A comparison of cell-free placental messenger ribonucleic acid and color Doppler ultrasound for the prediction of placental invasion in patients with placenta accreta


1 Department of Obstetrics and Genecology, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Genetics, Isfahan University of Medical Sciences, Isfahan, Iran


Background: The aim of the present study was to comparison between cell-free placental messenger ribonucleic acid (mRNA) and Doppler ultrasound for the prediction of placental invasion in women with placenta accreta.
Materials and Methods: In this cross-sectional study, 50 pregnant women at risk for placenta accreta underwent color Doppler and assessment of cell-free placental mRNA. Real-time reverse-transcription polymerase chain reaction was used for measurement of cell-free placental mRNA in maternal plasma. Based on the findings at cesarean delivery and histological examination, patients were divided into two groups of women with and without placenta accrete. To compare of the mean of mRNA levels between the two groups we used independent t-test and to compare of the mean of age and gestational age at sonography we used Mann-Whitney test. For determination of sensitivity and specificity and the cut-off point of mRNA levels we used the receiver operating characteristic curve.
Results: A total of 50 women with a mean age of 30.24 ± 4.905 years entered the study and 12 (24%) patients were diagnosed with placenta accreta. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Doppler ultrasound were 83.3%, 78.9%, 56% and 94%, respectively. Results of our study showed if we consider a cut-off point equal to 3.325, with sensitivity and specificity of 0.917 and 0.789, respectively and the sensitivity, specificity, PPV and NPV of mRNA with were cut-off point of 3.325 were 91.7%, 78.9%, 57.9% and 96.8%, respectively.
Conclusions: Cell-free mRNA is an acceptable, easy made, functional test with sensitivity, specificity, PPV and NPV more than Doppler ultrasound for diagnosis and prediction of incidence of placenta accrete and we recommend the use of cell-free mRNA test for diagnosis of placenta accreta.


Tantbirojn P, Crum CP, Parast MM. Pathophysiology of placenta creta: The role of decidua and extravillous trophoblast. Placenta 2008;29:639-45.  Back to cited text no. 1
Wu S, Kocherginsky M, Hibbard JU. Abnormal placentation: Twenty-year analysis. Am J Obstet Gynecol 2005;192:1458-61.  Back to cited text no. 2
Khong TY. The pathology of placenta accreta, a worldwide epidemic. J Clin Pathol 2008;61:1243-6.  Back to cited text no. 3
Warren R, Sabaratnam A, editors. Best Practice in Labour and Delivery. 1 st ed., 3 rd printing ed. Cambridge: Cambridge University Press; 2009. p. 108, 146.  Back to cited text no. 4
Hobbins JC. Obstetric Ultrasound: Artistry in Practice. Oxford: Blackwell; 2007. p. 10.  Back to cited text no. 5
Newton ER: Physiology of lactation and breast feeding. In: Gabbe SG, Niebyl JR, Simpson JL, et al., eds. Obstetrics-Normal and Problem Pregnancies. 4 th ed., Churchill Livingstone. Churchill Livingstone: New York, NY, 2002.  Back to cited text no. 6
ACOG Committee on Obstetric Practice. ACOG Committee opinion. Number 266, January 2002: Placenta accreta. Obstet Gynecol 2002;99:169-70.  Back to cited text no. 7
Aggarwal R, Suneja A, Vaid NB, Yadav P, Sharma A, Mishra K. Morbidly adherent placenta: A critical review. J Obstet Gynaecol India 2012;62:57-61.  Back to cited text no. 8
Lerner JP, Deane S, Timor-Tritsch IE. Characterization of placenta accreta using transvaginal sonography and color Doppler imaging. Ultrasound Obstet Gynecol 1995;5:198-201.  Back to cited text no. 9
Oyelese Y, Smulian JC. Placenta previa, placenta accreta, and vasa previa. Obstet Gynecol 2006;107:927-41.  Back to cited text no. 10
Ng EK, Tsui NB, Lau TK, Leung TN, Chiu RW, Panesar NS, et al. mRNA of placental origin is readily detectable in maternal plasma. Proc Natl Acad Sci U S A 2003;100:4748-53.  Back to cited text no. 11
Wataganara T, LeShane ES, Chen AY, Borgatta L, Peter I, Johnson KL, et al. Plasma gamma-globin gene expression suggests that fetal hematopoietic cells contribute to the pool of circulating cell-free fetal nucleic acids during pregnancy. Clin Chem 2004;50:689-93.  Back to cited text no. 12
Masuzaki H, Miura K, Yoshiura K, Yamasaki K, Miura S, Yoshimura S, et al. Placental mRNA in maternal plasma and its clinical application to the evaluation of placental status in a pregnant woman with placenta previa-percreta. Clin Chem 2005;51:923-5.  Back to cited text no. 13
El Behery MM, Rasha L E, El Alfy Y. Cell-free placental mRNA in maternal plasma to predict placental invasion in patients with placenta accreta. Int J Gynaecol Obstet 2010;109:30-3.  Back to cited text no. 14
Chadderton T, Wilson C, Bewick M, Glück S. Evaluation of three rapid RNA extraction reagents: Relevance for use in RT-PCR's and measurement of low level gene expression in clinical samples. Cell Mol Biol (Noisy-le-grand) 1997;43:1227-34.  Back to cited text no. 15
Lo YM, Lo ES, Watson N, Noakes L, Sargent IL, Thilaganathan B, et al. Two-way cell traffic between mother and fetus: Biologic and clinical implications. Blood 1996;88:4390-5.  Back to cited text no. 16
Poon LL, Leung TN, Lau TK, Chow KC, Lo YM. Differential DNA methylation between fetus and mother as a strategy for detecting fetal DNA in maternal plasma. Clin Chem 2002;48:35-41.  Back to cited text no. 17
Wright CF, Burton H. The use of cell-free fetal nucleic acids in maternal blood for non-invasive prenatal diagnosis. Hum Reprod Update 2009;15:139-51.  Back to cited text no. 18
Wright CF, Chitty LS. Cell-free fetal DNA and RNA in maternal blood: Implications for safer antenatal testing. BMJ 2009;339:b2451.  Back to cited text no. 19
Warshak CR, Eskander R, Hull AD, Scioscia AL, Mattrey RF, Benirschke K, et al. Accuracy of ultrasonography and magnetic resonance imaging in the diagnosis of placenta accreta. Obstet Gynecol 2006;108:573-81.  Back to cited text no. 20
Yang JI, Lim YK, Kim HS, Chang KH, Lee JP, Ryu HS. Sonographic findings of placental lacunae and the prediction of adherent placenta in women with placenta previa totalis and prior Cesarean section. Ultrasound Obstet Gynecol 2006;28:178-82.  Back to cited text no. 21
Shih JC, Palacios Jaraquemada JM, Su YN, Shyu MK, Lin CH, Lin SY, et al. Role of three-dimensional power Doppler in the antenatal diagnosis of placenta accreta: Comparison with gray-scale and color Doppler techniques. Ultrasound Obstet Gynecol 2009;33:193-203.  Back to cited text no. 22
Chou MM, Ho ES, Lee YH. Prenatal diagnosis of placenta previa accreta by transabdominal color Doppler ultrasound. Ultrasound Obstet Gynecol 2000;15:28-35.  Back to cited text no. 23
Woodring TC, Klauser CK, Bofill JA, Martin RW, Morrison JC. Prediction of placenta accreta by ultrasonography and color Doppler imaging. J Matern Fetal Neonatal Med 2011;24:118-21.  Back to cited text no. 24
Miura K, Miura S, Yamasaki K, Yoshida A, Yoshiura K, Nakayama D, et al. Increased level of cell-free placental mRNA in a subgroup of placenta previa that needs hysterectomy. Prenat Diagn 2008;28:805-9.  Back to cited text no. 25
Silva JM, Dominguez G, Silva J, Garcia JM, Sanchez A, Rodriguez O, et al. Detection of epithelial messenger RNA in the plasma of breast cancer patients is associated with poor prognosis tumor characteristics. Clin Cancer Res 2001;7:2821-5.  Back to cited text no. 26
Sayres LC, Cho MK. Cell-free fetal nucleic acid testing: A review of the technology and its applications. Obstet Gynecol Surv 2011;66:431-42.  Back to cited text no. 27
Reddy A, Zhong XY, Rusterholz C, Hahn S, Holzgreve W, Redman CW, et al. 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;29:942-9.  Back to cited text no. 28