Palliative Care Outcomes for Critically ill Children After Rapid Whole Genome Sequencing

Abstract

Objectives

Clinical utility of rapid whole genome sequencing (rWGS) has been reported in 30–70% of pediatric ICU patients who receive a molecular diagnosis. Rapid molecular diagnostic techniques have been increasingly integrated into critical care, yet the influence of genetic test results on palliative care related decision making is largely unknown. This study evaluates palliative care related outcomes after rWGS.

Design

Retrospective chart review

Setting

Tertiary children's hospital

Patients

Acutely ill children $\leq$ 18 years of age who received rWGS due to suspected genetic disease between July 2016 and November 2019

Interventions

rWGS with associated precision medicine

Measurements and Main Results

536 patients underwent rWGS, of whom 152 (28.4%) received a molecular diagnosis. Diagnostic rWGS was associated with more code status modifications, an increase in palliative care inpatient consultations, and greater enrollment in home-based palliative services. A comparison of diagnostic and nondiagnostic rWGS groups where palliative decisions were made prior to reporting of genomic testing results did not identify differences between the groups. In the subset of patients who had palliative care interventions (n = 57, 53% with diagnostic rWGS), time to palliative care consultation and time to compassionate extubation were shorter for patients with rWGS-based diagnoses (Kaplan-Meier method, P = .008; P = .015). Significantly more patients in this subgroup with diagnostic rWGS received home-based palliative care (Chi-squared, P = .025, 95% CI [−0.47, −0.05]). Univariate Poisson regression indicated that diagnostic rWGS is associated with significantly fewer emergency visits, PICU admissions, and unplanned intubations.

Conclusions

Diagnostic rWGS correlates with more rapid engagement of pediatric palliative care services, higher enrollment rates in home-based palliative care, and shorter time to compassionate extubation. Further studies are needed with larger cohort sizes and validated pediatric palliative care outcome measurement tools to accurately determine if this change in care is driven by the underlying condition or knowledge of a molecular diagnosis.

Keywords

rapid whole genome sequencing pediatric critical care pediatric palliative care

Get full access to this article

View all access options for this article.

References

Stevenson

Carey

. Contribution of malformations and genetic disorders to mortality in a children’s hospital. Am J Med Genet A. 2004;126A(4):393‐397. doi:10.1002/ajmg.a.20409

Wojcik

Schwartz

Yamin

, et al. Genetic disorders and mortality in infancy and early childhood: Delayed diagnoses and missed opportunities. Genet Med. 2018;20(11):1396‐1404. doi:10.1038/gim.2018.17

Mathews

. Trends in infant mortality in the United States, 2005–2014. NCHS Data Brief. 2017(279):8.

Weiner

Sharma

Lantos

Kilbride

. How infants die in the neonatal intensive care unit: Trends from 1999 through 2008. Arch Pediatr Adolesc Med. 2011;165(7):630‐634. doi:10.1001/archpediatrics.2011.102

Kingsmore

Henderson

Owen

, et al. Measurement of genetic diseases as a cause of mortality in infants receiving whole genome sequencing. NPJ Genom Med. 2020;5:49. doi:10.1038/s41525-020-00155-8

Owen

Wright

Batalov

, et al. Reclassification of the etiology of infant mortality with whole-genome sequencing. JAMA Netw Open. 2023;6(2):e2254069. doi:10.1001/jamanetworkopen.2022.54069

Farnaes

Hildreth

Sweeney

, et al. Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization. npj Genomic Med. 2018;3(1):1‐8. doi:10.1038/s41525-018-0049-4

Sanford

Clark

Farnaes

, et al. Rapid whole genome sequencing has clinical utility in children in the PICU*. Pediatr Crit Care Med. 2019;20(11):1007‐1020. doi:10.1097/PCC.0000000000002056

Willig

Petrikin

Smith

, et al. Whole-genome sequencing for identification of Mendelian disorders in critically ill infants: A retrospective analysis of diagnostic and clinical findings. Lancet Respir Med. 2015;3(5):377‐387. doi:10.1016/S2213-2600(15)00139-3

10.

Mestek-Boukhibar

Jones

, et al. Rapid paediatric sequencing (RaPS): Comprehensive real-life workflow for rapid diagnosis of critically ill children. J Med Genet. 2018;55(11):721‐728. doi:10.1136/jmedgenet-2018-105396

11.

Stavropoulos

Merico

Jobling

, et al. Whole genome sequencing expands diagnostic utility and improves clinical management in pediatric medicine. NPJ Genom Med. 2016:1. doi:10.1038/npjgenmed.2015.12

12.

Soden

Saunders

Willig

, et al. Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders. Sci Transl Med. 2014;6(265):265ra168. doi:10.1126/scitranslmed.3010076

13.

Petrikin

Cakici

Clark

, et al. The NSIGHT1-randomized controlled trial: Rapid whole-genome sequencing for accelerated etiologic diagnosis in critically ill infants. NPJ Genom Med. 2018;3:6. doi:10.1038/s41525-018-0045-8

14.

Maron

Kingsmore

Gelb

, et al. Rapid whole-genomic sequencing and a targeted neonatal gene panel in infants with a suspected genetic disorder. JAMA. 2023;330(2):161. doi:10.1001/jama.2023.9350

15.

Palliative Care Definition | What is palliative care. Accessed March 30, 2021. https://www.capc.org/about/palliative-care/

16.

National Consensus Project for Quality Palliative Care (NCP) | NCHPC | National coalition for hospice and palliative care. Accessed December 22, 2020. https://www.nationalcoalitionhpc.org/ncp/

17.

Feudtner

Kang

Hexem

, et al. Pediatric palliative care patients: A prospective multicenter cohort study. Pediatrics. 2011;127(6):1094‐1101. doi:10.1542/peds.2010-3225

18.

Ayres

Gallacher

Stark

Brett

. Genetic counseling in pediatric acute care: Reflections on ultra-rapid genomic diagnoses in neonates. J Genet Couns. 2019;28(2):273‐282. doi:10.1002/jgc4.1086

19.

Richards

Aziz

Bale

, et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med. 2015;17(5):405‐423. doi:10.1038/gim.2015.30

20.

Rafiq

Ullah

Naglak

Schneider

. Characteristics and outcomes of patients with partial do not resuscitate orders in a large community hospital. Cureus. 2019;11(11). doi:10.7759/cureus.6048

21.

De Clercq

Rost

Rakic

, et al. The conceptual understanding of pediatric palliative care: A Swiss healthcare perspective. BMC Palliat Care. 2019;18:55. doi:10.1186/s12904-019-0438-1

22.

Rost

Clercq

Wangmo

Elger

. The need for a shared understanding: Domains of care and composition of team in pediatric palliative care guidelines.

23.

OMIM Entry Statistics. Accessed June 24, 2021. https://www.omim.org/statistics/entry

24.

Petrikin

Willig

Smith

Kingsmore

. Rapid whole genome sequencing and precision neonatology. Semin Perinatol. 2015;39(8):623‐631. doi:10.1053/j.semperi.2015.09.009

25.

Hill

Hammond

Lewis

Mellis

Clement

Chitty

. Delivering genome sequencing for rapid genetic diagnosis in critically ill children: Parent and professional views, experiences and challenges. Eur J Hum Genet. 2020;28(11):1529‐1540. doi:10.1038/s41431-020-0667-z

26.

Vern-Gross

Lam

Graff

, et al. Patterns of End-of-life care in children with advanced solid tumor malignancies enrolled on a palliative care service. J Pain Symptom Manage. 2015;50(3):305‐312. doi:10.1016/j.jpainsymman.2015.03.008

27.

Lustbader

Mudra

Romano

, et al. The impact of a home-based palliative care program in an accountable care organization. J Palliat Med. 2017;20(1):23‐28. doi:10.1089/jpm.2016.0265

28.

Gomes

Calanzani

Curiale

McCrone

Higginson

. Effectiveness and cost-effectiveness of home palliative care services for adults with advanced illness and their caregivers. Cochrane Database Syst Rev. 2013;(6):CD007760. doi:10.1002/14651858.CD007760.pub2

29.

Ernecoff

Wessell

Bennett

Hanson

. Measuring goal-concordant care in palliative care research. J Pain Symptom Manage. 2021;62(3):e305‐e314. doi:10.1016/j.jpainsymman.2021.02.030

30.

The NICUSeq Study Group. Effect of whole-genome sequencing on the clinical management of acutely ill infants with suspected genetic disease: A randomized clinical trial. JAMA Pediatr. 2021;175(12):1218‐1226. doi:10.1001/jamapediatrics.2021.3496

31.

Gonzaludo

Belmont

Gainullin

Taft

. Estimating the burden and economic impact of pediatric genetic disease. Genet Med. 2019;21(8):1781‐1789. doi:10.1038/s41436-018-0398-5

32.

Gjorgioski

Halliday

Riley

Amor

Delatycki

Bankier

. Genetics and pediatric hospital admissions, 1985 to 2017. Genet Med. 2020;22(11):1777‐1785. doi:10.1038/s41436-020-0871-9

33.

Burns

Sellers

Meyer

Lewis-Newby

Truog

. Epidemiology of death in the pediatric intensive care unit at five U.S. Teaching Hospitals. Crit Care Med. 2014;42(9):2101‐2108. doi:10.1097/CCM.0000000000000498

34.

Saunders

Miller

Soden

, et al. Rapid whole-genome sequencing for genetic disease diagnosis in neonatal intensive care units. Sci Transl Med. 2012;4(154):154ra135. doi:10.1126/scitranslmed.3004041

35.

Chad

Anderson

Cagliero

Hayeems

Szuto

. Rapid genetic testing in pediatric and neonatal critical care: A scoping review of emerging ethical issues. Hosp Pediatr. 2022;12(10):e347‐e359. doi:10.1542/hpeds.2022-006654

36.

Stark

Ellard

. Rapid genomic testing for critically ill children: Time to become standard of care? Eur J Hum Genet. 2022;30(2):142‐149. doi:10.1038/s41431-021-00990-y

37.

Downing

Namisango

Harding

. Outcome measurement in paediatric palliative care: Lessons from the past and future developments. Ann Palliat Med. 2018;7(0):S151‐S15S163.

38.

Grosse

Farnaes

. Genomic sequencing in acutely ill infants: What will it take to demonstrate clinical value? Genet Med. 2019;21(2):269‐271. doi:10.1038/s41436-018-0124-3

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.05 MB