[en] The aim of this study was to test if maternal serum vascular endothelial growth factor (VEGF) or N-terminal pro B-type natriuretic peptide (NT-proBNP) predicts abnormally invasive placenta (AIP) better. Secondary objective was to test whether the serum levels of VEGF and NT-proBNP can predict the degree of invasion. In a multicenter case-control study design, gestational age-matched serum samples from pregnant women with AIP (n = 44) and uncomplicated pregnancies (n = 55) who had been enrolled at Charité - Universitätsmedizin Berlin, Germany and Centre Hospitalier Régional de la Citadelle in Liège, Belgium were analyzed. Maternal blood serum VEGF and NT-proBNP levels were immunoassayed from samples taken immediately before delivery (GA median: 35 weeks). Biomarker levels were compared between AIP and control group. The correlation of biomarker levels with the clinical AIP degree was assessed. The predictive biomarker ability was characterized through a multivariate regression model and receiver operating characteristic curves. Women with AIP had significantly lower maternal serum VEGF levels (AIP mean 285 pg/ml, 95% CI 248-322, vs. control: 391 pg/ml, 95% CI 356-426, p < 0.01) and higher NT-proBNP levels (AIP median 329 pg/ml, IQR 287-385, vs. control 295 pg/ml, IQR 273-356, p = 0.03). Maternal serum VEGF levels were able to predict AIP better (AUC = 0.729, 0.622-0.836, p < 0.001; VEGF + number of previous cesarean deliveries: AUC = 0.915, 0.853-0.977, p < 0.001). Maternal serum VEGF levels correlated inversely with the clinical AIP degree (r = - 0.32, p < 0.01). In short, maternal serum VEGF, more than NT-proBNP, can help in predicting AIP and hints at the degree of invasion.
Disciplines :
Reproductive medicine (gynecology, andrology, obstetrics)
Author, co-author :
Schwickert, Alexander ; Department of Obstetrics, Charité - Universitätsmedizin Berlin, Corporate Member
Chantraine, Frédéric ; Centre Hospitalier Universitaire de Liège - CHU > > Service de gynécologie-obstétrique (CHR) ; Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire de
Ehrlich, Loreen; Department of Obstetrics, Charité - Universitätsmedizin Berlin, Corporate Member
Henrich, Wolfgang; Department of Obstetrics, Charité - Universitätsmedizin Berlin, Corporate Member
Muallem, Mustafa Zelal; Department of Gynecology with Center for Oncological Surgery, Charité -
Nonnenmacher, Andreas; Department of Obstetrics, Charité - Universitätsmedizin Berlin, Corporate Member
Petit, Philippe ; Centre Hospitalier Universitaire de Liège - CHU > > Service de gynécologie-obstétrique (CHR) ; Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire de
Weizsäcker, Katharina; Department of Obstetrics, Charité - Universitätsmedizin Berlin, Corporate Member
Braun, Thorsten; Department of Obstetrics, Charité - Universitätsmedizin Berlin, Corporate Member ; Department of Experimental Obstetrics, Charité - Universitätsmedizin Berlin,
Language :
English
Title :
Maternal Serum VEGF Predicts Abnormally Invasive Placenta Better than NT-proBNP: a Multicenter Case-Control Study.
Chantraine F, Langhoff-Roos J. Abnormally invasive placenta – AIP. Awareness and pro-active management is necessary. Acta Obstet Gynecol Scand. 2013;92(4):369–71.
Collins SL, Alemdar B, van Beekhuizen HJ, Bertholdt C, Braun T, Calda P, et al. Evidence-based guidelines for the management of abnormally invasive placenta recommendations from the International Society for Abnormally Invasive Placenta. Am J Obstet Gynecol. 2019;220:511–26.
Jauniaux E, Ayres-de-Campos D, Langhoff-Roos J, Fox KA, Collins S. FIGO classification for the clinical diagnosis of placenta accreta spectrum disorders. Int J Gynaecol Obstet. 2019;146(1):20–4.
Jauniaux E, Bhide A. Prenatal ultrasound diagnosis and outcome of placenta previa accreta after cesarean delivery: a systematic review and meta-analysis. Am J Obstet Gynecol. 2017;217(1):27–36.
Jauniaux E, Bhide A, Kennedy A, Woodward P, Hubinont C, Collins S. FIGO consensus guidelines on placenta accreta spectrum disorders: prenatal diagnosis and screening. Int J Gynaecol Obstet. 2018;140(3):274–80.
Delli Pizzi A, Tavoletta A, Narciso R, Mastrodicasa D, Trebeschi S, Celentano C, et al. Prenatal planning of placenta previa: diagnostic accuracy of a novel MRI-based prediction model for placenta accreta spectrum (PAS) and clinical outcome. Abdom Radiol (NY). 2019;44(5):1873–82.
Lam G, Kuller J, McMahon M. Use of magnetic resonance imaging and ultrasound in the antenatal diagnosis of placenta accreta. J Soc Gynecol Investig. 2002;9(1):37–40.
Fitzpatrick KE, Sellers S, Spark P, Kurinczuk JJ, Brocklehurst P, Knight M. The management and outcomes of placenta accreta, increta, and percreta in the UK: a population-based descriptive study. BJOG. 2014;121(1):62–70 discussion 70-1.
Bailit JL, Grobman WA, Rice MM, Reddy UM, Wapner RJ, Varner MW, et al. Morbidly adherent placenta treatments and outcomes. Obstet Gynecol. 2015;125(3):683–9.
Thurn L, Lindqvist PG, Jakobsson M, Colmorn LB, Klungsoyr K, Bjarnadóttir RI, et al. Abnormally invasive placenta-prevalence, risk factors and antenatal suspicion: results from a large population-based pregnancy cohort study in the Nordic countries. BJOG. 2016;123(8):1348–55.
Palacios-Jaraquemada JM, D'Antonio F, Buca D, Fiorillo A, Larraza P. Systematic review on near miss cases of placenta accreta spectrum disorders: correlation with invasion topography, prenatal imaging, and surgical outcome. J Matern Fetal Neonatal Med. 2019;33(19):3377–3384. 10.1080/14767058.2019.1570494
Jauniaux E, Collins SL, Jurkovic D, Burton GJ. Accreta placentation: a systematic review of prenatal ultrasound imaging and grading of villous invasiveness. Am J Obstet Gynecol. 2016;215(6):712–21.
Melcer Y, Jauniaux E, Maymon S, et al. Impact of targeted scanning protocols on perinatal outcomes in pregnancies at risk of placenta accreta spectrum or vasa previa. Am J Obstet Gynecol. 2018;218(4):443.e1–8.
Kawashima A, Sekizawa A, Ventura W, Koide K, Hori K, Okai T, et al. Increased levels of cell-free human placental lactogen mRNA at 28-32 gestational weeks in plasma of pregnant women with placenta previa and invasive placenta. Reprod Sci. 2014;21(2):215–20.
Goh W, Yamamoto SY, Thompson KS, Bryant-Greenwood GD. Relaxin, its receptor (RXFP1), and insulin-like peptide 4 expression through gestation and in placenta accreta. Reprod Sci. 2013;20(8):968–80.
Gu Y, Meng J, Zuo C, Wang S, Li H, Zhao S, Huang T, Wang X, Yan J. Downregulation of MicroRNA-125a in placenta accreta spectrum disorders contributes antiapoptosis of implantation site intermediate trophoblasts by targeting MCL1. Reprod Sci. 2019;26(12):1582–1589. 10.1177/1933719119828040. DOI: 10.1177/1933719119828040
Brouillet S, Hoffmann P, Feige J-J, Alfaidy N. EG-VEGF: a key endocrine factor in placental development. Trends Endocrinol Metab. 2012;23(10):501–8.
Tseng JJ, Chou MM, Hsieh YT, Wen MC, Ho ESC, Hsu SL. Differential expression of vascular endothelial growth factor, placenta growth factor and their receptors in placentae from pregnancies complicated by placenta accreta. Placenta. 2006;27(1):70–8.
Junus K, Wikström A-K, Larsson A, Olovsson M. Placental expression of proBNP/NT-proBNP and plasma levels of NT-proBNP in early- and late-onset preeclampsia. Am J Hypertens. 2014;27(9):1225–30.
Shmilovich H, Ben-Shoshan J, Tal R, Afek A, Barshack I, Maysel-Auslander S, et al. B-type natriuretic peptide enhances vasculogenesis by promoting number and functional properties of early endothelial progenitor cells. Tissue Eng A. 2009;15(9):2741–9.
Wehrum MJ, Buhimschi IA, Salafia C, et al. Accreta complicating complete placenta previa is characterized by reduced systemic levels of vascular endothelial growth factor and by epithelial-to-mesenchymal transition of the invasive trophoblast. Am J Obstet Gynecol. 2011;204(5):411.e1–411.e11.
Ersoy AO, Oztas E, Ozler S, Ersoy E, Erkenekli K, Uygur D, et al. Can venous ProBNP levels predict placenta accreta? J Matern Fetal Neonatal Med. 2016;29(24):4020–4.
Uyanıkoğlu H, İncebıyık A, Turp AB, Çakmak G, Sak S, Hilali NG. Serum angiogenic and anti-angiogenic markers in pregnant women with placenta percreta. Balkan Med J. 2018;35(1):55–60.
Biberoglu E, Kirbas A, Daglar K, Biberoglu K, Timur H, Demirtas C, et al. Serum angiogenic profile in abnormal placentation. J Matern Fetal Neonatal Med. 2016;29(19):3193–7.
Gütling H, Bionaz M, Sloboda DM, Ehrlich L, Braun F, Gramzow AK, et al. The importance of selecting the right internal control gene to study the effects of antenatal glucocorticoid administration in human placenta. Placenta. 2016;44:19–22.
Braun T, Husar A, Challis JRG, Dudenhausen JW, Henrich W, Plagemann A, et al. Growth restricting effects of a single course of antenatal betamethasone treatment and the role of human placental lactogen. Placenta. 2013;34(5):407–15.
Braun F, Hardt AK, Ehrlich L, Sloboda DM, Challis JRG, Plagemann A, et al. Sex-specific and lasting effects of a single course of antenatal betamethasone treatment on human placental 11β-HSD2. Placenta. 2018;69:9–19.
Allen L, Jauniaux E, Hobson S, Papillon-Smith J, Belfort MA. FIGO consensus guidelines on placenta accreta spectrum disorders: nonconservative surgical management. Int J Gynaecol Obstet. 2018;140(3):281–90.
Collins SL, Ashcroft A, Braun T, Calda P, Langhoff-Roos J, Morel O, et al. Proposal for standardized ultrasound descriptors of abnormally invasive placenta (AIP). Ultrasound Obstet Gynecol. 2016;47(3):271–5.
Youden WJ. Index for rating diagnostic tests. Cancer. 1950;3(1):32–5.
Habibzadeh F, Habibzadeh P, Yadollahie M. On determining the most appropriate test cut-off value: the case of tests with continuous results. Biochem Med (Zagreb). 2016;26(3):297–307.
Chandraharan E, Rao S, Belli A-M, Arulkumaran S. The triple-P procedure as a conservative surgical alternative to peripartum hysterectomy for placenta percreta. Int J Gynaecol Obstet. 2012;117(2):191–4.
Al-Khan A, Gupta V, Illsley NP, et al. Maternal and fetal outcomes in placenta accreta after institution of team-managed care. Reprod Sci. 2014;21(6):761–71.
Bartels HC, Postle JD, Downey P, Brennan DJ. Placenta accreta spectrum: a review of pathology, molecular biology, and biomarkers. Dis Markers. 2018;2018:1507674.
Illsley NP, DaSilva-Arnold SC, Al-Khan A, Zamudio S. Trophoblast invasion: lessons from abnormally invasive placenta (placenta accreta). Placenta. 2020. 10.1016/j.placenta.2020.01.004 DOI: 10.1016/j.placenta.2020.01.004
Chantraine F, Blacher S, Berndt S, et al. Abnormal vascular architecture at the placental-maternal interface in placenta increta. Am J Obstet Gynecol. 2012;207(3):188.e1–9.
Wu F, Tian F-J, Lin Y. Oxidative stress in placenta: health and diseases. Biomed Res Int. 2015;2015:293271.
Kobayashi H, Kawahara N, Ogawa K, Yoshimoto C. A Relationship between endometriosis and obstetric complications. 10.1007/s43032-019-00118-0. Updated May 1, 2020. Accessed May 1, 2020.
Jauniaux E, Jurkovic D. Placenta accreta: pathogenesis of a 20th century iatrogenic uterine disease. Placenta. 2012;33(4):244–51.
Roeder HA, Cramer SF, Leppert PC. A look at uterine wound healing through a histopathological study of uterine scars. Reprod Sci. 2012;19(5):463–73.
Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, et al. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 1996;16(9):4604–13.
Wan J, Lata C, Santilli A, Green D, Roy S, Santilli S. Supplemental oxygen reverses hypoxia-induced smooth muscle cell proliferation by modulating HIF-alpha and VEGF levels in a rabbit arteriovenous fistula model. Ann Vasc Surg. 2014;28(3):725–36.
Hall C. Essential biochemistry and physiology of (NT-pro)BNP. Eur J Heart Fail. 2004;6(3):257–60.
Donnellan E, Phelan D. Biomarkers of cardiac stress and injury in athletes: what do they mean? Curr Heart Fail Rep. 2018;15(2):116–22.
Marlinge M, Coulange M, Fitzpatrick RC, Delacroix R, Gabarre A, Lainé N, et al. Physiological stress markers during breath-hold diving and SCUBA diving. Phys Rep. 2019;7(6):e14033.
Palm M, Basu S, Larsson A, Wernroth L, Åkerud H, Axelsson O. A longitudinal study of plasma levels of soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF), sFlt1: PlGF ratio and vascular endothelial growth factor (VEGF-A) in normal pregnancy. Acta Obstet Gynecol Scand. 2011;90(11):1244–51.
Bosio PM, Wheeler T, Anthony F, Conroy R, O'herlihy C, McKenna P. Maternal plasma vascular endothelial growth factor concentrations in normal and hypertensive pregnancies and their relationship to peripheral vascular resistance. Am J Obstet Gynecol. 2001;184(2):146–52.
Hunter A, Aitkenhead M, Caldwell C, McCracken G, Wilson D, McClure N. Serum levels of vascular endothelial growth factor in preeclamptic and normotensive pregnancy. Hypertension. 2000;36(6):965–9.
Franz MB, Andreas M, Schiessl B, et al. NT-proBNP is increased in healthy pregnancies compared to non-pregnant controls. Acta Obstet Gynecol Scand. 2009;88(2):234–7.
