Universal Newborn Screening Using Genome Sequencing: Early Experience from the GUARDIAN Study

Overview

Journal Pediatr Res

Specialties Biology
Pediatrics

Date 2024 Oct 25

PMID 39455856

Authors

Alban Ziegler

Wendy K Chung

Affiliations

Soon will be listed here.

Abstract

For more than 20 years there has been speculation about a future in which newborns are routinely screened at birth for genetic disorders using genome sequencing, but prospective large-scale studies assessing this vision have only recently begun. Genome sequencing may provide a means of expanding the scope of conditions included in newborn screening programs and improving the positive predictive value of traditional newborn screening. However, the use of genome sequencing for newborn screening has also raised concerns including acceptability, equity, and scalability. By reviewing the initial results of the GUARDIAN study and contrasting them with other pilot studies investigating the use of genome sequencing for large-scale newborn screening, we highlight how the lessons learned from these studies are shaping the future for the implementation of truly universal and equitable newborn genomic screening.

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References

Guthrie R, Susi A . A SIMPLE PHENYLALANINE METHOD FOR DETECTING PHENYLKETONURIA IN LARGE POPULATIONS OF NEWBORN INFANTS. Pediatrics. 1963; 32:338-43. View

Adhikari A, Gallagher R, Wang Y, Currier R, Amatuni G, Bassaganyas L . The role of exome sequencing in newborn screening for inborn errors of metabolism. Nat Med. 2020; 26(9):1392-1397. PMC: 8800147. DOI: 10.1038/s41591-020-0966-5. View

Bick D, Bick S, Dimmock D, Fowler T, Caulfield M, Scott R . An online compendium of treatable genetic disorders. Am J Med Genet C Semin Med Genet. 2020; 187(1):48-54. PMC: 7986124. DOI: 10.1002/ajmg.c.31874. View

Stark Z, Scott R . Genomic newborn screening for rare diseases. Nat Rev Genet. 2023; 24(11):755-766. DOI: 10.1038/s41576-023-00621-w. View

Downie L, Halliday J, Lewis S, Amor D . Principles of Genomic Newborn Screening Programs: A Systematic Review. JAMA Netw Open. 2021; 4(7):e2114336. PMC: 8293022. DOI: 10.1001/jamanetworkopen.2021.14336. View

Bick D, Ahmed A, Deen D, Ferlini A, Garnier N, Kasperaviciute D . Newborn Screening by Genomic Sequencing: Opportunities and Challenges. Int J Neonatal Screen. 2022; 8(3). PMC: 9326745. DOI: 10.3390/ijns8030040. View

Mochel F, Gras D, Luton M, Nizou M, Giovannini D, Delattre C . Prospective Multicenter Validation of a Simple Blood Test for the Diagnosis of Glut1 Deficiency Syndrome. Neurology. 2023; 100(23):e2360-e2373. PMC: 10256121. DOI: 10.1212/WNL.0000000000207296. View

Speiser P, Chawla R, Chen M, Diaz-Thomas A, Finlayson C, Rutter M . Newborn Screening Protocols and Positive Predictive Value for Congenital Adrenal Hyperplasia Vary across the United States. Int J Neonatal Screen. 2020; 6(2). PMC: 7422998. DOI: 10.3390/ijns6020037. View

van den Heuvel L, van der Pal S, Verschoof-Puite R, Klapwijk J, Elsinghorst E, Dekkers E . Psychosocial Impact of a True-Positive, False-Positive, or Inconclusive Newborn Bloodspot Screening Result: A Questionnaire Study among Parents. Int J Neonatal Screen. 2024; 10(1). PMC: 10971090. DOI: 10.3390/ijns10010018. View

10.

Cohen A, Berrios C, Zion T, Barrett C, Moore R, Boillat E . Genomic Answers for Kids: Toward more equitable access to genomic testing for rare diseases in rural populations. Am J Hum Genet. 2024; 111(5):825-832. PMC: 11080604. DOI: 10.1016/j.ajhg.2024.03.016. View

11.

Serrano J, OLeary M, VanNoy G, Mangilog B, Holm I, Fraiman Y . Advancing Understanding of Inequities in Rare Disease Genomics. Clin Ther. 2023; 45(8):745-753. PMC: 10527807. DOI: 10.1016/j.clinthera.2023.06.010. View

12.

Fatumo S, Chikowore T, Choudhury A, Ayub M, Martin A, Kuchenbaecker K . A roadmap to increase diversity in genomic studies. Nat Med. 2022; 28(2):243-250. PMC: 7614889. DOI: 10.1038/s41591-021-01672-4. View

13.

Mutze U, Mengler K, Boy N, Gleich F, Opladen T, Garbade S . How longitudinal observational studies can guide screening strategy for rare diseases. J Inherit Metab Dis. 2022; 45(5):889-901. DOI: 10.1002/jimd.12508. View

14.

Atkins A, Cogley M, Baker M . Newborn Screening for Severe Combined Immunodeficiency: Do Preterm Infants Require Special Consideration?. Int J Neonatal Screen. 2021; 7(3). PMC: 8293075. DOI: 10.3390/ijns7030040. View

15.

Clark R, Kelleher A, Chace D, Spitzer A . Gestational age and age at sampling influence metabolic profiles in premature infants. Pediatrics. 2014; 134(1):e37-46. DOI: 10.1542/peds.2014-0329. View

16.

Milko L, ODaniel J, DeCristo D, Crowley S, Foreman A, Wallace K . An Age-Based Framework for Evaluating Genome-Scale Sequencing Results in Newborn Screening. J Pediatr. 2019; 209:68-76. PMC: 6535354. DOI: 10.1016/j.jpeds.2018.12.027. View

17.

Holm I, Agrawal P, Ceyhan-Birsoy O, Christensen K, Fayer S, Frankel L . The BabySeq project: implementing genomic sequencing in newborns. BMC Pediatr. 2018; 18(1):225. PMC: 6038274. DOI: 10.1186/s12887-018-1200-1. View

18.

Balciuniene J, Liu R, Bean L, Guo F, Nallamilli B, Guruju N . At-Risk Genomic Findings for Pediatric-Onset Disorders From Genome Sequencing vs Medically Actionable Gene Panel in Proactive Screening of Newborns and Children. JAMA Netw Open. 2023; 6(7):e2326445. PMC: 10391308. DOI: 10.1001/jamanetworkopen.2023.26445. View

19.

Lombardo S, Seedat F, Elliman D, Marshall J . Policy-making and implementation for newborn bloodspot screening in Europe: a comparison between EURORDIS principles and UK practice. Lancet Reg Health Eur. 2023; 33:100714. PMC: 10636270. DOI: 10.1016/j.lanepe.2023.100714. View

20.

Loeber J, Platis D, Zetterstrom R, Almashanu S, Boemer F, Bonham J . Neonatal Screening in Europe Revisited: An ISNS Perspective on the Current State and Developments Since 2010. Int J Neonatal Screen. 2021; 7(1). PMC: 8006225. DOI: 10.3390/ijns7010015. View