Newborn Screening in the Era of Precision Medicine

  • Lan Yang
  • Jiajia Chen
  • Bairong ShenEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1005)


As newborn screening success stories gained general confirmation during the past 50 years, scientists quickly discovered diagnostic tests for a host of genetic disorders that could be treated at birth. Outstanding progress in sequencing technologies over the last two decades has made it possible to comprehensively profile newborn screening (NBS) and identify clinically relevant genomic alterations. With the rapid developments in whole-genome sequencing (WGS) and whole-exome sequencing (WES) recently, we can detect newborns at the genomic level and be able to direct the appropriate diagnosis to the different individuals at the appropriate time, which is also encompassed in the concept of precision medicine. Besides, we can develop novel interventions directed at the molecular characteristics of genetic diseases in newborns. The implementation of genomics in NBS programs would provide an effective premise for the identification of the majority of genetic aberrations and primarily help in accurate guidance in treatment and better prediction. However, there are some debate correlated with the widespread application of genome sequencing in NBS due to some major concerns such as clinical analysis, result interpretation, storage of sequencing data, and communication of clinically relevant mutations to pediatricians and parents, along with the ethical, legal, and social implications (so-called ELSI). This review is focused on these critical issues and concerns about the expanding role of genomics in NBS for precision medicine. If WGS or WES is to be incorporated into NBS practice, considerations about these challenges should be carefully regarded and tackled properly to adapt the requirement of genome sequencing in the era of precision medicine.


Newborn screening Precision medicine Whole-genome sequencing Whole-exome sequencing Genomics 



This study was supported by the National Natural Science Foundation of China (NSFC) (grant nos. 31670851, 31470821, and 91530320) and National Key R&D Programs of China (2016YFC1306605).


  1. 1.
    National newborn screening report. National Newborn Screening and Genetics Resource Center. 2013. http://genes-rus.uthscsa.edn/resources/newborn/00/ch2_complete.pdf
  2. 2.
    Recommended Uniform Screening Panel of the Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children. Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children. 2012.
  3. 3.
    Exe N, et al. Genetic testing stories. Washington, DC: Genetic Alliance; 2006.Google Scholar
  4. 4.
    Wright C. Next steps in the sequence: the implications of whole genome sequencing for health in the UK. Cambridge: PHG Foundation; 2011.Google Scholar
  5. 5.
    Scaria V. Personal genomes to precision medicine. Mol Cytogenet. 2014;7(Suppl 1 Proceedings of the International Conference on Human):I28.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Goldenberg AJ, Sharp RR. The ethical hazards and programmatic challenges of genomic newborn screening. JAMA. 2012;307(5):461–2.CrossRefPubMedGoogle Scholar
  7. 7.
    Knoppers BM, et al. Whole-genome sequencing in newborn screening programs. Sci Transl Med. 2014;6(229):229cm2.CrossRefPubMedGoogle Scholar
  8. 8.
    Ulm E, et al. Genetics professionals’ opinions of whole-genome sequencing in the newborn period. J Genet Couns. 2015;24(3):452–63.CrossRefPubMedGoogle Scholar
  9. 9.
    Millington DS, et al. Digital microfluidics: a future technology in the newborn screening laboratory? Semin Perinatol. 2010;34(2):163–9.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Tarini BA, Goldenberg AJ. Ethical issues with newborn screening in the genomics era. Annu Rev Genomics Hum Genet. 2012;13:381–93.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Evans JP, et al. We screen newborns, don’t we?: realizing the promise of public health genomics. Genet Med. 2013;15(5):332–4.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Calonge N, et al. Committee report: method for evaluating conditions nominated for population-based screening of newborns and children. Genet Med. 2010;12(3):153–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Loeber JG, et al. Newborn screening programmes in Europe; arguments and efforts regarding harmonization. Part 1. From blood spot to screening result. J Inherit Metab Dis. 2012;35(4):603–11.CrossRefPubMedGoogle Scholar
  14. 14.
    Moyer VA, et al. Expanding newborn screening: process, policy, and priorities. Hast Cent Rep. 2008;38(3):32–9.CrossRefGoogle Scholar
  15. 15.
    Ombrone D, et al. Expanded newborn screening by mass spectrometry: new tests, future perspectives. Mass Spectrom Rev, vol. 35; 2015. p. 71–84.Google Scholar
  16. 16.
    Wilson K, Kennedy SJ, Potter B, Geraghty MT, Chakraborty P. Developing a national newborn screening strategy for Canada. Health Law Rev. 2010;18:31–19.Google Scholar
  17. 17.
    Kapoor S, Gupta N, Kabra M. National newborn screening program still a hype or a hope now? Indian Pediatr. 2013;50(7):639–43.CrossRefPubMedGoogle Scholar
  18. 18.
    US Department of Health and Human Services. Discretionary Advisory Committee on Heritable Disorders in Newborns and Children. Recommended Uniform Screening Panel. 2013.
  19. 19.
    Grosse SD, et al. From public health emergency to public health service: the implications of evolving criteria for newborn screening panels. Pediatrics. 2006;117(3):923–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Serving the family from birth to the medical home. Newborn screening: a blueprint for the future – a call for a national agenda on state newborn screening programs. Pediatrics. 2000;106(2 Pt 2):389–422.Google Scholar
  21. 21.
    Howard HC, et al. Whole-genome sequencing in newborn screening? A statement on the continued importance of targeted approaches in newborn screening programmes. Eur J Hum Genet. 2015;23:1593–600.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Wade CH, Tarini BA, Wilfond BS. Growing up in the genomic era: implications of whole-genome sequencing for children, families, and pediatric practice. Annu Rev Genomics Hum Genet. 2013;14:535–55.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    SNS General guidelines for neonatal screening. International Society for Neonatal Screening. 2013.
  24. 24.
    Castellani C, Massie J. Newborn screening and carrier screening for cystic fibrosis: alternative or complementary? Eur Respir J. 2014;43(1):20–3.CrossRefPubMedGoogle Scholar
  25. 25.
    Khoo SK, et al. Acquiring genome-wide gene expression profiles in Guthrie card blood spots using microarrays. Pathol Int. 2011;61(1):1–6.CrossRefPubMedGoogle Scholar
  26. 26.
    Hollegaard MV, et al. Archived neonatal dried blood spot samples can be used for accurate whole genome and exome-targeted next-generation sequencing. Mol Genet Metab. 2013;110(1–2):65–72.CrossRefPubMedGoogle Scholar
  27. 27.
    Clark MJ, et al. Performance comparison of exome DNA sequencing technologies. Nat Biotechnol. 2011;29(10):908–14.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Burgard P, et al. Newborn screening programmes in Europe; arguments and efforts regarding harmonization. Part 2. From screening laboratory results to treatment, follow-up and quality assurance. J Inherit Metab Dis. 2012;35(4):613–25.CrossRefPubMedGoogle Scholar
  29. 29.
    de Ligt J, et al. Detection of clinically relevant copy number variants with whole-exome sequencing. Hum Mutat. 2013;34(10):1439–48.CrossRefPubMedGoogle Scholar
  30. 30.
    Landau YE, Lichter-Konecki U, Levy HL. Genomics in newborn screening. J Pediatr. 2014;164(1):14–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Bernhardt BA, et al. Incorporating direct-to-consumer genomic information into patient care: attitudes and experiences of primary care physicians. Pers Med. 2012;9(7):683–92.CrossRefGoogle Scholar
  32. 32.
    Waisbren SE, et al. Parents are interested in newborn genomic testing during the early postpartum period. Genet Med. 2015;17(6):501–4.CrossRefPubMedGoogle Scholar
  33. 33.
    Lanie AD, et al. Exploring the public understanding of basic genetic concepts. J Genet Couns. 2004;13(4):305–20.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Cooper GM, Shendure J. Needles in stacks of needles: finding disease-causal variants in a wealth of genomic data. Nat Rev Genet. 2011;12(9):628–40.CrossRefPubMedGoogle Scholar
  35. 35.
    Prados MD, et al. Toward precision medicine in glioblastoma: the promise and the challenges. Neuro-Oncology. 2015;17(8):1051–63.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Roberts JS, Dolinoy DC, Tarini BA. Emerging issues in public health genomics. Annu Rev Genomics Hum Genet. 2014;15:461–80.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Mardis ER. The $1,000 genome, the $100,000 analysis? Genome Med. 2010;2(11):84.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Highnam G, Mittelman D. Personal genomes and precision medicine. Genome Biol. 2012;13(12):324.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Yu H, Zhang VW. Precision medicine for continuing phenotype expansion of human genetic diseases. Biomed Res Int. 2015;2015:745043.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Nicholls SG, et al. Public attitudes towards genomic risk profiling as a component of routine population screening. Genome. 2013;56(10):626–33.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Knoppers BM, Thorogood A, Chadwick R. The human genome organisation: towards next-generation ethics. Genome Med. 2013;5(4):38.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Goldenberg AJ, et al. Parents’ interest in whole-genome sequencing of newborns. Genet Med. 2014;16(1):78–84.CrossRefPubMedGoogle Scholar
  43. 43.
    Platt LD, et al. The international study of pregnancy outcome in women with maternal phenylketonuria: report of a 12-year study. Am J Obstet Gynecol. 2000;182(2):326–33.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Center for Systems BiologySoochow UniversitySuzhouChina
  2. 2.Center of prenatal diagnosis, Wuxi Maternal and Child Health HospitalNanjing Medical UniversityWuxiChina
  3. 3.School of Chemistry, Biology and Materials EngineeringSuzhou University of Science and TechnologySuzhouChina
  4. 4.Suzhou Institute of Biomedical Engineering and TechnologyChinese Academy of SciencesSuzhouChina
  5. 5.Medical College of Guizhou UniversityGuiyangChina

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