Factors Affecting Cell-free DNA Fetal Fraction: Statistical Analysis of 13,661 Maternal Plasmas for Non-invasive Prenatal Screening

Overview

Journal Hum Genomics

Publisher Biomed Central

Specialty Genetics

Date 2019 Dec 6

PMID 31801621

Citations 31

Authors

Yaping Hou

Jiexia Yang

Yiming Qi

Fangfang Guo

Haishan Peng

Dongmei Wang

Yixia Wang

Xiaohui Luo

Yi Li

Aihua Yin

Affiliations

Soon will be listed here.

Abstract

Background: The identification of cell-free fetal DNA (cffDNA) facilitated non-invasive prenatal screening (NIPS) through analysis of cffDNA in maternal plasma. However, challenges regarding its clinical implementation become apparent. Factors affecting fetal fraction should be clarified to guide its clinical application.

Results: A total of 13,661 pregnant subjects with singleton pregnancies who undertook NIPS were included in the study. Relationship of gestational age, maternal BMI, and maternal age with the cffDNA fetal fraction in maternal plasmas for NIPS was investigated. Compared with 13 weeks (12.74%) and 14-18 weeks group (12.73%), the fetal fraction in gestational ages of 19-23 weeks, 24-28 weeks, and more than 29 weeks groups significantly increased to 13.11%, 16.14%, and 21.17%, respectively (P < 0.01). Compared with fetal fraction of 14.54% in the maternal BMI group of < 18.5 kg/m, the percentage of fetal fraction in the group of 18.5-24.9 kg/m (13.37%), 25-29.9 kg/m (12.20%), 30-34.9 kg/m (11.32%), and 35-39.9 kg/m (11.57%) decreased significantly (P < 0.01). Compared with the fetal fraction of 14.38% in the group of 18-24 years old, the fetal fraction in the maternal age group of 25-29 years old group (13.98%) (P < 0.05), 30-34 years old group (13.18%) (P < 0.01), 35-39 years old group (12.34%) (P < 0.01), and ≥ 40 years old (11.90%) group (P < 0.01) decreased significantly.

Conclusions: The percentage of fetal fraction significantly increased with increase of gestational age. Decreased fetal fraction with increasing maternal BMI was found. Maternal age was also negatively related to the fetal fraction.

Citing Articles

The association between the amount of fetal fraction in cell-free DNA testing and adverse pregnancy outcomes: A cohort study.

Aryavand M, Nurzadeh M, Ghaemi M, Eskandari Delfan S, Marsoosi V Int J Reprod Biomed. 2025; 22(11):919-926.

PMID: 39866589 PMC: 11757670. DOI: 10.18502/ijrm.v22i11.17824.

Artificial intelligence and machine learning in cell-free-DNA-based diagnostics.

Tsui W, Ding S, Jiang P, Lo Y Genome Res. 2025; 35(1):1-19.

PMID: 39843210 PMC: 11789496. DOI: 10.1101/gr.278413.123.

Longitudinal integrative cell-free DNA analysis in gestational diabetes mellitus.

Tang Z, Wang S, Li X, Hu C, Zhai Q, Wang J Cell Rep Med. 2024; 5(8):101660.

PMID: 39059385 PMC: 11384941. DOI: 10.1016/j.xcrm.2024.101660.

Advancements of non-invasive prenatal testing: the role of obstetricians.

Eltabbakh N, Mohasin Y, Jeddy R Front Med (Lausanne). 2024; 11:1388481.

PMID: 38938382 PMC: 11208619. DOI: 10.3389/fmed.2024.1388481.

Enhancing fetal outcomes in GCK-MODY pregnancies: a precision medicine approach via non-invasive prenatal mutation detection.

Schwitzgebel V, Blouin J, Dehos B, Kohler-Ballan B, Puder J, Rieubland C Front Med (Lausanne). 2024; 11:1347290.

PMID: 38745742 PMC: 11091329. DOI: 10.3389/fmed.2024.1347290.

References

Liao C, Yin A, Peng C, Fu F, Yang J, Li R . Noninvasive prenatal diagnosis of common aneuploidies by semiconductor sequencing. Proc Natl Acad Sci U S A. 2014; 111(20):7415-20. PMC: 4034209. DOI: 10.1073/pnas.1321997111. View

Lo Y, Zhang J, Leung T, Lau T, Chang A, Hjelm N . Rapid clearance of fetal DNA from maternal plasma. Am J Hum Genet. 1999; 64(1):218-24. PMC: 1377720. DOI: 10.1086/302205. View

Wang E, Batey A, Struble C, Musci T, Song K, Oliphant A . Gestational age and maternal weight effects on fetal cell-free DNA in maternal plasma. Prenat Diagn. 2013; 33(7):662-6. DOI: 10.1002/pd.4119. View

Shaffer B, Norton M . Cell-Free DNA Screening for Aneuploidy and Microdeletion Syndromes. Obstet Gynecol Clin North Am. 2018; 45(1):13-26. DOI: 10.1016/j.ogc.2017.10.001. View

Illanes S, Denbow M, Kailasam C, Finning K, Soothill P . Early detection of cell-free fetal DNA in maternal plasma. Early Hum Dev. 2007; 83(9):563-6. DOI: 10.1016/j.earlhumdev.2006.11.001. View

Ashoor G, Syngelaki A, Poon L, Rezende J, Nicolaides K . Fetal fraction in maternal plasma cell-free DNA at 11-13 weeks' gestation: relation to maternal and fetal characteristics. Ultrasound Obstet Gynecol. 2012; 41(1):26-32. DOI: 10.1002/uog.12331. View

Koumbaris G, Kypri E, Tsangaras K, Achilleos A, Mina P, Neofytou M . Cell-Free DNA Analysis of Targeted Genomic Regions in Maternal Plasma for Non-Invasive Prenatal Testing of Trisomy 21, Trisomy 18, Trisomy 13, and Fetal Sex. Clin Chem. 2016; 62(6):848-55. DOI: 10.1373/clinchem.2015.252502. 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

Revello R, Sarno L, Ispas A, Akolekar R, Nicolaides K . Screening for trisomies by cell-free DNA testing of maternal blood: consequences of a failed result. Ultrasound Obstet Gynecol. 2016; 47(6):698-704. DOI: 10.1002/uog.15851. View

10.

Vora N, Johnson K, Basu S, Catalano P, Hauguel-De Mouzon S, Bianchi D . A multifactorial relationship exists between total circulating cell-free DNA levels and maternal BMI. Prenat Diagn. 2012; 32(9):912-4. PMC: 3432738. DOI: 10.1002/pd.3919. View

11.

Canick J, Palomaki G, Kloza E, Lambert-Messerlian G, Haddow J . The impact of maternal plasma DNA fetal fraction on next generation sequencing tests for common fetal aneuploidies. Prenat Diagn. 2013; 33(7):667-74. DOI: 10.1002/pd.4126. View

12.

Chiu R, Akolekar R, Zheng Y, Leung T, Sun H, Chan K . Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ. 2011; 342:c7401. PMC: 3019239. DOI: 10.1136/bmj.c7401. View

13.

Kinnings S, Geis J, Almasri E, Wang H, Guan X, McCullough R . Factors affecting levels of circulating cell-free fetal DNA in maternal plasma and their implications for noninvasive prenatal testing. Prenat Diagn. 2015; 35(8):816-22. DOI: 10.1002/pd.4625. View

14.

Twiss P, Hill M, Daley R, Chitty L . Non-invasive prenatal testing for Down syndrome. Semin Fetal Neonatal Med. 2013; 19(1):9-14. DOI: 10.1016/j.siny.2013.10.003. View

15.

Lun F, Chiu R, Chan K, Leung T, Lau T, Lo Y . Microfluidics digital PCR reveals a higher than expected fraction of fetal DNA in maternal plasma. Clin Chem. 2008; 54(10):1664-72. DOI: 10.1373/clinchem.2008.111385. View

16.

Kim S, Hannum G, Geis J, Tynan J, Hogg G, Zhao C . Determination of fetal DNA fraction from the plasma of pregnant women using sequence read counts. Prenat Diagn. 2015; 35(8):810-5. DOI: 10.1002/pd.4615. View

17.

Quezada M, Gil M, Francisco C, Orosz G, Nicolaides K . Screening for trisomies 21, 18 and 13 by cell-free DNA analysis of maternal blood at 10-11 weeks' gestation and the combined test at 11-13 weeks. Ultrasound Obstet Gynecol. 2014; 45(1):36-41. DOI: 10.1002/uog.14664. View

18.

Alberry M, Maddocks D, Jones M, Hadi M, Abdel-Fattah S, Avent N . Free fetal DNA in maternal plasma in anembryonic pregnancies: confirmation that the origin is the trophoblast. Prenat Diagn. 2007; 27(5):415-8. DOI: 10.1002/pd.1700. View

19.

Jensen T, Zwiefelhofer T, Tim R, Dzakula Z, Kim S, Mazloom A . High-throughput massively parallel sequencing for fetal aneuploidy detection from maternal plasma. PLoS One. 2013; 8(3):e57381. PMC: 3590217. DOI: 10.1371/journal.pone.0057381. View

20.

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