Introduction: With the development of xenotransplantation (XTx), relevant stakeholders must be involved to address many of the topics (informed consent; risk-benefit analysis; xenozoonosis; xenograft candidacy) in order to develop policy and practice solutions ethically. For pediatric XTx, ethical frameworks and discussions are not as advanced as for adult XTx. Unique ethical challenges exist in XTx for children, and patients who have been excluded historically due to perceived unfavorable benefit-to-risk or benefit-to-resource use ratio may require a novel assessment. If XTx resolves concerns of organ availability, ethical considerations may further support revisiting criteria for patients previously denied from physiological limitations.

Methods: We review whether XTx in children can ethically be pursued before obtaining safety and efficacy data in adults. Specifically, trial design, trial recruitment, organ growth and harm, and psychosocial and moral hazard issues are explored. Arguments for XTx as bridge-to-allotransplantation or as therapy for those with genetic conditions are examined as future directions for XTx, and disability biases are addressed.

Results: Proactive attention to ethical issues may allow pediatric XTx trials prior to obtaining safety and efficacy data in adults, supporting ethical arguments of justice and beneficence to allow potential benefits. Additionally, when considering any patient that may benefit, a subset are denied based on genetic comorbidities due to the presumption of limited benefit rather than poor outcomes. Ethical justification for denial based on resource limitation will lose strength with XTx, and some disease states and syndromes may no longer qualify as absolute contraindications to transplantation (e.g. T21 patients are being considered for allotransplantation with waitlist/post-transplant outcomes comparable to other patients). Patients with other contraindications may warrant individual consideration rather than automatic disqualification, (i.e. trisomy 18).  Select patients may benefit from prolonged survival and increased QOL, even if QOL remains limited.

Conclusion: In pediatrics, XTx specific guidance is required to address minimum regulatory terms for an appropriate benefit-to-risk ratio and candidate identification. Successful pediatric XTx may subsequently drive re-evaluation of contraindications, such as genetic syndromes, driving individual assessment rather than automatic disqualification.