Evaluation of The Relationship between Cell-Free DNA Fetal Fraction of The Circulatory System and Fetal and Maternal Pregnancy Prognosis: A Prospective Study

Document Type : Original Article

Authors

1 Zabol Medicinal Plants Research Center, Zabol University of Medical Sciences, Zabol, Iran

2 Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, ACECR, Tehran, Iran

3 Zabol University of Medical Sciences, Zabol, Iran

4 School of Medicine, Shaheed Beheshti University of Medical Sciences, Tehran, Iran

5 Omid Fertility Clinic, Tehran, Iran

6 Zahedan University of Medical Science, Zahedan, Iran

7 Pediatric Gastroenterology and Hepatology Research Center, Zabol University of Medical Sciences, Zabol, Iran

Abstract

Background: Non-invasive prenatal testing (NIPT), sometimes called noninvasive prenatal screening (NIPS), is a non-invasive prenatal genetic test using cell-free DNA in maternal blood. This method is used to diagnose fetal aneuploidy disorders such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13), which causes disability disorders or significant postpartum defects. The aim of this study was to investigate the relationship between high and low fetal fraction (FF) and prognosis of maternal pregnancy.
Materials and Methods: In this prospective study, after obtaining informed consent, 10 ml of blood was collected from 450 mothers with singleton pregnancies with gestational age above 11 weeks (11-16) at the request of NIPT for cell-free DNA BCT test. After obtaining the test results, maternal and embryonic results were evaluated based on the amount of non-cellular DNA FF. Data analysis was performed by using SPSS software version 21 and independent t test, chi-square statistical tests.
Results: Based on test results, 20.5% of women were nulli par. The mean FF index in the studied women was 8.3% with a standard deviation of 4.6. The minimum and maximum values were 0 and 27, respectively. The frequency of normal, low and high FFs was 73.2, 17.3 and 9.5%, respectively.
Conclusion: High FF has fewer risks to the mother and fetus than low FF. The use of FF level (high or low) can help us determining the prognosis of pregnancy and using it to better manage the pregnancy.

Keywords

References

1. Allyse M, Minear MA, Berson E, Sridhar S, Rote M, Hung A, et al. Non-invasive prenatal testing: a review of international implementation and challenges. Int J Womens Health. 2015; 7: 113-126.
2. Minear MA, Lewis C, Pradhan S, Chandrasekharan S. Global perspectives on clinical adoption of NIPT. Prenat Diagn. 2015; 35(10): 959-967.
3. Tamminga S, van Maarle M, Henneman L, Oudejans CB, Cornel MC, Sistermans EA. Maternal Plasma DNA and RNA sequencing for prenatal testing. Adv Clin Chem. 2016; 74: 63-102.
4. Nicolaides KH. Nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities. Am J Obstet Gynecol. 2004; 191(1): 45-67.
5. Lo YM, Zhang J, Leung TN, Lau TK, Chang AM, Hjelm NM. Rapid clearance of fetal DNA from maternal plasma. Am J Hum Genet. 1999; 64(1): 218-224.
6. Alberry M, Maddocks D, Jones M, Abdel Hadi M, Abdel-Fattah S, Avent N, et al. Free fetal DNA in maternal plasma in anembryonic pregnancies: confirmation that the origin is the trophoblast. Prenat Diagn. 2007; 27(5): 415-418.
7. Boggian FCTS, Pinto ALC, Silvestre MA, Jaime JC, e Silva KSF, Silva CTX. Noninvasive pre-natal diagnosis of sex by maternal cell-free plasma fetal DNA analysis. Genet Mol Res. 2020; 19 (2): gmr18559.
8. Ashoor G, Syngelaki A, Wang E, Struble C, Oliphant A, Song K, et al. Trisomy 13 detection in the first trimester of pregnancy using a chromosome-selective cell-free DNA analysis method. Ultrasound Obstet Gynecol. 2013; 41(1): 21-25.
9. Hahn S, Rusterholz C, Hösli I, Lapaire O. Cell-free nucleic acids as potential markers for preeclampsia. Placenta. 2011; 32 Suppl: S17-S20.
10. Wang JW, Cao SS, Hu RY, Wang M. Association between cigarette smoking during pregnancy and gestational diabetes mellitus: a meta-analysis. J Matern Fetal Neonatal Med. 2020; 33(5): 758-767.
11. Wong D, Moturi S, Angkachatchai V, Mueller R, DeSantis G, van den Boom D, et al. Optimizing blood collection, transport and storage conditions for cell free DNA increases access to prenatal testing. Clin Biochem. 2013; 46(12): 1099-1104.
12. Ghulmiyyah L, Sibai B. Maternal mortality from preeclampsia/eclampsia. Semin Perinatol. 2012; 36(1): 56-59.
13. Nygren AO, Dean J, Jensen TJ, Kruse S, Kwong W, van den Boom D, et al. Quantification of fetal DNA by use of methylation-based DNA discrimination. Clin Chem. 2010; 56(10): 1627-1635.
14. Porreco RP, Garite TJ, Maurel K, Marusiak B; Obstetrix Collaborative Research Network, Ehrich M, et al. Noninvasive prenatal screening for fetal trisomies 21, 18, 13 and the common sex chromosome aneuploidies from maternal blood using massively parallel genomic sequencing of DNA. Am J Obstet Gynecol. 2014; 211(4): 365. e1-12.
15. Grati FR, Ferreira JC, Bajaj K. Noninvasive prenatal screening for fetal trisomies 21, 18, 13 and the common sex chromosome aneuploidies from maternal blood using massively parallel genomic sequencing of DNA. Am J Obstet Gynecol. 2014; 211(6): 711-712.
16. Baktashian M, Sedghi M, Salehi M, Zarean E, Baghersad A, Valian S, et al. Study of prenatal screening tests in pregnant women and comparison with fetal karyotype results. The Iranian Journal of Obstetrics, Gynecology and Infertility. 2018; 20(11): 22-28.
17. Ashoor G, Syngelaki A, Poon LC, Rezende JC, Nicolaides KH. Fetal fraction in maternal plasma cell-free DNA at 11-13 weeks' gestation: relation to maternal and fetal characteristics. Ultrasound Obstet Gynecol. 2013; 41(1): 26-32.
18. Gerson KD, Truong S, Haviland MJ, O'Brien BM, Hacker MR, Spiel MH. Low fetal fraction of cell-free DNA predicts placental dysfunction and hypertensive disease in pregnancy. Pregnancy Hypertens. 2019; 16: 148-153.
19. Rolnik DL, da Silva Costa F, Lee TJ, Schmid M, McLennan AC. Association between fetal fraction on cell-free DNA testing and first-trimester markers for pre-eclampsia. Ultrasound Obstet Gynecol. 2018; 52(6): 722-727.
20. Krishna I, Badell M, Loucks TL, Lindsay M, Samuel A. Adverse perinatal outcomes are more frequent in pregnancies with a low fetal fraction result on noninvasive prenatal testing. Prenat Diagn. 2016; 36(3): 210-215.
21. Sifakis S, Koukou Z, Spandidos DA. Cell-free fetal DNA and pregnancy-related complications (review). Mol Med Rep. 2015; 11(4): 2367-2372.
22. Bramham K, Parnell B, Nelson-Piercy C, Seed PT, Poston L, Chappell LC. Chronic hypertension and pregnancy outcomes: systematic review and meta-analysis. BMJ. 2014; 348: g2301.
23. Mansour E, Eissa AN, Mohamed Nofal L, Kharboush IF. Incidence and factors leading to low birth weight in Egypt. Int Pediatr. 2002; 17(4): 223-230.
International Journal of Fertility and Sterility
Volume 17, Issue 2
April 2023
Pages 115-119

Files

Cited by

Share

How to cite

Statistics