Table 1.
Studies of the diagnostic performance, change in management and outcome, and time to result (TAT) of URGS, RGS and RES in seriously ill children in intensive care units
| Ref. | Year | Country | Study Type | Test | Enrollment Criteria | Study size | Dx Rate | Δ Mx | Δ Outcome | TAT (days) |
|---|---|---|---|---|---|---|---|---|---|---|
| 7 | 2012 | USA | Cases | URGS | NICU infants; Susp. genetic dis. | 4 | 75% | n.d. | n.d. | 2 |
| 48 | 2015 | USA | Cohort | RGS | <4 months of age; Susp. actionable genetic dis. | 35 | 57% | 31% | 29% | 23 |
| 50 | 2017 | USA | Cohort | RES | <100 days old; Susp. genetic dis. | 63 | 51% | 37% | 19% | 13 |
| 51 | 2017 | Holland | Cohort | RGS | Infants; NICU, PICU; Susp. genetic dis. | 23 | 30% | 22% | 22% | 12 |
| 52 | 2018 | USA | RCT | RGS, SOC | <4 months of age; Susp. genetic dis. | 32 | 41% | 31% | n.d. | 13 |
| 53 | 2018 | USA | Cohort | RGS | Infants; Susp. genetic dis. | 42 | 43% | 31% | 26% | 23 |
| 54 | 2018 | Aust | Cohort | RES | Acutely ill children with susp. genetic dis. | 40 | 53% | 30% | 8% | 16 |
| 55 | 2018 | UK | Cohort | RGS | Children; PICU and Cardiovascular ICU | 24 | 42% | 13% | n.d. | 9 |
| 56 | 2019 | USA | Cohort | RGS | 4 months-18 years; PICU; Susp. genetic dis. | 38 | 48% | 39% | 8% | 14 |
| 57 | 2019 | UK | Cohort | RGS | Susp. genetic dis. | 195 | 21% | 13% | n.d. | 21 |
| 12 | 2019 | USA | Cases | URGS | Infants; ICU; Susp. genetic dis. | 7 | 43% | 43% | n.d. | 0.8 |
| 58 | 2020 | USA | Cohort | RES | <6 months old; ICU; hypotonia, seizures, metabolic, multiple congenital anomalies | 50 | 58% | 48% | n.d. | 5 |
| 59 | 2019 | Canada | Cohort | RES | NICU; infants; susp. genetic dis. | 25 | 72% | 60% | n.d. | 7.2 |
| 60 | 2019 | Taiwan | Cohort | RES | PICU and other; children; susp. genetic dis. | 40 | 53% | 43% | n.d. | 6 |
| 61 | 2020 | China | Cohort | RES | NICU & PICU; complex | 130 | 48% | 23% | n.d. | 3.8 |
| 62 | 2020 | USA | Cohort | RES | Critical illness; medical genetics selected | 46 | 43% | 52% | n.d. | 9 |
| 63 | 2020 | USA | Cohort | RES | PICU; < 6 years; new metabolic/neurologic dis. | 10 | 50% | 30% | n.d. | 9.8 |
| 64 | 2020 | USA | Cohort | RES | ICU; infants | 368 | 27% | n.d. | n.d. | n.d. |
| 65 | 2020 | China | Cohort | RES | Infants; ICU and inpatient | 102 | 31% | 27% | n.d. | 11 |
| 66 | 2020 | USA | Cohort | RES | Various | 41 | 32% | n.d. | n.d. | 7 |
| 67 | 2020 | Aust | Implem | URES | <18 year; NICU and PICU | 108 | 51% | 44% | n.d. | 3 |
| 68 | 2020 | Poland | Cohort | RES | Infants; NICU, PICU; susp. genetic dis. | 18 | 83% | 61% | n.d. | 14 |
| 69 | 2020 | China | Cohort | URES | Infants; NICU, PICU; susp. genetic dis. | 33 | 70% | 30% | 30% | 1 |
| 32,70,71,169 | 2019, 2020,2023 | USA | RCT | RGS | Infants; dis. of unknown etiology; within 96 h of admission | 94 | 19% | 24% | 10% | 11 |
| 32,70,71,169 | 2019, 2020,2023 | USA | RCT | RES | Infants; dis. of unknown etiology; within 96 h of admission | 95 | 20% | 20% | 18% | 11 |
| 32,70,71,169 | 2019, 2020,2023 | USA | RCT | URGS | Infants; dis. of unknown etiology; within 96 h of admission | 24 | 46% | 63% | 25% | 4.6 |
| 73 | 2021 | USA | Implem | URGS | Medicaid infants; unknown etiology; within 1 week of admission | 184 | 40% | 32% | n.d. | 3 |
| 74 | 2021 | China | Cohort | RES | Critically ill; 6 days - 15 years; susp. genetic dis. | 40 | 43% | 31% | n.d. | 5 |
| 75 | 2021 | Germany | Cohort | RES | NICU, PICU, infants; sup. genetic dis. | 61 | 43% | 11% | n.d. | 60 |
| 76 | 2021 | USA | RTDCT | RGS, WGS | <120 days old; ICU; susp. genetic dis. | 354 | 31% | 25% | n.d. | 15 |
| 38 | 2021 | China | Crossover | RES | Critically ill infants with susp. genetic heterogeneous dis. | 202 | 20% | n.d. | n.d. | 20 |
| 38 | 2021 | China | Crossover | RGS | Critically ill infants with susp. genetic heterogeneous disorders | 202 | 37% | 7% | n.d. | 7 |
| 77 | 2022 | France | Cohort | RGS | Critically ill infants with susp. genetic heterogeneous disorders | 37 | 57% | n.d. | n.d. | 43 |
| 78 | 2022 | UAE | Cohort | URGS | Infants in ICU with complex multisystem dis. | 5 | 60% | 20% | 20% | 1.5 |
| 79 | 2022 | USA | Implem | RES | NICU infants with susp. genetic dis. | 80 | 28% | 18% | n.d. | 13 |
| 80 | 2022 | USA | Cohort | RGS | Children in ICU with dis. of unknown etiology | 65 | 40% | n.d. | n.d. | 12 |
| 81 | 2022 | France | Cohort | RES | Infants in ICU with susp. genetic dis. | 15 | 40% | 53% | n.d. | 16 |
| 82 | 2023 | USA | Implem | RGS | NICU, PICU with dis. of unknown etiology | 89 | 39% | 27% | n.d. | n.d. |
| 72,83 | 2021, 2023 | USA | Crossover | RGS, panel | NICU with dis. of unknown etiology | 400 | 49% | 19% | n.d. | 6 |
| 84 | 2023 | USA | Cohort | RGS | Acutely ill inpatient infants; susp. genetic dis. | 188 | 35% | 32% | n.d. | 6 |
| 85 | 2023 | Belgium | Cohort | URGS | NICU, PICU, neurologic inpatients with susp. genetic dis. | 21 | 57% | 57% | n.d. | 1 |
| Weighted Average | 3609 | 37% | 26% | 18% | n.d. |
Study size refers to the number of probands. Studies are listed from oldest to newest.
Ref. reference, Δ Change, Dx diagnosis, Mx management, TAT turnaround time, n.d. not done, d days, RCT Randomized Controlled Trial, SOC standard of care, Implem implementation science design, RTDCT randomized time delayed clinical trial, Crossover Patients received both interventions, Dis. disease, Susp. suspected, Aust Australia, UAE United Arab Emirates.