Reasons for Failure of Noninvasive Prenatal Test for Cell-free Fetal DNA in Maternal Peripheral Blood

Overview

Journal Mol Genet Genomic Med

Specialty Genetics

Date 2024 Jan 29

PMID 38284448

Authors

Xiangsha Kong

Lin Zhang

Ruifeng Yang

Haiying Zhang

Meihong Ren

Xiang Wang

Ling Zhu

Hongsong Chen

Huiying Rao

Affiliations

Soon will be listed here.

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.

Citing Articles

A Decade of Non-Invasive Prenatal Testing (NIPT) for Chromosomal Abnormalities in Croatia: First National Monocentric Study to Inform Country's Future Prenatal Care Strategy.

Podobnik P, Mestrovic T, dordevic A, Kurdija K, Jelcic D, Ogrin N Genes (Basel). 2025; 15(12.

PMID: 39766857 PMC: 11675109. DOI: 10.3390/genes15121590.

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

Kong X, Zhang L, Yang R, Zhang H, Ren M, Wang X Mol Genet Genomic Med. 2024; 12(1):e2351.

PMID: 38284448 PMC: 10795076. DOI: 10.1002/mgg3.2351.

References

Hui L, Bianchi D . Fetal fraction and noninvasive prenatal testing: What clinicians need to know. Prenat Diagn. 2019; 40(2):155-163. PMC: 10040212. DOI: 10.1002/pd.5620. View

Hui C, Tan W, Tan E, Tan L . Repeated failed non-invasive prenatal testing in a woman with immune thrombocytopenia and antiphospholipid syndrome: lessons learnt. BMJ Case Rep. 2016; 2016. PMC: 5174759. DOI: 10.1136/bcr-2016-216593. View

Borth H, Teubert A, Glaubitz R, Knippenberg S, Kutur N, Winkler T . 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. Arch Gynecol Obstet. 2020; 303(6):1407-1414. PMC: 8087552. DOI: 10.1007/s00404-020-05856-0. View

Grace M, Hardisty E, Dotters-Katz S, Vora N, Kuller J . Cell-Free DNA Screening: Complexities and Challenges of Clinical Implementation. Obstet Gynecol Surv. 2016; 71(8):477-87. PMC: 5548289. DOI: 10.1097/OGX.0000000000000342. View

Hartwig T, Ambye L, Sorensen S, Jorgensen F . Discordant non-invasive prenatal testing (NIPT) - a systematic review. Prenat Diagn. 2017; 37(6):527-539. DOI: 10.1002/pd.5049. View

Yu B, Lu B, Zhang B, Zhang X, Chen Y, Zhou Q . Overall evaluation of the clinical value of prenatal screening for fetal-free DNA in maternal blood. Medicine (Baltimore). 2017; 96(27):e7114. PMC: 5502138. DOI: 10.1097/MD.0000000000007114. View

Wang W, Duan H, Ding W, Zhang Y, Zhu R, Li J . [Analysis to the failure rate and causes of noninvasive prenatal testing based on high-throughput sequencing]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021; 38(12):1171-1175. DOI: 10.3760/cma.j.cn511374-20200916-00672. View

Scott F, Menezes M, Palma-Dias R, Nisbet D, Schluter P, da Silva Costa F . Factors affecting cell-free DNA fetal fraction and the consequences for test accuracy. J Matern Fetal Neonatal Med. 2017; 31(14):1865-1872. DOI: 10.1080/14767058.2017.1330881. View

Gromminger S, Erkan S, Schock U, Stangier K, Bonnet J, Schloo R . The influence of low molecular weight heparin medication on plasma DNA in pregnant women. Prenat Diagn. 2015; 35(11):1155-7. DOI: 10.1002/pd.4668. View

10.

Xu L, Huang H, Lin N, Wang Y, He D, Zhang M . Non-invasive cell-free fetal DNA testing for aneuploidy: multicenter study of 31 515 singleton pregnancies in southeastern China. Ultrasound Obstet Gynecol. 2019; 55(2):242-247. DOI: 10.1002/uog.20416. View

11.

Willems P, Dierickx H, Vandenakker E, Bekedam D, Segers N, Deboulle K . The first 3,000 Non-Invasive Prenatal Tests (NIPT) with the Harmony test in Belgium and the Netherlands. Facts Views Vis Obgyn. 2014; 6(1):7-12. PMC: 4086005. View

12.

Hui L, Bethune M, Weeks A, Kelley J, Hayes L . Repeated failed non-invasive prenatal testing owing to low cell-free fetal DNA fraction and increased variance in a woman with severe autoimmune disease. Ultrasound Obstet Gynecol. 2014; 44(2):242-3. DOI: 10.1002/uog.13418. View

13.

Lo Y, Corbetta N, Chamberlain P, Rai V, Sargent I, Redman C . Presence of fetal DNA in maternal plasma and serum. Lancet. 1997; 350(9076):485-7. DOI: 10.1016/S0140-6736(97)02174-0. View

14.

Yaron Y . The implications of non-invasive prenatal testing failures: a review of an under-discussed phenomenon. Prenat Diagn. 2016; 36(5):391-6. DOI: 10.1002/pd.4804. View

15.

Pergament E, Cuckle H, Zimmermann B, Banjevic M, Sigurjonsson S, Ryan A . Single-nucleotide polymorphism-based noninvasive prenatal screening in a high-risk and low-risk cohort. Obstet Gynecol. 2014; 124(2 Pt 1):210-218. PMC: 4144440. DOI: 10.1097/AOG.0000000000000363. View

16.

Norton M, Jacobsson B, Swamy G, Laurent L, Ranzini A, Brar H . Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med. 2015; 372(17):1589-97. DOI: 10.1056/NEJMoa1407349. View

17.

Kong X, Zhang L, Yang R, Zhang H, Ren M, Wang X . Reasons for failure of noninvasive prenatal test for cell-free fetal DNA in maternal peripheral blood. Mol Genet Genomic Med. 2024; 12(1):e2351. PMC: 10795076. DOI: 10.1002/mgg3.2351. View