Evidence map›Paper›PMID 39642868›Full record

ArticleAmerican journal of human genetics2024

Genome-based newborn screening for severe childhood genetic diseases has high positive predictive value and sensitivity in a NICU pilot trial.

Stephen F Kingsmore, Meredith Wright, Lauren Olsen, Brandan Schultz, Liana Protopsaltis, Dan Averbuj, Eric Blincow, Jeanne Carroll, Sara Caylor, Thomas Defay and 25 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Progress and Prospects of Newborn Screening in China.International journal of neonatal screening · 2026
    Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Revisiting the Genetics of Hypophosphatasia.Journal of inherited metabolic disease · 2025
    Review
  7. Analytical Validation of a Genomic Newborn Screening Workflow.International journal of neonatal screening · 2025
    Article
  8. Article
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

35 authors.

Stephen F KingsmoreRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA. Electronic address: skingsmore@rchsd.org.
Meredith WrightRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA.
Lauren OlsenRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA.
Brandan SchultzRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA.
Liana ProtopsaltisRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA.
Dan AverbujRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA.
Eric BlincowRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA.
Jeanne CarrollRady Children's Hospital, San Diego, CA 92123, USA; Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA.
Sara CaylorRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA.
Thomas DefayAlexion, Astra Zeneca Rare Disease, Boston, MA 02210, USA.
Katarzyna EllsworthRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA.
Annette FeigenbaumRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA; Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA.
Mia GoverRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
Lucia GuidugliRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA.
Christian HansenRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA.
Lucita Van Der KraanRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA.
Chris M KunardIllumina, Inc., San Diego, CA 92122, USA.
Hugh KwonRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA.
Lakshminarasimha MadhavraoRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA.
Jeremy LeipzigTileDB, Inc., Cambridge, MA 02142, USA.
Yupu LiangAlexion, Astra Zeneca Rare Disease, Boston, MA 02210, USA.
Rebecca MardachRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA; Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA.
William R MowreyAlexion, Astra Zeneca Rare Disease, Boston, MA 02210, USA.
Hung NguyenRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA.
Anna-Kaisa NiemiRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA; Department of Pediatrics, University of California, San Diego, San Diego, CA 92093, USA.
Danny OhRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA.
Muhammed SaadRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA.
Gunter ScharerRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
Jennifer SchleitRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
Shyamal S MehtaliaIllumina, Inc., San Diego, CA 92122, USA.
Erica SanfordRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
Laurie D SmithRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
Mary J WillisRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
Kristen WigbyRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA.
Rebecca ReimersRady Children's Institute for Genomic Medicine, San Diego, CA 92123, USA; Rady Children's Hospital, San Diego, CA 92123, USA; Scripps Research Translational Institute, La Jolla, CA 92037, USA.

Funding

Scripps Clinical and Translational Science HubUM1TR004407 · NCATS · SCRIPPS RESEARCH INSTITUTE, THE · PI Eric Jeffrey Topol · 2023 to 2026
$24.2M
Genomic and Environmental Determinants of Infant Deaths in San Diego County in 2015-2022R01HD101540 · NICHD · RADY PEDIATRIC GENOMICS & SYSTEMS MEDICINE INSTITUTE · PI CHAMBERS, CHRISTINA, KINGSMORE, STEPHEN FRANCIS · 2020 to 2024
$3.5M
NCATS NIH HHS UM1 TR004407NICHD NIH HHS R01 HD101540
6 · The paper itself

Abstract

Large prospective clinical trials are underway or planned that examine the clinical utility and cost effectiveness of genome-based newborn screening (gNBS). One gNBS platform, BeginNGS, currently screens 53,575 variants for 412 severe childhood genetic diseases with 1,603 efficacious therapies. Retrospective evaluation of BeginNGS in 618,290 subjects suggests adequate sensitivity and positive predictive value (PPV) to proceed to prospective studies. To inform pivotal clinical trial design, we undertook a pilot clinical trial. We enrolled 120 infants in a regional neonatal intensive care unit (NICU) who were not under consideration for rapid diagnostic genome sequencing (RDGS). Each enrollee received BeginNGS and two index tests (California state NBS and RDGS). California NBS identified 4 of 4 true positive (TP) findings (TP rate 3.6%, sensitivity 100%) and 11 false positive (FP) findings (PPV 27%). RDGS identified 41 diagnostic findings in 36 neonates (diagnostic rate 30%). BeginNGS identified 5 of 6 on-target TP disorders (TP rate 4.2%, 95% confidence interval 1%-8%, sensitivity 83%) and no FPs (PPV 100%). Changes in management were anticipated following the return of 27 RDGS results in 25 enrollees (clinical utility [CU] 21%), 3 of 4 NBS TPs (CU 2.7%), and all BeginNGS TPs (CU 4.2%). The incidence of actionable genetic diseases in NICU infants not being considered for RDGS suggests (1) performance of RDGS in ∼20% of admissions misses many genetic diagnoses, (2) NICU enrollment in gNBS trials will greatly increase power to test endpoints, and (3) NICUs may be attractive for early implementation of consented BeginNGS screening.

Indexed as

Genetic Diseases, InbornIntensive Care Units, NeonatalNeonatal ScreeningFemaleGenetic TestingGenome, HumanHumansInfant, NewbornMalePilot ProjectsPredictive Value of TestsSensitivity and Specificityclinical trialclinical utilitygenome sequencinginfantneonatal intensive care unitnewborn screeningpositive predictive valuerapid diagnostic genome sequencingsensitivitysevere childhood genetic disease

Identifiers

PMID39642868
PMCPMC11639094

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