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. 2025 Sep;120(9):935-943.
doi: 10.1111/vox.70062. Epub 2025 Jun 9.

Noninvasive fetal antigen genotyping: Results from a survey on the status of clinical implementation

Frederik Banch Clausen  1   2 , Åsa Hellberg  2   3 , Cécile Toly-Ndour  4 , Emilie Thorup Nielsen  5 , Masja de Haas  6   7 ; Noninvasive Fetal Antigen Genotyping Survey Group
Collaborators, Affiliations

Noninvasive fetal antigen genotyping: Results from a survey on the status of clinical implementation

Frederik Banch Clausen et al. Vox Sang. 2025 Sep.

Abstract

Background and objectives: Noninvasive fetal antigen genotyping can assist the management of immunized pregnant women, and fetal RHD genotyping can be used as a screening assay to guide restricted use of Rh prophylaxis. Based on a survey, we present an overview of the implementation of noninvasive fetal antigen genotyping into clinical practice.

Materials and methods: A survey was developed and sent out to the members of the International Society of Blood Transfusion (ISBT) working party on Red Cell Immunogenetics and Blood Group Terminology and to participants of the international noninvasive fetal RHD genotyping programme from the Danish Institute for External Quality Assurance for Laboratories in the health sector (DEKS). The survey contained four sections: fetal RHD screening, fetal RHD genotyping for RhD immunized women, fetal genotyping of other antigen targets than RhD and a section for collecting topics for future collaboration. The survey data were evaluated by the core author group.

Results: Fifty-two survey responders were from 22 countries. Fetal RHD screening was implemented by 73%, foremost using real-time PCR with in-house assays, primarily, or commercially available kits. Most laboratories use the same assay for RhD immunized women. Thirty-eight percent of the responders test for other antigen targets than RhD, using either real-time PCR, droplet digital PCR (ddPCR) or DNA sequencing. There was an interest in collaborations on topics across methodology, technology, strategy and health care regulations.

Conclusion: In general, we found that noninvasive fetal blood group antigen genotyping is well implemented. However, our results are biased towards high-income countries, Europe and laboratories already running noninvasive fetal antigen genotyping.

Keywords: HDFN; RhD; blood group; cell‐free fetal DNA; prophylaxis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
The country distribution of the survey responders (n = 52).
FIGURE 2
FIGURE 2
(a) How many fetal RHD screening samples do you test per year? The y‐axis shows the number of samples tested per year and the x‐axis shows the number of laboratories in each group. (b) In which gestational week is the fetal RHD screening performed? The x‐axis shows the week and the y‐axis shows the number of laboratories. (c) How many samples do you test per year for immunized women, non‐RHD target? The x‐axis shows the number of samples and the y‐axis shows the number of laboratories in each category. (d) How many years of experience does your laboratory have with fetal genotyping? The x‐axis shows the number of years and the y‐axis shows the number of laboratories in each category.
See this image and copyright information in PMC

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