Diagnostic and service impact of genomic testing technologies in a neonatal intensive care unit

Abstract

Aim: To investigate the diagnostic and service impact of chromosomal microarray and whole exome sequencing (WES) in a neonatal intensive care unit (NICU). Methods: This was a retrospective medical record review of NICU patients referred for genetics consultation at three time points over a 9-year period at a single centre to determine referral indications, genetic consultation outcomes and time to diagnosis. Results: The number of NICU patients referred for genetics consultation increased from 44 in 2007 to 95 in 2015. The proportion of NICU patients suspected of having a genetic condition following clinical geneticist assessment remained stable, averaging 5.3% of all admissions. The proportion of patients receiving a confirmed diagnosis rose from 21% in 2007 to 53% in 2015, with a shift from primarily chromosomal abnormalities to a broad range of monogenic disorders, increasingly diagnosed by WES as a first-tier test. The average age at diagnosis in 2015 was 19 days (range 12-38 days) for chromosomal abnormalities and 138 days (range 10-309 days) for monogenic conditions. Conclusions: The adoption of new genetic technologies at our centre has increased the proportion of patients receiving a confirmed genetic diagnosis. This study provides important benchmark data to measure further improvements as turn-around times for genomic testing decrease.

Use of medical exome sequencing for identification of underlying genetic defects in NICU: Experience in a cohort of 2303 neonates in China

“…Early data for the application of NGS technologies such as wholegenome or whole-exome sequencing (WGS or WES, respectively) have demonstrated a diagnostic rate of $13%-57% [4][5][6][7][8][9] with a short turnaround time (TAT) in NICU patients. The WES/WGS results also enabled precision medical intervention in a significant proportion of severely ill neonates, which correlated with decreased infant morbidity.…”

“…4,10 The cost-effectiveness of rapid, first-line WES/WGS in the NICU is reflected in shorter periods of hospitalization and significantly lower costs per diagnosis compared to traditional cascade testing. 8,9,11,12 Genetic diagnosis for NICU patients in developing countries currently faces several challenges, including shortages of well-trained clinical geneticists, limited NBS, and limited options for genetic testing of suspected conditions. In this study, we have developed a first-line test to identify the multiple types of genome-wide, disease-causing genetic alterations in a large cohort of 2303 NICU patients with minimal clinical presentation selection in China.…”

Perspectives of United States neonatologists on genetic testing practices

“…Our results suggest a need for increased clinical genetics involvement in NICU settings, where test availability has lagged behind current research, because karyotyping or CMA are unlikely to identify all infants with rare genetic disorders. 2,4,17,18 Because the diagnostic and clinical utility of ES/GS in this population is known be high, 1,5,6,10 further investigation on incorporation of these diagnostic techniques into the NICU setting seems warranted, particularly where clinical genetics teams are not available.…”

U.S. Genetic counselors’ perceptions of inpatient genetic counseling: A valuable model for medically complex patients

“…Recent studies show that GCs are already practicing in the inpatient care setting. For example, their role in the neonatal and pediatric critical care units is to facilitate pre-test genetic counseling and explain and interpret results for rapid exome or genome sequencing (Ayres et al, 2019;Clowes Candadai et al, 2019;Deuitch et al, 2019;Stark et al, 2018;Tan et al, 2019). In the absence of GCs, some non-genetics healthcare providers with limited training in genetics provide genetic services (Bensend et al, 2014;Brierley et al, 2010Brierley et al, , 2012.…”

“…Embedding a GC in inpatient care settings, where time is of the utmost importance, can add needed genetics expertise to a team that is already multidisciplinary in nature. While data is beginning to emerge on the use of inpatient genetic counseling (Ayres et al, 2019;Clowes Candadai et al, 2019;Deuitch et al, 2019;Magness et al 2021;Stark et al, 2018;Tan et al, 2019), it is unknown in a broad sense how this care is provided, in which genetic sub-specialties, or what the impact is on patients, the GCs themselves or other healthcare providers.…”