. Pregnancy itself does not appear to adversely affect stable graft function. Among liver recipients, those with recurrent viral hepatitis may have deterioration of graft function with subsequent pregnancies. These recipients should be apprised accordingly, as maternal deaths have occurred in this setting. Postpartum depression and potential for medication noncompliance require vigilance. The safety of pregnancy from the NTPR analysis to date has been largely derived from the experience with CsA-based regimens. For recipients on CsA there have been good maternal outcomes without any specific or predominant malformation patterns in the offspring. For the general population, malformations occur in approximately 3% of live births. To date, there is no indication that this incidence has increased despite the complex medical regimens of transplant recipients. Data are accruing with tacrolimus and Neoral. Continuing data entry and continued follow-up of off-spring will allow for further recommendations, especially in light of the new medications and combinations. Recipients should be advised to wait one to 2 years after transplant before considering pregnancy. Those with stable graft function, and with no rejection, graft dysfunction, or deterioration should still be apprised of the high risk of prematurity and low birthweight, although maternal risks appear low. These are high-risk pregnancies, requiring close communication and cooperation between the high-risk obstetrician and the transplant team. The use of the FDA pregnancy categories should not be the sole reason for choosing a particular immunosuppressive drug. Agents such as Neoral and tacrolimus would appear to offer some advantage as blood levels can be measured. At present, no safety guidelines can be given for mycophenolate mofetil, OKT3, or ATG. Identification of prepregnancy factors predictive of higher risks and appropriate counseling and management guidelines are major NTPR goals, and depend on the continued assistance and cooperation of the transplant community.
Article
To measure the relative importance people place on prognosis and retransplantation status in allocating scarce transplantable livers. 138 subjects were asked to distribute scarce livers amongst transplant candidates with either a 70% chance or a 30% chance of surviving if transplanted. In one group of subjects, the prognostic difference was based on the presence or absence of a 'blood marker.' In the other group, the prognostic difference was based on whether candidates had been previously transplanted or not, with retransplant candidates having a 30% chance of surviving if transplanted. Subjects answering the retransplantation survey gave a higher percentage of organs to the better prognostic group than subjects answering the blood marker survey, with a mean of 71.6% versus 65.0%, although this difference fell just short of statistical significance (P = 0.0581). Retransplantation survey respondents were significantly less likely to want to ignore prognostic information than were blood marker respondents (P = 0.026). Subjects in both survey groups were equally unwilling to abandon the poor prognostic group, with only 18% in each group choosing to give all the available organs to the better prognostic group. Respondents reacted more strongly to prognostic differences when they were due to retransplant status than to the results of a blood test. However, most people were not solely interested in the aggregate medical benefit brought by different allocation systems, but were also interested in the amount of benefit brought to the worst off.
Article
To assess the current physical status and developmental outcome of children born to mothers following renal transplantation. A cross-sectional prevalence survey of 48 children born to 34 women transplanted at a single centre from 1971 to 1992 was performed. Data on maternal renal disease, immunosuppression, pregnancy, delivery and child development were collected using hospital records and parental questionnaire. Children underwent physical examination, urinalysis and urinary tract ultrasound examination (US). Maternal renal failure was due to reflux nephropathy/chronic pyelonephritis (16), chronic glomerulonephritis (eight) and other causes (10). All mothers received prednisolone immunosuppression, as sole therapy (one), as part of triple therapy (one). Sixteen (47%) received azathioprine/prednisolone and 16 (47%) cyclosporin/prednisolone. Twenty-three girls and 25 boys aged 9 months to 18 years were studied (median age 5.2 years); 27/48 (56%) were born prematurely, 21/48 (44%) with birthweight (BW) < 2500 g 21/48 (44%) were small for gestation (BW < 10th centile). General health and physical assessment were unremarkable in 45/48 (94%) and 41/43 (95%), respectively. Development was considered normal in 47/48 (98%). Four of 40 (10%) had urinary tract abnormalities on US. Despite a high incidence of preterm delivery, low birth weight, intrauterine growth retardation and urinary tract abnormalities, the overall outcome for children of renal transplant recipient mothers is good.
Article
Some patients treated by transplantation of haemopoietic stem cells (peripheral blood or bone marrow) become permanently infertile, but others retain or recover fertility. We assessed the outcome of conception in women, and partners of men previously treated by autologous or allogeneic stem cell transplantation (SCT). We sent questionnaires to 229 centres of the European Group for Blood and Marrow Transplantation. We sought details about the original disease, transplant procedure, and outcome of conception for both male and female patients. 199 centres gave information relating to 19412 allogeneic and 17950 autologous transplant patients. 232 (0.6%) patients conceived after SCT. Crude annual birth rate for 4-month survivors of SCT was lower than the national average for England and Wales at 1.7 per 1000 patients. 312 conceptions were reported in 113 patients (74 allograft) and partners of 119 patients (93 allograft). Most pregnancies were uncomplicated and resulted in 271 livebirths. 28 (42%) of 67 allograft recipients had caesarean section compared with 16% in the normal population (difference =26% [95% CI 15-38]), 12 (20%) of 59 had preterm delivery compared with a normal rate of 6% (14% [4-24]), and 12 (23%) of 52 had low birthweight singleton offspring compared with a normal rate of 6% (17% [6-29]). Pregnancy after SCT is likely to have a successful outcome. Pregnancies in allograft patients who have received total body irradiation should be treated as high risk for maternal and fetal complications.
Article
Safety of pregnancy in the female transplant recipient population must include consideration of 3 outcomes--mother, baby and transplanted graft. In the majority of female recipients studied, pregnancy does not appear to cause excessive or irreversible problems with graft function, if the function of the transplant organ is stable prior to pregnancy. However, a small percentage of recipients identified within each organ system may develop rejection, graft dysfunction and/or graft loss that may be related to the pregnancy and may occur unpredictably. Outcomes are not entirely similar among all organ systems, and one must consider risks on an individual organ basis. It appears reasonable to advise female recipients to wait one or 2 years after transplantation before attempting pregnancy to insure that function of the transplanted organ is adequate and stable and also to allow for stabilization of immunosuppressive medications. Favorable outcomes, however, have occurred when recipients have become pregnant less than one year from transplant, so cases must be analyzed individually. Immunosuppressive medications may have to be adjusted during pregnancy, and in some cases, rejections occur requiring additional immunosuppressive regimens (steroids and in several cases OKT3). Whether increasing immunosuppressive doses during pregnancy to adjust for falling levels lessens the rejection risk has never been studied prospectively. There is concern based on animal reproductive studies that the risk of birth defects and/or spontaneous miscarriage is increased in women exposed to MMF during pregnancy. Of the 9 pregnancies reported to the registry to date, there have been no birth defects noted among 5 liveborn of female recipients exposed to MMF. Data remain limited. For female recipients, a high incidence of low birth-weight and prematurity compared to the general population has been a consistent outcome, however, there has been no specific pattern of malformation in their newborn or any apparent increase in the incidence of small-for-gestational-age newborn. Long-term follow-up of children to date by the NTPR has been encouraging. A recent report in the literature has suggested impairment of immune function in newborn of CsA-treated mothers. Further study is needed. Some mothers have chosen to breastfeed. The potential risk to the newborn of ingested immunosuppressives compared with the potential benefits of breastfeeding is unknown and options must be discussed with the recipient. From earlier registry reports, recipients with deteriorating graft function, such as liver recipients with recurrent hepatitis C and/or other recipients with deteriorating graft function, appear to be at risk for worsened graft function with pregnancy. Outcomes of male recipient fathered pregnancies have been favorable and appear to be similar to the general population, but this group has not been as well studied as female recipients. No structural problems have been noted in the 38 offspring of males on MMF at the time of conception. Within each organ group, some female recipients have reported more than one pregnancy, sometimes on differing immunosuppressive regimens. If there is stable graft function, additional successful pregnancies are possible. Continued entries to the registry, especially in light of newer immunosuppressives and combinations of agents, are needed to continue to provide guidelines for management. The NTPR acknowledges the cooperation of transplant recipients and over 200 centers nationwide who have contributed their time and information to the registry. The NTPR is supported by grants from Novartis Pharmaceuticals Corp., Fujisawa Healthcare, Inc., Roche Laboratories Inc. and Wyeth-Ayerst Pharmaceuticals, Inc.
Article
Previously, we have been able to isolate IgA1 from IgA nephropathy (IgAN) patients, that could accumulate in rat glomeruli (glomerulophilic IgA1). The 'glomerulophilic IgA1' was determined to be under-O-glycosylated in its hinge region, suggesting that under-O-glycosylation in the IgA1 hinge region plays a role in its glomerular deposition in IgAN. To confirm this, the accumulation of enzymatically under-glycosylated IgA1 in rat kidney was examined. Human IgA1 was isolated from healthy individuals by Jacalin-affinity chromatography. Desialylated (deS IgA1) or further degalactosylated IgA1 (deS/deGal IgA1) molecules were then prepared using neuraminidase and beta-galactosidase. Two or five mg of IgA1 were injected into the left renal artery of Wistar rats. The rats were sacrificed at various time intervals (3, 9, 24 h) and the perfused part of the renal cortex was removed for immunofluorescence and for light and electron microscopy. Distinct amounts of deS IgA1 and deS/deGal IgA1 were observed in rat glomeruli. On the other hand, untreated IgA1 molecules (native IgA1) did not show any obvious accumulation. In rats injected with under-glycosylated IgA1, accumulation of polymorphonuclear cells (PMN) was also observed. These results confirmed that under-glycosylation of IgA1 played an important role in the glomerular accumulation of IgA1, which was followed by infiltration of PMN into glomeruli.
Article
Over the last few decades, the number of pregnant women under immunosuppressive (IS) therapy following transplantation or autoimmune diseases has increased. At first, IS drugs, including prednisone, azathioprine, and cyclosporine A were used, but now new molecules such as tacrolimus and mycophenolate mofetil have appeared. These IS drugs cross the placental barrier and enter into the fetal circulation, which poses a risk for fetal development. Experimental data have shown that IS drugs often have deleterious effects on fetuses, while human data have reported an increased rate of abortion, prematurity, intrauterine growth retardation (IUGR), and low birth weight, without significant increases in malformation rates. However, only limited information is available about the newly used molecules. Although fetal and neonatal data are reassuring, long-term effects of IS drugs on fertility, immune response and renal function, as well as the consequences of prematurity and IUGR, should be monitored.
Article
To evaluate pregnancy course, complications, and outcomes in liver transplant recipients. We conducted a retrospective review of 38 pregnancies conceived between 1992 and 2002 in 29 women who underwent liver transplantation at Mount Sinai Medical Center. The most common primary liver disease was autoimmune hepatitis. All patients were on immunosuppressive regimens that included cyclosporine A or tacrolimus. There were four spontaneous first-trimester abortions and ten first-trimester terminations for worsening liver function. The interval from transplantation to pregnancy was shorter in the group that had abortions and terminations (24.4 +/- 24.3 months) as compared with the group that had live births (47.8 +/- 28.7 months), P =.02. There were 24 live births to 20 patients. The mean gestational age at delivery was 36.4 weeks, and the mean birth weight was 2762 g. Pregnancy complications included preeclampsia (20.8%), chronic hypertension (20.8%), hemolysis, elevated liver enzymes, low platelets syndrome (8.3%), creatinine 1.3 mg/dL or more (25.0%), anemia (33.3%), diabetes (37.5%), cesarean delivery (45.8%), preterm birth less than 37 weeks (29.2%), intrauterine growth restriction (16.7%), and biopsy-proven graft rejection during pregnancy (16.7%). There were no intrauterine or neonatal deaths. All 5-minute Apgar scores were greater than 7. Four minor congenital anomalies were noted. Before 1997, there were five maternal deaths, 10-54 months after pregnancy. Pregnancy complications in our population were more common in those patients who delivered from 1992 to 1997 than in those who delivered from 1998 to 2002. Pregnancy planned at least 2 years after liver transplantation with stable allograft function can have excellent maternal and neonatal outcome.
Article
IN May, 1956, one of a pair of twenty-one-year-old identical twin females from Oklahoma was being studied as a potential recipient for a kidney transplant from her twin sister. Both were childless, having been married for less than a year. The ailing twin, with a three-year history of chronic glomerulonephritis, was in a dire preterminal state, with hypertension (blood pressure of 190 systolic, 120 diastolic), congestive heart failure only partially helped by digoxin and severe oral and gastrointestinal hemorrhage. Extra-corporeal hemodialyses were required on three occasions to sustain life until the necessary preliminary studies were completed. At that time there . . .
Article
For women with end-stage renal failure of child-bearing age, renal transplantation offers a chance to start a family. Pregnancies in renal transplant recipients involve risks for graft and fetus, and need to be carefully managed. To identify graft, fetal and maternal outcomes in our patients, and compare our results with those of the large national transplant registries. Retrospective case-note review. We assessed the outcomes of 48 pregnancies in 24 renal transplant recipients. Obstetric data and renal parameters were examined in 27-30 pregnancies that progressed to delivery. Mean time from transplantation to pregnancy was 6.5 years, with an unfavourable outcome in patients who conceived within 1 year. There was a 41% incidence of fetal growth restriction (FGR), and 33% of infants were small for gestational age. FGR was associated with maternal hypertension, a pre-pregnancy serum creatinine (SCr) >/= 133 micro mol/l (1.5 mg/dl), calcineurin inhibitors and the use of cardioselective beta blockers. Two patients with pre-pregnancy SCr > 200 micro mol/l lost their grafts within 3 years of delivery. A permanent significant decline in graft function occurred in 20%, by 6 months post delivery. FGR with SGA infants occurs frequently. Atenolol should be avoided in pregnancy and Metoprolol should not be combined with calcineurin inhibitors. Pregnancy appeared to have a deleterious effect on graft function in patients with SCr > 155 micro mol (1.75 mg/dl). Patients with pre-pregnancy SCr 200 micro mol/l are at greatest risk.
Article
Mycophenolate mofetil has teratogenic properties in rats and rabbits. Previous human studies have reported an increased rate of fetal losses with its use. We report a case of major fetal malformations due to mycophenolate mofetil. The patient was treated with mycophenolate mofetil before conception and during the first trimester of pregnancy. The fetus had multiple malformations, specifically, facial dysmorphology and midline anomalies, including agenesis of the corpus callosum. This case of fetal malformation attributable to mycophenolate mofetil must be taken into consideration when considering pregnancy in an organ-transplant recipient.
Cognitive and behavioral outcomes of school-aged children who were born premature: a meta-analysis Educational and behavioural problems in babies of 32-35 weeks gestation
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Cognitive and behavioral outcomes of school-aged children who were born premature: a meta-analysis
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Bhutta AT, Cleves MA, Casey PH, Cradock MM, Anand KJS. Cognitive and behavioral outcomes of school-aged children who were born premature: a meta-analysis. JAMA 2002;288:728-37.
Family bonds: adoption and the politics of parenting
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Bartholet E. Family bonds: adoption and the politics of parenting. Boston: Houghton Mifflin, 1993.
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Transplantation ethics
  • R M Veatch