Ethical Issues in Pediatric Cardiology and Congenital Heart Disease

Historical Context

Many of the issues remain from those raised by the sentinel 1998 article where Goldmuntz described a large proportion of patients with conotruncal defects with a 22q11.2 deletion syndrome. The article recommended wide routine screening for the presence of the microdeletion for at risk neonates, arguing families and providers would want to know if their child was also at risk for the frequently associated developmental, speech and feeding difficulties, and late incidence of schizophrenia, as well as hypocalcemia and immune disorders. The argument against large-scale screening at the time highlighted the variability of the phenotypic spectrum, whether the knowledge of the deletion could really predict outcomes, how knowledge would affect carriers, the importance of genetic counseling, and risk of discrimination from insurance companies and employers.

Since the Goldmuntz article and subsequent review, more studies have concluded that patients with CHD and genetic syndromes have worse outcomes and higher mortality than those with CHD alone. Those with an associated genetic cause have inferior operative outcomes, longer hospitalizations, greater length of stay in intensive care units (ICUs), and greater resource utilization. Several studies have found that children with CHD and chromosomal abnormalities had significantly lower median scores for total pediatric QOL, physical summary scores, and school functioning and significant challenges in the cognitive social and emotional domains. As knowledge increased about the effect of syndromes and disorders on important outcomes, parents and clinicians have increasingly wanted to obtain this information as soon as possible.

Genetic Tests and CHD

Genetic tests can by divided into three main types: (1) those identifying large chromosomal deletions or duplications by karyotype (e.g., trisomy 21); (2) those identifying subtle microdeletions and duplications using fluorescence in situ hybridization or cytogenic microarray (e.g., 22q11.2, Williams syndrome); and (3) single gene testing or whole exome sequencing. Specific genetic panels are currently available for certain single gene disorders such as those seen in cardiomyopathy and arrhythmias and syndromic CHD (such as Holt-Oram, Noonan, Alagile, Kabuki, and isomerism, as well as certain associations of congenital abnormalities such as those described as CHARGE and VACTERL associations). The most comprehensive whole genome sequencing (or microarrays of the whole exome) can detect single nucleotide changes, insertions, and deletions across the entire genome and are even available in the prenatal period. The sum of testing has produced a whole new class of test results labeled variants of unclear significance. Families and providers are often left with ambiguous understanding of these complex results that have little clinical applicability, and the potential that a negative test has not ruled out a genetic cause. In other cases, incidental findings may lead to clinical justifications to limit highly expensive technologies (e.g., extracorporeal membrane oxygenation [ECMO] or transplant). This genetic technology is still new and hard to interpret, and predictive validity has not been well validated.

Risks of Genetic Testing and Autonomy Considerations

When direct and clear benefit of testing exists for a child, genetic testing is broadly accepted in North America. What is more challenging, and more commonly found, is that no current or specific medical intervention or prevention measure can be provided. Identical pathogenic mutations cause a variety of distinct malformations, implying that higher-order interactions account for specific phenotypes. From an ethicist's perspective, the right of the parents to have knowledge of their child's genetic disorder must be weighed with the right of the child to have autonomous decision-making. The child may become the recipient of testing without his or her consent and then lives with the knowledge of future implications. Therefore some recommend to postpone testing until the child can consent. The libertarian perspective might argue that personal autonomy has the highest moral value, whereas a utilitarian perspective argues that moral decisions should be decided by calculating a burden versus benefit ratio from a societal perspective.

The psychosocial impact of genetic testing also bears regard because results of testing may affect family dynamics, psychological burden, self-esteem, alterations of the family’s view of the child, perceived child vulnerability, parent-child bonding, and self and partner blame. Concerns can arise for stigmatization or for legal implications. The United States Genetic Information Non-Discrimination Act instituted in 2009 was a positive step, creating protections against discrimination from insurance companies and employers, although more awareness and advocacy are required to ensure continued protections.

Benefits of Genetic Testing

Knowledge of a genetic disorder provides some clear benefits. The parents and providers may gain the ability to anticipate potential or likely outcomes and medical issues and to undertake early interventions where available. The knowledge of a disorder might help to unify features and events for a family as to understand why certain medical conditions are present. Learning about any increased risk for additional challenges for the child can prepare the family and empower the parents to learn more, pursue research, contribute to advocacy organizations, or galvanize the research community to find a cure. Reproductive counseling regarding future children, as well as screening relatives for affected individuals, also becomes possible.

Recommendations

Although there are several screening guidelines detailing which patients with CHD should be tested, the importance of genetic counseling, particularly during the assent and consent process, cannot be underestimated. When these steps are glossed over, the ethical principles of autonomy, justice, and nonmaleficence ( Table 83.2 ) are jeopardized.

General pediatricians and the pediatric cardiac community remain reluctant to incorporate genetic testing as part of their routine clinical care, and the practical reality remains that most clinicians do not have the proper training nor access to staff who can perform appropriate genetic counseling. Selection of the best test can be complicated, and choosing incorrectly can result in wasting time and resources. Coordination of practice between cardiologists and geneticists might help to improve cost utilization and facilitate individualized patient care. Broad access to training is necessary, and more research is required to understand who benefits the most from genetic testing, when testing is optimized, and how to best use a multidisciplinary approach.

Maternal Rights and Fetal Interests

The goal of fetal intervention is to improve the health of children by intervening before birth to correct or treat prenatally diagnosed abnormalities. This implies a beneficence obligation to the fetus. However, the interests of the fetus are inextricably linked to the mother. To intervene on the fetus, one must access through the pregnant woman's body either by surgical or interventional means, or by having her comply with specific medical therapies. Because intervention on the fetus has implications for the pregnant woman and engenders some risk to her, respect for her person requires that she give explicit consent. For fetal therapy to be ethically permissible, it must therefore be: (1) life-saving, or prevent or mitigate serious or irreversible disease of the future child; (2) of minimal mortality risk for the fetus and low or manageable risk to the future born child; and (3) be of low or manageable risk for mortality and morbidity to the mother.

The pregnant woman also retains a right to informed refusal. In the large majority of cases, maternal and fetal interests are aligned and the mother will choose a beneficence obligation to the fetus, opting for minimally invasive procedures of low risk to herself. However, unlike the parent whose decision may be overridden in favor of the child after birth, even the strongest evidence for fetal benefit would be insufficient to override a pregnant woman's decision to forgo therapy prior to birth. This follows from a fundamental ethical tenet of the autonomy rights of the person.

It is important to recognize that designation of “fetus as a person” only after birth is highly significant from an ethical perspective and is variable between countries and cultures. Personhood grants full status and rights as a moral being. Should the fetus have moral rights assigned prior to birth, the determination of which moral agents’ rights are dominant—woman or fetus—becomes significantly more difficult. This emotionally charged territory, that often prompts argument based in religious beliefs, is at the crux of abortion debates, and a full exploration is well outside the scope of this chapter. Legal authority, in most high-income nations, remains with the pregnant woman, who has no enforceable duty to choose any specific type of fetal therapy and retains a right to refuse any and all medical interferences with her body.

This does not make obligations to the fetus irrelevant. Although much debate has existed on the definition of “fetus as patient” in so far as this might imply personhood, the concept of “fetus as patient” is generally accepted once the fetus is viable and the decision of a woman to continue or terminate her previable pregnancy has been made. The fetal patient then obliges the physician to attend to fetal beneficence while also attending to obligations of maternal autonomy and maternal beneficence. The balance of these obligations is what limits fetal therapy to severe malformations or potentially lethal conditions in which the fetal therapy has been proven to improve the survival and preserve normal or near normal function of the future child.

Innovative Practice

Fetal diagnosis and treatment are borne out of innovative practices. However, the heterogeneous nature of the conditions treated, the invasiveness of the proposed intervention, the potential complications to both fetus and mother associated with fetal therapy, and the paucity of data on long-term outcomes significantly complicate the choices of our current therapeutic options and parental decision-making. Furthermore, due to rapid development, technologies for fetal intervention need monitoring and long-term follow-up to protect pregnant women and their fetuses from the risks of unproven therapies. Nonetheless, a procedure is not automatically researched because it is different or untested. It may be undertaken for the specific interests of a specific situation and fetal condition, with full understanding of the untested nature of the intervention and express consent by the pregnant woman. However, after proof of concept is achieved, formal research should be undertaken. If a few cases have indicated that fetal intervention is of sufficient potential benefit to the fetus, of reliably low risk to the pregnant woman, but involves risk for morbidity or death of the fetus, it should be moved into an experimental phase and offered only within a large controlled research trial. Efficacy and safety need to be proved before it can be considered standard of care, and the experimental nature needs to be fully and clearly disclosed to the parent to be ethically appropriate. The parent(s) need to clearly understand that research is for purposes of generalizable knowledge and different than therapeutic goals for cure, treatment, or palliation. A final note is made in that the underlying concepts herein regarding innovative practice are relevant beyond the context of fetal intervention alone.

Fetal Centers and Resource Allocation

Fetal centers are increasingly organized, and a growing enthusiasm continues to drive development in fetal medicine. However, it is important to recognize that these centers operate at high cost and provide benefit to only a very few pregnant women and their fetuses. This has brought into question whether undertaking fetal therapy in fetal centers is a fair distribution of resources. (See also “ Social Justice Considerations in Pediatric Cardiology ” section.) However, there is a lack of data to truly inform cost effectiveness of fetal intervention at this time. In addition, if a fetal intervention is not performed in most instances and the prenatal counseling constitutes the main component of care, it may justify the resource utilization with or without cost-effectiveness data. Finally, balancing a limitation of fetal interventions to a few specialized centers that maintain quality and expertise due to higher patient volume against the geographical and financial barriers that then may limit access is difficult and currently unresolved. Regardless, collaborative research networks are needed, particularly for rare diseases and procedures, to cumulate more robust short- and long-term maternal and fetal outcome data so as to inform this debate.

Counseling

One of the most important roles of the fetal cardiologist regarding fetal intervention is that of prenatal counseling. The need for interdisciplinary counseling and provision of care for pregnant women who are candidates for fetal therapy has been emphasized on many fronts. Reducing variability in prenatal care and counseling may improve quality of care overall to mother and fetus, as well as future child, and better meets the ethical duty for fully informed consent.

Counseling should involve sharing information that is thorough and unbiased, with acknowledgment of the paucity of data on fetal outcomes, conflicts in data, risks and benefits to the fetus and mother, risks and benefits of standard obstetric care, and outcomes of standard neonatal interventions. In addition, a range of outcomes beyond the technical success of the procedure should be well described. Ideally, this is done by a multidisciplinary team, particularly due to differences in knowledge of results of fetal and standard therapies and varying impressions of longer-term outcomes. Some ethicists and clinicians have called for standardized information sheets for prenatal counseling. These would not eliminate the biases of the provider doing counseling necessarily but might ensure a baseline source of accurate information.

A full breadth of options needs to be discussed during counseling. These include pregnancy termination, compassionate terminal care at birth (if appropriate to the CHD diagnosed), fetal intervention (even if not offered at that institution), and standard postnatal intervention. Should pregnancy termination be chosen, appropriate resources and support need to be made available. Where appropriate to the severity of the underlying diagnosis, compassionate terminal care (or hospice) for the neonate may be chosen. Here, the support of palliative care teams, or development of palliative care skills sets within the fetal team, can help to fully inform the parents on pathways of care that are not directed toward intervention. Without an explanation of palliative EOL care services for the newborn, a risk of misunderstanding exists for a stark choice between pregnancy termination and intervention as the only options for parents facing either a diagnosis of severe underlying CHD or other congenital anomalies that impact outcomes. It is also important to recognize that many things are done in the care of the newborn undergoing compassionate terminal care, so as to take away the implications that come in descriptions of doing “nothing” versus “something.” As the capacity to intervene improves outcomes for the newborn, palliative terminal care becomes a less appropriate option.

Finally, it must be recognized that a large variation in counseling is generated by clinician judgments of future QOL. Research indicates that clinicians generally rank QOL much lower than the individuals with a lived experience of the outcome, and in some cases clinician predictions are completely unrelated to later measurements. Because a child is affected by not only cognitive or physical limitations but also by family attitudes, values, and environment, it is necessary to consider family input in determining best interests ( Table 83.3 ) of the future child and aiding in decisions about the breadth of options for the fetus.