Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-5f56664f6-n72nm Total loading time: 0 Render date: 2025-05-07T20:47:46.379Z Has data issue: false hasContentIssue false

Chapter 28 - Pregnancy Loss: From Cytogenetics to Genomics

Published online by Cambridge University Press:  16 April 2025

By
Christina G. Tise ,
Kajal Verma  and
Ruth B. Lathi
Edited by
Roy G. Farquharson ,
Mary D. Stephenson  and
Mariëtte Goddijn
Roy G. Farquharson
Affiliation:
Liverpool Women’s Hospital
Mary D. Stephenson
Affiliation:
University of Illinois, Chicago
Mariëtte Goddijn
Affiliation:
Amsterdam University Medical Centers
Get access

Summary

This chapter discusses the common occurrence of miscarriage in pregnancy and reviews the current genetic methodologies, from cytogenetics to genomics, available to aid individuals and families suffering from pregnancy loss. While often unexplored, a genetics evaluation should be offered in all cases of pregnancy loss given the high diagnostic yield and therapeutic value of providing families with answers. This chapter walks the reader through the available technologies to evaluate chromosome content, which provide an explanation for approximately half of pregnancy losses, as well as current and future genetic and genomic evaluations that can be used to further increase diagnostic yield and identify couples at increased risk of recurrence.

Keywords

pregnancy lossmiscarriagegenetic testingcytogeneticsgenomics
Type
Chapter
Information
Early Pregnancy , pp. 299 - 316
Publisher: Cambridge University Press
Print publication year: 2025

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Practice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril. 2012;98(5):1103–11.Google Scholar
Edmonds, D. K., Lindsay, K. S., Miller, J. F., Williamson, E., Wood, P. J.. Early embryonic mortality in women. Fertil Steril. 1982;38(4):447–53.CrossRefGoogle Scholar
Wilcox, A. J., Weinberg, C. R., O’Connor, J. F., Baird, D. D., Schlatterer, J. P., Canfield, R. E., et al. Incidence of early loss of pregnancy. N Engl J Med. 1988;319(4):189–94.CrossRefGoogle ScholarPubMed
Tise, C. G., Byers, H. M.. Genetics of recurrent pregnancy loss: a review. Curr Opin Obstet Gynecol. 2021;33(2):106–11.CrossRefGoogle ScholarPubMed
Zegers-Hochschild, F., Adamson, G. D., Dyer, S., Racowsky, C., de Mouzon, J., Sokol, R., et al. The international glossary on infertility and fertility care, 2017. Fertil Steril. 2017;108(3):393–406.CrossRefGoogle ScholarPubMed
Quenby, S., Gallos, I. D., Dhillon-Smith, R. K., Podesek, M., Stephenson, M. D., Fisher, J., et al. Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss. Lancet. 2021;397(10285):1658–67.CrossRefGoogle ScholarPubMed
Kersting, A., Wagner, B.. Complicated grief after perinatal loss. Dialogues Clin Neurosci. 2012;14(2):187–94.CrossRefGoogle ScholarPubMed
Farren, J., Jalmbrant, M., Falconieri, N., Mitchell-Jones, N., Bobdiwala, S., Al-Memar, M., et al. Posttraumatic stress, anxiety and depression following miscarriage and ectopic pregnancy: a multicenter, prospective, cohort study. Am J Obstet Gynecol. 2020;222(4):367.e1–22.CrossRefGoogle ScholarPubMed
Stephenson, M. D., Awartani, K. A., Robinson, W. P.. Cytogenetic analysis of miscarriages from couples with recurrent miscarriage: a case-control study. Hum Reprod. 2002;17(2):446–51.CrossRefGoogle ScholarPubMed
van den Berg, M. M. J., van Maarle, M. C., van Wely, M., Goddijn, M.. Genetics of early miscarriage. Biochim Biophys Acta. 2012;1822(12):1951–59.Google ScholarPubMed
Ogasawara, M., Aoki, K., Okada, S., Suzumori, K.. Embryonic karyotype of abortuses in relation to the number of previous miscarriages. Fertil Steril. 2000;73(2):300–304.CrossRefGoogle Scholar
Finley, J., Hay, S., Oldzej, J., Meredith, M. M., Dzidic, N., Slim, R., et al. The genomic basis of sporadic and recurrent pregnancy loss: a comprehensive in-depth analysis of 24,900 miscarriages. Reprod Biomed Online. 2022;45(1):125–34.CrossRefGoogle Scholar
Sugiura-Ogasawara, M., Ozaki, Y., Katano, K., Suzumori, N., Kitaori, T., Mizutani, E.. Abnormal embryonic karyotype is the most frequent cause of recurrent miscarriage. Hum Reprod. 2012;27(8):2297–303.CrossRefGoogle Scholar
ESHRE Guideline Group on RPL, Bender Atik, R., Christiansen, O. B., Elson, J., Kolte, A. M., Lewis, S., et al. ESHRE guideline: recurrent pregnancy loss: an update in 2022. Hum Reprod Open. 2023;2023(1):hoad002.Google ScholarPubMed
Foyouzi, N., Cedars, M. I., Huddleston, H. G.. Cost-effectiveness of cytogenetic evaluation of products of conception in the patient with a second pregnancy loss. Fertil Steril. 2012;98(1):151–55.e3.CrossRefGoogle ScholarPubMed
Popescu, F., Jaslow, C. R., Kutteh, W. H.. Recurrent pregnancy loss evaluation combined with 24-chromosome microarray of miscarriage tissue provides a probable or definite cause of pregnancy loss in over 90% of patients. Hum Reprod. 2018;33(4):579–87.CrossRefGoogle ScholarPubMed
Best, S., Wou, K., Vora, N., Van der Veyver, I. B., Wapner, R., Chitty, L. S.. Promises, pitfalls and practicalities of prenatal whole exome sequencing. Prenat Diagn. 2018;38(1):10–19.CrossRefGoogle ScholarPubMed
Dawes, R., Lek, M., Cooper, S. T.. Gene discovery informatics toolkit defines candidate genes for unexplained infertility and prenatal or infantile mortality. NPJ Genom Med. 2019;4(1):1–11.CrossRefGoogle ScholarPubMed
Aminbeidokhti, M., Qu, J. H., Belur, S., Cakmak, H., Jaswa, E., Lathi, R. B., et al. Preconception genetic carrier screening for miscarriage risk assessment: a bioinformatic approach to identifying candidate lethal genes and variants. medRxiv. 2023. doi.org/10.1101/2023.05.25.23290518.CrossRefGoogle Scholar
Byrne, A. B., Arts, P., Ha, T. T., Kassahn, K. S., Pais, L. S., O’Donnell-Luria, A., et al. Genomic autopsy to identify underlying causes of pregnancy loss and perinatal death. Nat Med. 2023;29(1):180–89.CrossRefGoogle ScholarPubMed
Sahajpal, N. S., Mondal, A. K., Fee, T., Hilton, B., Layman, L., Hastie, A. R., et al. Clinical validation and diagnostic utility of optical genome mapping in prenatal diagnostic testing. J Mol Diagn. 2023;25(4):234–46.CrossRefGoogle ScholarPubMed
Prefumo, F., Jauniaux, E.. Amniocentesis for fetal karyotyping: the end of an era? BJOG. 2016;123(1):99.CrossRefGoogle ScholarPubMed
Blue, N. R., Page, J. M., Silver, R. M.. Genetic abnormalities and pregnancy loss. Semin Perinatol. 2019;43(2):66–73.CrossRefGoogle ScholarPubMed
Levy, B., Sigurjonsson, S., Pettersen, B., Maisenbacher, M. K., Hall, M. P., Demko, Z., et al. Genomic imbalance in products of conception: single-nucleotide polymorphism chromosomal microarray analysis. Obstet Gynecol. 2014;124(2 Pt 1):202–9.CrossRefGoogle ScholarPubMed
Benn, P.. Trisomy 16 and trisomy 16 mosaicism: A review. Am J Med Genet. 1998;79(2):121–33.3.0.CO;2-T>CrossRefGoogle ScholarPubMed
Jarzembowski, J. A.. Trisomies. In McManus, L. M., Mitchell, R. N., eds., Pathobiology of human disease. Elsevier; 2014. doi.org/10.1016/B978-0-12-386456-7.01503-3.Google Scholar
Nussbaum, R. L., McInnes, R. R., Willard, H. F.. Genetic counseling and risk assessment. In Thompson & Thompson genetics and genomics in medicine. 8th ed.: Elsevier; 2016:333–48.Google Scholar
Witters, G., Van Robays, J., Willekes, C., Coumans, A., Peeters, H., Gyselaers, W., et al. Trisomy 13, 18, 21, triploidy and Turner syndrome: the 5T’s. Look at the hands. Facts Views Vis Obgyn. 2011;3(1):15–21.Google Scholar
Hassold, T., Hunt, P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet. 2001;2(4):280–91.CrossRefGoogle Scholar
Jyothy, A., Kumar, K. S., Mallikarjuna, G. N., Babu Rao, V., Uma Devi, B., Sujatha, M., et al. Parental age and the origin of extra chromosome 21 in Down syndrome. J Hum Genet. 2001;46(6):347–50.CrossRefGoogle ScholarPubMed
Fisch, H., Hyun, G., Golden, R., Hensle, T. W., Olsson, C. A., Liberson, G. L.. The influence of paternal age on down syndrome. J Urol. 2003;169(6):2275–78.CrossRefGoogle ScholarPubMed
Driscoll, D. A., Simpson, J. L., Holzgreve, W., Otaño, L.. Genetic screening and prenatal genetic diagnosis. In Gabbe, S. G., Niebyl, J. R., Simpson, J. L., Landon, M. B., Galan, H. L., Jauniaux, E. R. M., et al., eds. Obstetrics: normal and problem pregnancies. 7th ed.: Elsevier; 2017:193–218. doi.org/10.1016/B978-0-323-32108-2.00010-X.CrossRefGoogle Scholar
Simpson, J. L., Jauniaux, E. R. M.. Early pregnancy loss and stillbirth. In Gabbe, S. G., Niebyl, J. R., Simpson, J. L., Landon, M. B., Galan, H. L., Jauniaux, E. R. M., et al., eds. Obstetrics: normal and problem pregnancies. 7th ed.: Elsevier; 2017:578–94. doi.org/10.1016/B978-0-323-32108-2.00010-X.Google Scholar
Hall, H., Hunt, P., Hassold, T.. Meiosis and sex chromosome aneuploidy: how meiotic errors cause aneuploidy; how aneuploidy causes meiotic errors. Curr Opin Genet Dev. 2006;16(3):323–29.CrossRefGoogle ScholarPubMed
Kajii, T., Ohama, K.. Inverse maternal age effect in monosomy X. Hum Genet. 1979;51(2):147–51.CrossRefGoogle ScholarPubMed
Warburton, D., Kline, J., Stein, Z., Susser, M.. Monosomy X: a chromosomal anomaly associated with young maternal age. Lancet. 1980;1(8161):167–69.Google ScholarPubMed
Li, H., Mao, Y., Jin, J.. The correlation between maternal age and fetal sex chromosome aneuploidies: a 8-year single institution experience in China. Mol Cytogenet. 2021;14(1):25.CrossRefGoogle ScholarPubMed
Toufaily, M. H., Roberts, D. J., Westgate, M. N., Holmes, L. B.. Triploidy: Variation of Phenotype. Am J Clin Pathol. 2016;145(1):86–95.CrossRefGoogle ScholarPubMed
Kolarski, M., Ahmetovic, B., Beres, M., Topic, R., Nikic, V., Kavecan, I., et al. Genetic counseling and prenatal diagnosis of triploidy during the second trimester of pregnancy. Med Arch. 2017;71(2):144–47.CrossRefGoogle ScholarPubMed
Kavalier, F.. Investigation of recurrent miscarriages. BMJ. 2005;331(7509):121–22.CrossRefGoogle ScholarPubMed
Priya, P. K., Mishra, V. V., Roy, P., Patel, H.. A study on balanced chromosomal translocations in couples with recurrent pregnancy loss. J Hum Reprod Sci. 2018;11(4):337–42.Google Scholar
Nonaka, T., Takahashi, M., Nonaka, C., Enomoto, T., Takakuwa, K.. The analysis of chromosomal abnormalities in patients with recurrent pregnancy loss, focusing on the prognosis of patients with inversion of chromosome (9). Reprod Med Biol. 2019;18(3):296–301.CrossRefGoogle ScholarPubMed
Chien, C. W., Chao, A. S., Chang, Y. L., Chen, K. J., Peng, H. H., Lin, Y. T., et al. Frequency and clinical significance of chromosomal inversions prenatally diagnosed by second trimester amniocentesis. Sci Rep. 2022;12(1):2215.CrossRefGoogle ScholarPubMed
Zhang, X., Shi, Q., Liu, Y., Jiang, Y., Yang, X., Liu, R., et al. Fertility problems in males carrying an inversion of chromosome 10. Open Med (Wars). 2021;16(1):316–21.Google ScholarPubMed
Zhang, T., Sun, Y., Chen, Z., Li, T.. Traditional and molecular chromosomal abnormality analysis of products of conception in spontaneous and recurrent miscarriage. BJOG. 2018;125(4):414–20.CrossRefGoogle ScholarPubMed
Lathi, R. B., Gustin, S. L. F., Keller, J., Maisenbacher, M. K., Sigurjonsson, S., Tao, R., et al. Reliability of 46,XX results on miscarriage specimens: a review of 1,222 first-trimester miscarriage specimens. Fertil Steril. 2014;101(1):178–82.CrossRefGoogle ScholarPubMed
Shearer, B. M., Thorland, E. C., Carlson, A. W., Jalal, S. M., Ketterling, R. P.. Reflex fluorescent in situ hybridization testing for unsuccessful product of conception cultures: a retrospective analysis of 5555 samples attempted by conventional cytogenetics and fluorescent in situ hybridization. Genet Med. 2011;13(6):545–52.CrossRefGoogle ScholarPubMed
Jobanputra, V., Esteves, C., Sobrino, A., Brown, S., Kline, J., Warburton, D.. Using FISH to increase the yield and accuracy of karyotypes from spontaneous abortion specimens. Prenat Diagn. 2011;31(8):755–59.CrossRefGoogle Scholar
Karaoguz, M. Y., Nas, T., Konac, E., Ince, D., Pala, E., Menevse, S.. Is cytogenetic diagnosis of 46,XX karyotype spontaneous abortion specimens erroneous? Fluorescence in situ hybridization as a confirmatory technique. J Obstet Gynaecol Res. 2005;31(6):508–13.CrossRefGoogle ScholarPubMed
Levy, B., Wapner, R.. Prenatal diagnosis by chromosomal microarray analysis. Fertil Steril. 2018;109(2):201–12.CrossRefGoogle ScholarPubMed
Wang, Y., Li, Y., Chen, Y., Zhou, R., Sang, Z., Meng, L., et al. Systematic analysis of copy-number variations associated with early pregnancy loss. Ultrasound Obstet Gynecol. 2020;55(1):96–104.CrossRefGoogle ScholarPubMed
Dar, P., Jacobsson, B., Clifton, R., Egbert, M., Malone, F., Wapner, R. J., et al. Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome. Am J Obstet Gynecol. 2022;227(1):79.e1–11.CrossRefGoogle ScholarPubMed
Committee on Genetics and the Society for Maternal–Fetal Medicine. Committee opinion no.682: microarrays and next-generation sequencing technology the use of advanced genetic diagnostic tools in obstetrics and gynecology. Obstet Gynecol. 2016;128(6):e262–68.Google Scholar
American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine in collaboration with Metz, T. D., Berry, R. S., Fretts, R. C., Reddy, U. M., et al. Obstetric care consensus #10: management of stillbirth: (replaces practice bulletin number 102, March 2009). Am J Obstet Gynecol. 2020;222(3):B2–20.CrossRefGoogle Scholar
Hay, S. B., Sahoo, T., Travis, M. K., Hovanes, K., Dzidic, N., Doherty, C., et al. ACOG and SMFM guidelines for prenatal diagnosis: is karyotyping really sufficient? Prenat Diagn. 2018;38(3):184–89.CrossRefGoogle ScholarPubMed
Schaeffer, A. J., Chung, J., Heretis, K., Wong, A., Ledbetter, D. H., Lese Martin, C.. Comparative genomic hybridization–array analysis enhances the detection of aneuploidies and submicroscopic imbalances in spontaneous miscarriages. Am J Hum Genet. 2004;74(6):1168–74.CrossRefGoogle ScholarPubMed
Benkhalifa, M., Kasakyan, S., Clement, P., Baldi, M., Tachdjian, G., Demirol, A., et al. Array comparative genomic hybridization profiling of first-trimester spontaneous abortions that fail to grow in vitro. Prenat Diagn. 2005;25(10):894–900.CrossRefGoogle ScholarPubMed
Warren, J. E., Turok, D. K., Maxwell, T. M., Brothman, A. R., Silver, R. M.. Array comparative genomic hybridization for genetic evaluation of fetal loss between 10 and 20 weeks of gestation. Obstet Gynecol. 2009;114(5):1093–102.CrossRefGoogle ScholarPubMed
Reddy, U. M., Page, G. P., Saade, G. R., Silver, R. M., Thorsten, V. R., Parker, C. B., et al. Karyotype versus microarray testing for genetic abnormalities after stillbirth. N Engl J Med. 2012;367(23):2185–93.CrossRefGoogle ScholarPubMed
Rao, H., Zhang, H., Zou, Y., Ma, P., Huang, T., Yuan, H., et al. Analysis of chromosomal structural variations in patients with recurrent spontaneous abortion using optical genome mapping. Front Genet. 2023;14;1248755.CrossRefGoogle ScholarPubMed
Sahajpal, N. S., Mondal, A. K., Ananth, S., Pundkar, C., Jones, K., Williams, C., et al. Optical genome mapping and single nucleotide polymorphism microarray: an integrated approach for investigating products of conception. Genes (Basel). 2022;13(4):643.CrossRefGoogle ScholarPubMed
Brody, S., Dubuc, A. M., Kim, A. S.. Optical genome mapping: a ‘tool’ with significant potential from discovery to diagnostics. College of American Pathologists. Accessed July 21, 2024. www.cap.org/member-resources/articles/optical-genome-mapping-a-tool-with-significant-potential-from-discovery-to-diagnostics.Google Scholar
Avram, C. M., Caughey, A. B., Norton, M. E., Sparks, T. N.. Cost-effectiveness of exome sequencing versus targeted gene panels for prenatal diagnosis of fetal effusions and non-immune hydrops fetalis. Am J Obstet Gynecol MFM. 2022;4(6):100724.CrossRefGoogle ScholarPubMed
Sparks, T. N., Lianoglou, B. R., Adami, R. A., Pluym, I. D., Holliman, K., Duffy, J., et al. Exome sequencing for prenatal diagnosis in nonimmune hydrops fetalis. N Eng J Med. 2020;383(18):1746–56.CrossRefGoogle ScholarPubMed
Monaghan, K. G., Leach, N. T., Pekarek, D., Prasad, P., Rose, N. C., ACMG Professional Practice and Guidelines Committee. The use of fetal exome sequencing in prenatal diagnosis: a points to consider document of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2020;22(4):675–80.CrossRefGoogle ScholarPubMed
Shear, M., Swanson, K., Norton, M. E., Sparks, T. N.. Prenatal exome sequencing versus targeted gene panel for evaluation of fetal congenital heart defects. Am J Obstet Gynecol. 2023;228(1):S697–98.CrossRefGoogle Scholar
Belyeu, J. R., Brand, H., Wang, H., Zhao, X., Pedersen, B. S., Feusier, J., et al. De novo structural mutation rates and gamete-of-origin biases revealed through genome sequencing of 2,396 families. Am J Hum Genet. 2021;108(4):597–607.CrossRefGoogle ScholarPubMed
Kong, A., Frigge, M. L., Masson, G., Besenbacher, S., Sulem, P., Magnusson, G., et al. Rate of de novo mutations, father’s age, and disease risk. Nature. 2012;488(7412):471–75.CrossRefGoogle Scholar
Rahbari, R., Wuster, A., Lindsay, S. J., Hardwick, R. J., Alexandrov, L. B., Turki, S. A., et al. Timing, rates and spectra of human germline mutation. Nat Genet. 2016;48(2):126–33.CrossRefGoogle ScholarPubMed
Goldmann, J. M., Wong, W. S. W., Pinelli, M., Farrah, T., Bodian, D., Stittrich, A. B., et al. Parent-of-origin-specific signatures of de novo mutations. Nat Genet. 2016;48(8):935–39.CrossRefGoogle ScholarPubMed
Francioli, L. C., Polak, P. P., Koren, A., Menelaou, A., Chun, S., Renkens, I., et al. Genome-wide patterns and properties of de novo mutations in humans. Nat Genet. 2015;47(7):822–26.CrossRefGoogle Scholar
Acuna-Hidalgo, R., Veltman, J. A., Hoischen, A.. New insights into the generation and role of de novo mutations in health and disease. Genome Biol. 2016;17(1):241.CrossRefGoogle Scholar
Taylor, J. L., Debost, J.-C. P. G., Morton, S. U., Wigdor, E. M., Heyne, H. O., Lal, D., et al. Paternal-age-related de novo mutations and risk for five disorders. Nat Commun. 2019;10:3043.CrossRefGoogle ScholarPubMed
Wood, K. A., Goriely, A.. The impact of paternal age on new mutations and disease in the next generation. Fertil Steril. 2022;118(6):1001–12.CrossRefGoogle ScholarPubMed
Toriello, H. V., Meck, J. M.. Statement on guidance for genetic counseling in advanced paternal age. Genet Med. 2008;10(6):457–60.CrossRefGoogle ScholarPubMed
Cuckle, H., Morris, J.. Maternal age in the epidemiology of common autosomal trisomies. Prenat Diagn. 2021;41(5):573–83.Google ScholarPubMed
Harper, P. S.. Special problems in genetic counselling. In Harper, P. S., ed. Practical genetic counselling. 3rd ed.: Butterworth-Heinemann; 1988:112–24. doi.org/10.1016/B978-0-7236-1019-9.50015-1.Google Scholar
Najafi, K., Mehrjoo, Z., Ardalani, F., Ghaderi-Sohi, S., Kariminejad, A., Kariminejad, R., et al. Identifying the causes of recurrent pregnancy loss in consanguineous couples using whole exome sequencing on the products of miscarriage with no chromosomal abnormalities. Sci Rep. 2021;11(1):6952.CrossRefGoogle ScholarPubMed
Stanley, K. E., Giordano, J., Thorsten, V., Buchovecky, C., Thomas, A., Ganapathi, M., et al. Causal genetic variants in stillbirth. N Eng J Med. 2020;383(12):1107–16.CrossRefGoogle ScholarPubMed
Columbia University Department of Obstetrics & Gynecology. Fetal sequencing consortium. Accessed July 21, 2024. www.obgyn.columbia.edu/fsc.Google Scholar
Stefka, J., El-Khechen, D., Cain, T., Blanco, K., Feldmann, B., Towne, M. C., et al. Misattributed parentage identified through diagnostic exome sequencing: frequency of detection and reporting practices. J Genet Couns. 2022;31(3):631–40.CrossRefGoogle ScholarPubMed
Sanghvi, R. V., Buhay, C. J., Powell, B. C., Tsai, E. A., Dorschner, M. O., Hong, C. S., et al. Characterizing reduced coverage regions through comparison of exome and genome sequencing data across ten centers. Genet Med. 2018;20(8):855–66.CrossRefGoogle Scholar
Deignan, J. L., De Castro, M., Horner, V. L., Johnston, T., Macaya, D., Maleszewski, J. J., et al. Points to consider in the practice of postmortem genetic testing: a statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2023;25(5):100017.CrossRefGoogle ScholarPubMed
Cohen, J. L., Chakraborty, P., Fung-Kee-Fung, K., Schwab, M. E., Bali, D., Young, S. P., et al. In utero enzyme-replacement therapy for infantile-onset Pompe’s disease. N Eng J Med. 2022;387(23):2150–58.CrossRefGoogle ScholarPubMed
Norton, M. E., Chauhan, S. P., Dashe, J. S.. Society for Maternal–Fetal Medicine (SMFM) clinical guideline #7: nonimmune hydrops fetalis. Am J Obstet Gynecol. 2015;212(2):127–39.CrossRefGoogle Scholar
Quinn, A. M., Valcarcel, B. N., Makhamreh, M. M., Al-Kouatly, H. B., Berger, S. I.. A systematic review of monogenic etiologies of nonimmune hydrops fetalis. Genet Med. 2021;23(1):3–12.CrossRefGoogle ScholarPubMed
Santolaya, J., Alley, D., Jaffe, R., Warsof, S. L.. Antenatal classification of hydrops fetalis. Obstet Gynecol. 1992;79(2):256–59.Google ScholarPubMed
Hamdan, M. A., El-Zoabi, B. A., Begam, M. A., Mirghani, H. M., Almalik, M. H.. Antenatal diagnosis of Pompe disease by fetal echocardiography: impact on outcome after early initiation of enzyme replacement therapy. J Inherit Metab Dis. 2010;33(Suppl 3):S333–39.CrossRefGoogle ScholarPubMed
Lee, K., Fisher, R., Quinonez, S.C., Ahmad, A.. Infantile onset Pompe disease presenting with non-immune hydrops fetalis. Mol Genet Metab Rep. 2019;21:100503.Google ScholarPubMed
Chien, Y.-H., Lee, N.-C., Thurberg, B. L., Chiang, S.-C., Zhang, X. K., Keutzer, J., et al. Pompe Disease in infants: improving the prognosis by newborn screening and early treatment. Pediatrics. 2009;124(6):e1116–25.CrossRefGoogle ScholarPubMed
Li, C., Desai, A. K., Gupta, P., Dempsey, K., Bhambhani, V., Hopkin, R. J., et al. Transforming the clinical outcome in CRIM-negative infantile Pompe disease identified via newborn screening: the benefits of early treatment with enzyme replacement therapy and immune tolerance induction. Genet Med. 2021;23(5):845–55.CrossRefGoogle ScholarPubMed
HRSA. Recommended uniform screening panel. Accessed June 21, 2024. www.hrsa.gov/advisory-committees/heritable-disorders/rusp.Google Scholar
Mackenzie, T.. In utero enzyme replacement therapy for prenatally diagnosed lysosomal storage disorders (IUERT). Report no. NCT04532047. Last updated September 21, 2023. https://clinicaltrials.gov/study/NCT04532047.Google Scholar
Committee opinion no. 690 summary: carrier screening in the age of genomic medicine. Obstet Gynecol. 2017;129(3):e35–40.CrossRefGoogle Scholar
Gregg, A. R., Aarabi, M., Klugman, S., Leach, N. T., Bashford, M. T., Goldwaser, T., et al. Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23(10):1793–806.Google ScholarPubMed
Stoll, K.. ACMG carrier screening guideline: the hypothetical “tier 3” panel. The DNA Exchange. 2022. https://thednaexchange.com/2022/03/30/acmg-carrier-screening-guideline-the-hypothetical-tier-3-panel.Google Scholar
Dungan, J. S., Klugman, S., Darilek, S., Malinowski, J., Akkari, Y. M. N., Monaghan, K. G., et al. Noninvasive prenatal screening (NIPS) for fetal chromosome abnormalities in a general-risk population: An evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2023;25(2):100336.CrossRefGoogle Scholar
Hartwig, T. S., Ambye, L., Gruhn, J. R., Petersen, J. F., Wrønding, T., Amato, L., et al. Cell-free fetal DNA for genetic evaluation in Copenhagen Pregnancy Loss Study (COPL): a prospective cohort study. Lancet. 2023;401(10378):762–71.Google Scholar
Balaguer, N., Rodrigo, L., Mateu-Brull, E., Campos-Galindo, I., Castellón, J. A., Al-Asmar, N., et al. Non-invasive cell-free DNA-based approach for the diagnosis of clinical miscarriage: a retrospective study. BJOG. 2023;131(2):213–21.Google ScholarPubMed
Yan, J., Qin, Y., Zhao, H., Sun, Y., Gong, F., Li, R., et al. Live birth with or without preimplantation genetic testing for aneuploidy. N Eng J Med. 2021;385(22):2047–58.CrossRefGoogle ScholarPubMed
Cascante, S. D., Besser, A., Lee, H. L., Wang, F., McCaffrey, C., Grifo, J. A.. Blinded rebiopsy and analysis of noneuploid embryos with 2 distinct preimplantation genetic testing platforms for aneuploidy. Fertil Steril. 2023;120(6):1161–69.CrossRefGoogle ScholarPubMed
Lathi, R. B.. Transfer of aneuploid or mosaic embryos following preimplantation genetic testing. Report no. NCT04109846. Last updated January 26, 2024. https://clinicaltrials.gov/study/NCT04109846.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×