Foetal Diagnosis

Abstract

New genetic testing approaches as well as a constant progress in the imaging technologies of the foetus have changed the practice of prenatal diagnosis during the past decade fundamentally. The greatly improved noninvasive risk assessment for common foetal aneuploidies by recent cell‐free DNA (cfDNA) testing technologies on maternal plasma (NIPT or NIPS) has been much acclaimed by pregnant women and their doctors as well and resulted in a significant decline of invasive testing requiring chorionic villus sampling or amniocentesis. Exclusion of foetal aneuploidy is still by far the most frequent indication for prenatal testing, and the growing number of options must be addressed in routine care for all pregnancies. Pregnancies at high risk for foetal aneuploidy or other copy number variations profit from high‐resolution karyotyping using chromosomal microarrays. Noninvasive prenatal diagnosis (NIPD) is established for the foetal sex or blood group markers and progressing for numerous monogenic conditions.

Key Concepts

  • Noninvasive testing of cell‐free DNA in the maternal plasma is an established screening tool for trisomy 21 and other common trisomies and has caused a significant decrease of invasive testing.
  • Cell‐free DNA testing for common aneuploidies with current technologies will likely not become diagnostic owing to its origin from trophoblast cells.
  • Targeted cell‐free DNA testing is a diagnostic option for a growing number of monogenic conditions.
  • Genomic testing approaches such as symptom‐ or disease‐based gene panels or whole‐exome sequencing spread slowly into invasive as well as noninvasive prenatal testing.
  • Genetic testing on amniotic fluid cells or placental villi is most comprehensive and accurate and remains the gold standard of foetal diagnosis.

Keywords: prenatal screening; prenatal diagnosis; noninvasive prenatal testing; noninvasive prenatal diagnosis; chorionic villus biopsy; amniocentesis

References

American College of Obstetricians and Gynecologists (2016) Microarrays and next‐generation sequencing technology: the use of advanced genetic diagnostic tools in obstetrics and gynecology. Committee Opinion No. 682. Obstetrics and Gynecology 128: e262–e268.

Akolekar R, Beta J, Picciarelli G, 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: 16–26.

Alberry M, Maddocks D, Jones M, et al. (2007) Free fetal DNA in maternal plasma in anembryonic pregnancies: confirmation that the origin is the trophoblast. Prenatal Diagnosis 27: 415–418.

Bell CJ, Dinwiddie DL, Miller NA, et al. (2011) Carrier testing for severe childhood recessive diseases by next‐generation sequencing. Science Translational Medicine 3 (65): 65ra4.

Benn P, Borell A, Chiu R, et al. (2013) Position statement from the Aneuploidy Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis. Prenatal Diagnosis 33: 622–629.

Best S, Wou K, Vora N, et al. (2018) Promises, pitfalls and practicalities of prenatal whole exome sequencing. Prenatal Diagnosis 38 (1): 10–19. DOI: 10.1002/pd.5102.

Bianchi DW, Simpson JL, Jackson LG, et al. (2002) Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data. National Institute of Child Health and Development Fetal Cell Isolation Study. Prenatal Diagnosis 22: 609–615.

Chitty LS, Mason S, Barrett AN, et al. (2015) Non‐invasive prenatal diagnosis of achondroplasia and thanatophoric dysplasia: next‐generation sequencing allows for a safer, more accurate, and comprehensive approach. Prenatal Diagnosis 35: 656–662.

Croonen EA, Nillesen WM, Stuurman KE, et al. (2013) Prenatal diagnostic testing of the Noonan syndrome genes in foetuses with abnormal ultrasound findings. European Journal of Human Genetics 21: 936–942.

Curnow KJ, Wilkins‐Haug L, Ryan A, et al. (2015) Detection of triploid, molar, and vanishing twin pregnancies by a single‐nucleotide polymorphism‐based noninvasive prenatal test. American Journal of Obstetrics and Gynecology 212: e1–e9.

Dan S, Yuan Y, Wang Y, et al. (2016) Non‐invasive prenatal diagnosis of lethal skeletal dysplasia by targeted capture sequencing of maternal plasma. PLoS One 11: e0159355.

Dar P, Curnow KJ, Gross SJ, et al. (2014) Clinical experience and follow‐up with large scale single‐nucleotide polymorphism‐based noninvasive prenatal aneuploidy testing. American Journal of Obstetrics and Gynecology 211: 527.e1–527.17.

Devaney SA, Palomaki GE, Scott JA, et al. (2011) Noninvasive fetal sex determination using cell‐free fetal DNA: a systematic review and meta‐analysis. JAMA 306: 627–636.

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

Fan HC, Gu W, Wang J, et al. (2012) Non‐invasive prenatal measurement of the fetal genome. Nature 487: 320–324.

Fasano RM (2016) Hemolytic disease of the fetus and newborn in the molecular era. Seminars in Fetal and Neonatal Medicine 21: 28–34.

Filges I and Friedman JM (2015) Exome sequencing for gene discovery in lethal fetal disorders–harnessing the value of extreme phenotypes. Prenatal Diagnosis 35: 1005–1009.

Gil MM, Quezada MS, Revello R, et al. (2015) Analysis of cell‐free DNA in maternal blood in screening for fetal aneuploidies: updated meta‐analysis. Ultrasound in Obstetrics and Gynecology 45: 249–266.

Grace MR, Hardisty E, Green NS, et al. (2015) Cell free DNA testing‐interpretation of results using an online calculator. American Journal of Obstetrics and Gynecology 213: 30–32.

Gregg AR, Skotko BG, Benkendorf JL, et al. (2016) Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genetics in Medicine 18: 1056–1065.

Hahn S, Sant R and Holzgreve W (1998) Fetal cells in maternal blood: current and future perspectives. Molecular Human Reproduction 4: 515–521.

Hartwig TS, Ambye L, Sørensen S and Jørgensen FS (2017) Discordant non‐invasive prenatal testing (NIPT) – a systematic review. Prenatal Diagnosis 37: 527–539.

Hercher L, Uhlmann WR, Hoffman EP, et al. (2016) Prenatal testing for adult‐onset conditions: the position of the national society of genetic counselors. Journal of Genetic Counseling 25: 1139–1145.

Hill M, Lewis C, Jenkins L, et al. (2012) Implementing noninvasive prenatal fetal sex determination using cell‐free fetal DNA in the United Kingdom. Expert Opinion on Biological Therapy 12 (Suppl 1): S119–S126.

Horn R and Parker M (2018) Opening Pandora's box?: ethical issues in prenatal whole genome and exome sequencing. Prenatal Diagnosis 38 (1): 20–25. DOI: 10.1002/pd.5114.

Hudecova I and Chiu RW (2017) Non‐invasive prenatal diagnosis of thalassemias using maternal plasma cell free DNA. Best Practice & Research. Clinical Obstetrics & Gynaecology 39: 63–73.

Hui L, Hutchinson B, Poulton A, et al. (2017) Population‐based impact of noninvasive prenatal screening on screening and diagnostic testing for fetal aneuploidy. Genetics in Medicine 19 (12): 1338–1345. DOI: 10.1038/gim.2017.55.

Iwarsson E, Jacobsson B, Dagerhamn J, et al. (2017) Analysis of cell‐free fetal DNA in maternal blood for detection of trisomy 21, 18 and 13 in a general pregnant population and in a high risk population – a systematic review and meta‐analysis. Acta Obstetricia et Gynecologica Scandinavica 96: 7–18.

Kitzman JO, Snyder MW, Ventura M, et al. (2012) Noninvasive whole‐genome sequencing of a human fetus. Science Translational Medicine 4: 137ra76.

Kølvraa S, Singh R, Normand EA, et al. (2016) Genome‐wide copy number analysis on DNA from fetal cells isolated from the blood of pregnant women. Prenatal Diagnosis 36: 1127–1134.

Liu L, Li K, Fu X, et al. (2016) A forward look at noninvasive prenatal testing. Trends in Molecular Medicine 22: 958–968.

Lo YM, Corbetta N, Chamberlain PF, et al. (1997) Presence of fetal DNA in maternal plasma and serum. Lancet 350: 485–487.

Lo YM, Chan KC, Sun H, et al. (2010) Maternal plasma DNA sequencing reveals the genome‐wide genetic and mutational profile of the fetus. Science Translational Medicine 2: 61ra91.

Lo KK, Karampetsou E, Boustred C, et al. (2016) Limited clinical utility of non‐invasive prenatal testing for subchromosomal abnormalities. American Journal of Human Genetics 98: 34–44.

Lun FM, Tsui NB, Chan KC, et al. (2008) Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma. Proceedings of the National Academy of Sciences of the United States of America 105: 19920–19925.

Mackie FL, Hemming K, Allen S, et al. (2017) The accuracy of cell‐free fetal DNA‐based non‐invasive prenatal testing in singleton pregnancies: a systematic review and bivariate meta‐analysis. BJOG 124: 32–46.

Malone FD, Canick JA, Ball RH, et al. (2005) First‐trimester or second‐trimester screening, or both, for Down's syndrome. The New England Journal of Medicine 353: 2001–2011.

Mardy A and Wapner RJ (2016) Confined placental mosaicism and its impact on confirmation of NIPT results. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics 172: 118–122.

Morain S, Greene MF and Mello MM (2013) A new era in noninvasive prenatal testing. The New England Journal of Medicine 369: 499–501.

National Registry for Amniocentesis Study Group (1976) Midtrimester amniocentesis for prenatal diagnosis. Safety and accuracy. JAMA 236: 1471–1476.

Norton ME, Jacobsson B, Swamy GK, et al. (2015) Cell‐free DNA analysis for noninvasive examination of trisomy. The New England Journal of Medicine 372: 1589–1597.

Oepkes D, Page‐Christiaens GC, Bax CJ, et al. (2016) Trial by Dutch laboratories for evaluation of non‐invasive prenatal testing. Part I‐clinical impact. Prenatal Diagnosis 36: 1083–1090.

Oneda B, Steindl K, Masood R, et al. (2016) Noninvasive prenatal testing: more caution in counseling is needed in high risk pregnancies with ultrasound abnormalities. European Journal of Obstetrics, Gynecology, and Reproductive Biology 200: 72–75.

Simpson JL (2012) Invasive procedures for prenatal diagnosis: any future left? Best Practice & Research. Clinical Obstetrics & Gynaecology 26: 625–638.

Stevens B, Krstic N, Jones M, et al. (2017) Finding middle ground in constructing a clinically useful expanded carrier screening panel. Obstetrics and Gynecology 130: 279–284.

Tabor A, Philip J, Madsen M, et al. (1986) Randomised controlled trial of genetic amniocentesis in 4606 low‐risk women. Lancet 1: 1287–1293.

Taylor‐Phillips S, Freeman K, Geppert J, et al. (2016) Accuracy of non‐invasive prenatal testing using cell‐free DNA for detection of Down, Edwards and Patau syndromes: a systematic review and meta‐analysis. BMJ Open 6: e010002.

Teitelbaum L, Metcalfe A, Clarke G, et al. (2015) Costs and benefits of non‐invasive fetal RhD determination. Ultrasound in Obstetrics and Gynecology 45: 84–88.

Van Opstal D and Srebniak MI (2016) Cytogenetic confirmation of a positive NIPT result: evidence‐based choice between chorionic villus sampling and amniocentesis depending on chromosome aberration. Expert Review of Molecular Diagnostics 16: 513–520.

van den Veyver IB and Eng CM (2015) Genome‐wide sequencing for prenatal detection of fetal single‐gene disorders. Cold Spring Harbor Perspectives in Medicine 5: a023077.

Vora NL, Powell B, Brandt A, et al. (2017) Prenatal exome sequencing in anomalous fetuses: new opportunities and challenges. Genetics in Medicine 19 (11): 1207–1216. DOI: 10.1038/gim.2017.33.

Wax JR, Chard R, Cartin A, et al. (2014) Noninvasive prenatal testing: the importance of pretest trisomy risk and posttest predictive values. American Journal of Obstetrics and Gynecology 212: 548–549.

Wulff CB, Gerds TA, Rode L, et al. (2016) Risk of fetal loss associated with invasive testing following combined first‐trimester screening for Down syndrome: a national cohort of 147,987 singleton pregnancies. Ultrasound in Obstetrics and Gynecology 47: 38–44.

Further Reading

Beaudet AL (2016) Using fetal cells for prenatal diagnosis: history and recent progress. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics 172: 123–127.

Bianchi D, Crombleholme T, D'Alton M, et al. (eds) (2010) Fetology: Diagnosis and Management of the Fetal Patient, 2nd edn. New York: McGraw‐Hill Professional.

Bredenoord AL, de Vries MC and van Delden JJ (2013) Next‐generation sequencing: does the next generation still have a right to an open future? Nature Reviews Genetics 14: 306.

Milunsky A and Milunsky JM (eds) (2015) Genetic Disorders and the Fetus: Diagnosis, Prevention and Treatment, 7th edn. Hoboken, NJ: John Wiley & Sons, Inc.

Minear MA, Alessi S, Allyse M, et al. (2015) Noninvasive prenatal genetic testing: current and emerging ethical, legal, and social issues. Annual Review of Genomics and Human Genetics 16: 369–398.

Wald NJ, Rodeck C, Hackshaw AK, et al. (2003) First and second‐trimester antenatal screening for Down's syndrome: the results of the serum, urine and ultrasound screening study (SURUSS). Journal of Medical Screening 10: 56–104.

Yurkiewicz IR, Korf BR and Lehmann LS (2014) Prenatal whole‐genome sequencing is the quest to know a fetus's future ethical? The New England Journal of Medicine 370: 195–197.

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Miny, Peter, Filges, Isabel, Tercanli, Sevgi, and Holzgreve, Wolfgang(Sep 2018) Foetal Diagnosis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0027053]