A Prospective Study of Parental Perceptions of Rapid Whole-Genome and -Exome Sequencing among Seriously Ill Infants

Abstract

Rapid diagnostic genomic sequencing recently became feasible for infants in intensive care units (ICUs). However, research regarding parents' perceived utility, adequacy of consent, and potential harms and benefits is lacking. Herein we report results of parental surveys of these domains from the second Newborn Sequencing in Genomic Medicine and Public Health (NSIGHT2) study, a randomized, controlled trial of rapid diagnostic genomic sequencing of infants in regional ICUs. More than 90% of parents reported feeling adequately informed to consent to diagnostic genomic sequencing. Despite only 23% ( 27) of 117 infants receiving genomic diagnoses, 97% (156) of 161 parents reported that testing was at least somewhat useful and 50.3% (88/161) reported no decisional regret (median 0, mean 10, range 0-100). Five of 117 families (4.3%) reported harm. Upon follow-up, one (1%) confirmed harm to child and parent related to negative results/no diagnosis, two (2%) reported stress or confusion, and two (2%) denied harm. In 81% (89) of 111 infants, families and clinicians agreed that genomic results were useful. Of the families for whom clinicians perceived harm from genomic testing, no parents reported harm. Positive tests/genomic diagnosis were more frequently perceived to be useful by parents, to benefit their infant, and to help manage potential symptoms (p < .05). In summary, the large majority of parents felt that first-tier, rapid, diagnostic genomic sequencing was beneficial for infants lacking etiologic diagnoses in ICUs. Most parents in this study perceived being adequately informed to consent, understood their child's results, and denied regret or harm from undergoing sequencing.

An RCT of Rapid Genomic Sequencing among Seriously Ill Infants Results in High Clinical Utility, Changes in Management, and Low Perceived Harm

“…38 As previously noted, to achieve optimal reductions in morbidity and mortality, rapid genomic sequencing must be implemented within a comprehensive precision medicine delivery system. 38 Finally, NSIGHT2 examined clinician perceptions of some potential harms of rapid genomic sequencing 35 (parental perceptions of the benefits and harms of rapid genomic sequencing in the NSIGHT2 study are reported in the accompanying paper 36 ). When surveyed regarding their perceptions of increased stress or confusion among families or clinical staff as a result of genomic sequencing, clinicians reported this in only 3% of cases.…”

“…35 Parental perceptions of benefits and harms in the NSIGHT2 study are reported in the accompanying article. 36 Here we report clinician perceptions of benefits and harms of genomic sequencing in infants. Of 207 clinician responses, 84 (41%) disclosed that diagnostic genomic sequencing improved communication with families regarding infant outcomes, expectations, and prognosis.…”

“…6,35 Previously, we reported results from NSIGHT2 related to the analytic and diagnostic performance of singleton and trio rWES and rWGS. 6 The accompanying article 36 reports parental perceptions of benefits and harms. However, the primary hypothesis tested in NSIGHT2 was that rWGS has greater clinical utility for a subset of ill infants and their families than rWES.…”

Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG)

“…Of note, parents placed strong value on negative test results, emphasizing that diagnostic yield is not a good proxy for parental perceived utility. 76 Nondiagnostic results can still be useful to help exclude (or make less likely) genetic conditions that may have prognostic implications (e.g., increased risk of seizures, cancer, or vision loss as examples) or other clinical management (e.g., contraindication to anesthesia/surgery).…”

Utility of Genetic Testing from the Perspective of Parents/Caregivers: A Scoping Review

“…Of these, 105 were excluded based on lack of empirical results, or study designs that focused on hypothetical response to genetic testing, pre-test perceptions of genetic testing, and/or non-parent/caregiver reported outcomes. Thirty-three [ 15 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ] met all inclusion criteria Figure 1 . All full texts were reviewed for inclusion by two independent reviewers, with an inter-rater agreement of 83.4%.…”