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Practicing Prenatal Medicine in a Genomic Future: How the Practice of Pediatrics May (Or May Not) Change with the Introduction of Widespread Prenatal Sequencing

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Born Well: Prenatal Genetics and the Future of Having Children

Part of the book series: The International Library of Bioethics ((ILB,volume 88))

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Abstract

Expanded usage of next generation sequencing technologies in prenatal medicine is advancing simultaneously around the world, and diagnosis is shifting from the postnatal to the prenatal context. Practitioners caring for mother and baby have historically dichotomized their practices into prenatal and postnatal care, but the fetal genome remains unchanged and will likely be analyzed by the same genomicists across that continuum of care. This chapter addresses ways in which the future of children and pediatric medicine could be shaped by development of and access to prenatal genomic tests and the importance of educating future parents and their providers to make informed reproductive choices, especially during the current dynamic phase of genomics in which many variants identified are not definitively interpretable. Genetics and genomic technologies have been a valuable asset to prenatal diagnosis, and the role of genetic screening and diagnosis have increased significantly in the last decade. Similarly, pediatric diagnostic testing has improved significantly with the addition of genomic testing including initially chromosome microarray and then exome/genome sequencing. As methods to analyze and interpret the genome have improved on the postnatal side, the same strategies are used increasingly although with greater challenges due in part to incomplete phenotypes on the prenatal side. As reference data sets have improved to catalog normal variants and as turn-around times have shortened to meet the clinical needs of prenatal diagnosis, it is now becoming feasible to further expand genomic prenatal screening and diagnostic testing to improve the health of children. We look forward to how the future of children and pediatric medicine could be shaped by development of and access to prenatal genomic tests and the importance of educating future parents and their providers to make informed reproductive choices, especially during the current dynamic phase of genomics in which many variants identified are not definitively interpretable. Hopefully, the next generation of children will be healthier and have greater access to medical care that can prevent disease with early diagnosis of health threats.

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References

  • Akolekar, R., et al. 2015. Procedure-related risk of miscarriage following amniocentesis and chorionic villus sampling: A systematic review and meta-analysis. Ultrasound in Obstetrics and Gynecology 45 (1): 16–26.

    Article  Google Scholar 

  • Alamillo, C.M., M. Fiddler, and E. Pergament. 2012. Increased nuchal translucency in the presence of normal chromosomes: What’s next? Current Opinion in Obstetrics and Gynecology 24 (2): 102–108.

    Article  Google Scholar 

  • Alamillo, C.L., et al. 2015. Exome sequencing positively identified relevant alterations in more than half of cases with an indication of prenatal ultrasound anomalies. Prenatal Diagnosis 35 (11): 1073–1078.

    Article  Google Scholar 

  • Allyse, M., et al. 2015. Non-invasive prenatal testing: A review of international implementation and challenges. Int J Womens Health 7: 113–126.

    Article  Google Scholar 

  • Bianchi, D.W., et al. 2014. DNA sequencing versus standard prenatal aneuploidy screening. New England Journal of Medicine 370 (9): 799–808.

    Article  Google Scholar 

  • Boycott, K.M., et al. 2017. International Cooperation to Enable the Diagnosis of All Rare Genetic Diseases. American Journal of Human Genetics 100 (5): 695–705.

    Article  Google Scholar 

  • Brambati, B., and G. Simoni. 1983. Diagnosis of fetal trisomy 21 in first trimester. Lancet 1 (8324): 586.

    Google Scholar 

  • Callaway, J.L., et al. 2013. The clinical utility of microarray technologies applied to prenatal cytogenetics in the presence of a normal conventional karyotype: A review of the literature. Prenatal Diagnosis 33 (12): 1119–1123.

    Article  Google Scholar 

  • Carss, K.J., et al. 2014. Exome sequencing improves genetic diagnosis of structural fetal abnormalities revealed by ultrasound. Human Molecular Genetics 23 (12): 3269–3277.

    Article  Google Scholar 

  • Chan, K.C., et al. 2016. Second generation noninvasive fetal genome analysis reveals de novo mutations, single-base parental inheritance, and preferred DNA ends. Proc Natl Acad Sci U S A 113 (50): E8159-e8168.

    Article  Google Scholar 

  • Committee Opinion No. 2017. 691: Carrier Screening for Genetic Conditions. Obstetrics and Gynecology 129 (3): e41–e55.

    Article  Google Scholar 

  • Creasman, W.T., R.A. Lawrence, and H.A. Thiede. 1968. Fetal complications of amniocentesis. JAMA 204 (11): 949–957.

    Article  Google Scholar 

  • Crombag, N.M., et al. 2014. Explaining variation in Down’s syndrome screening uptake: Comparing the Netherlands with England and Denmark using documentary analysis and expert stakeholder interviews. BMC Health Services Research 14: 437.

    Article  Google Scholar 

  • Drury, S., et al. 2015. Exome sequencing for prenatal diagnosis of fetuses with sonographic abnormalities. Prenatal Diagnosis 35 (10): 1010–1017.

    Article  Google Scholar 

  • Edwards, J.G., et al. 2015. Expanded carrier screening in reproductive medicine-points to consider: A joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine. Obstetrics and Gynecology 125 (3): 653–662.

    Article  Google Scholar 

  • Farrell, R.M., et al. 2014. It’s More Than a Blood Test: Patients’ Perspectives on Noninvasive Prenatal Testing. Journal of Clinical Medicine 3 (2): 614–631.

    Article  Google Scholar 

  • Finkel, R.S., et al. 2016. Treatment of infantile-onset spinal muscular atrophy with nusinersen: A phase 2, open-label, dose-escalation study. Lancet 388 (10063): 3017–3026.

    Article  Google Scholar 

  • Gasperini, M., L. Starita, and J. Shendure. 2016. The power of multiplexed functional analysis of genetic variants. Nature Protocols 11 (10): 1782–1787.

    Article  Google Scholar 

  • Gitsels-van der Wal, J.T., et al. 2014. Factors affecting the uptake of prenatal screening tests for congenital anomalies; a multicentre prospective cohort study. BMC Pregnancy Childbirth 14: 264.

    Google Scholar 

  • Goriely, A., and A.O. Wilkie. 2012. Paternal age effect mutations and selfish spermatogonial selection: Causes and consequences for human disease. American Journal of Human Genetics 90 (2): 175–200.

    Article  Google Scholar 

  • Gregg, A.R., et al. 2013. ACMG statement on noninvasive prenatal screening for fetal aneuploidy. Genetics in Medicine 15 (5): 395–398.

    Article  Google Scholar 

  • Haque, I.S., et al. 2016. Modeled Fetal Risk of Genetic Diseases Identified by Expanded Carrier Screening. JAMA 316 (7): 734–742.

    Article  Google Scholar 

  • Henneman, L., et al. 2001. Participation in preconceptional carrier couple screening: Characteristics, attitudes, and knowledge of both partners. Journal of Medical Genetics 38 (10): 695–703.

    Article  Google Scholar 

  • Hook, E.B. 1976. Estimates of maternal age-specific risks of Down-syndrome birth in women aged 34–41. Lancet 2 (7975): 33–34.

    Article  Google Scholar 

  • Houweling, A.C., et al. 2010. Prenatal detection of Noonan syndrome by mutation analysis of the PTPN11 and the KRAS genes. Prenatal Diagnosis 30 (3): 284–286.

    Article  Google Scholar 

  • Iglesias, A., et al. 2014. The usefulness of whole-exome sequencing in routine clinical practice. Genetics in Medicine 16 (12): 922–931.

    Article  Google Scholar 

  • Jacobs, P.A., and J.A. Strong. 1959. A case of human intersexuality having a possible XXY sex-determining mechanism. Nature 183 (4657): 302–303.

    Article  Google Scholar 

  • Kaback, M., et al. 1993. Tay-Sachs disease--carrier screening, prenatal diagnosis, and the molecular era. An international perspective, 1970 to 1993. The International TSD Data Collection Network. JAMA 270(19): 2307–15.

    Google Scholar 

  • Kalia, S.S., et al. (2017). Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genetics Medicine 19(2): 249–255.

    Google Scholar 

  • Kitzman, J.O., et al. 2012. Noninvasive whole-genome sequencing of a human fetus. Science Translational Medicine 4(137): p. 137ra76.

    Google Scholar 

  • Larion, S., et al. 2014. Uptake of noninvasive prenatal testing at a large academic referral center. American Journal of Obstetrics and Gynecology 211 (6): 651.e1–7.

    Article  Google Scholar 

  • Lefkowitz, R.B., et al. 2016. Clinical validation of a noninvasive prenatal test for genomewide detection of fetal copy number variants. American Journal of Obstetrics and Gynecology 215 (2): 227.e1-227.e16.

    Article  Google Scholar 

  • Lejeune, J., M. Gauthier, and R. Turpin. 1959. Human chromosomes in tissue cultures. Comptes Rendus Hebdomadaires Des Séances De L’académie Des Sciences 248 (4): 602–603.

    Google Scholar 

  • Liley, A.W. 1965. AMNIOCENTESIS. New England Journal of Medicine 272: 731–732.

    Article  Google Scholar 

  • Little, S.E., et al. 2010. The cost-effectiveness of prenatal screening for spinal muscular atrophy. American Journal of Obstetrics and Gynecology 202 (3): 253.e1–7.

    Article  Google Scholar 

  • Lo, Y.M., et al. 2010. Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Science Translational Medicine 2(61): p. 61ra91.

    Google Scholar 

  • Loane, M., et al. 2013. Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe: Impact of maternal age and prenatal screening. European Journal of Human Genetics 21 (1): 27–33.

    Article  Google Scholar 

  • Lovrecic, L., et al. 2016. Clinical utility of array comparative genomic hybridisation in prenatal setting. BMC Medical Genetics 17 (1): 81.

    Article  Google Scholar 

  • Mackie, F.L., et al. 2014. Exome Sequencing in Fetuses with Structural Malformations. Journal of Clinical Medicine 3 (3): 747–762.

    Article  Google Scholar 

  • McCandless, S.E., J.W. Brunger, and S.B. Cassidy. 2004. The burden of genetic disease on inpatient care in a children’s hospital. American Journal of Human Genetics 74 (1): 121–127.

    Article  Google Scholar 

  • Natoli, J.L., et al. 2012. Prenatal diagnosis of Down syndrome: A systematic review of termination rates (1995–2011). Prenatal Diagnosis 32 (2): 142–153.

    Article  Google Scholar 

  • Northrup, H., and D.A. Krueger. 2013. Tuberous sclerosis complex diagnostic criteria update: Recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference. Pediatric Neurology 49 (4): 243–254.

    Article  Google Scholar 

  • O’Malley, M., and R.G. Hutcheon. 2007. Genetic disorders and congenital malformations in pediatric long-term care. Journal of the American Medical Directors Association 8 (5): 332–334.

    Article  Google Scholar 

  • Oneda, B., et al. 2014. High-resolution chromosomal microarrays in prenatal diagnosis significantly increase diagnostic power. Prenatal Diagnosis 34 (6): 525–533.

    Article  Google Scholar 

  • Palomaki, G.E., et al. 2011. DNA sequencing of maternal plasma to detect Down syndrome: An international clinical validation study. Genetics in Medicine 13 (11): 913–920.

    Article  Google Scholar 

  • Petrikin, J.E., et al. 2015. Rapid whole genome sequencing and precision neonatology. Seminars in Perinatology 39 (8): 623–631.

    Article  Google Scholar 

  • Plantinga, M., et al. 2016. Population-based preconception carrier screening: How potential users from the general population view a test for 50 serious diseases. European Journal of Human Genetics 24 (10): 1417–1423.

    Article  Google Scholar 

  • Reiff, M., et al. 2012. What does it mean?”: Uncertainties in understanding results of chromosomal microarray testing. Genetics in Medicine 14 (2): 250–258.

    Article  Google Scholar 

  • Reiff, M., et al. 2013. Physicians’ perspectives on the uncertainties and implications of chromosomal microarray testing of children and families. Clinical Genetics 83 (1): 23–30.

    Article  Google Scholar 

  • Retterer, K., et al. 2016. Clinical application of whole-exome sequencing across clinical indications. Genetics in Medicine 18 (7): 696–704.

    Article  Google Scholar 

  • Ropers, H.H. 2012. On the future of genetic risk assessment. Human Frontier Science Program 3 (3): 229–236.

    Google Scholar 

  • Sahoo, T., et al. 2016. Expanding noninvasive prenatal testing to include microdeletions and segmental aneuploidy: Cause for concern? Genetics in Medicine 18 (3): 275–276.

    Article  Google Scholar 

  • Sayres, L.C., et al. 2014. Demographic and experiential correlates of public attitudes towards cell-free fetal DNA screening. Journal of Genetic Counseling 23 (6): 957–967.

    Article  Google Scholar 

  • Scott, S.A., et al. 2010. Experience with carrier screening and prenatal diagnosis for 16 Ashkenazi Jewish genetic diseases. Human Mutation 31 (11): 1240–1250.

    Article  Google Scholar 

  • Shkedi-Rafid, S., et al. 2016. What results to disclose, when, and who decides? Healthcare professionals’ views on prenatal chromosomal microarray analysis. Prenatal Diagnosis 36 (3): 252–259.

    Article  Google Scholar 

  • Srebniak, M.I., et al., 2017. The influence of SNP-based chromosomal microarray and NIPT on the diagnostic yield in 10,000 fetuses with and without fetal ultrasound anomalies. Hum Mutat, 2017.

    Google Scholar 

  • Taneja, P.A., et al. 2016. Noninvasive prenatal testing in the general obstetric population: Clinical performance and counseling considerations in over 85 000 cases. Prenatal Diagnosis 36 (3): 237–243.

    Article  Google Scholar 

  • Walser, S.A., et al. 2015. Comparing genetic counselor’s and patient’s perceptions of needs in prenatal chromosomal microarray testing. Prenatal Diagnosis 35 (9): 870–878.

    Article  Google Scholar 

  • Wapner, R.J., et al. 2012. Chromosomal microarray versus karyotyping for prenatal diagnosis. New England Journal of Medicine 367 (23): 2175–2184.

    Article  Google Scholar 

  • Wapner, R.J., et al. 2015. Expanding the scope of noninvasive prenatal testing: Detection of fetal microdeletion syndromes. American Journal of Obstetrics and Gynecology 212 (3): 332.e1–9.

    Article  Google Scholar 

  • Werner-Lin, A., et al. 2017. They Can’t Find Anything Wrong with Him, Yet”: Mothers’ experiences of parenting an infant with a prenatally diagnosed copy number variant (CNV). American Journal of Medical Genetics. Part A 173 (2): 444–451.

    Article  Google Scholar 

  • Wiener-Megnazi, Z., R. Auslender, and M. Dirnfeld. 2012. Advanced paternal age and reproductive outcome. Asian Journal of Andrology 14 (1): 69–76.

    Article  Google Scholar 

  • Williamson, R., et al. 1981. Direct gene analysis of chorionic villi: A possible technique for first-trimester antenatal diagnosis of haemoglobinopathies. Lancet 2 (8256): 1125–1127.

    Article  Google Scholar 

  • Yang, Q., et al. 2007. Paternal age and birth defects: How strong is the association? Human Reproduction 22 (3): 696–701.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Columbia University, New York, NY, USA

    Volkan Okur & Wendy K. Chung

  2. Department of Medicine, Columbia University, New York, NY, USA

    Wendy K. Chung

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  1. Volkan Okur
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  2. Wendy K. Chung
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Correspondence to Wendy K. Chung .

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Editors and Affiliations

  1. Program in Biomedical Ethics Research, Mayo Clinic, Jacksonville, FL, USA

    Megan A. Allyse

  2. Department of Bioethics, Case Western Reserve University, Cleveland, OH, USA

    Marsha Michie

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Okur, V., Chung, W.K. (2022). Practicing Prenatal Medicine in a Genomic Future: How the Practice of Pediatrics May (Or May Not) Change with the Introduction of Widespread Prenatal Sequencing. In: Allyse, M.A., Michie, M. (eds) Born Well: Prenatal Genetics and the Future of Having Children. The International Library of Bioethics, vol 88. Springer, Cham. https://doi.org/10.1007/978-3-030-82536-2_2

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