Noninvasive Prenatal Diagnostics: Recent Developments Using Circulating Fetal Nucleated Cells

  • Pin-Jung Chen
  • Pai-Chi Teng
  • Yazhen Zhu
  • Yu Jen Jan
  • Matthew Smalley
  • Yalda Afshar
  • Li-Ching Chen
  • Margareta D. PisarskaEmail author
  • Hsian-Rong TsengEmail author
High-risk Gestation and Prenatal Medicine (T-F Chan, Section Editor)
Part of the following topical collections:
  1. Topical Collection on High-risk Gestation and Prenatal Medicine


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.


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.


Noninvasive prenatal diagnostic Circulating fetal nucleated red blood cell Circulating trophoblast Whole genome amplification Array comparative genomic hybridization Short tandem repeat 


Compliance with Ethical Standards

Conflict of Interest

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.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Pin-Jung Chen
    • 1
  • Pai-Chi Teng
    • 1
  • Yazhen Zhu
    • 1
  • Yu Jen Jan
    • 2
  • Matthew Smalley
    • 1
  • Yalda Afshar
    • 3
  • Li-Ching Chen
    • 4
  • Margareta D. Pisarska
    • 3
    • 5
    Email author
  • Hsian-Rong Tseng
    • 1
    Email author
  1. 1.Department of Molecular and Medical Pharmacology, California NanoSystems Institute (CNSI), Crump Institute for Molecular ImagingUniversity of California, Los AngelesLos AngelesUSA
  2. 2.Urologic Oncology Program and Uro-Oncology Research Laboratories, Cedars-Sinai Medical CenterSamuel Oschin Comprehensive Cancer InstituteLos AngelesUSA
  3. 3.Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, David Geffen School of MedicineUniversity of CaliforniaLos AngelesUSA
  4. 4.Department of Obstetrics and GynecologyCathay General HospitalTaipeiTaiwan
  5. 5.Department of Obstetrics and GynecologyCedars-Sinai Medical CenterLos AngelesUSA

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