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Noninvasive Prenatal Diagnostics: Recent Developments Using Circulating Fetal Nucleated Cells

  • High-risk Gestation and Prenatal Medicine (T-F Chan, Section Editor)
  • Published:
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Abstract

Purpose of Review

The purpose of this review is to highlight recent research advances in noninvasive prenatal diagnostic methods.

Recent Findings

Recent studies developing noninvasive prenatal diagnostic (NIPD) methods have been focused on either fetal nucleated red blood cells (fNRBCs) or circulating trophoblasts (cTBs). Enriched cTBs were successfully utilized for whole genome profiling and short tandem repeat (STR) identification to confirm feto-maternal relationship. However, further analysis of isolated fNRBCs remains confined to examining fetal cytogenetics.

Summary

Invasive prenatal diagnostic procedures, amniocentesis, and chorionic villus sampling, are the gold standard for the diagnosis of fetal chromosomal abnormalities and genetic disorders. Meanwhile, noninvasive techniques of analyzing circulating cell-free fetal DNA (cffDNA) have been limited to screening tools and are highly fragmented and confounded by maternal DNA. By detecting circulating fetal nucleated cells (CFNCs) we are able to noninvasively confirm fetal chromosomal abnormalities, truly realizing the concept of “noninvasive prenatal diagnostics”. The primary technical challenge is the enrichment of the low abundance of CFNCs in maternal peripheral blood. For any cell-based NIPD method, both fetal whole genome profiling and confirmation of the feto-parental relationship are essential. This has been successfully performed using enriched and isolated cTBs, making cTB a better candidate for NIPD. cTB enumeration also correlates with abnormal fetal or placental development. On the other hand, downstream analysis of fNRBCs remains limited to examining fetal sex and aneuploidies. Furthermore, trophoblast-based NIPD via an endocervical sample is also promising because of reduced dilution from hematologic cells.

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Author notes

  1. Pin-Jung Chen and Pai-Chi Teng contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular and Medical Pharmacology, California NanoSystems Institute (CNSI), Crump Institute for Molecular Imaging, University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA, 90095-1770, USA

    Pin-Jung Chen, Pai-Chi Teng, Yazhen Zhu, Matthew Smalley & Hsian-Rong Tseng

  2. Urologic Oncology Program and Uro-Oncology Research Laboratories, Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA

    Yu Jen Jan

  3. Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Mark Goodson Building, Suite 1002, 444 S. San Vicente Blvd, Los Angeles, CA, 90048, USA

    Yalda Afshar & Margareta D. Pisarska

  4. Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan

    Li-Ching Chen

  5. Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Margareta D. Pisarska

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Pin-Jung Chen, Pai-Chi Teng, Yazhen Zhu, Yu Jen Jan, Yalda Afshar, Li-Ching Chen, Margareta D. Pisarska, and Hsian-Rong Tseng declare no conflict of interest. Dr. Smalley reports personal fees from CytoLumina.

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Chen, PJ., Teng, PC., Zhu, Y. et al. Noninvasive Prenatal Diagnostics: Recent Developments Using Circulating Fetal Nucleated Cells. Curr Obstet Gynecol Rep 8, 1–8 (2019). https://doi.org/10.1007/s13669-019-0254-x

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