Randomized Controlled Trial

. 2021 Jul;23(7):1372-1375.

doi: 10.1038/s41436-021-01146-5. Epub 2021 Mar 26.

Discordant results between conventional newborn screening and genomic sequencing in the BabySeq Project

Monica H Wojcik^{1

2

3}, Tian Zhang⁴, Ozge Ceyhan-Birsoy⁵, Casie A Genetti⁴, Matthew S Lebo^{6

7}, Timothy W Yu⁴, Richard B Parad⁸, Ingrid A Holm⁴, Heidi L Rehm^{9

6

7}, Alan H Beggs⁴, Robert C Green^{9

10

11}, Pankaj B Agrawal^{12

13

14}; BabySeq Project Team

Collaborators, Affiliations

Collaborators

Affiliations

¹ Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA, USA. monica.wojcik@childrens.harvard.edu.
² Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. monica.wojcik@childrens.harvard.edu.
³ Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. monica.wojcik@childrens.harvard.edu.
⁴ Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
⁵ Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁶ Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Cambridge, MA, USA.
⁷ Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Department of Pediatric Newborn Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁹ Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰ Department of Medicine (Genetics), Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹¹ Ariadne Labs, Boston, MA, USA.
¹² Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA, USA. pagrawal@enders.tch.harvard.edu.
¹³ Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. pagrawal@enders.tch.harvard.edu.
¹⁴ Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. pagrawal@enders.tch.harvard.edu.

PMID: 33772220
PMCID: PMC8263473
DOI: 10.1038/s41436-021-01146-5

Randomized Controlled Trial

Discordant results between conventional newborn screening and genomic sequencing in the BabySeq Project

Monica H Wojcik et al. Genet Med. 2021 Jul.

. 2021 Jul;23(7):1372-1375.

doi: 10.1038/s41436-021-01146-5. Epub 2021 Mar 26.

Authors

Collaborators

Affiliations

¹ Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA, USA. monica.wojcik@childrens.harvard.edu.
² Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. monica.wojcik@childrens.harvard.edu.
³ Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. monica.wojcik@childrens.harvard.edu.
⁴ Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
⁵ Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁶ Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Cambridge, MA, USA.
⁷ Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Department of Pediatric Newborn Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁹ Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰ Department of Medicine (Genetics), Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹¹ Ariadne Labs, Boston, MA, USA.
¹² Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA, USA. pagrawal@enders.tch.harvard.edu.
¹³ Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. pagrawal@enders.tch.harvard.edu.
¹⁴ Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. pagrawal@enders.tch.harvard.edu.

PMID: 33772220
PMCID: PMC8263473
DOI: 10.1038/s41436-021-01146-5

Abstract

Purpose: Newborn screening (NBS) is performed to identify neonates at risk for actionable, severe, early-onset disorders, many of which are genetic. The BabySeq Project randomized neonates to receive conventional NBS or NBS plus exome sequencing (ES) capable of detecting sequence variants that may also diagnose monogenic disease or indicate genetic disease risk. We therefore evaluated how ES and conventional NBS results differ in this population.

Methods: We compared results of NBS (including hearing screens) and ES for 159 infants in the BabySeq Project. Infants were considered "NBS positive" if any abnormal result was found indicating disease risk and "ES positive" if ES identified a monogenic disease risk or a genetic diagnosis.

Results: Most infants (132/159, 84%) were NBS and ES negative. Only one infant was positive for the same disorder by both modalities. Nine infants were NBS positive/ES negative, though seven of these were subsequently determined to be false positives. Fifteen infants were ES positive/NBS negative, all of which represented risk of genetic conditions that are not included in NBS programs. No genetic explanation was identified for eight infants referred on the hearing screen.

Conclusion: These differences highlight the complementarity of information that may be gleaned from NBS and ES in the newborn period.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Statement: Dr. Green has received compensation for advising the following companies: AIA, Grail, Humanity, Kneed Media, Plumcare, UnitedHealth, Verily, VibrentHealth, Wamberg; and is co-founder of Genome Medical, Inc. Dr. Agrawal is on the Clinical Advisory Board of Illumina Inc. and GeneDx. Dr. Rehm is a compensated scientific advisory board member of Genome Medical. The other authors have no relevant conflicts of interest to disclose.

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References

1. Kemper AR, Boyle CA, Aceves J, et al. Long-term follow-up after diagnosis resulting from newborn screening: statement of the US Secretary of Health and Human Services’ Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children. Genet Med. 2008;10:259–261. - PubMed
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Discordant results between conventional newborn screening and genomic sequencing in the BabySeq Project

Collaborators

Affiliations

Discordant results between conventional newborn screening and genomic sequencing in the BabySeq Project

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical