Ethical Considerations for Equitable Access to Genomic Sequencing for Critically Ill Neonates in the United States

Abstract

Rare diseases impact all socio-economic, geographic, and racial groups indiscriminately. Newborn screening (NBS) is an exemplary international public health initiative that identifies infants with rare conditions early in life to reduce morbidity and mortality. NBS theoretically promotes equity through universal access, regardless of financial ability. There is however heterogeneity in access to newborn screening and conditions that are screened throughout the world. In the United States and some other developed countries, NBS is provided to all babies, subsidized by the local or federal government. Although NBS is an equitable test, infants admitted to neonatal intensive care units (NICUs) may not receive similar benefits to healthier infants. Newborns in the NICU may receive delayed and/or multiple newborn screens due to known limitations in interpreting the results with prematurity, total parenteral nutrition, blood transfusions, infection, and life support. Thus, genomic technologies might be needed in addition to NBS for equitable care of this vulnerable population. Whole exome (WES) and genome sequencing (WGS) have been recently studied in critically ill newborns across the world and have shown promising results in shortening diagnostic odysseys and providing clinical utility. However, in certain circumstances several barriers might limit access to these tests. Here, we discuss some of the existing barriers to genomic sequencing in NICUs in the United States, explore the ethical implications related to low access, consider ways to increase access to genomic testing, and offer some suggestions for future research in these areas.

Genetic counselling considerations with genetic/genomic testing in Neonatal and Pediatric Intensive Care Units: A scoping review

“…A total of 170 articles were included in the final review (alphabetically ordered based on author in Supplementary Table 2). 1,2,7–50,55,56,68–189 A PRISMA flow diagram is presented to track the process and number of studies included and excluded (Figure 1).…”

“…When providing genetic consultation to families with infants or pediatric patients with rare disorders, genetic counselling is recommended to accompany early diagnosis 94 . Different studies emphasized the importance of a rapid diagnosis and timely genetic counselling of families 92,118,128,163 . When a rare disorder has been identified in an ICU setting, it is important to involve highly trained genetic counsellors to provide clinical genomic interpretation 84 and explain potential customized timely treatments 118,164 …”

“…94 Different studies emphasized the importance of a rapid diagnosis and timely genetic counselling of families. 92,118,128,163 When a rare disorder has been identified in an ICU setting, it is important to involve highly trained genetic counsellors to provide clinical genomic interpretation 84 and explain potential customized timely treatments. 118,164 Genetic counselling was important at both pre-test and post-test stages in order to effectively communicate possible causes and treatments, inform regarding future pregnancies, and provide comfort by showing empathy (due to difficulties in establishing a diagnosis, lack of treatment options, etc.).…”

“…92,118,128,163 When a rare disorder has been identified in an ICU setting, it is important to involve highly trained genetic counsellors to provide clinical genomic interpretation 84 and explain potential customized timely treatments. 118,164 Genetic counselling was important at both pre-test and post-test stages in order to effectively communicate possible causes and treatments, inform regarding future pregnancies, and provide comfort by showing empathy (due to difficulties in establishing a diagnosis, lack of treatment options, etc.). 137 Pre-test counselling was recommended for emotional support for caregivers while addressing issues pertaining to genetic testing, risks and benefits of the genetic testing process, and the possibility of incidental findings.…”

Rapid Whole-Genomic Sequencing and a Targeted Neonatal Gene Panel in Infants With a Suspected Genetic Disorder

“…T o improve clinical diagnosis in acutely ill neonates and infants, genomic sequencing must provide timely and accurate molecular diagnoses without the ethical burden of identifying unintended secondary findings. [1][2][3][4][5][6][7][8][9][10][11][12] Commercially available targeted-sequencing tests can interrogate a finite number of genes associated with specific genetic disorders. These panels are less expensive than genomic sequencing, return results faster, and rarely identify secondary findings.…”