There have been steadily improving outcomes for many neonatal and pediatric conditions, as medical and surgical care evolve. Trisomy 13 and 18 (different conditions with outcomes similar enough to be grouped together for many studies, as well as this paper), previously thought to be lethal, are associated with universally significant neurodevelopmental impairment, frequent multiorgan involvement, and the growing recognition that survival is possible, albeit with significantly shortened lifespan. Depending on the study, as well as the interventions offered and provided, 5-15% of children with trisomy 13/18 live beyond the first year of life1,2. Evolving data show potential for even long-term survival, coinciding temporally with increasing parental requests for intervention, requests which have been met with varying degrees of support from healthcare teams.3,4 These conditions highlight several tensions within medicine, including the challenge of delineating the boundaries of when to offer interventions, when to deny parental requests, and what degree of anticipated disability and/or perceived poor quality of life (QOL) is “too much” to permit ongoing life-sustaining interventions. Of note, contentious discussions have also arisen around extreme prematurity (discussed elsewhere in this issue) and center on the risk for morbidity and mortality, especially as it relates to the potential for significant cognitive and neurodevelopmental impairment (NDI). A key distinction is the broad spectrum of short and long-term NDI seen with extreme prematurity, which includes normal developmental outcomes for some patients, in contrast to the universally profound NDI with severely life-limiting conditions such as trisomy 13/18. This essay is intended to focus on the latter group.

Historically, trisomy 13/18 were considered lethal conditions which were “incompatible with life,” and therefore any treatment or resuscitation would be inherently futile. The framing of all interventions for a specific diagnosis as futile without consideration of goals of care, or what may be physiologically achievable, potentially avoids the difficult ethical work of diving into deeper conversations with a family, to elucidate how they perceive the benefits/burdens of a specific intervention for their child. Clinicians are not obligated to offer nor provide futile therapies, even if requested by a patient or their family. Defining what is futile, however, has been fraught with difficulty, given the challenges inherent in determining with certainty that a particular treatment has no chance of achieving the intended physiological outcome for a specific patient. Ethicists have thus recommended moving away from use of the term “futile,” in favor of “potentially inappropriate,” with an emphasis on open communication and explanation of potential care pathways.5 Weighing the possible benefits of a specific treatment against risks and burdens is the critical work involved when assessing what is ethically appropriate to offer. Notably, the self-fulfilling prophecy is a risk for patients with life-limiting diagnoses, who might have benefited from interventions such as tube-feeding, respiratory support, or cardiac surgery, but subsequently died from a potentially treatable condition, with their death then attributed to the underlying genetic diagnosis.6,7 There is significant difficulty with individualized prognostication in trisomy 13/18, but work to identify risk factors in this population is ongoing, which will help guide future decision-making.8, 9, 10 It is critical to counsel every family using clear, literature-driven information, rather than utilizing an overly broad presumption of futility based solely on a genetic diagnosis, when there is a known broad spectrum of outcomes, though it does always include profound NDI, and, importantly, when there is a broad spectrum among families of goals for their child.

Looking beyond trisomy 13/18, congenital malformations occur in 2% of births and continue to be the leading cause of infant mortality in the United States.11 Numerous genetic, neurologic, and multisystemic conditions can lead to varying degrees of long-term, often lifelong, medicalized care and neurodevelopmental impairment. These include chromosomal deletion and duplication disorders, single gene deletions, mitochondrial disease, and various syndromes/sequences with significant impact on the patients’ short and long-term outcomes.12 Each diagnosis affects few patients, but in total this category leads to a significant portion of the mortality in the first few years of life.13 There has been a long-standing and pervasive distinction for trisomy 13/18 as a specified contraindication to various medical and surgical interventions, despite the non-unique nature of outcomes for this population compared to similarly impactful conditions.14,15 This distinction may be due in part to the greater prevalence of fetal and neonatal patients with trisomy 13/18, as compared to more rare diagnoses, which in totality compose a much larger portion of the impacted neonatal population but for which the medical team lacks familiarity and thus may not be as deeply associated with preconceived notions about futility.12 It is impossible for clinicians to maintain sufficient working knowledge of each of these diagnoses, and often available outcomes data are scant or based on low numbers, such that counseling may lean towards offering uncertainty in the prognosis, leaving more room for hope, and a “wait and see” approach.

How much anticipated disability is “too much” for a particular intervention to be ethically permissible to offer? There is a degree of impairment and/or physiological instability for which life-sustaining medical treatment (LSMT) is not appropriate, but this threshold is difficult to identify, outside the seemingly bright line of brain death. In the not-so-distant past, conditions such as trisomy 21 were seen as leading to such poor QOL that withholding treatment was considered ethically permissible, including for easily surgically correctable lesions such as duodenal atresia or esophageal atresia, as was seen in the famous Baby Doe cases in 1982.16 This decision to withhold treatment in 1982 precipitated the implementation of federal regulations which attempted to limit the withholding of treatments based solely on the presence of disability.16 Trisomy 21 has a significantly more favorable spectrum of developmental and cognitive outcomes than trisomy 13/18 and this is thus not a perfect comparison; the point is that ethical permissibility is a moving target, based on prognosis with and without treatment, benefits and burdens, feasibility, as well as societal perceptions about disability and related QOL.7 In the U.S. families are no longer permitted to decline basic medical care or uncomplicated surgical repairs for infants with trisomy 21, believing that QOL is high enough to require intervention. Where, then, should the line be drawn? There are no easy answers, but clinicians must look carefully at current relevant data to help determine the permissible choices.

Research has shown that clinicians consistently underrate the current and expected QOL for their patients with disabilities, when compared to parents, as well as the patients themselves, which has been described as the “disability paradox.”17,18 When providing outcome data for a fetus or newborn with a genetic condition such as trisomy 13/18 or an extremely preterm birth, pervasive biases may lead to potentially inaccurate portrayals with more negative predictions for outcomes. The language utilized by clinicians often reflects this unconscious bias, for example using the subjective and value-laden term “severe”, which can be replaced with a less biased term such as “significant.”19 The use of the term “significant” could reasonably be used instead when discussing anticipated disabilities with families, though it should always be accompanied by an honest description of those disabilities. Families report feeling pressured to elect termination, comfort care, or withdrawal of LSMT, once the diagnosis of trisomy 13/18 is suspected or confirmed, often with an emphasis by the clinicians on the expectation of poor QOL due to significant disability.20, 21, 22, 23 Many parents report that children with significant NDI, including those with trisomy 13/18, have positive experiences, are generally happy and comfortable, and are important members of their families and communities.21, 22, 23 The concept of relational potential is particularly relevant in the defense of supporting parental choice for infants with life-limiting conditions and anticipated NDI.24,25 The presence of significant disability does not preclude an individual from participating in a meaningful dynamic with those around them, and it is reasonable for a family to include this potential in their decision-making process, if it aligns with their values. Ritchie et al analyzed 17 articles on the experience of families of children with trisomy 13/18 and noted that “quality of life, quantity of life, and the value of ‘togetherness’…[are] significant values that are often held by parents simultaneously.”26 Though it is important to acknowledge that a selection bias likely exists in favor of families who have chosen interventions, these studies support the possibility of a positive QOL for children with life-limiting conditions and/or significant NDI, as assessed by those who know them best – their family. For some families, burdens such as financial impact, and effects on siblings or other family members are also important factors that play a valid role in their decision. T Parental values should be carefully elicited and respected during a shared decision-making process for a fetus or neonate with a condition that is life-limiting or associated with anticipated profound disability.27,28 Additional studies will be needed to assess how families make decisions, as counseling practices evolve to consistently discuss interventions as well as comfort care.

Perceptions about moral status also play an important role in determining ethical permissibility. Moral status is the notion that a particular being is deserving of rights and protections, and whose interests carry moral weight. An adult human might be seen to have “full” moral status, an animal something less, and an inanimate object less still, or no moral status.29 This concept has been explored elsewhere, with many thoughtful discussions evaluating the time point in human life at which moral status begins and ends.30,31 Some argue that full moral status begins at conception, others when sentience is achieved, and still others contend that it is conferred at the time of a live birth, with various time points in between proposed. Thus, over the course of a pregnancy, an increasing number of individuals would agree that a being has full or at least substantial moral status with rights, and therefore obligations on the part of physicians, parents, and society. Moreover, moral status may be perceived by some as increasing over the course of pregnancy and infancy, with corresponding increasing obligation to provide LSMT – a so-called gradualist approach.32 This evolving moral status is reflected in the assessment of premature infants, with the perception by some of a “lesser” moral status as compared to older children and adults, and a stronger reliance on predictions of disability to guide decision-making.33,34 Without the formation of definitive interpersonal dynamics, it is perhaps understandable that some might view the death of a preterm newborn as less tragic than the loss of an older child, who has built long-standing emotional connections and developed an externally validated “self.”This same phenomenon could perhaps be evident for an infant with anticipated significant disability; the perceived moral status of the infant may be less than that of an older child, and thus LSMT seen as less obligatory.

Within neonatology (and throughout medicine), interventions are offered for patients with a relatively low likelihood of long-term survival; for example, resuscitation at 22 weeks, extracorporeal membrane oxygenation for severe congenital diaphragmatic hernia, gastrostomy tubes for life-limiting genetic conditions, and, much more frequently, prolonged ventilation for critically ill and even terminally ill elderly people.35 It can be challenging for clinicians who counsel families of patients with life-limiting conditions and potentially significant disability, including trisomy 13/18, to determine which specific interventions are appropriate to offer or withhold. Clinicians can apply existing ethical frameworks alongside available data for a specific diagnosis, with self-awareness of the disability paradox, to determine a reasonable course of action. The best interest standard is the most widely used pediatric framework, with a focus on the child and what would be considered “best” for that individual, in both the short and long-term.36,37 Determinations of what is “best” can be highly subjective, and reasonable people may disagree about what is best for a specific situation. It is thus critical to assess all relevant benefits, risks, and burdens of the treatment in question, in the short term, as well as the medium- and long-term. Short-term suffering is often necessary to achieve survival and improved QOL, as seen, for example, with cardiac surgery for any neonate with heart failure related to a large ventricular septal defect. These assessments should be data-driven and based on the best available information for a specific diagnosis, obtained from a thorough literature review, potentially referring to similar conditions if limited data are available, to provide the best foundation for a shared decision-making process.

The impermissible-permissible-obligatory (IPO) framework is an excellent tool for difficult cases, evaluating the threshold of parental choice in a specific treatment/patient context.7 This framework compiles the benefits, burdens, risks, and feasibility of the treatment in question, with a resulting assessment that it would be considered ethically impermissible (should not be offered and should not be done even if requested), ethically permissible (would be acceptable to perform the action if parents consent), or ethically obligatory (should be done, even over parental objections, with state intervention if necessary). Assignment to one of these categories is based largely on the prognosis with and without the proposed treatment. The ethically permissible category is comparable to Gillam’s “zone of parental discretion.”38 Many treatment options for infants and children with severely life-limiting conditions and/or anticipated profound disability could fall into the “permissible” category, so long as the burdens do not outweigh the benefits, the proposed treatment is feasible and not physiologically futile, and it does not lead to significant suffering with no significant benefit to the patient, or simply prolong the dying process.

A rights-based analysis of a particular medical or surgical intervention must include the rights of the child- to treatment, to equitable care, to the relief of suffering, as well as the rights of the parents- to protection of their parental authority and to complete, accurate information, among others. A child’s right to available, indicated treatment is based on their inherent human dignity, which is intact, regardless of their underlying diagnosis. Justice demands that equals be treated equally.39 Thus, if there is a treatment which would be offered (but not necessarily required) for a patient with a life-limiting diagnosis and anticipated significant NDI, information or interventions should not be withheld for a newborn or child with trisomy 13/18 with a similar prognosis, based solely on the genetic diagnosis. Every child is deserving of attempted relief of their suffering, which may include interventions with associated risks. Medicine has made tremendous progress in pain relief strategies and therefore isolated concern for potential suffering should not always be a barrier to a parent choosing intervention for their child. Parental authority is an established right, based on the presumption that they have specific knowledge about the child (perhaps less relevant for the newborn patient), are motivated to promote the child’s best interest, are responsible for the long-term consequences of the decisions regarding the child, and are best able to assess the relevant family dynamics.36 Parents have a right to receive all relevant information, which should be provided equally to all families, without requiring them to possess enough pre-existing knowledge to explicitly ask for a given treatment, which could lead to what has been called the “savviness requirement”.7 Families with less knowledge or means to access information could potentially be offered fewer options than more educated families that were savvy enough to ask, which would be inherently unjust.

One must also consider the feasibility of performing interventions and offer only what is possible for a particular patient. Justice concerns are relevant for consideration of costly interventions, but rationing care at the bedside generally should not occur; these decisions are best made at the societal level, so clinicians are able to advocate for their patients and the doctor-patient relationship is protected. Arguments have been made that providing resource-intensive care for some patients with shortened lifespans and significant disability is not appropriate; this is perhaps an ableist viewpoint, and thus to be applied only with great caution. Outcome data for interventions such as tracheostomy and cardiac surgery for patients with trisomy 13/18 and other life-limiting conditions are increasingly being published, improving the accuracy of prognostication on a case-by-case basis, rather than blanket statements based on diagnosis alone.3,40, 41 It is important to highlight that medical and surgical interventions for patients with severely life-limiting conditions and/or anticipated profound disabilities are generally not ethically obligatory. Palliative care teams can help families facing difficult decisions and potentially prolonged hospital stays, though unfortunately access to this resource is limited.42 Other team members, such as social work, pastoral care, psychology, and community pediatricians, also support these families, and longitudinal relationships can be particularly helpful.

The evolving literature and ethical frameworks widely (though perhaps not universally) unite in their agreement that medically indicated interventions should be explained and offered to all families of a fetus, infant, or child with anticipated disability and/or life-limiting conditions, regardless of the severity of NDI, including those with trisomy 13/18. For those patients whose “prognosis is uncertain but likely to be very poor” with survival accompanied by a significant risk for “permanent, severe neurodevelopmental and other special health care needs,” it is appropriate to also offer the process of withholding or withdrawing of LSMTs.26,27 It is ethically impermissible to deny families the information they need to make a decision. Parental preferences, as guided by their personal values, should be the determining factor for any child with a severely life-limiting condition, and this should apply equally to equally severe conditions, regardless of the underlying genetic diagnosis, congenital malformation, metabolic disorder, etc.

It can be difficult to overcome the cognitive dissonance associated with learning that a previously widely accepted practice should potentially be revised, based on new data, especially when prior decisions may have led to a patient’s death. We must remember that clinicians approach patients with positive intentions and generally make decisions based on the best information they have at the time. A willingness to change one’s approach should not be perceived as an indictment of past practice, and openness to altering recommendations moving forward is laudatory. The literature shows that parents of patients with profound disability and/or life-limiting conditions sometimes lovingly choose comfort care. Other parents lovingly choose interventions for their infants, some of whom survive with a positive QOL and relational potential. These revelations should make us, as clinicians, proud of our successes and willing to change our counseling to include the option for medically indicated interventions for patients with anticipated significant disability, alongside the more frequently chosen path of comfort care, based on the considerations described above.