Journal of Perinatology (2009) 29, 662–667 r 2009 Nature Publishing Group All rights reserved. 0743-8346/09 $32 www.nature.com/jp ORIGINAL ARTICLE Medical and ethical considerations in discordant for serious cardiac disease

A Malhotra1, S Menahem2,3,4, P Shekleton2 and L Gillam4,5 1Department of Neonatalogy, Monash Medical Centre, Melbourne, Australia; 2Fetal Cardiac Unit, Monash Medical Centre, Melbourne, Australia; 3Department of Pediatrics and Psychological Medicine, Monash University, Melbourne, Australia; 4Murdoch Children’s Research Institute, Melbourne, Australia and 5Children’s Bioethics Centre, Royal Children’s Hospital, Melbourne, Australia

Conclusion: Attention is drawn to the complexities of the issues involved Objective: Prenatal ultrasound has led to the early diagnosis of major in twin pregnancies complicated by a serious cardiac condition in one of anomalies. However, the ready availability of this technology has led to the . Optimal counseling requires sound clinical knowledge about increasing challenges for physicians counseling affected parents, which is the medical risks to the mother and her twins, and a clear understanding all the more difficult in a twin with only one affected . This of the key ethical considerations. Such an approach will assist parents in paper reviews the medical and ethical considerations in twin pregnancies their very difficult decision making. discordant for a serious cardiac condition. Journal of Perinatology (2009) 29, 662–667; doi:10.1038/jp.2009.88; Study Design: Six recent twin pregnancies discordant for a serious published online 23 July 2009 cardiac condition and their outcomes are presented. Options considered in the management of the pregnancy were to continue or terminate the Keywords: cardiac disease; fetus; ethics; termination; twins pregnancy, selectively terminate the affected twin or to decide whether to treat the affected twin once delivered. An approach to decision making in Introduction such situations has been formulated after critical analysis of the factors Prenatal ultrasound has revolutionized the detection of major involved. congenital anomalies. The ready availability of this technology has led to increasing challenges for perinatologists. Counseling parents Results: Four of the six pregnancies were monochorionic twins. Two sets following the detection of anomalies and their impact on the fetus, of parents decided to terminate the pregnancy. In the four that continued, pregnancy, birth and future of the infant is one of the most two opted for the affected twin to be appropriately managed once difficult issues to deal with.1,2 Cardiac anomalies and disorders delivered. A further two considered selective termination but opted to form a significant and important group of conditions picked up by continue the pregnancy because of the risk of premature labor and/or prenatal ultrasound. The challenge the obstetrician/cardiologist cerebral hypoxia following such intervention. They sought a commitment, and others face is the need to accurately diagnose the disorder and however, that they be given the option whether to treat the affected twin to counsel the family in an unbiased, ethically appropriate manner following delivery. Eventually both elected to have their babies treated, drawing on a sound knowledge background. The challenge is one of whom died in the postoperative period. magnified and complicated many fold when a serious cardiac Discussion: Medical considerations included the risks of continuation of condition is noted during a twin pregnancy but affecting only one the pregnancy for the mother and her twins, the safety of termination twin. This paper explores this complex issue and discusses the (total or selective), and the risks to the unaffected fetus. Ethical issues medical and ethical issues, which may influence the manner in revolved around concepts of autonomy, beneficence and justice from the which clinicians are able to counsel parents. standpoint of the family and the twins. The gestation and the viability of the twins played an important role in decision making and approaches, taking into account the local legal and other considerations. Case studies Mrs A A 31-year-old primipara with a monochorionic diamniotic twin Correspondence: Professor S Menahem, Fetal Cardiac Unit, Monash Medical Centre, 246, pregnancy was referred to the Fetal-Diagnostic Unit at 14 weeks of Clayton Road, Melbourne, Vic 3168, Australia. E-mail: [email protected] gestation with increased nuchal translucency in one twin. A serious cardiac anomaly was suspected at 16 weeks, which was confirmed Presented in part to the Perinatal Society of Australia and New Zealand, Australia, April 2008. Received 30 September 2008; revised 14 April 2009; accepted 8 May 2009; published online 23 by a detailed cardiac assessment at 20 weeks. That showed a July 2009 hypoplastic right heart with an intact ventricular system, Twin pregnancies discordant for cardiac disease A Malhotra et al 663 pulmonary atresia and coronary artery/right ventricular sinusoids. a Cesarean section. The postnatal echocardiogram of the affected The other twin appeared normal. Normal growth and liquor infant confirmed the prenatal diagnosis of pulmonary atresia, volumes were noted in both twins. The parents were informed ventricular septal defect with probable aortopulmonary collaterals about the serious nature of the complex heart abnormality, its (MAPCAs). She was initially commenced on a prostaglandin management and likely outcomes. They were given the option of infusion, which was ceased when MAPCAs were confirmed by a continuing the pregnancy, or selective termination of the affected spiral CT scan. She proceeded to a central shunt (ascending aorta twin. After seriously considering selective termination, they opted to pulmonary artery) at 4 weeks of age. for the former because of the risk of premature labor and possibility of cerebral involvement in the normal fetus. They, Mrs D however, wanted to retain the option to decide whether to have the A 33-year-old nullipara with dichorionic twins underwent a fetal baby treated once delivered. The twins were born at 36 weeks and scan at 20 weeks that revealed one twin with a complete heart the affected twin’s cardiac condition was confirmed. The parents block. She was positive for Ro and La antibodies and was already opted for full treatment of the affected infant who went on to have being treated for thyrotoxicosis. The affected twin’s ventricular rate an atrial septostomy and a shunt procedure soon after. The parents continued to run at 60 to 65 per min with good left ventricular were content with their decision to keep both twins and to proceed function. At 26 weeks, fetal growths were normal. However, the twin with the recommended treatment of the affected twin. with the heart block showed a small pericardial effusion, which may or may not have been related to its cardiac status. The parents Mrs B opted for continuation of the pregnancy and they were satisfied A 28-year-old primipara with monochorionic diamniotic twins was with their decision. The heart block was confirmed in the affected diagnosed at 20 weeks gestation as having a hypoplastic left heart neonate. Pacemaker insertion has been planned at a later stage. syndrome in one twin. The other twin had a suspicion of a small ventricular septal defect. The twins continued to grow normally Mrs E and a repeat scan at 22 weeks confirmed the major defect. The A 35-year-old multipara with monochorionic twins was counseled parents were counseled as to the seriousness of the cardiac at 22 weeks when one twin was shown to have a hypoplastic right anomaly and the availability of a staged repair with about a 35% ventricle with pulmonary atresia and an intact ventricular septum. mortality for the first operation (Norwood stage 1).3 The parents In addition, like the affected twin of Mrs A, this twin also had decided to continue the pregnancy, though seriously considered features suggestive of coronary artery/right ventricular sinusoids. and then rejected the option of selective termination for reasons as The issues associated with the management of this twin were noted with Mrs A. They too asked to be given the option of not discussed with both parents. They too were wary of the risks of treating the affected infant once delivered. Mother was delivered at premature labor and cerebral involvement of the normal twin if 35 weeks by a Cesarean section. The affected infant was confirmed as selective termination was carried out. They decided to terminate the having a hypoplastic left heart syndrome. Both parents opted for full pregnancy including the normal fetus leading to considerable treatment for the affected baby despite its low birth weight of 2.1 kg. distress for the parents, especially the mother. After initial stabilization on a prostaglandin E1 infusion, he proceeded to a Norwood stage 1 but died 2 weeks later. The parents were reconciled Mrs F in that they had done all they could for their baby. They subsequently A 26-year-old primipara had a monochorionic twin pregnancy with transferred their full attention to the normal surviving twin. evidence of twin–twin transfusion at 22 weeks. The recipient twin also showed profound right heart failure, with low velocity, moderately severe tricuspid regurgitation and systolic pulmonary Mrs C regurgitation, there being reverse ductal flow (left to right). The A 36-year-old primipara with dichorionic diamniotic twins right ventricle was dilated and contracted very poorly. The other underwent a fetal scan at 20 weeks. That showed a ventricular twin appeared to be well. The likelihood of demise of the recipient septal defect with an overriding aorta. It was not possible to twin may have resulted in a 30% risk of cerebral hypoxia in the visualize the central pulmonary artery, which was suggestive of donor twin. Laser separation of the was suggested, but the pulmonary atresia, with a malaligned ventricular septal defect and parents opted for termination of the pregnancy altogether at 24 possible aortopulmonary collaterals. A truncus arteriosus or weeks. They were comfortable with the decision they had made. ventricular septal defect/pulmonary atresia of Fallot type were also considered. A fetal echocardiogram 2 weeks later confirmed pulmonary atresia with a malaligned ventricular septal defect and an overriding aorta. After detailed counseling, the parents decided Discussion to continue with the pregnancy. They did not consider any of the Caring for patients when a fetal diagnosis of a major abnormality other options raised. The infants were born at 36 weeks gestation by is made can raise considerable challenges for the attending

Journal of Perinatology Twin pregnancies discordant for cardiac disease A Malhotra et al 664 clinicians.1,2 Few situations are as difficult as counseling couples of The risks are magnified in the setting of a monozygotic twin twin pregnancies where one twin is discordant for a major life pregnancy. In monochorionic twin pregnancies (which constitute threatening abnormality. The management of such clinical ethical two-thirds of monozygotic twin pregnancies), selective termination challenges depends on a clear understanding not only of the needs to be performed by ensuring complete and permanent medical issues in question, the risks involved with possible occlusion of both the arterial and venous flows in the umbilical interventions and the likely outcomes, but also of the ethical cord of the affected twin. That procedure avoids acute hemorrhage considerations which guide the counseling. Compassionate from the co-twin into the dying fetus and its placental share, which handling of the parents throughout the pregnancy and beyond may lead to hypotension and, in turn, to the co-twin’s own death remains paramount. or organ injury, especially to the brain. There are multiple In the six sets of twins presented, four were monochorionic and techniques available: cord ligation,5 laser coagulation,6 interstitial two were dichorionic. Each of the pregnancies had one twin with a laser,7 monopolar/dipolar coagulation and radiofrequency severe cardiac condition likely to compromise his/her long-term ablation.8 Fetoscopic laser-guided cord coagulation can be well-being. Our case studies also highlighted the parental responses performed at 16 weeks, but ultrasound-guided bipolar cord to the decisions they made in such situations. It may have been coagulation is the preferred method at a later gestation, especially more informative if the physicians’ perceptions of the parents’ in twins with discordant anomalies. Various studies using response to their decisions were prospectively obtained with ultrasound-guided bipolar cord coagulation have shown a survival structured or other interview instruments but that was not possible. rate of between 75 and 90% of the unaffected twin, and an intact survival (free of neurodevelopmental disability/delay) of 70 to 80%. Medical issues Other risks involve preterm prelabor rupture of membranes, The considerations in such pregnancies are diverse. The type and and maternal mirror syndrome.9–12 severity of the cardiac condition is obviously critical. The For anomalies with a high likelihood of intrauterine fetal death chorionicity, gestation and local options available are also (IUFD), selective feticide may be specifically justified as a important in any situation whether the pregnancy is continued, therapeutic intervention for the unaffected twin. Sudden IUFDs not terminated or selective termination is sought. One needs to be directly related to the cardiac condition cannot be predicted, and aware that there is always a very small but definite risk to the should be made clear to the parents. IUFD of one twin may lead to mother and fetus with any pregnancy. The technical and medical death of the other in 10 to 25% of cases, and cerebral damage in 25 risks of continuation or termination to the normal twin need to be to 45%, as well as the risks of severe prematurity.13–15 For considered in light of the likely outcomes for the affected twin. For anomalies that do not threaten fetal well-being, delay of a selective example, in twin–twin transfusion syndrome, spontaneous in feticide procedure at least to 26 weeks may be prudent, depending utero death of the affected twin may result in physical compromise on the local medicolegal considerations. The advantage of such a of the second twin. In our other cases, the choice to terminate is strategy is to reduce the potential adverse complications of the aimed to avoid the birth of a child who may have a life procedure on the morbidity of the nonaffected twin arising from compromised by a life threatening disorder. prematurity. Selective termination is an option, which is being increasingly made available. In dizygotic twin pregnancies, there is a small but Ethical issues not insignificant risk to the onset of premature labor following The management of these patients is an ethically complex selective termination. It nevertheless gives the parents the option of situation,16 partly because of the prognostic uncertainties, but more discontinuing the life of a fetus with potentially a poor long-term so because of the contested moral status of the fetus, and the on- outcome.4 However, the medically optimal at which going debate over .17 There are at least two sets of ethical to perform the termination still remains unresolved, and is not considerations that must be borne in mind when counseling necessarily available to all patients, depending on the local legal parents in these situations: the best interests of the fetus; the and other restrictions, provider availability, in addition to the autonomy and best interests of the pregnant woman. We cannot cultural and religious issues. The mortality of selective feticide for deal with these in depth here, but highlight those which bear the surviving twin is around 10% and largely attributed to directly on the question of what would be ethically appropriate for and severe preterm delivery, which is also associated a physician to counsel parents where there is a discordant twin with severe morbidity. The risk of cross-circulation in a dichorionic pregnancy. pregnancy between the twins generally is very unlikely to occur Promoting the best interest of the fetus, as required by the because of the lack of placental anastomoses. Hence, termination principles of beneficence and nonmaleficence, is complicated in can be performed by injecting potassium chloride into the itself, given that the fate of one fetus may affect the fate of the circulation (either heart or umbilical cord) of the affected twin to other. If the death of the affected twin in utero is inevitable (that is, induce fetal asystole. where the diagnosis is definitive and death is certain), there is

Journal of Perinatology Twin pregnancies discordant for cardiac disease A Malhotra et al 665 sound ethical reason18 to consider the interests of the unaffected moral status as a baby.23 This is the premise on which twin as paramount. However, in general, the outcomes are not so terminations for social or maternal reasons become acceptable, clear-cut. Where there is a reasonable chance that the affected twin and it would be the same here in discordant twin pregnancies. will survive to birth and beyond, the ethical principle of justice The ethical obligation of physicians when dealing with a would seem to require that the interests of both twins be considered woman in this situation is to provide the best information as being equally important in principle. The problem is that the available, while respecting the woman’s decision. The information interests of each twin may come into conflict. Even in serious needed by patients includes information not only about the cardiac cardiac conditions, such clear differentiation of poor outcomes is condition detected, but also about all the options which are not always possible. Few cardiac conditions are not amenable to at available to them. If termination or selective abortion in least palliative surgery, if not complete repair.19 In most cases the permissible and accessible within their community and at that neurological development is normal or close to normal.20 The stage of gestation, then women should be informed about that decision to selectively terminate a twin means the death of a fetus option. It is not the role of physicians to work out if they think where there was a chance of survival, perhaps with a reasonable termination is best or acceptable in this instance before mentioning quality of life (however defined), but a decision not to terminate it as an option.2 If women ask for guidance from the physician, it may put the unaffected twin at serious risk of avoidable death or is ethically appropriate to give it, but only in a way that leaves the disability, for example, in the case of twin–twin transfusion. patients free to make the ultimate decision themselves. Balancing the competing interests of the affected and unaffected Physicians, who regard the fetus as having full rights, either twins is ethically complex, especially because of the contested from conception or from some particular point in gestation, are in moral status of the fetus. The first ethical consideration, however, an especially difficult position in regard to counseling parents in is not how to do the balancing, but rather who should do it. It is situations of discordant twin pregnancies. Such physicians would not at all obvious that this is the appropriate role of the physician. presumably regard both selective abortion and termination of the If the are regarded as patients,21 the parents become the pregnancy as morally wrong. It would be best for them to hand decision makers for the medical treatment of their children, and over care to another physician on the grounds of conscientious physicians may intervene or override the parental decision if it is objection, which preserves their own integrity, while still respecting clearly detrimental to the twins’ best interests. For example, if the the right of the parents to make their own moral decisions.2 affected twin has a minor or readily treatable cardiac condition. If One additional ethical problem is possible disagreement between the balance of potential risks and benefits is not entirely clear, then clinicians once the infant is delivered especially if the attending there would not be solid grounds for intervening or directing the physician is the neonatologist and the pediatric cardiologist acts as parents which would apply both before birth, as discussed here, and the consultant. The former, as occurred with one of our cases, was after birth, for example, in the case of whose not prepared to allow the parents the option of nontreatment of the interests compete. On this interpretation of the situation, the affected twin once delivered, based on the information provided physician has some role in making a judgement about balancing that the mortality of a shunt procedure was of the order of 1 to 2% the interests of the affected and unaffected twin, but only a limited and the cumulative mortality for a two-stage Fontan repair was one. This would be somewhat analogous to the more commonly about 5%. This not uncommon situation of multiple care providers discussed situations of ‘maternal–fetal conflict’, where the highlights the importance of carefully considering the various pregnant woman’s decision to use recreational drugs, for example, options, and drawing the parents’ attention to any uncertainties. It is clearly detrimental to the fetus.22 However, the situations would be advisable to consult early with physicians, nursing and discussed in our review are grey, with considerations both ways and other staff who will be involved in the birth and treatment of the no obvious ‘right thing to do’. It may not be the role of the neonate/s, so that parents can take into account the possibility physician to resolve the balancing act which many consider the of such disagreements before they make a final decision about role of the parents.2 what to do. If the fetuses are not regarded as patients, in circumstances where termination of pregnancy is offered as an option, then the Counseling the parents ethical situation differs. The pregnant woman, in consultation with The approach we recommend to handle these complex issues can her partner, if she chooses, would be the decision maker. She be summarized as follows: would be exercising her right to autonomy by deciding to terminate a pregnancy for her own reasons, which may legitimately include Step 1. Establish what the management options are. In theory, what she feels is best for her (for example, not having a child with there are four: a disability), and not just what is best for the future child. Where abortion is regarded as ethically acceptable, the whole premise for (a) Continue the pregnancy and treat the affected infant following this is that the fetus is not a patient, and does not have the same delivery.

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(b) Continue the pregnancy but not commit to treatment of the women/couples have decided in similar situations. A second and affected twin following delivery, keeping open the option of third medical opinion may also be beneficial, as might the option palliative care provided that is acceptable local practice and to discuss matters with a genetic counselor, social worker or hence a real option. religious adviser. (c) Selective termination of the affected twin. In summary, this paper highlights the medical considerations (d) Termination of the pregnancy. and the ethical issues relating to twin pregnancies discordant for a major cardiac abnormality. In principle, the risks and benefits of Local legal practices and cultural/religious issues might limit these continuing or terminating the pregnancy or affected twin need to options, or rule out some, depending on the gestational age. The be considered and balanced, but the ultimate decision lies with the attending physician needs to know what the local ‘rules’ are. In parents, except in extreme circumstances where the parents’ addition, if the attending physician has strong ethical objections to decision is clearly contrary to the twins’ best interests. It is essential termination, which may be legally permissible, this may well be an to assist the couple to make an informed and considered decision appropriate point to hand over care to a colleague. in an emotionally charged and distressing situation.

Step 2. Estimate the possible risks and likely outcomes of all options for the affected fetus, normal fetus and the pregnant woman. In addition, there may be emotional and psychological Conflict of interest issues for both the woman and her partner. The distress The authors declare no conflict of interest. experienced by them can occur both before and after termination (for example, risk of on-going unresolved guilt about terminating the healthy twin as suggested in one of our mothers). Such distress References may also occur following a decision to continue the pregnancy, because of the concerns of having a child with an ongoing 1 Menahem S, Grimwade J. Counselling strategies in the prenatal diagnosis of major heart abnormality. Heart Lung Circ 2004; 13(3): 261–265. disability, and may include depression, financial stress, marriage 2 Menahem S, Gillam L. Fetal diagnosisFobligations of the clinician. Case studies in breakdown and so on. the prenatal diagnosis of major heart abnormality. Fetal Diagn Ther 2007; 22(3): 233–237. Step 3. Convey this information sensitively but clearly to the 3 Tibballs J, Cantwell-Bartell A. Outcomes of management decisions by parents for their infants with hypoplastic left heart syndrome born with and without a prenatal pregnant woman and her partner together. It is important that they diagnosis. J Paediatr Child Health 2008; 44(6): 321–324. are explicitly made aware of the option of termination of 4 Evans MI, Goldberg JD, Dommergues M, Wapner RJ, Lynch L, Dock BS et al. Efficacy pregnancy, including selective termination if available, as they may of second-trimester selective termination for fetal abnormalities: international not know that these are possible. The information is complex, collaborative experience among the world’s largest centers. Am J Obstet Gynecol 1994; potentially confronting and takes time to understand and 171(1): 90–94. assimilate. One needs to make known the uncertainty about how 5 Challis D, Gratacos E, Deprest JA. Cord occlusion techniques for selective termination in monochorionic twins. J Perinat Med 1999; 27: 327–338. the infant will be affected especially if there is an evolving cardiac 6 Hecher K, Hackeloer BJ, Ville Y. Umbilical cord coagulation by operative lesion, what may happen to the unaffected twin if selective microendoscopy at 16 weeks’ gestation in an acardiac twin. Ultrasound Obstet termination is attempted, or if the pregnancy is allowed to Gynecol 1997; 10: 130–132. continue.2 This all needs to be done in an empathic and caring 7 Jolly M, Taylor M, Rose G, Govender L, Fisk NM. Interstitial laser: a new surgical manner. technique for twin reversed arterial perfusion sequence in early pregnancy. Br J Obstet Gynaecol 2001; 108: 1098–1102. 8 Shevell T, Malone FD, Weintraub J, Thaker HM, D’Alton ME. Radiofrequency ablation Step 4. Assist the couple in the decision making, but do not in a monochorionic twin discordant for fetal anomalies. Am J Obstet Gynecol 2004; make the decision for them. There is no medically correct course of 190: 575–576. action, and the final choice will depend as much on the personal 9 Lewi L, Gratacos E, Ortibus E, Van Schoubroeck D, Carreras E, Higueras T. Pregnancy values and preferences of the parents as on the medical and infant outcome of 80 consecutive cord coagulations in complicated monochorionic multiple pregnancies. Am J Obstet Gynecol 2006; 194: 782–789. information provided. Guidance needs to be given to the affected 10 Ville Y, Hyett JA, Vandenbussche FP, Nicolaides KH. Endoscopic laser coagulation of parties in interpreting the information, seeking more information umbilical cord vessels in twin reversed arterial perfusion sequence. Ultrasound Obstet if required and identifying what may be really important for this Gynecol 1994; 4: 396–398. couple in this situation to make a decision. The physician can, 11 Deprest JA, Audibert F, Van Schoubroeck D, Hecher K, Mahieu-Caputo D. Bipolar cord with sensitive and thoughtful questions, help the woman consider coagulation of the umbilical cord in complicated monochorionic twin pregnancy. Am J Obstet Gynecol 2000; 182: 340–345. what her key concerns are, what outcomes would be worst for her, 12 Nicolini U, Poblete A, Boschetto C, Bonati F, Roberts A. Complicated monochorionic what would be nonnegotiable from her or her partner’s perspective, twin pregnancies: experience with bipolar cord coagulation. Am J Obstet Gynecol 2000; and so on. It may be helpful for them to know what other 185: 703–707.

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