Potential of angiogenesis-related serum markers for predicting placenta accreta spectrum in pregnant women with placenta previa


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Objective: To investigate the predictive value of angiogenesis-related serum markers in the third trimester of pregnancy to assess the likelihood of placenta accreta spectrum (PAS) and the prognosis of emergency delivery in patients with placenta previa. Materials and methods: This case-control study included women in the third trimester of pregnancy (2638 weeks) with (group I, n=46) and without PAS (group 2, n=42) managed at the Perinatal Center of Krasnodar Regional Clinical Hospital No. 2. All participants were tested for serum vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), determined by enzyme-linked immunosorbent assay. PAS was verified intraoperatively during delivery and by histological examination of the surgical specimens. The correlation between biomarker levels of and the depth of placental implantation was analyzed. The predictive value of biomarkers was assessed using multivariate logistic regression and ROC analysis. Results: With an increase in gestational age, patients with PAS group had significantly higher levels PlGF and lower sFlt-1/PlGF ratio than patients without PAS with a difference between groups at ≥37+0 weeks gestation [Me (IQR) : 778 (751-1057) versus 190 (171-369) pg/ml, p=0.005 and 1.1 (0.8-1.4) versus 8.0 (2.8-20.3), p=0.003, respectively]. The ratio of sFlt-1/PlGF <2.5 predicts PAS with sensitivity (Se) of 65.2% (49.8-78.6%), specificity (Sp) of 59.5%, (43.3-74, 4%), positive predictive value (PPV) of 63.8% (53.6-72.9%), negative predictive value (NPV) of61.0% (45.9-71.4%), area under ROC-curve (AUC) of0.624 (0.514-0.725), p=0.018. The inclusion of maternal age and a history of caesarean section in the predictive model increases the predictive accuracy: Se = 87.0% (73.7-95.1%), Sp = 78.6% (63.2-89.7%), PPV = 81.6% (71.1-89.9%), NPV = 84.6% (72.0-92.1%), aUc=0.886 (0.800-0.944), p<0.001. The PIGFlevel (pg/ml) statistically significantly correlates with the PAS depth (Spearman's rho=0.292; p<0.01). The sFlt-1/PlGF ratio <2.5, combined with maternal age and a history of cesarean section predicts the likelihood of emergency delivery with placenta previa with Se=40.0% (21.1-61.3%), Sp=92, 1% (82.4-97.4%), PPV=66.7% (38.4-88.2%), NPV=79.5% (68.480.0%), AUC=0.789(0.689-0.869), p<0.001. Conclusion: Increased levels of angiogenesis-related serum markers in the third trimester can be used to predict PAS and emergency delivery in pregnant women with placenta previa.

Full Text

Restricted Access

About the authors

Tatiana B. Makukhina

Kuban State Medical University Ministry of Health of Russia; Perinatal Center of Krasnodar Regional Clinical Hospital No. 2 Ministry of Health of Krasnodar Region

Email: soltatiana@mailru
Krasnodar, Russia

Gregory A. Penzhoyan

Kuban State Medical University Ministry of Health of Russia

Email: pga05@mail.ru
Krasnodar, Russia

Arpine M. Amirkhanyan

Kuban State Medical University Ministry of Health of Russia; Perinatal Center of Krasnodar Regional Clinical Hospital No. 2 Ministry of Health of Krasnodar Region

Email: arm2035@yandex.ru
Krasnodar, Russia

References

  1. El Gel any S., Mosbeh M.H., Ibrahim E.M., Mohammed M., Khalifa E.M., Abdelhakium A.K. et al. Placenta Accreta Spectrum (PAS) disorders: incidence, risk factors and outcomes of different management strategies in a tertiary referral hospital in Minia, Egypt: a prospective study. BMC Pregnancy Childbirth. 2019; 19(1): 313. https://dx.doi.org/10.1186/s12884-019-2466-5.
  2. Забелина Т.М., Васильченко О.Н., Каримова Г.Н., Ежова Л.С., Учеваткина П.В., Шмаков Р.Г. Родоразрешение беременных с врастанием плаценты без рубца на матке. Акушерство и гинекология. 2021; 4: 150-6. https://dx.doi.org/10.18565/aig.2021.4.150-156.
  3. Баринов С.В., Медянникова И.В., Тирская Ю.И., Безнощенко Г.Б., Кадцына Т.В., Лазарева О.В., Биндюк А.В., Неустроева Т.Н., Степанов С.С. Прогнозирование приращения плаценты при ее предлежании. Акушерство и гинекология. 2021; 1: 61-9. https://dx.doi.org/10.18565/aig.2021.1.61-69.
  4. Курцер М.А., Бреслав И.Ю., Григорьян А.М., Латышкевич О.А., Кутакова Ю.Ю., Кондратьева М.А. Временная баллонная окклюзия общих подвздошных артерий при осуществлении органосохраняющих операций у пациенток с врастанием плаценты. Акушерство и гинекология: новости, мнения, обучение. 2018; 6(4): 31-7. https://dx.doi.org/10.24411/2303-9698-2018-14003.
  5. Jauniaux E., Hussein А.M., Fox K.A., Collins S.L. New evidence-based diagnostic and management strategies for placenta accreta spectrum disorders. Best Pract. Res. Clin. Obstet. Gynaecol. 2019; 61: 75-88. https://dx.doi.org/10.1016/j.bpobgyn.2019.04.006.
  6. Пенжоян Г.А. Служба родовспоможения в крупном городе. Проблемы социальной гигиены, здравоохранения и истории медицины. 2003; 3: 37.
  7. Пенжоян Г.А. Эффективность современных перинатальных технологий. Проблемы социальной гигиены, здравоохранения и истории медицины. 2002; 6: 42.
  8. Ornaghi S., Maraschini A., Donati S.; Regional Obstetric Surveillance System Working Group. Characteristics and outcomes of pregnant women with placenta accreta spectrum in Italy: A prospective population-based cohort study. PLoS One. 2021; 16(6): e0252654. https://dx.doi.org/10.1371/journal.pone.0252654.
  9. Лисицына О.И., Низяева Н.В., Михеева А.А. Врастание плаценты. Эволюция знаний и умений. Акушерство и гинекология. 2021; 6: 34-40. https://dx.doi.org/10.18565/aig.2021.6.34-40.
  10. Гус А.И., Бойкова Ю.В., Ярыгина Т.А., Яроцкая Е.Л. Современные подходы к пренатальной диагностике и скринингу врастания плаценты (обзор рекомендаций). Акушерство и гинекология. 2020; 10: 5-12. https://dx.doi.org/10.18565/aig.2020.10.5-12.
  11. Philips J., Gurganus M., De Shields S., Cunningham T., Sinkovskaya E., Kanaan C. et al. Prevalence of sonographic markers of placenta accreta spectrum in low-risk pregnancies. Am. J. Perinatol. 2019; 36(8): 773-80. https://dx.doi.org/10.1055/s-0038-1676488.
  12. Wehrum M.J., Buhimschi I.A., Salafia C., Thung S., Bahtiyar M.O., Werner E.F. 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. https://dx.doi.org/10.1016/j.ajog.2010.12.027.
  13. 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.https://dx.doi.org/10.3109/14767058.2015.1118044.
  14. Uyanıkoglu H., Incebıyık A., Turp A.B., Çakmak G., Sak S., Hilali N.G. Serum angiogenic and anti-angiogenic markers in pregnant omen with placenta percreta. Balkan Med. J. 2018; 35(1): 55-60. https://dx.doi.org/10.4274/balkanmedj.2016.1890.
  15. Bartels H.C., Postle J.D., Downey P., Brennan D.J. Placenta Accreta Spectrum: A review of pathology, molecular biology, and biomarkers. Dis Markers. 2018; 2018: 1507674. https://dx.doi.org/10.1155/2018/1507674.
  16. Timofeeva A.V., Fedorov I.S., Pirogova M.M., Vasilchenko O.N., Chagovets V.V., Ezhova L.S. et al. Clusterin and its potential regulatory microRNAs as a part of secretome for the diagnosis of abnormally invasive placenta: Accreta, increta, and percreta cases. Life (Basel). 2021; 11(4): 270. https://dx.doi.org/10.3390/life11040270.
  17. Al-Khan A., Youssef Y.H., Feldman K.M., Illsley N.P., Rem ache Y., Alvarez-Perez J. et al. Biomarkers of abnormally invasive placenta. Placenta. 2020; 91: 37-42. https://dx.doi.org/10.1016/j.placenta.2020.01.007.
  18. Макухина Т.Б., Пенжоян Г.А., Лебеденко Е.С., Хорольский В.А., Солнцева А.В., Казанчи Ф.Б. Возможности раннего прогнозирования перинатальных исходов в I триместре у пациенток с предлежанием плаценты, осложнившимся ее аномальной инвазией. Акушерство и гинекология: новости, мнения, обучение. 2020; 8(1): 47-52. https://dx.doi.org/10.24411/2303-9698-2020-11006.
  19. Schwickert A., Chantraine F., Ehrlich L., Henrich W., Muallem M.Z., Nonnenmacher A. et al. Maternal serum VEGF predicts abnormally invasive placenta better than NT-proBNP: A Multicenter Case-Control Study. Reprod. Sci. 2021; 28(2): 361-70. https://dx.doi.org/10.1007/s43032-020-00319-y.
  20. Виницкий А.А., Шмаков Р.Г. Современные представления об этиопатогенезе врастания плаценты и перспективы его прогнозирования молекулярными методами диагностики. Акушерство и гинекология. 2017; 2: 5-10. https://dx.doi.org/10.18565/aig.2017.2.5-10.
  21. McMahon K., Karumanchi S.A., Stillman I.E., Cummings P., Patton D., Easterling T. Does soluble fms-like tyrosine kinase-1 regulate placental invasion? Insight from the invasive placenta. Am. J. Obstet. Gynecol. 2014; 210(1): 68.e1-4. https://dx.doi.org/10.1016/j.ajog.2013.08.032.
  22. Иванец Т.Ю., Алексеева М.Л., Кан Н.Е., Тютюнник В.Л., Амирасланов Э.Ю., Насонова Д.М., Фанченко Н.Д. Диагностическая значимость определения плацентарного фактора роста и растворимой fms-подобной тирозинкиназы-1 в качестве маркеров преэклампсии. Проблемы репродукции. 2015; 21(4): 129-33. https://dx.doi.org/10.17116/repro2015214129-133.
  23. Umapathy A., Chamley L. W., James J.L. Reconciling the distinct roles of angiogenic/anti-angiogenic factors in the placenta and maternal circulation of normal and pathological pregnancies. Angiogenesis. 2020; 23(2): 105-17. https://dx.doi.org/10.1007/s10456-019-09694-w.
  24. Гурьева В.М., Травкина А.А., Матвеев М.О., Морохотова Л.С., Будыкина Т.С, Котов Ю.Б., Семенова Т.А. Клиническое значение sFlt-1/ PlGF в диагностике и прогнозировании преэклампсии. Акушерство и гинекология. 2021; 7: 195-200. https://dx.doi.org/10.18565/aig.2021.7.195-200.
  25. Jauniaux E., Ayres-de-Campos D., Langhoff-Roos J., Fox K.A., Collins S.; FIGO Placenta Accreta Diagnosis and Management Expert Consensus Panel. FIGO classification for the clinical diagnosis of placenta accreta spectrum disorders.Int. J. Gynaecol. Obstet. 2019; 146(1): 20-4. https://dx.doi.org/10.1002/ijgo.12761.
  26. Шифман Е.М., Куликов А.В., Проценко Д.Н., Овезов А.М., Заболотских И.Б., Артымук Н.В., Белокриницкая Т.Е., Пенжоян Г.А., Братищев И.В., Дробинская А.Н., Ситкин С.И., Роненсон А.М., Распопин Ю.С., Матковский А.А., Рязанова О.В., Блауман С.И., Швечкова М.В., Абазова И.С., Китиашвили И.З., Бухтин А.А. и др. Анестезия и интенсивная терапия при массивной кровопотере в акушерстве. Клинические рекомендации (протоколы лечения). Вопросы гинекологии, акушерства и перинатологии. 2018; 17(3): 81-100.
  27. Nicolaides K.H., Wright D., Syngelaki A., Wright A., Akolekar R. Fetal medicine foundation fetal and neonatal population weight charts. Ultrasound Obstet. Gynecol. 2018; 52: 44-51. https://dx.doi.org/10.1002/uog.19073.
  28. Bowman Z.S., Eller A.G., Bardsley T.R., Greene T., Varner M.W., Silver R.M. Risk factors for placenta accreta: a large prospective cohort. Am. J. Perinatol. 2014; 31(9): 799-804. https://dx.doi.org/10.1055/s-0033-1361833.
  29. Соколов Д.И., Колобов А.В., Лесничия М.В., Костючек И.Н., Боля К.В., Аржанова О.Н., Кветной И.М., Сельков С.А. Роль проангиогенных и антиангиогенных факторов в развитии плаценты. Медицинская иммунология. 2008; 10(4-5): 347-52.
  30. Palm M., Basu S., Larsson A., Wernroth L., Äkerud H., Axelsson O. A longitudinal study of plasma levels of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), sFlt-1: PlGF ratio and vascular endothelial growth factor (VEGF-A) in normal pregnancy. Acta Obstet. Gynecol. Scand. 2011; 90(11): 1244-51. https://dx.doi.org/10.1111/j.1600-0412.2011.01186.x.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2022 Bionika Media

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies