Ethical and Legal Issues Surrounding Genetic Testing in the Neonatal Intensive Care Unit

Abstract

Clinicians practicing in a modern neonatal intensive care unit (NICU) will have noticed an increase in the proportion of patients who undergo genetic testing as well as changes in the types of genetic testing they receive. These trends are unsurprising given increasing recognition of the genetic causes of neonatal illness and recent advances in genetic technology. Yet, the expansion of genetic testing in the NICU also raises a number of ethical questions. Here, we review the ethical issues raised by genetic testing with a focus on the practical implications for neonatologists. First, we outline the complexities of measuring benefit, or utility, for neonatal genetic testing. Next, we will discuss potential harms: inequity, unexpected findings, disability biases, and legal risks. We conclude with a discussion of ethical issues related to consent for genetic testing. Throughout this article, we highlight solutions to challenges toward the ultimate goal of minimizing harms and maximizing the substantial potential benefits of genetic medicine in the neonatal intensive care unit.

Introduction

Clinicians practicing in a modern neonatal intensive care unit (NICU) will have noticed an increase in the proportion of patients who undergo genetic testing as well as changes in the types of genetic testing they receive. These trends are unsurprising given increasing recognition of the genetic causes of neonatal illness and recent advances in genetic technology. Depending on the population selected for testing, 20–60% of patients in Level IV NICUs undergoing genome sequencing will have abnormal findings.¹ Genetic disease is a leading cause of infant mortality in developed countries.² Correspondingly, a growing proportion of newborns in the neonatal intensive care unit (NICU) undergo genetic testing, and patients are receiving broader and faster testing. Exome and genome sequencing are now clinically available, particularly in Level IV NICUs.³ Both of these technologies allow clinicians to look for genetic changes broadly rather than just looking for specific changes in genes associated with a suspected disease. Additionally, information can now be returned in days to weeks, instead of months, making it available for intensive care decisions.⁴ Making genetic diagnoses, and making them faster, has the potential to improve outcomes for critically ill neonates.

Yet, the expansion of genetic testing in the NICU also raises a number of ethical questions, some that also have a legal dimension. As genetic testing becomes broader, clinicians are receiving increasingly complex genetic information that can be difficult to understand without substantial training in genetics.⁵ A genetic diagnosis also frequently carries uncertainty; even a diagnostic finding may not correlate neatly with a patient’s phenotype or provide a reliable prognosis. Despite these challenges, neonatologists will increasingly be required to understand and apply genetic information as growth in genetic testing outpaces growth in the traditional genetic workforce, which has included medical geneticists and genetic counselors.⁶ Neonatologists must therefore be prepared to thoughtfully engage in interprofessional and patient-oriented communication about an expanding volume of genetic information in both the pre- and post-test phases of care.

Here, we review the ethical issues raised by genetic testing with a focus on the practical implications for neonatologists. A key element of ethics, of course, is the weighing of benefits and harms. First, we outline the complexities of measuring benefit, or utility, for neonatal genetic testing. Next, we discuss potential harms: inequity, unexpected findings, disability biases, and legal risks. We conclude with a discussion of ethical considerations related to consent for genomic sequencing in the NICU. The accompanying NeoReviews articles provide more information on the practicalities of whole genome sequencing (Suhrie article) and parent perspectives on genetic testing (Salih article). We focus on issues pertaining to critically ill neonates; the large body of work that addresses the ethical challenges raised by genetic sequencing in healthy newborns lies outside the scope of this article.⁷

Difficulty Measuring the Utility of Genetic Tests

Utility refers to the likelihood that a genetic test will be of benefit. Clinicians and researchers agree that genetic testing holds great benefit for a subset of NICU patients, but measuring the utility of genetic tests is more complex than measuring the utility of many other types of medical tests.^8,9 Genetic tests can lead to a broad range of findings with diverse implications for care, so they cannot be tied to one easily measurable outcome.¹⁰ Genetic testing is most often valuable in clarifying either the cause of patient’s medical problems or the prognosis, which often informs care without necessarily improving survival or decreasing length of stay. Despite advances in targeted therapies for rare genetic diseases, treatable genetic diseases with neonatal onset remain uncommon.¹¹

These complexities have led to a simplistic reliance on “change in management” as the primary measure of utility for genetic testing in the NICU.¹² Changes in management typically include modified treatment (e.g. medications, surgeries), additional screenings for potential future complications, reproductive counseling for the child’s parents, and redirection to palliative care. The connections from a diagnosis to a change in management and from a change in management to an improved outcome are difficult to establish.^9,10 For example, imagine a diagnosis for a genetic etiology for seizures results in the change of an antiepileptic drug. Determining whether the genetic diagnosis was the reason for the medication change is frequently difficult given the multitude of factors clinicians consider in complex medical decisions. Furthermore, whether this change in medication will affect the patient’s long-term seizure control or overall outcome is also difficult to deduce, and few studies even attempt to assess the link between change and benefit.¹³

At the same time, genetic diagnoses, as well as genetic test results that are both negative and uncertain, may provide valuable information even when they do not change management.¹⁴ Personal utility is a term used to encompass a wide range of patient- or parent-endorsed benefits, for instance the value of having an explanation for illness, a clearer sense of the future, or the ability to join a disease-specific support group.¹⁵ Negative genetic test results are also frequently perceived to be helpful, as they reassure both parents and clinicians that they are not missing a treatable condition.⁸ Genetic testing is also believed to help alleviate parental guilt, although the relationship between genetic findings and guilt is complex. For some parents, a diagnosis alleviates concerns that they could have prevented illness by taking different actions, while for others an inherited cause of disease increases feelings of guilt.¹⁴ The accompanying article by Salih et al. more comprehensively reviews parent perspectives on genetic testing.

There is a great deal of work taking place to develop more nuanced frameworks for measuring utility, with the goal of addressing both the limitations of “change in management” as a utility measure and to better account for the non-clinical benefits of receiving a genetic diagnosis.^16,17 These measures promise more precise and comprehensive measures of utility in the future. Ultimately, measuring the benefit of genetic testing has both clinical and ethical importance, as it determines how benefit is weighed against costs and potential harms.

Potential Harms of Genetic Testing

At the inception of the Human Genome Project, the National Human Genome Research Institute recognized the potential ethical, legal, and social implications (ELSI) of genetic progress.¹⁸ Resultingly, there have been thoughtful investigations into many of the potential ethical issues that arise with increasing use of genetic testing in the NICU (and beyond). Ethical questions raised by genetic tests are not entirely unique and overlap questions raised by other types of complex medical tests. Some researchers have therefore highlighted that genetic tests should not be held to a different ethical standard, rejecting “genetic exceptionalism.”¹⁹ Nevertheless, we will here outline a number of potential harms related to increasing use of genetic testing in the NICU.

Exacerbating Inequity

One of the chief ethical concerns about the genetic testing is that benefit may be unequally distributed among populations—defined by race or ethnicity, geography, or other sociodemographic characteristics—thereby exacerbating existing health disparities.²⁰ Most studies in this area are not specific to a NICU context, but nevertheless hold generalizable lessons. First, genetic research has disproportionately included participants of European and Asian ancestry, leading to genomic databases that contain more information from these populations.²¹ As a result, patients from underrepresented ancestry groups are more likely to have variants classified as uncertain,²² or have normal variants that are incorrectly classified as pathogenic.²³ When genetic testing is linked to intervention, inequitable representation in genomic databases can lead to inequities in care.²³ This effect could be less prominent in the NICU, since many of the neonatal conditions that require intensive treatment result from de novo variants rather than those that are inherited. For these types of genetic changes, testing parents in conjunction with an infant, termed trio testing, improves the accuracy of pathogenicity predictions and can reduce such inequities. At the same time, the availability of both biological parents for testing, a factor that is itself driven by social determinants of health, may create additional inequities.²⁴

Second, patients from different populations also have unequal access to genetic testing on a hospital or individual level. Rates of genetic testing vary significantly between NICUs at different hospitals, and this variation is only minimally explained by differences in patient illness severity.³ Genetic testing, and particularly exome and genome sequencing, are more readily available at urban, academic referral centers, as such hospitals have the genetic workforce required to support the services and counseling these tests have traditionally required.²⁵ These hospitals are also able to absorb the costs of genetic testing that is not ultimately covered by insurance. Currently, many state and federal programs often do not cover inpatient genetic tests, so the cost is bundled in daily NICU bills. Often some or all is not paid by insurance and must be covered by the hospital, or in some cases even the patients’ famililes.²⁶ Patients from underrepresented racial or ethnic minorities, those from lower income households, and those in medically underserved areas are more likely to be hospitalized in community or rural NICUs with less access to genetic testing, perpetuating inequality.²⁷

Even within the same NICU, patients may not have equal access to genetic tests. The index of suspicion for a genetic disorder depends on the phenotype of the infant, and infants with classical presentations of genetic disorders may be more likely to receive testing than those with atypical presentations. Genetic conditions that have external physical features that are evident in the newborn period may be more likely to receive testing. Dysmorphic features, which commonly trigger genetics consultation and/or testing may be recognized less frequently in patients of racial or ethnic backgrounds that are underrepresented in dysmorphology atlases.²⁸ Genetics consultation requests may also reflect the neonatologist’s perception of family readiness for genetics consult, which may be impacted by real and perceived health literacy of the family. Additionally, the comfort level of medical interpreters in discussing genetic testing may impact a family’s readiness to consent to genetic testing. Finally, NICU patients who have an identified genetic disease often require follow up with clinical geneticists and other subspecialists which are more difficult for underserved populations to access.²⁹ Concerns about inequitable distribution of genetic resources continue to expand with the development of targeted therapies for genetic conditions, such as nusinersen for spinal muscular atrophy, that are expensive and require access to specialized centers.³⁰

An additional complexity is that families of minoritized racial and ethnic groups have historically been less likely to consent to clinical genetic testing or genetic research.³¹ Systemic racism and historical injustices within medicine have understandably contributed to greater mistrust of genetic technology among racial and ethnic minorities. Additionally, families of minority groups may face language or cultural barriers that make understanding and consenting to genetic testing more difficult. ²⁰ When families of racial and ethnic minorities decline to participate in genetic research, inequities in the utility of the genetic tests themselves, as discussed above, are exacerbated, creating a vicious cycle.

Addressing these issues and improving equity in genetic testing in the NICU will require a multi-pronged approach. Efforts to study the comparative effectiveness of genetic tests in different populations are essential and have begun. For example, this was the express goal of the federally funded Clinical Sequencing Evidence-Generating Research Consortium.³² Ongoing research will need to address and mediate barriers to enrolling in genetic research or clinical testing.²⁰ Efforts to improve the availability of genetic testing must also include expanding the genetic workforce, including developing virtual genetic services and educating neonatologists to expand their skills in this arena.²⁷ Compared to the outpatient setting, the NICU patients are at least already connected to healthcare, and are by definition early in their medical trajectories, so one can imagine that with dedicated effort the NICU could lead the way toward more equitable genetic testing practices.

Implications Regarding Disability

Many of the benefits of genetic testing in the NICU stem from its ability to provide prognostic information, though this also creates ethical questions. Prognostication in the NICU is particularly difficult because even typical neonates have a limited range of capabilities. Unlike older patients, neonates also have no ‘prior baseline’ with which to compare their current status. Physical and developmental abilities are therefore largely abstract, future concepts. Our current tools to predict these abilities are quite poor. Virtually every neonatologist can cite a case where a patient exceeded expectations, or a patient expected to flourish ultimately did very poorly. In such a context, the opportunity to use genetic tests to shine light on a baby’s future – complete with abilities and disabilities—is understandably appealing. Prognostication is particularly important when the prognosis seems grim, and clinicians and parents must consider whether to continue invasive care. While the prognostic power of genetic testing has been touted to facilitate end-of-life decision making,^33,34 utilizing genetic test results in this way is fraught with ethical pitfalls. Information about future disabilities has the potential to be misused or used in ways that perpetuate biases against people with disabilities.³⁵ This type of error is referred to as “ableism,” which includes, among other prejudices, the tendency to undervalue the lives of individuals with disabilities. While these issues are also inherent in other prognostic technologies such as neuroimaging, they are raised on a large scale and with some additional complexities in a genetic context. The Baby Doe case has played a critical role in the history of disability and ableism in the context of neonatal genetic conditions.

Baby Doe was born in 1982 in Bloomington, Indiana, with both tracheoesophageal fistula and esophageal atresia (TEF/EA) associated with Trisomy 21.³⁶ At the time, survival rates for patients with TEF/EA were over 90%, but the obstetrician caring for the infant’s mother recommended against surgery given the expected developmental disability associated with Trisomy 21. Baby Doe’s parents agreed to comfort care, withholding fluid and nutrition. A pediatrician involved in the case felt it was unacceptable to withhold surgery, and the ensuing disagreement rose to national attention. Ultimately, Baby Doe died during the legal proceedings, but the federal government took extensive action to prevent similar outcomes.³⁷ The resultant “Baby Doe Laws” aimed to prohibit discrimination based solely on handicap. Posters placed in NICUs described bans on discrimination based on disability and included a toll-free phone number to report violations. Only 19 months later, the Supreme Court struck down these regulations on the ground that they lacked a statutory foundation. Congress responded by enacting a new, much narrower law that does not apply to health care institutions and providers.³⁸

This case and its aftermath remain a critical backdrop to contemporary NICU decision-making. Neonatologists widely agree that parents have the right to refuse potentially life-saving medical interventions in some circumstances, but the zone of permissible choices has boundaries.^39,40 Physicians have a responsibility to use their medical expertise to frame choices that would be outside of this zone, clarifying for families that some interventions are so likely to be of benefit that they are required, while other interventions are so unlikely to be of benefit that providing them would be impermissible.³⁹ Parents can decide what care is most likely to support the interests of their child within this zone. In making these difficult decisions, physicians and parents often incorporate expected future disability. There is an enduring concern, however, that both NICU providers and parents struggle to tease apart concerns about an infant’s chance of survival from the potential impacts of disability over the course of their expected lifespan.⁴¹ Genetic diagnoses are often factored into such decisions as they inform our conception of patients’ futures. This raises two difficult questions: (1) what level of disability expected based on a genetic diagnosis justifies withholding life-sustaining treatment? and (2) with what certainty must we be able to predict disability to incorporate it into difficult decision making?

To address the first question, since the era of Baby Doe, the degree of expected disability that doctors agree justifies withholding of life sustaining treatment has shifted. Today, there is a consensus that the disability expected for Trisomy 21 is insufficient to justify discontinuing life-sustaining treatment.³⁷ By contrast, the disability associated with Trisomy 13 or 18 could justify withholding treatments.^37,42 For these conditions, parents are typically permitted to decline life-sustaining interventions based on the profound disability expected for these conditions, despite growing evidence that these conditions are more survivable than previously believed.⁴³ Beyond these well-known examples, the threshold of condition severity at which withholding life-sustaining interventions remains in the zone of parental discretion is not clearly demarcated. Disability rights advocates have raised concerns that the placement of this threshold, and the practice of redirecting care based on expected disability in general, reflect ableism. This bias may lead both parents and clinicians to perceive information about future disability as worse than it really is, or worse than somebody who actually has the disability would experience it to be. Indeed, many people who live with disabilities, as well as their families, regularly report that life with even profound disability is not inherently tragic, laden with constant suffering, or an extraordinary burden for caretakers.³⁵ A concerning possibility is that genetic diagnoses associated with future disabilities might bias clinicians to recommend, or parents to elect, comfort care in cases where patients would have gone on to have fulfilling lives. A hypothetical vignette study showed that neonatologists are indeed more likely to recommend comfort care for a sick patient when a genetic diagnosis heralds even mild neurodevelopmental disability.⁴⁴

An additional complexity is that prognostic genetic information is frequently uncertain.⁴⁵ Genetic variants may be of uncertain significance or associated with a broad range of potential outcomes. Trisomy 13, 18, and 21 are often suspected even without molecular testing, but as genetic testing expands, we are detecting genetic changes that may not be obvious on exam. The correlation between genotype and phenotype is frequently imprecise. Current outcomes data for genetic conditions likely reflect the more severe end of the phenotypic spectrum, as severely affected patients were historically the ones tested and diagnosed. Additionally, for diagnoses that are considered severe, if care is frequently redirected to comfort care only, this will cause outcome data to look worse, creating a self-fulfilling prophecy.⁴⁶ How certain a genetic prediction of disability must be, and how severe that disability must be, to justify withholding life-sustaining remain enduring unanswered ethical questions.

The risks to disabled persons created by genetic predictions extend beyond end-of-life decision making. Counseling about genetic disability that reflects ableism, particularly so early in life, could influence family members to adopt these biases themselves, making it more difficult for children who do survive with disabilities and their families to forge happy futures.⁴⁷ Applying genetic information to end-of-life decisions also has the potential to send a hateful message about the value of people with disabilities more broadly, beyond the NICU, thereby perpetuating stigmatization and discrimination based on disability.³⁵ Neonatologists therefore need complete and current education about living with disabilities so that they can provide balanced counseling. Neonatal genetics research needs to be intentional and thoughtful in shaping the messages it sends about disability. Combating ableism will require broader discussions that include the direct participation of people who live with disabilities as well as disability advocates in genetic research.⁴⁸

Unexpected Findings

As exome and genome sequencing are increasingly used in clinical practice, ethical complexities arise related to these tests’ ability to uncover findings unrelated to the indication for sending the test. Microarrays also carry this risk, but at a lower frequency. Some of these findings have implications for family members which requires additional consideration. Secondary findings are genetic variants unrelated to the indication for testing that laboratories intentionally identify because they are believed to have potential medical value.^49–51 These include, for example, cancer predisposition syndromes such as hereditary breast and ovarian cancer caused by BRCA1 variants, or genes predisposing to arrhythmias, such as long QT syndrome.⁵⁰ Incidental findings are genetic variants that are unrelated to the reason for testing, but cannot be avoided due to the testing methodology.⁵¹ The discovery of chromosomal differences, like Klinefelter syndrome (47,XXY), are one example of incidental findings that can be discovered through exome or genome sequencing.

Limited evidence exists on the balance of risks and benefits created by disclosing these secondary and incidental findings. Disclosing both incidental and secondary findings might provide benefit for the child as they get older and may also prompt beneficial testing in family members. The American College of Medical Genetics (ACMG) publishes and regularly updates a list of genetic variants associated with “high likelihood of severe disease that is preventable if identified before symptoms occur.”^49,50 However, this list is not targeted to the intensive care setting. The downsides of disclosing secondary and incidental findings include the possibility of inciting worry and distracting families from focusing on the underlying condition that prompted sequencing.⁵⁰ Whether to test for and disclose secondary findings in the NICU remains controversial. Most hospitals require a separate consent to receive secondary findings, and some do not routinely offer parents this option. Incidental findings by definition cannot be avoided, so will continue to be something neonatologists encounter. If the incidental finding has clinical implications, clinicians may face liability for failing to disclose it.⁵²

Genetic tests may also reveal consanguinity or, when the parents are sequenced, non-paternity. Procedures for dealing with these possibilities are less standardized. Pretest counseling should always include discussion of these possibilities. In the case of consanguinity, the finding should be reported to both parents given its relevance to health and implications for future reproduction. Although consanguineous relationships between siblings and first cousins are not legally permissible in many jurisdictions, physicians generally do not have an obligation to report when these relationships are uncovered through genetic testing. The breach of patient confidentiality and potential downstream harms to the child are strong counterbalancing concerns that tend to outweigh potential benefits from reporting.^53,54 If one parent is a minor and the consanguinity may reflect child abuse or rape, clinicians have an obligation report the concern.^53,54

When non-paternity is discovered, there is little consensus on the correct course of action. Some have argued that the finding should be revealed to both parents because of physicians’ duty to be truthful and the parents’ right to know. Others have contested that because only the mother’s fidelity is at stake, there is asymmetry of risk which justifies disclosing the finding only to the mother. More recently, experts have suggested that non-paternity should not be part of routine genetic testing unless specifically requested.⁵⁴ Supporters of this position argue that physicians should not interfere in a matter which has the potential to harm many relationships, harms which pose significant risks to the well-being of the child. Given the absence of clear guidelines surrounding non-paternity, hospitals need institution-specific policies to which they adhere and clinicians should be diligent about knowing the policies of genetic testing laboratories to which they send parent samples. Many hospitals currently do not offer paternity testing and ask parents to use direct-to-consumer testing to address paternity if they desire to do so. However, hospitals and neonatologists need to also consider the reporting standards of the labs they work with. Because both parents are likely to have access to the lab report and/or discuss test results, an astute parent may infer that non-paternity even if it is not explicitly disclosed. Genetic testing might also reveal non-maternity in cases of assisted reproduction (e.g. embryo mix-up). This is sufficiently rare such that no clear recommendations for handling the finding exist. In both cases, genetic counselors who have extensive professional training in supporting families through such disclosures and should be engaged.

Legal Risks: Security and Regulatory Issues

The risks of genetic testing extend beyond a clinical context. In recent years, there has been significant debate about whether people should be able to control access to genetic data about themselves or their children.⁵⁵ A concern about genetic testing in the NICU is that results could be used for unplanned purposes outside of a baby’s medical care, such as for research, to deny employment or insurance, or in criminal investigations. Neonatologists should know, however, that the use and sharing of genetic data about children is legally constrained in a number of ways. The Privacy Rule of the Health Insurance Portability and Accountability Act (HIPAA) ^56,57 and the Information Blocking Exceptions of the 21^st Century Cures Act⁵⁸ have provisions that can be used to prevent the disclosure of this type of information, whether the sequencing is done locally or at a commercial laboratory.

As for research, parents in the NICU might gain access to genetic testing through interventional clinical trials that involve genetic testing. This type of research should include disclosure during the consent process about the management of genetic data. As for other deidentified results, deidentified genetic results can be used for secondary research without a consented research protocol. Although not legally required, parents generally should be informed of this possibility as a part of pre-test counseling. Increasingly, institutions are informing patients of these research uses to increase transparency and enhance trust.

Parents may also express concern about whether they or their child will have trouble getting a job or health insurance because of documented genetic abnormalities. The Genetic Information Nondiscrimination Act (GINA), which forbids genetic discrimination in employment and health insurance decisions, provides little protection to a child hospitalized in the NICU with a genetic condition since it does not apply to people who are already symptomatic from their genetic condition.^59,60 GINA also does not extend to members of the military, so secondary findings in parents may result in ineligibility for military service. Fortunately, numerous other laws provide more protection,⁶⁰ including the Patient Protection and Affordable Care Act, which forbids excluding coverage for pre-existing conditions, and the Americans with Disabilities Act, which requires most employers to provide reasonable accommodations for people with disabilities.

There are certain public purpose exceptions to the protections of HIPAA including legal investigation of a crime with a court order, warrant, or subpoena. Although such searches are quite uncommon, a recent search involving a state-run newborn screening sample, obtained in a completely separate system from clinical sequencing, received significant publicity.⁶¹ Parents should also be counseled that they are entitled to obtain clinical data, including genetic testing results, about their child^58,62 and are free to share their child’s health information with others, which many parents do in order to obtain social support.⁶³ However, if they do so, they should be aware that the people they share this information with may not have the same ethical and legal obligations to protect their family’s privacy that apply to health care providers.

Consent: Weighing Benefits and Harms

Given the issues discussed above, education and consent for genetic testing and particularly for exome and genome sequencing, are unsurprisingly complex. The goals and benefits are harder to define and measure than for most other medical tests sent in the NICU, and potential risks evolve alongside genetic technology. Comprehensive informed consent is unsuitable for genetic tests since it would be impractical, if not impossible, to provide information about every condition tested for.⁶⁴ These challenges require novel approaches, such as binning information about similar conditions and offering tiered levels of information based on parent preferences.⁶⁵ As the turnaround time for genetic tests shortens and they are used more frequently in acute care, this adds time pressure to consent discussions. Simultaneously, some have argued that because genetic tests are noninvasive, they should not require explicit informed consent, but rather be included in the overall consent implied by hospital admission.⁵³ There is no federal policy requiring specific informed consent for clinical genetic testing and many states do not require written consent.⁶⁶ Neonatologists order other complex noninvasive tests without explicit consent, such as brain magnetic resonance imaging (MRI). Many of these tests, like MRI, share with genetics tests the potential to make unexpected discoveries and predict disability. Ultimately, the form consent or assent takes is secondary to the importance of maximizing benefit of the test by setting realistic expectations and minimizing harms by discussing the range of possible findings and implications.⁶⁴ This is a difficult task even for professionals trained in genetics, and currently neonatologists report feeling unprepared for consenting to genetic testing.⁶⁷ The expansion of genetic testing in the NICU, and shortages of genetic professionals, will likely require neonatologists to become competent in this task, at least in uncomplicated cases. Perhaps this can be used as an opportunity for neonatologists to learn about and reflect on both the great benefits and the potential harms associated with this powerful technology.

Looking to the Future

In this article, we highlight the ethical challenges raised by genetic testing in the NICU. All technological advances require consideration of their ethical implications. The goal of ELSI investigation should be to maximize benefit and minimize harms, rather than to limit progress. The solutions we present hinge on awareness of the ethical questions by those practicing in the modern NICU, collaboration between neonatology and genetics, and intentional research efforts to understand and address challenges. The intention of this review is to raise awareness of ELSI topics for neonatologists, and in doing serve a small role in such forward progress. The opportunity to improve NICU care through genetic testing is tremendous, and this testing will provide the greatest net benefit when clinicians remain mindful of the potential ethical and legal pitfalls that can arise with this practice.

Content Specifications:

Recognize the controversies associated with the introduction of new genetic tests for rare and common diseases that present in the neonatal period (19.B.b.1)

Recognize the controversies associated with the development of gene-based therapies to treat neonatal conditions (19.B.b.12)

Practice Gaps or Education Gaps:

Neonatologists must be prepared to thoughtfully engage in interprofessional and patient-oriented communication about an expanding volume of genetic information in both the pre- and post-test phases of care. Understanding the ethical controversies surrounding use of genetic information in neonates is essential to this task.

Learning Objectives:

1. To recognize the complexities of measuring benefit, or utility, for neonatal genetic testing.

2. To recognize the potential harms of genetic testing and genetic information in neonates, namely inequity, unexpected findings, disability biases, and legal risks.

Abbreviations:

ACMG

American College of Medical Genetics

ELSI

Ethical, legal, and social implications

GINA

Genetic Information Nondiscrimination Act

HIPAA

Health Insurance Portability and Accountability Act

MRI

Magnetic resonance imaging

NICU

Neonatal intensive care unit