Ethics of Procuring and Using Organs or Tissue from Infants and Newborns for Transplantation, Research, or Commercial Purposes: Protocol for a Bioethics Scoping Review

According to the 1997 Convention for the Protection of Human Rights and Dignity of the Human Being with Regard to the Application of Biology and Medicine↗ (hereafter referred to as the "Oviedo Convention" because the conference was held in Oviedo, Spain), no tissue or organ shall be procured from a person who lacks the capacity to consent. However, this has not been interpreted as implying that all living individuals incapable of providing meaningful consent should be absolutely barred from becoming organ donors, or otherwise having their organs or tissues removed for biomedical purposes. Instead, Article 20/2 of the Oviedo Convention describes a set of conditions that may, when combined with other ethical, legal, or regulatory factors, allow for certain exceptions to be made. These conditions include the unavailability of a compatible donor who has the capacity to consent; the recipient being a sibling of the donor; the donation having the potential to be life-saving for the recipient; and the potential donor not objecting to donation.

How these considerations apply, or should apply, to infants and young children remains controversial. Indeed, the procurement of tissues or organs from infants, whether pre-mortem or post-mortem, has always been controversial. For instance, in 1999, it was revealed that Alder Hey Children's Hospital in Liverpool, UK had stored thousands of organs and body parts, including hearts and brains, from infants and young children after post-mortem examinations↗. These tissues were used for research and teaching without the parents' knowledge or consent. This incident, known as the 'Alder Hey scandal', led to a public outcry that eventually triggered the events that resulted in the introduction of the Human Tissue Bill (2004) and the repeal of the Human Tissue Act (1961) in the UK ( Ellis, 2004).

The ethics, criteria for, and regulation of obtaining organs or tissues from minors are especially controversial, whether for transplants, research, paediatric biobanking, or commercial use ( Thys et al., 2016; Van Assche et al., 2016). Given, among other issues, the severe shortage of organs and tissues for transplantation in infants due to their size-related characteristics, the need for a clear and appropriately justified ethical framework to govern the procurement or use of tissues and organs from infants is evident ( Caplan, 1987).

The Dead Donor Rule (DDR), a widely used standard in transplantation medicine, is associated with its own ethical issues in this context. DDR permits the recovery of vital organs only if the donor is confirmed dead, either by neurological or circulatory criteria. While DDR allows organ donation from individuals declared brain-dead, applying the rule to premature infants (born before 37 weeks) is challenging due to the lack of consensus on determining 'brain death' in these cases, as noted by the American Academy of Pediatrics ( AAP Committee on Bioethics, 2013). Furthermore, brain death in infants under one year old is rare, which underscores the difficulty in establishing robust criteria that can be universally applied to this population. Given that most infants in need of tissue or organ transplants are awaiting heart transplants, finding suitable donors is a significant challenge. Since almost all organ donors are brain-dead, the criteria for brain death remain critical. The rarity of brain death in young children exacerbates the difficulty of finding appropriate donors, which can impact the availability of organs for transplantation.

Although tissue or organ procurement after circulatory or brain death is possible yet controversial for major organs such as the heart ( Dalle Ave et al., 2016), the absence of suitable recipients for such small organs may limit its practicality and raise the question of whether the procured tissues or organs should be discarded or used for research purposes. This practical issue complicates the already nuanced ethical considerations of organ removal or use in the paediatric population, particularly in premature infants. The issue is significant because nearly 1 in 10 babies is born prematurely ( Ohuma et al., 2023), and complications of preterm birth are a leading cause of infant mortality ( Siffel et al., 2022). In premature babies, brain stem reflexes may not be fully developed, making it impossible for these reflexes to disappear - a necessary condition for diagnosing brain death according to current criteria. Without clear criteria for diagnosing brain death in preterm infants, ethical and legal decisions regarding organ recovery ¹ from this specific subpopulation of infants are particularly challenging ( Nakagawa et al., 2011).

Until recently, the use of infant organs or tissues has been limited ( Workman et al., 2013). For example, in the decade between 2010 and 2020, between 3 and 21 neonatal (infants from birth to 28 days of age) "donors" were identified annually in the US, representing 0.03% to 0.21% of the total number of transplant organ donors in a given year ( Anderson et al., 2020). However, as of 5 September 2024, there were 106 infants on the waiting list for donation in the US, highlighting the substantial mismatch between the number of actual infant donors and the number of infants waiting to donate; approximately 1 donor for every 5 infants waiting↗.

The number of neonatal organ donors for purposes of research is even lower, as families with prenatally diagnosed lethal anomalies, or those experiencing neonatal death, are not typically informed about research donation options ( Anderson et al., 2020). Perhaps more important is the fact that clinicians, the individuals actually approaching the families, are not typically informed about potential research options either ( Vileito et al., 2020). There has thus been an ongoing significant disparity between the desire among medical professionals to use infant organs or tissues for transplantation or research and their availability ( Watts, 2006).

In the mid-2010s, however, some prospective parents dealing with diagnoses of lethal anomalies in their foetuses began choosing to carry pregnancies to term, hoping to then donate (i.e., give permission for retrieval and use of) their neonate’s organs after natural death. These parents contacted the International Institute for the Advancement of Medicine (IIAM), an Organ Procurement Organization (OPO) that annually handles over 15,000 referrals and has placed over 14,000 research organs in the past 20 years ( Anderson et al., 2020). Since then, the use of neonatal organs and tissues for research in areas including “diabetes, pulmonary, gastrointestinal, genitourinary and neurological development, rheumatoid arthritis, autism, childhood psychiatric and neurologic disorders, treatment of MRSA infection and paediatric emergency resuscitation” has risen rapidly ( Anderson et al., 2020). Moreover, not only neonatal but also infant organs and tissues are increasingly used in the cosmetics industry for experimental studies investigating their rejuvenating properties ( Cannovo et al., 2020; Oliveira et al., 2018; Vig et al., 2017). Given that the ethical justification for some of these uses may be considered controversial, it is necessary to comprehensively evaluate existing ethical arguments surrounding infant tissue and organ procurement and use for various purposes in the biomedical context. The primary objective of this review is to identify, systematise, and critically evaluate the ethical arguments for and against the procurement and use of tissue and organs from infants (including neonates and newborns up to 1 year of age) in biomedical contexts.

Numerous arguments surrounding the ethics of consent to organ donation in adults and assent for paediatric populations more generally exist in the bioethics literature ( Katz et al., 2016; Prabhu, 2019; Spriggs, 2023). In this scoping review, we hope to lay the groundwork for a comprehensive ethical analysis of arguments that support or oppose such procurement and use.

Our project thus differs from that of, for instance, Weiss et al. (2016), who published a scoping review of bioethical arguments surrounding paediatric organ donation after circulatory determination of death (commonly referred to as DCD). In contrast, our scoping review recognises that there are other contexts - apart from a circulatory determination of death - in which paediatric tissue and organ procurement may occur, particularly when considering the case of paediatric biobanks that collect, store, and manage biological samples ² (such as blood, tissue, DNA, and other bodily materials) from children, typically for medical research or clinical purposes ( Casati et al., 2022). Our review will consider tissue and organ procurement from infants who have been declared dead according to any accepted criteria (e.g., brain death), as well as from living, healthy infants where applicable, ³ for relevant biomedical purposes, including transplantation, research, and commercial applications (such as in the skin cosmetics industry). Moreover, the use of leftover tissues from diagnostic testing for transplantation, research or commercial purposes will also be considered. However, the review will not consider issues related to the secondary use of such materials. Therefore, issues like the storage of newborn blood spots collected at birth for routine diagnostic screening for genetic diseases are beyond the scope of this review. We will primarily focus on the use of infant tissues or organs for the benefit of others or third parties.

Our project also differs from that of Bluhme, Henckel, and Jorns who produced a scoping review in which they analysed neonatal organ use from a clinical perspective ( Bluhme et al., 2023). While the review by Bluhme and colleagues summarises the available scientific literature on the potential for neonatal organ procurement and analyses published medical cases of neonatal organ transplantation, ethical arguments regarding whether the procedure itself is justifiable in a biomedical context were not commented upon in that review. On the contrary, our scoping review will focus on ethical issues that are distinctive or different in infants, not only in neonates, while the technical or medical issues will be set aside, except where they generate ethical considerations.

A scoping review was determined to be the ideal method for organising the arguments surrounding the ethics of infant organ or tissue procurement for transplantation, research, and commercial purposes for three main reasons. Firstly, the circumscribed nature of the topic made a comprehensive approach to capturing the existing literature involving the identification of all major perspectives a sensible objective. Secondly, the authors aim to pinpoint knowledge gaps within the current body of research, a task well-suited to the broad and exploratory scope of this review method. Thirdly, the issue involves a wide range of stakeholders, including medical practitioners, researchers, commercial entities, and the infants themselves. A scoping review following the guidelines suggested by JBI aligns with all three of these goals.

Moreover, this scoping review will specifically focus on infants, rather than the broader paediatric population, for several reasons. First, infants, especially those born prematurely or with severe conditions, face unique ethical and clinical challenges, such as brain death determination and the impact of premature birth on organ viability, which differ from those of older children. Second, developmental differences in infants affect both their physiological responses to and the ethical considerations relating to organ procurement. A focused review allows for a detailed exploration of these age-specific factors. Third, ethical issues like brain death determination in very young infants are more complex and less standardised, requiring separate attention to address parental consent and family impact effectively. Fourth, guidelines and regulations for infant organ procurement may differ from those for older children, necessitating a thorough examination of policies tailored to this age group. Fifth, unborn foetuses are excluded because organ and tissue procurement tends to occur outside the mother’s body, while biopsies such as may be taken during pregnancy for diagnostic purposes are excluded. Finally, research on infant organ procurement may highlight distinct trends and challenges compared to broader paediatric studies, offering deeper insights and contributing to specialised protocols and ethical guidelines.

Many studies have addressed bioethical issues surrounding the donation/procurement of infant tissues or organs. However, after conducting a search with the descriptors “bioethics,” “ethics,” “infant or neonatal or newborn” and “organ or tissue donation or transplantation” in the Joanna Briggs Institute Evidence-Based Practice Database, Cochrane Library, PubMed, and Scholar Google, no systematic reviews, overviews, or scoping overviews were found in this specific context.

Study objectives include:

A scoping review is a type of systematic review, mapping concepts and findings related to the topic of interest using the knowledge synthesis approach (i.e., the method of systematically collecting, analysing and synthesising evidence from multiple studies or sources to develop a comprehensive understanding of a particular topic or issue). This approach aims to consolidate existing knowledge, identify gaps, and provide evidence-based conclusions or recommendations ( Munn et al., 2018). This scoping review uses all types of evidence at various levels and it employs the well-established scoping review methodology, as described by the Joanna Briggs Institute (JBI)↗, consisting of five-stages: (1) determining the research question, (2) search strategy, (3) inclusion criteria, (4) data extraction, and (5) analysis and presentation of the results.

We will search for relevant studies in the National Library of Medicine (including PubMed and MEDLINE), Web of Science↗, Google Scholar, EBSCO, Virtual Health Library, The Bioethics Literature Database (BELIT)↗, EthxWeb↗, and PhilPapers↗. Grey literature sources will be searched as well to identify relevant non-indexed literature. Third, the reference lists of selected reports and articles will be hand searched for additional studies. The results will be reported in accordance with PRISMA-ScR guidelines. ⁴ Study activities including the writing of this protocol will occur between June 2024-January 2025 or until finished. Ethics Review Board approval is not required for this scoping review.

Patients or the public were not involved in the design, conduct, reporting, or dissemination of our research.

Ethical approval is not required as this review is a retrospective review of publicly available sources. The review findings will be disseminated via publication in a peer-reviewed journal, symposia and conference presentations. The findings from this review will inform, through the translation of knowledge, organ procurement organisations (OPO), educational institutions developing infant tissue/organ donation training programs for medical professionals, paediatric and neonatal intensive care professionals.

Not required.

N/A.

This work was supported by the Wellcome Trust [Grant number: 226801] for Discovery Research Platform for Transformative Inclusivity in Ethics and Humanities Research (ANTITHESES).

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

No data are associated with this article.