ETHICS Ethical Considerations Regarding Pregnancy in Chronic Kidney Disease Sara N. Davison 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. © 2007 by the National Kidney Foundation, Inc. Index Words: Chronic kidney disease; kidney transplant; pregnancy; ethics; assisted reproductive technologies P regnancy in a woman with chronic kidney disease (CKD) has long been recognized as dangerous. Historically, women with CKD were discouraged from becoming pregnant, and termination of pregnancy was often recommended. However, with the improvements in treatment for CKD, including the increased amount of dialysis delivered to most patients and the use of synthetic erythropoietin, not only are more women with CKD becoming pregnant but also successful pregnancy outcomes may be increasing, with the majority of these patients delivering a surviving infant. Add to this development the increasing numbers of women who receive a successful kidney transplant, and the rates of conception are likely to continue to increase, posing new medical and ethical challenges to the health-care teams that care for these patients. This paper discusses ethical issues regarding pregnancy in CKD and highlights the controversies surrounding parental, fetal, and societal rights. Informed Consent and Counseling Patients are entitled to make informed decisions about their medical care and, therefore, From the Division of Nephrology and Immunology, University of Alberta, Edmonton, Alberta, Canada. Address correspondence to Sara N. Davison, MD, Division of Nephrology and Immunology, University of Alberta, 11-107 Clinical Sciences Building Edmonton, Alberta, T6G 2G3 Canada. E-mail: sara.davison@ualberta.ca © 2007 by the National Kidney Foundation, Inc. 1548-5595/07/1402-0013$32.00/0 doi:10.1053/j.ackd.2007.01.010 206 have the right to be given all available information relevant to such decisions.1 The physician’s obligation to provide such information in the consent process is grounded in the ethical principles of patient autonomy and respect for persons and is affirmed by North American law and professional policy.1 Because conceiving a child does not always involve a deliberate, active choice on the part of the woman, physicians are obliged to engage women with CKD of childbearing age and their partners in this process, regardless of whether or not they actively request information about pregnancy. Patients should be informed of fertility rates: these rates have been reported as 0.3 per 100 patient-years in women of childbearing age in a Belgium study2 or a similar rate of 2.2% over 4 years in a United States registry.3 Providing outcome information is integral to this process of informed decision making and consent. Women and their partners need to be informed of maternal risks, including dialysis needs, infant survival, alternatives to biological parenthood, and options for pregnancy termination.4 Doing so not only promotes patient autonomy but also fulfils physicians’ ethical obligations of beneficence and nonmaleficence by preventing unnecessary maternal and fetal risk. Maternal risks of pregnancy in woman with CKD include new or worsening hypertension, diabetes, infection, preeclampsia, and a decline in graft-kidney or native-kidney function. Although pregnancy in patients with a serum creatinine less than 1.4 mg/dL typically leads to a successful obstetrical outcome without affecting the course Advances in Chronic Kidney Disease, Vol 14, No 2 (April), 2007: pp 206-211 Ethical Considerations Regarding Pregnancy in CKD of the maternal kidney disease, the outlook is not as optimistic for patients with moderate or severe renal impairment. In patients with a serum creatinine greater than 2.0 mg/dL at the time of conception, one-third progress to end-stage renal disease (ESRD) over the postpartum year of follow-up.3,5 If a pregnant dialysis patient chooses to continue her pregnancy, she will need to commit to an intensive dialysis regimen of 20 hours per week or more.6 Potentially fetotoxic agents (eg, angiotensin-converting enzyme inhibitors) must be stopped before conception. The question of which drugs to use during pregnancy is difficult, especially for kidneytransplant recipients, given limited outcomes data. Although the frequency of birth defects in infants born to women who receive immunosuppressive agents does not appear statistically different from that in the general population, evidence suggests increased fetal risk in animal models and, therefore, present cause for concern.7,8 In addition to decisions on which immunosuppressants to continue during pregnancy, dosing adjustments must be considered because of changing total-body volumes and changes in hepatic metabolism throughout pregnancy. Although fetal outcomes are more optimistic with the recent improvements in prenatal and neonatal care, women with CKD and their partners must be aware of several potential risks to the child-to-be. Significant intrauterine growth restriction that results in small-for-gestational age (SGA) infants and preterm labor commonly occurs. Premature and SGA infants have higher mortality than do term and appropriately sized infants of the same gestational age. Children born to mothers with CKD are also more likely to have neurodevelopmental impairment and considerable long-term health and educational needs. Long-term or late-onset medical complications of immunosuppressive therapy to the children born to women who take immunosuppressive agents are as yet unknown. Potential parents must be made aware that the child may need additional resources, including psychosocial and caretaker support. As the majority of pregnancies associated with CKD result in live-born infants, the long-term 207 cognitive, developmental, and functional outcome of these infants is of increasing importance to prospective parents, as well as to the medical community that must provide the appropriate support services. Unfortunately, nephrologists rarely discuss fertility and contraception with their premenopausal patients.9 Because half of all pregnancies in CKD are unintended, occurring even in patients already established on dialysis, physicians should not wait to raise the issue until patients express concern or interest. Rather, nephrologists should address fertility and contraception with all women with CKD of child-bearing age. These issues are of particular importance before transplantation because of the likelihood of improved fertility after transplantation. Some transplant programs include contraceptive counseling in their patient-education programs, and the American Society of Transplant Physicians recommends this counseling as part of the transplant evaluation. For those patients not interested in pregnancy, contraception must be explored. Professionals from multiple disciplines, such as fertility clinics, obstetrics, social work, perinatology, and nephrology, should be utilized for counseling. Genetic counseling may be required to discuss the risk of offspring acquiring parental primary-organ disease. Shortened Life Expectancy Historically, some physicians have counseled women not to become pregnant when they have a life expectancy that is shortened or have a chronic illness that impinges on their ability to rear children because of concern for the welfare of the potential child.10,11 The same concern could be extended to men with CKD wishing to father a child. These parents may not live to rear their children or might not be able to cope with a child when dealing with the physical and psychosocial difficulties of living with CKD. How should patient autonomy be balanced against their limited life expectancy or ability to care for a child? Some argue that a child is not ethically wronged by being born to a parent with a chronic illness such as CKD, because no parent is guaranteed to remain healthy or live to rear a child until 208 Sara N. Davison adulthood.4 In fact, couples are increasingly having children much later in life, and elderly parents, who would be expected to have a relatively shortened life expectancy, are not uncommon. Nevertheless, the greater likelihood of decreased parental life expectancy is morally relevant, and I believe that physicians have an obligation to encourage patients to consider their reproductive decisions both from their own perspective and from that of the child-to-be. Patients should contemplate who will help rear a child with health or developmental problems and whether someone else is willing to take over primary caregiving responsibilities in the case of disability or death.4 Ideally, these issues should be examined by all prospective parents, even those who are healthy. Another caution against counseling patients with limited life expectancy not to conceive on the basis of “interests of the potential child” is that such counseling appears to claim that nonexistence is better than having one’s parent die or being ill when one is still quite young.10 No one can say when nonexistence would be better; the intrinsic worth of an individual’s life cannot readily be quantified, least of all when that life has not yet started. The argument has been made that the level of parenting would have to be extremely low for nonexistence to be preferable to being a child of those parents. Society’s reluctance to step in and take a child into care except under the most dire circumstances of appalling parenting confirms this belief.10 Fetus As a Patient In caring for pregnant women, physicians may view the fetus as a second patient. Ethical issues can arise if the physician feels the patient’s decisions place the fetus at increased risk. This circumstance places maternal autonomy in direct conflict with fetal nonmaleficence and social justice, in view of the resources that may be required to manage fetal complications. However, competent adult women have the right to accept or refuse any and all medical treatment, even when pregnant. Health-care professionals have to respect a woman’s decision, even if it places the fetus at increased risk. Although a woman has a moral obligation to consider the interests of her fetus in her decision making, patient autonomy trumps most considerations in Western countries, and North American law has upheld women’s right to life, liberty, and security of the person and has not recognized fetal rights. A woman is not required to act in a fetus’s best interest, and she cannot be compelled to do so by her physician or the courts.12 Rights The principle of reproductive freedom is the widely accepted right of people to make their own reproductive choices. Some people believe that this principle means individuals have a “positive” right to reproduce, thus imposing duties on others to provide them with the means (including financial) to do so. The argument has been made this is belief is justified by the deep value attached to parenthood by human beings and its crucial role in their well-being.13 Others, however, believe that reproductive freedom is a “negative” right. People should be free to reproduce if they choose so or can do so naturally, but they are not necessarily entitled to financial assistance and do not have the right to excessively burden the health-care system with their choices.14 The following discussion around the ethical issues of resource allocation as they pertain to dialysis, organ allocation, and assisted reproductive technologies (ARTs) in the context of pregnancy in CKD will depend in large part on whether society views pregnancy as a positive or negative right and whether it views this right to be strong enough to compete with conflicting societal considerations. Resource Allocation Rising public and professional expectations, an expanding pool of treatable patients, and costly new technology must be balanced against health-care budgets.15 In a world where resources are limited, questions about the right to parenthood can be formulated as questions about priority in allocation. Despite fetal and maternal risks, including accelerated progression to ESRD, patients with advanced Ethical Considerations Regarding Pregnancy in CKD CKD who wish to conceive may choose to do so. Do patients have a right to take this risk, given the tremendous resource implications resulting from maternal and fetal complications? The decision to conceive is generally accepted to be a personal decision and supported by the ethical principle of patient autonomy. We currently dialyze patients who have ESRD caused by other high-risk behaviors, such as drug abuse, smoking, and obesity. Also, a prediction of who will and will not progress to ESRD with pregnancy is difficult to make. I believe the major issue is how we should counsel patients with more advanced CKD who wish to have children, given that our responsibility lies not only with them but also with other patients and a judicious use of societal resources. Should we advise women to wait until ESRD and hope for a successful transplant, or should they proceed with trying to conceive while they retain residual kidney function? No professional guidelines exist to help physicians or patients with this decision making. As previously outlined, conceiving with stage 3 to 5 CKD is associated with significant maternal and fetal risks, which in turn have significant resource implications, especially if pregnancy results in the need for renal-replacement therapy. These risks vary among women, depending upon the degree of kidney failure and comorbidity. Pregnancy also causes sensitization to transplant antigens, making an appropriate donor kidney more difficult to find in the future. These risks, however, must be weighed against the increased wait time to kidney transplant and the fact a successful transplant is not guaranteed. For some, the opportunity to conceive may be missed. However, if conception occurs after transplantation with a well-functioning graft, maternal and fetal risk would be greatly reduced. The nephrology team will have to raise these issues with patients so that each individual is able to weigh the risks and benefits and make a very personal decision for herself. Pregnancy after transplantation also has ethical implications with respect to organ allocation. Physicians must consider the effect that pregnancy may have on the patient’s allograft. Although concern has been expressed that the increased glomerular fil- 209 tration rate caused by pregnancy might lead to hyperfiltration and glomerulosclerosis in kidney-transplant recipients, impairment of kidney function during pregnancy among transplant patients appears to parallel the natural course of kidney dysfunction in all transplant recipients.16 The expert consensus, therefore, is that pregnancy does not compromise kidney allograft function when the allograft is stable before pregnancy. On the basis of limited data, transplant recipients are advised to wait approximately 1 year after transplantation to conceive to ensure stable graft function before pregnancy. However, concern is warranted when graft function is compromised. In this setting, pregnancy, like that in CKD of native kidneys, is likely to accelerate the loss of kidney function. What are the ethical issues related to retransplantation if allograft loss occurs as a result of pregnancy? Some ethicists have argued that patients who lose their grafts because of voluntary risk-taking activities should be given lower priority for retransplantation. Does this penalty apply to pregnancy, or is pregnancy in the context of CKD still considered a “right”? Although pregnancy is not a voluntary activity for all women, the claim raises the issue of personal responsibility and its relation to organ allocation.4 Kidney-graft failure, however, is usually the result of a number of interacting factors, many of which are beyond the control of the transplant recipient. To blame the woman for the organ failure may unfairly place the blame on one factor, pregnancy, which only partly explains the organ failure. Given the importance of biological parenthood, a policy that requires a woman who risks her graft by becoming pregnant to be given lower priority for a second organ demands too high a price.4 Thus, transplant centers typically do not discriminate against women who lose either native-kidney or graft-kidney function while pregnant. Patient autonomy in the context or pregnancy would be seen by the medical community to trump societal concerns regarding distributive justice, even with respect to a scare resource such as deceased-donor kidneys. Whether this view is shared by society is unknown. 210 Sara N. Davison Assisted Reproductive Technologies As pregnancy becomes more accepted in women with CKD, treatment of infertility and access to funded ARTs by these patients is likely to rouse increased ethical and public debate. Childlessness has been associated with significant personal suffering, and couples who want children will go to great lengths to have them. Currently, three options exist: to adopt, to choose other life goals, or to attempt assisted reproduction. ARTs enable many women to have children who would otherwise have remained childless. What type of treatment should be offered if CKD patients have infertility problems? In the past, certain groups of women, such as single or older women and those whose ability to rear children was questioned, particularly women with chronic illnesses or disabilities, had been denied access to ART.17 This practice is no longer the case, but the ethical arguments used to justify selection of women for ARTs were based on social concerns or scarcity of resources. The argument to limit the positive right to parenthood on the basis of social concerns centers around concern for the welfare of the potential child. Given the limited survival and physical and psychosocial difficulties of living with CKD, parents with CKD may not live to rear their children or have the ability to adequately care for them. Because no parent guaranteed to remain healthy or survive throughout the offspring’s childhood, this practice may constitute an inappropriate discrimination that excludes women with potentially debilitating and life-limiting chronic illnesses such as CKD from access to funded ARTs.17 Although requiring a contingency plan for a child’s upbringing is not practical for ART programs, physicians should be aware of these issues and discuss childrearing in the context of the mother’s chronic illness and possible incapacity or premature death, before proceeding with ART. The second argument for limiting access to funded ART to CKD patients is based on the idea that society has a right to refuse to pay for ART if it does not regard infertility as a priority health concern, either because of cost or because the burden of taking care of the potential children would likely fall on society’s own shoulders. The cost for ART itself is considerable, which would be further added to by the additional short-term and long-term complications associated with pregnancy in CKD. If ART resources are limited, couples may need to justify why they should have assistance to conceive in preference to other couples. Ability to care for the potential child or the additional costs associated with either maternal or fetal complications may be among the factors considered. In cases in which burden for caring for the child will likely fall on society’s shoulders, the individual is not only requesting help in procreating but is also requesting significant help from society in rearing the child. In such cases, society seems to be entitled to a say about how its money is to be used and about the burdens it agrees to take upon itself.13 When resources for health care are scarce, we need to consider the opportunity costs. Although infertility can cause psychological distress, a better use of resources may be to offer counseling to facilitate couples’ acceptance of childlessness and to facilitate their ability to cope with the expectations of relatives and friends.18 A reasonable action is for nephrologists to contact local infertility providers to promote mutual understanding about issues such as specific local criteria for fertility therapy, infertility providers’ attitudes toward treatment of infertility in patients with chronic diseases, and their expectations for preconception preparation. Responsibility for Increased Research and Public Debate Minimal literature has been published regarding pregnancy and contraceptive outcomes in CKD, and risks remain difficult to adequately define. For example, concerns regarding contraception exist over and above those in the general population that need to be taken into consideration. Oral contraceptive pills are contraindicated in patients with significant cardiovascular disease, and several relative contraindications such as systemic lupus erythematosis, hypertriglyceridemia, hypertension, and diabetes mellitus may also be relevant to CKD patients. Intrauterine devices may be problematic for peritoneal dialysis and immunocompromised Ethical Considerations Regarding Pregnancy in CKD transplant patients because of risk of infection and reduced effectiveness.19 The medical profession has an obligation to collect these outcomes data. The national Transplantation Pregnancy Registry was established in 1991, but a similar registry has not yet been established for collection of outcomes data specific to patients with CKD. In addition, many of the ethical issues of pregnancy in CKD involve allocation of societal resources and concerns for potential children. The medical profession has an obligation to engage the public in open debate to determine societal priorities and preferences. Many of these decisions cannot be ethically solved by opinion leaders or the medical profession in isolation. Summary The coexistence of CKD and pregnancy remains 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. A major issue is how and when nephrologists should address fertility issues with patients, knowing that the interest in parenthood must be balanced against the interests of the potential child and those of society in general. In the interests of the child, comorbidity that affects the parents’ life expectancy or ability to care for the child should be discussed with potential parents before conception. Society may decide as a matter of policy that it will not fund ART for certain patients, such as those with CKD. However, such decisions will require significant public debate and justification. References 1. Etchells E, Sharpe G, Walsh P, et al: Bioethics for clinicians: 1. Consent. CMAJ 155:177-180, 1996 211 2. Bagon JA, Vernaeve H, De Muylder X, et al: Pregnancy and dialysis. Am J Kidney Dis 31:756-765, 1998 3. Okundaye I, Abrinko P, Hou S: Registry of pregnancy in dialysis patients. Am J Kidney Dis 31:766-773, 1998 4. Ross LF: Ethical considerations related to pregnancy in transplant recipients. N Engl J Med 354:1313-1316, 2006 5. Toma H, Tanabe K, Tokumoto T, et al: Pregnancy in women receiving renal dialysis or transplantation in Japan: A nationwide survey. Nephrol Dial Transplant 14:1511-1516, 1999 6. Hou S: Modification of dialysis regimens for pregnancy. Int J Artif Organs 25:823-826, 2002 7. Armenti VT, Radomski JS, Moritz MJ, et al: Report from the National Transplantation Pregnancy Registry (NTPR): Outcomes of pregnancy after transplantation. Clin Transpl 121-130, 2002 8. Armenti VT, Moritz MJ, Davison JM: Drug safety issues in pregnancy following transplantation and immunosuppression: Effects and outcomes. Drug Saf 19:219-232, 1998 9. Holley JL, Schmidt RJ, Bender FH, et al: Gynecologic and reproductive issues in women on dialysis. Am J Kidney Dis 29:685-690, 1997 10. Hope T, Lockwood G, Lockwood M: An ethical debate: Should older women be offered in vitro fertilisation? The interests of the potential child. BMJ 310: 1455-1456, 1995 11. Kass NE: Policy, ethics, and reproductive choice: Pregnancy and childbearing among HIV-infected women. Acta Paediatr 400:95-98, 1994 (suppl) 12. Flagler E, Baylis F, Rodgers S: Bioethics for clinicians: 12. Ethical dilemmas that arise in the care of pregnant woman: Rethinking “maternal-fetal conflicts”. CMAJ 156:1729-1732, 1997 13. Statman D: The right to parenthood: An argument for a narrow interpretation. Ethical Perspect 10:224-235, 2003 14. Robertson JA: Children of Choice: Freedom and the New Reproductive Technologies. Princeton, NJ, Princeton University Press, 1994 15. McKneally MF, Dickens BM, Meslin EM, et al: Bioethics for clinicians: 13. Resource allocation. CMAJ 157: 163-167, 1997 16. Lessan-Pezeshki M: Pregnancy after renal transplantation: Points to consider. Nephrol Dial Transplant 17:703-707, 2002 17. Peterson MM: Assisted reproductive technologies and equity of access issues. J Med Ethics 31:280-285, 2005 18. Shickle D, Donnelly P, Hopkins S, et al: Should older woman be offered in vitro fertilisation? Counselling may be a better use of resources. BMJ 311:689-690, 1995 19. Zerner J, Doil KL, Drewry J, et al: Intrauterine contraceptive device features in renal transplant patients. J Reprod Med 26:99-102, 1981