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. 2024 Jan;12(1):e2351.
doi: 10.1002/mgg3.2351.

Reasons for failure of noninvasive prenatal test for cell-free fetal DNA in maternal peripheral blood

Xiangsha Kong  1 , Lin Zhang  2 , Ruifeng Yang  1 , Haiying Zhang  1 , Meihong Ren  2 , Xiang Wang  3 , Ling Zhu  1 , Hongsong Chen  1 , Huiying Rao  1
Affiliations

Reasons for failure of noninvasive prenatal test for cell-free fetal DNA in maternal peripheral blood

Xiangsha Kong et al. Mol Genet Genomic Med. 2024 Jan.

Abstract

Background: To explore reasons for the failure of noninvasive prenatal test (NIPT) for cell-free fetal DNA (cffDNA) in maternal peripheral blood, and discuss appropriate treatment schemes after the failure of the test.

Methods: Altogether 41,136 pregnant women participated in NIPT. Blood samples were taken again from pregnant women who failed the first blood collection upon their informed consent. Prenatal genetic counseling or prenatal diagnosis was recommended for pregnant women with final NIPT failure.

Results: The first failure rate of NIPT was 0.737% (303/41136), and the reason for the failure was the low ratio of cffDNA in 135 (44.6%) of the 303 pregnant women. After the second or third blood sampling, the final failure rate was 0.182% (75/41136). The low ratio of cffDNA was the main reason for test failure in 42 (56.0%) of the 75 pregnant women who finally failed NIPT, among whom 44 (58.7%) had underlying diseases, including 21 (47.7%) with more than two coexisting underlying diseases. Only 27 (36.0%) of the 75 pregnant women with NIPT failure underwent interventional prenatal diagnosis.

Conclusions: The main reason for NIPT failure was the low ratio of cffDNA. Postponing the gestational weeks of blood collection may improve the success rate. Resampling and retesting upon informed consent in pregnant women who failed the first test could improve the success rate. For pregnant women who finally failed NIPT, it is suggested strengthening the genetic counseling, prenatal examination, and ultrasound evaluation, and carry out interventional prenatal diagnosis if necessary.

Keywords: NIPT; cffDNA; failure.

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Conflict of interest statement

The authors declare that the research is conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Treatment process after failure to obtain effective NIPT results. T21 is trisomy 21, T18 is trisomy 18, T13 is trisomy 13. NIPT, noninvasive prenatal test.
FIGURE 2
FIGURE 2
Analysis of the gestational days and age among the pregnant women who failed to obtain effective results in the first test, and who failed to obtain effective results in the final test, and who succeeded in the final test. 2a) was the analysis of the gestational days among the pregnant women. We converted the gestational week into gestational days, and conducted the statistical analysis of the gestational days among the three groups. 2b) was the analysis of the gestational age among the pregnant women.
FIGURE 3
FIGURE 3
Changes in cffDNA ratio with increasing gestational weeks. Cases 1 to 4 had been underwent three blood sampling, and obtained effective results. The cffDNA ratio from cases 1 to 4 evidently increased with the increase of the gestational weeks. Cases 5 and 6 had been underwent three blood sampling, but failed to obtained effective results. The cffDNA ratio from cases 5 and 6 increased with the increase of gestational weeks very slowly. cffDNA, cell‐free fetal DNA.
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References

    1. Borth, H. , Teubert, A. , Glaubitz, R. , Knippenberg, S. , Kutur, N. , Winkler, T. , & Eiben, B. (2021). Analysis of cell‐free DNA in a consecutive series of 13,607 routine cases for the detection of fetal chromosomal aneuploidies in a single center in Germany. Archives of Gynecology and Obstetrics, 303(6), 1407–1414. 10.1007/s00404-020-05856-0 - DOI - PMC - PubMed
    1. Grace, M. R. , Hardisty, E. , Dotters‐Katz, S. K. , Vora, N. L. , & Kuller, J. A. (2016). Cell‐free DNA screening: Complexities and challenges of clinical implementation. Obstetrical & Gynecological Survey, 71(8), 477–487. 10.1097/OGX.0000000000000342 - DOI - PMC - PubMed
    1. Grömminger, S. , Erkan, S. , Schöck, U. , Stangier, K. , Bonnet, J. , Schloo, R. , Schubert, A. , Prott, E. C. , Knoll, U. , Stumm, M. , von Kalle, C. , & Hofmann, W. (2015). The influence of low molecular weight heparin medication on plasma DNA in pregnant women. Prenatal Diagnosis, 35(11), 1155–1157. 10.1002/pd.4668 - DOI - PubMed
    1. Hartwig, T. S. , Ambye, L. , Sørensen, S. , & Jørgensen, F. S. (2017). Discordant non‐invasive prenatal testing (NIPT)—A systematic review. Prenatal Diagnosis, 37(6), 527–539. 10.1002/pd.5049 - DOI - PubMed
    1. Health and Family Planning Committee, P. R. China . (2016). Technical specification for prenatal screening and diagnosis of fetal free DNA in maternal peripheral blood[S].

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