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.
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.
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.
Allyse, M., et al. 2015. Non-invasive prenatal testing: A review of international implementation and challenges. Int J Womens Health 7: 113–126.
Bianchi, D.W., et al. 2014. DNA sequencing versus standard prenatal aneuploidy screening. New England Journal of Medicine 370 (9): 799–808.
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.
Brambati, B., and G. Simoni. 1983. Diagnosis of fetal trisomy 21 in first trimester. Lancet 1 (8324): 586.
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.
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.
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.
Committee Opinion No. 2017. 691: Carrier Screening for Genetic Conditions. Obstetrics and Gynecology 129 (3): e41–e55.
Creasman, W.T., R.A. Lawrence, and H.A. Thiede. 1968. Fetal complications of amniocentesis. JAMA 204 (11): 949–957.
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.
Drury, S., et al. 2015. Exome sequencing for prenatal diagnosis of fetuses with sonographic abnormalities. Prenatal Diagnosis 35 (10): 1010–1017.
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.
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.
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.
Gasperini, M., L. Starita, and J. Shendure. 2016. The power of multiplexed functional analysis of genetic variants. Nature Protocols 11 (10): 1782–1787.
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.
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.
Gregg, A.R., et al. 2013. ACMG statement on noninvasive prenatal screening for fetal aneuploidy. Genetics in Medicine 15 (5): 395–398.
Haque, I.S., et al. 2016. Modeled Fetal Risk of Genetic Diseases Identified by Expanded Carrier Screening. JAMA 316 (7): 734–742.
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.
Hook, E.B. 1976. Estimates of maternal age-specific risks of Down-syndrome birth in women aged 34–41. Lancet 2 (7975): 33–34.
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.
Iglesias, A., et al. 2014. The usefulness of whole-exome sequencing in routine clinical practice. Genetics in Medicine 16 (12): 922–931.
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.
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.
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.
Kitzman, J.O., et al. 2012. Noninvasive whole-genome sequencing of a human fetus. Science Translational Medicine 4(137): p. 137ra76.
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.
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.
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.
Liley, A.W. 1965. AMNIOCENTESIS. New England Journal of Medicine 272: 731–732.
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.
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.
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.
Lovrecic, L., et al. 2016. Clinical utility of array comparative genomic hybridisation in prenatal setting. BMC Medical Genetics 17 (1): 81.
Mackie, F.L., et al. 2014. Exome Sequencing in Fetuses with Structural Malformations. Journal of Clinical Medicine 3 (3): 747–762.
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.
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.
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.
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.
Oneda, B., et al. 2014. High-resolution chromosomal microarrays in prenatal diagnosis significantly increase diagnostic power. Prenatal Diagnosis 34 (6): 525–533.
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.
Petrikin, J.E., et al. 2015. Rapid whole genome sequencing and precision neonatology. Seminars in Perinatology 39 (8): 623–631.
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.
Reiff, M., et al. 2012. What does it mean?”: Uncertainties in understanding results of chromosomal microarray testing. Genetics in Medicine 14 (2): 250–258.
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.
Retterer, K., et al. 2016. Clinical application of whole-exome sequencing across clinical indications. Genetics in Medicine 18 (7): 696–704.
Ropers, H.H. 2012. On the future of genetic risk assessment. Human Frontier Science Program 3 (3): 229–236.
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.
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.
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.
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.
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.
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.
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.
Wapner, R.J., et al. 2012. Chromosomal microarray versus karyotyping for prenatal diagnosis. New England Journal of Medicine 367 (23): 2175–2184.
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.
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.
Wiener-Megnazi, Z., R. Auslender, and M. Dirnfeld. 2012. Advanced paternal age and reproductive outcome. Asian Journal of Andrology 14 (1): 69–76.
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.
Yang, Q., et al. 2007. Paternal age and birth defects: How strong is the association? Human Reproduction 22 (3): 696–701.
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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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