Serbest fetal DNA fraksiyonu plasental problemlere bağlı gebelik sonuçlarında değişir mi?

Year 2022, , 176 - 180, 15.10.2022

Bertan Akar , Emre Köle , Canan Özcan , Merve Çakır Köle

https://doi.org/10.53446/actamednicomedia.1173411

Abstract

Amaç: Cff-DNA’nın non-invazif tanı uygulamaları dışında, bu biyobelirtecin preeklampsi, IUGR, preterm doğum gibi önemli obstetrik komplikasyonları belirlemede yerini araştırmak.
Yöntemler: Çalışmamız eylül 2019-mart 2020 tarihleri arasında, kliniğimize başvuran 10-24. Gebelik haftaları arasında kendi isteği, ileri anne yaşı olan (≥40) ve ikili testte artmış trizomi 13, 18 ve 21 riski nedeniyle serbest fetal DNA analizi (HarmonyTM Prenatal Test; Ariosa Diagnostics Inc., San Jose, Calif., USA) yapılan 131 hastalarda tek merkezli retrospektif çalışma olarak planlandı.
Bulgular: Çalışmamızda hastaların 10’ unda (%8,1) oligohidramnios, 10’ unda (%8,1) gestasyonel diyabet, 7’ sinde de (%8,6) preeklampsi gözlenmiştir. 2 hastada da (%1,2) dekolman plasenta izlenmiştir. 10-24. gebelik haftaları arası ölçülen hücre dışı fetal DNA fraksiyonlarının artmış düzeyleri IUGR ile sonuçlanan gebelikleri öngörmede anlamlı bulunmuştur (p< 0.01). Diğer gebelik sonuçları ( preeklampsi, GDM, preterm eylem, oligohidroamnios, dekolman plasenta ) ve hücre dışı fetal DNA fraksiyon düzeyleri ile anlamlı ilişki bulunamamıştır.
Sonuç: Cff-DNA’nın prenatal taramada bir dizi değerli uygulamaya sahiptir ancak gebelik komplikasyonlarını öngörmede cff-DNA’nın düzeyleri ile ilişkisi klinik uygulamada henüz yeri netleşmemiştir. Bu nedenle çalışmalar, cff-DNA’nın potansiyel öngörüsü ve tanısal uygulamalarını belirlemek için gebelikteki patolojik koşullar altındaki düzeylerinin belirlemesini amaçlamalıdır.

Keywords

cffDNA, gebelik, plasenta, gebelik sonuçları

DO THE LEVELS OF cffDNA FRACTION CHANGE IN PREGNANCIES WITH PLACENTAL PROBLEMS?

Abstract

Aim : To investigate the value of the cell free fetal DNA (cff-DNA) for determining the important obstetric complications such as preeclampsia, intrauterine growth retardation (IUGR) and, preterm labor other than prenatal screening of fetal aneuploidies.
Material and Methods : Our single center- retrospective study included 131 pregnant women in their 10-24th weeks of gestation, between the dates September 2019 and March 2020 who applied for cff-DNA analysis (HarmonyTM Prenatal Test; Ariosa Diagnostics Inc., San Jose, Calif., USA) with indications including advanced maternal age (≥40) and high risk for trisomy 13, 18 and 21 according to the results of the first trimester prenatal screening or solely on their own desire.
Results : Oligohydraamnios was observed in 10 (%8,1) patients, gestational diabetes in 10 patients (%8,1) , preeclampsia in 7 ( %8,6) patients and ablatio plasenta in 2 (%1,2) patients in this study. Increasing levels of the extracellular fetal DNA fractions in 10-24th gestational weeks showed statistically significant correlation for predicting the risk for IUGR (p< 0.01). There was not a statistically significant difference between the level of extracellular fetal DNA fractions and the other obstetric complications (preeclampsia, preterm labor, GDM, oligohydraamnios).
Conclusion : Although cff-DNA has many valuable implications as a novel biomarker for prenatal screening for special fetal aneuploidies, the association between the levels of cff-DNA and the risk of obstetric complications in clinical practice has not been clarified yet . Further studies should aim to investigate the cff-DNA levels in patients with pathological obstetric conditions in order to detect its potential predictive value and diagnostic implementation.

Keywords

cffDNA, pregnancy, placenta, pregnancy outcomes

References

• 1) ACOG PRACTICE BULLETIN. Screening for Fetal Chromosomal Abnormalities. OBSTETRICS & GYNECOLOGY. 2020; 226: 136, 4, 48-69. doi:10.1097/AOG.0000000000004084.
• 2) Chitty LS, Khalil A, Barrett AN, Pajkrt E, Griffin D8R, Cole TJ, et al. Safe, accurate, prenatal diagnosis of thanatophoric dysplasia using ultrasound and free fetal DNA. Prenat Diagn. 2013; 33(5) :416-23. doi: 10.1002/pd.4066. Epub 2013 Feb 14.
• 3) 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;41:26–32. (Level II-3) doi: 10.1002/uog.12331. Epub 2012 Dec 4.
• 4) 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: 662–6. (Level II-3) doi: 10.1002/pd.4119. Epub 2013 May 9.
• 5) Struble CA, Syngelaki A, Oliphant A, Song K, Nicolaides KH. Fetal fraction estimate in twin pregnancies using directed cell-free DNA analysis. Fetal Diagn Ther 2014; 35:199–203. (Level II-2) doi: 10.1159/000355653. Epub 2013 Dec 7.
• 6) Revello R, Sarno L, Ispas A, Akolekar R, Nicolaides KH. Screening for trisomies by cell-free DNA testing of maternal blood: consequences of a failed result. Ultrasound Obstet Gynecol 2016;47:698–704. (Level II-2) doi: 10.1002/uog.15851. Epub 2016 Apr 25.
• 7) Palomaki GE, Kloza EM. Prenatal cell-free DNA screening test failures: a systematic review of failure rates, risks of Down syndrome, and impact of repeat testing. Genet Med 2018;20:1312–23. (Systematic Review and Meta-Analysis) doi: 10.1038/gim.2018.22. Epub 2018 Apr 26.
• 8) Palomaki GE, Kloza EM, Lambert-Messerlian GM, van den Boom D, Ehrich M, Deciu C, et al. Circulating cell free DNA testing: are some test failures informative? Prenat Diagn 2015;35:289–93. (Level II-2) doi: 10.1002/pd.4541. Epub 2015 Jan 8.
• 9) Badeau M, Lindsay C, Blais J, Nshimyumukiza L, Takwoingi Y, Langlois S, et al. Genomics‐based non‐invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women. Cochrane Database of Systematic Reviews 2017, Issue 11. Art. No.: CD011767. DOI: 10.1002/14651858.CD011767.pub2. (Systematic Review and Meta-Analysis) doi: 10.1002/14651858.CD011767.pub2.
• 10) Curnow KJ, Wilkins-Haug L, Ryan A, Kirkizlar E, Stosic M, Hall MP, et al. Detection of triploid, molar, and vanishing twin pregnancies by a single-nucleotide polymorphismbased noninvasive prenatal test. Am J Obstet Gynecol 2015;212:79.e1–9. (Level II-3) doi: 10.1016/j.ajog.2014.10.012. Epub 2014 Oct 15. doi: 10.1016/j.ajog.2014.10.012. Epub 2014 Oct 15.
• 11) Lefkowitz RB, Tynan JA, Liu T, Wu Y, Mazloom AR, Almasri E, et al. Clinical validation of a noninvasive prenatal test for genomewide detection of fetal copy number variants. Am J Obstet Gynecol 2016;215: 227.e1–16. (Level II-3) doi: 10.1016/j.ajog.2016.02.030. Epub 2016 Feb 17.
• 12) Lim JH, Park SY, Ryu HM. Non-invasive prenatal diagnosis of fetal trisomy 21 using cell-free fetal DNA in maternal blood. Obstet Gynecol Sci. 2013;56(2):58-66 doi: 10.5468/OGS.2013.56.2.58. Epub 2013 Mar 12.
• 13) Contro E, Bernabini D, Farina A. Cell-Free Fetal DNA for the Prediction of Pre-Eclampsia at the First and Second Trimesters: A Systematic Review and Meta-Analysis. Mol Diagn Ther. 2017 Apr;21(2):125-135. doi: 10.1007/s40291-016-0245-9.
• 14) Sifakis S, Koukou Z, Spandidos DA. Cell-free fetal DNA and pregnancy-related complications (review). Mol Med Rep. 2015 Apr;11(4):2367-72. doi: 10.3892/mmr.2014.3118. Epub 2014 Dec 19.
• 15) Tarquini F, Picchiassi E, Centra M, Pennacchi L, Galeone F, Bini V, Di Renzo GC, Coata G. Maternal smoking does not affect the amount of cell-free fetal DNA in maternal plasma during the 1st trimester of pregnancy. J Obstet Gynaecol. 2015 Jan;35(1):42-5. doi: 10.3109/01443615.2014.930100. Epub 2014 Jul 2.
• 16) Hahn S, Huppertz B, Holzgreve W. Fetal cells and cell free fetal nucleic acids in maternal blood: new tools to study abnormal placentation?. Placenta. 2005 Aug;26(7):515-26. doi: 10.1016/j.placenta.2004.10.017. Epub 2004 Dec 23.
• 17) Reddy A, Zhong XY, Rusterholz C, Hahn S, Holzgreve W, Redman CW, Sargent IL. The effect of labour and placental separation on the shedding of syncytiotrophoblast microparticles, cell-free DNA and mRNA in normal pregnancy and pre-eclampsia. Placenta. 2008 Nov;29(11):942-9. doi: 10.1016/j.placenta.2008.08.018. Epub 2008 Oct 1.
• 18) Taglauer ES, Wilkins-Haug L, Bianchi DW. Review: cell-free fetal DNA in the maternal circulation as an indication of placental health and disease. Placenta. 2014 Feb;35 Suppl(Suppl):S64-8. doi: 10.1016/j.placenta.2013.11.014. Epub 2013 Dec 1.
• 19) Sekizawa A, Jimbo M, Saito H, Iwasaki M, Matsuoka R, Okai T, Farina A. Cell-free fetal DNA in the plasma of pregnant women with severe fetal growth restriction. Am J Obstet Gynecol. 2003 Feb;188(2):480-4. doi: 10.1067/mob.2003.27.
• 20) Al Nakib M, Desbriere R, Bonello N, Bretelle F, Boubli L, Gabert J, Levi-Mozziconacci A. Total and fetal cell-free DNA analysis in maternal blood as markers of placental insufficiency in intrauterine growth restriction. Fetal Diagn Ther. 2009;26:24–28. doi: 10.1159/000236355. Epub 2009 Oct 10.
• 21) Levine RJ, Qian C, Leshane ES, Yu KF, England LJ, Schisterman EF, Wataganara T, Romero R, Bianchi DW. Two-stage elevation of cell-free fetal DNA in maternal sera before onset of preeclampsia. Am J Obstet Gynecol. 2004;190:707–713. doi: 10.1016/j.ajog.2003.12.019.
• 22) Thurik FF, Lamain-de Ruiter M, Javadi A, Kwee A, Woortmeijer H, Page-Christiaens GC, Franx A, van der Schoot CE, Koster MP. Absolute first trimester cell-free DNA levels and their associations with adverse pregnancy outcomes. Prenat Diagn. 2016 Dec;36(12):1104-1111. doi: 10.1002/pd.4940. Epub 2016 Nov 10.
• 23) Poon LC, Musci T, Song K, Syngelaki A, Nicolaides KH. Maternal plasma cell-free fetal and maternal DNA at 11–13 weeks’ gestation: relation to fetal and maternal characteristics and pregnancy outcomes. Fetal Diagn Ther. 2013;33:215–223 doi: 10.1159/000346806. Epub 2013 Mar 5.
• 24) Sifakis S, Zaravinos A, Maiz N, Spandidos DA, Nicolaides KH. First-trimester maternal plasma cell-free fetal DNA and preeclampsia. Am J Obstet Gynecol. 2009;201:e1–e7. doi: 10.1016/j.ajog.2009.05.025. Epub 2009 Jul 24.
• 25) Illanes S, Gomez R, Fornes R, Figueroa-Diesel H, Schepeler M, Searovic P, Serra R, Perez A, Nien JK. Free fetal DNA levels in patients at risk of preterm labour. Prenat Diagn. 2011;31:1082–1085. doi: 10.1002/pd.2838. Epub 2011 Sep 14.
• 26) Leung TN, Zhang J, Lau TK, Chan LY, Lo YM. Increased maternal plasma fetal DNA concentrations in women who eventually develop preeclampsia. Clin Chem. 2001;47:137–139.25.
• 27) Farina A, LeShane ES, Romero R, Gomez R, Chaiworapongsa T, Rizzo N, Bianchi DW. High levels of fetal cell-free DNA in maternal serum: a risk factor for spontaneous preterm delivery. Am J Obstet Gynecol. 2005;193:421–425. doi: 10.1016/j.ajog.2004.12.023.
• 28) Quezada MS, Francisco C, Dumitrascu-Biris K, Nicolaides KH, Poon LC. Fetal fraction of cell-free DNA in maternal plasma in the prediction of spontaneous preterm delivery. Ultrasound Obstet Gynecol. 2014;34:274–282. doi: 10.1002/uog.14666. Epub 2014 Nov 28.
• 29) Bauer M, Hutterer G, Eder M, Majer S, Leshane E, Johnson KL, Peter I, Bianchi DW, Pertl B. A prospective analysis of cell-free fetal DNA concentration in maternal plasma as an indicator for adverse pregnancy outcome. Prenat Diagn. 2006 Sep;26(9):831-6. doi: 10.1002/pd.1513.