Importance: Genomic medicine holds promise to revolutionize care for critically ill infants by tailoring treatments for patients and providing additional prognostic information to families. However, measuring the utility of genomic medicine is not straightforward and has important clinical and ethical implications.

Objective: To review the ways that researchers measure or neglect to measure the utility of genomic medicine for critically ill infants.

Evidence Review: This systematic review included prospective full-text studies of genomic medicine of both whole exome and genome sequencing in critically ill infants younger than 1 year. PubMed, Embase, Scopus, and Cochrane Library databases, the Cochrane Database of Systematic Reviews, and the ClinicalTrials.gov register were searched with an English language restriction for articles published from the inception of each database through May 2022. Search terms included variations of the following: gene, sequencing, intensive care, critical care, and infant. From the included articles, information on how utility was defined and measured was extracted and synthesized. Information was also extracted from patient cases that authors highlighted by providing additional information. Spearman rank-order correlation was used to evaluate the association between study size and utility.

Findings: Synthesized data from the 21 included studies reflected results from 1654 patients. A mean of 46% (range, 15%-72%) of patients had a positive genetic test result, and a mean of 37% (range, 13%-61%) met the criteria for experiencing utility. Despite heterogeneity in how studies measured and reported utility, a standardized framework was created with 5 categories of utility: treatment change, redirection of care, prognostic information, reproductive information, and screening or subspecialty referral. Most studies omitted important categories of utility, notably personal utility (patient-reported benefits) (20 studies [95%]), utility of negative or uncertain results (15 [71%]), and disutility (harms) (20 [95%]). Studies disproportionally highlighted patient cases that resulted in treatment change. Larger studies reported substantially lower utility (r = -0.65; P = .002).

Conclusions and Relevance: This systematic review found that genomic medicine offered various categories of utility for a substantial proportion of critically ill infants. Studies measured utility in heterogeneous ways and focused more on documenting change than assessing meaningful benefit. Authors' decisions about which cases to highlight suggest that some categories of utility may be more important than others. A more complete definition of utility that is used consistently may improve understanding of potential benefits and harms of genetic medicine.

<p><strong>BACKGROUND AND OBJECTIVES: </strong>Genetic testing is expanding among ill neonates, yet the influence of genetic results on medical decision-making is not clear. With this study, we sought to determine how different types of genetic information with uncertain implications for prognosis influence clinicians' decisions to recommend intensive versus palliative care.</p>

<p><strong>METHODS: </strong>We conducted a national study of neonatologists using a split sample experimental design. The questionnaire contained 4 clinical vignettes. Participants were randomly assigned to see one of 2 versions that varied only regarding whether they included the following genetic findings: (1) a variant of uncertain significance; (2) a genetic diagnosis that affects neurodevelopment but not acute survival; (3) a genetic versus nongenetic etiology of equally severe pathology; (4) a pending genetic testing result. Physicians answered questions about recommendations they would make for the patient described in each vignette.</p>

<p><strong>RESULTS: </strong>Vignette versions that included a variant of uncertain significance, a diagnosis foreshadowing neurodevelopmental impairment, or a genetic etiology of disease were all associated with an increased likelihood of recommending palliative rather than intensive care. A pending genetic test result did not have a significant effect on care recommendations.</p>

<p><strong>CONCLUSIONS: </strong>Findings from this study of hypothetical cases suggest neonatologists apply uncertain genetic findings or those that herald neurodevelopmental disability in problematic ways. As genetic testing expands, understanding how it is used in decision-making and educating clinicians regarding appropriate use are paramount.</p>