Developing a model of placental lesions prediction in varicose veins patients
https://doi.org/10.29235/1814-6023-2021-18-3-327-339
Abstract
The objective of the study was to identify predictive biomarkers and generate the model to predict placental lesions in women with varicose veins. We collected serial serum specimens from 128 women with varicose veins between 22 and 24 weeks’ gestation. The investigation includes ultrasound findings, blood analysis of endothelin-1, vascular endothelial growth factor (VEGF), CRP, coagulation factors as well as BMI. We used machine learning algorithm and multivariable logistic regression with Lasso method to predict placental lesions among the pregnant patients with varicose veins.
A total of 47 (36.7 %) women with varicose veins subsequently developed placental insufficiency. Mean serum VEGF were higher in women who developed placental insufficiency – 29 (27–31) pg/ml, as compared with women without varicose disease – 24 (22–25) pg/ml, p < 0.001. The performance of the model trained with all the most valuable tests (VEGF, endothelin, CRP, D-dimers, fibrinogen, CEAP class) is admissible (AUC 0.94; CI 0.842–0.956; p < 0.001).
We identified novel combination of clinical and laboratory predictive markers that provide pathophysiological insights and could help future improvements of diagnosis and treatment of placental lesions in women with varicose veins.
About the Authors
L. F. Mozhejko
Belarusian State Medical University
Belarus
Belarus
Liudmila F. Mozhejko – D. Sc. (Med.), Professor, Head of the Department
83, Dzerzhinski Ave., 220116, Minsk
Ya. V. Tsikhanovich
Belarusian State Medical University
Belarus
Belarus
Yauheniya V. Tsikhanovich – Assistant
83, Dzerzhinski Ave., 220116, Minsk
References
1. Ryabova S. A. Predictive and diagnostic significance of methods for assessing the fetus state in placental insufficiency. Abstract of Ph. D. diss. Samara, 2017. 28 p. (in Russian).
2. Tezikov Yu. V. Prediction, early diagnosis and prevention of severe forms of placental insufficien. Abstract of Ph. D. diss. Samara, 2013. 56 p. (in Russian).
3. García-Honduvilla N., Ortega M. A., Asúnsolo Á., Álvarez-Rocha M. J., Romero B., De León-Luis J., Álvarez-Mon M., Buján J. Placentas from women with pregnancy-associated venous insufficiency show villi damage with evidence of hypoxic cellular stress. Human Pathology, 2018, vol. 77, pp. 45–53. https://doi.org/10.1016/j.humpath.2018.03.022
4. Sterpu I., Anfelter P., Wray S., Kaihola H., Åkerud H., Wiberg-Itzel E. The association of second trimester biomarkers in amniotic fluid and fetal outcome. Journal of Maternal-Fetal and Neonatal Medicine, 2019, vol. 32, no. 21, pp. 3627‒3632. https://doi.org/10.1080/14767058.2018.1469127
5. Romero R., Nien J. K., Espinoza J., Todem D., Fu W., Chung H. [et al.]. A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate. Journal of Maternal-Fetal and Neonatal Medicine, 2008, vol. 21, no. 1, pp. 9‒23. https://doi.org/10.1080/14767050701830480
6. Nikitina A. M. Endothelial dysfunction in the development of varicose veins of the lower extremities and the possibility of its correction. Abstract of Ph. D. diss. Moscow, 2014. 114 p. (in Russian).
7. Budzyń M., IskraM., Turkiewicz W., Krasiński Z., Gryszczyńska B., Kasprzak M. P. Plasma concentration of selected biochemical markers of endothelial dysfunction in women with various severity of chronic venous insufficiency. PLoS ONE, 2018, vol. 13, no. 1, p. e0191902. https://doi.org/10.1371/journal.pone.0191902
8. Botasheva T. L., Rudova O. I., Gudz’ E. B., Zheleznyakova E. V., Babayan K. T., Ganikovskaya Yu. V. Influence of blood flow in the veins of the lower extremities on hemodynamic processes in the uteroplacental-fetal complex with different stereofunctional organization of the “mother‒placenta‒fetus” system. Sovremennye problemy nauki i obrazovaniya [Modern problems of science and education], 2017, vol. 7, no. 89, p. 87 (in Russian).
9. Ordiyants I. M., Dzhabiev A. V., Dzhabieva A. A., Smirnova T. V. The second wave of cytotrophoblast invasion in pregnant women with complicated and normal pregnancy. Vestnik Rossiiskogo universiteta druzhby narodov. Seriya Meditsina [Bulletin of the Peoples’ Friendship University of Russia. Medicine series], 2012, no. 6, pp. 193‒197 (in Russian).
10. Weel I. C., Baergen R. N., Romão-Veiga M., Borges V. T., Ribeiro V. R., Witkin S. S., Bannwart-Castro C., Peraçoli J. C., De Oliveira L., Peraçoli M. T. Association between placental lesions, cytokines and angiogenic factors in pregnant women with preeclampsia. PLoS ONE, 2016, vol. 11, no. 6, p. e0157584. https://doi.org/10.1371/journal.pone.0157584
11. Barber G. A., Weller C. D., Gibson S. J. Effects and associations of nutrition in patients with venous leg ulcers: a systematic review. Journal of Advanced Nursing, 2018, vol. 74, no. 4, pp. 774‒787. https://doi.org/10.1111/jan.13474
12. Schulz E. V., Cruze L., Wei W., Gehris J., Wagner C. L. Maternal vitamin D sufficiency and reduced placental gene expression in angiogenic biomarkers related to comorbidities of pregnancy. Journal of Steroid Biochemistry and Molecular Biology, 2017, vol. 173, pp. 273‒279. https://doi.org/10.1016/j.jsbmb.2017.02.003
13. Mosteller F., Tukey J. W. Data analysis, including statistics. Handbook of Social Psychology. Addison–Wesley, 1968, pp. 80‒203.
14. Friedman J., Hastie T., Tibshirani R. Regularization paths for generalized linear models via coordinate descent. Journal of Statistical Software, 2010, vol. 33, no. 1, pp. 1–22. https://doi.org/10.18637/jss.v033.i01
15. Hastie T., Tibshirani R., Friedman J. The elements of statistical learning: data mining, inference, and prediction. New York, Springer-Verlag, 2009. 745 p.
16. Chawla N. V., Bowyer K. W., Hall L. O., Kegelmeyer W. P. Smote: synthetic minority over-sampling technique. Journal of Artificial Intelligence Research, 2002, vol. 16, pp. 321–357. https://doi.org/10.1613/jair.953
17. Tsukanov Yu. T., Tsukanov A. Yu. Varicose veins of the lower extremities as a consequence of connective tissue dysplasia. Angiologiya i sosudistaya khirurgiya [Angiology and vascular surgery], 2004, vol. 10, no. 2, pp. 84‒90 (in Russian).
18. Fukaya E., Flores A. M., Lindholm D., Gustafsson S., Zanetti D., Ingelsson E., Leeper N. J. Clinical and genetic determinants of varicose veins. Circulation, 2018, vol. 138, no. 25, pp. 2869‒2880. https://doi.org/10.1161/circulationaha. 118.035584
19. Li Y., Liu J. MicroRNA-206 predicts raised fetal growth retardation risk through the interaction with vascular endothelial growth factor in pregnancies. Medicine, 2020, vol. 99, no. 7, p. e18897. https://doi.org/10.1097/md.0000000000018897
20. Hitzerd E., Neuman R. I., Broekhuizen M., Simons S. H. P., Schoenmakers S., Reiss I. K. M., Koch B. C. P., van den Meiracker A. H., Versmissen J., Visser W., Danser A. H. J. Transfer and vascular effect of endothelin receptor antagonists in the human placenta. Hypertension, 2020, vol. 75, no. 3, pp. 877‒884. https://doi.org/10.1161/HYPERTENSIONAHA.119.14183
21. Bränn E., Edvinsson Å., Rostedt Punga A., Sundström-Poromaa I., Skalkidou A. Inflammatory and anti-inflammatory markers in plasma: from late pregnancy to early postpartum. Scientific Reports, 2019, vol. 9, no. 1863, pp. 1‒10. https://doi.org/10.1038/s41598-018-38304-w
22. Shiny applications on the Web (2020): R Studio, PBC. Available at: https://www.shinyapps.io (accessed 12.03.2021).
Review
For citations:
Mozhejko L.F., Tsikhanovich Ya.V. Developing a model of placental lesions prediction in varicose veins patients. Proceedings of the National Academy of Sciences of Belarus, Medical series. 2021;18(3):327-339. (In Russ.) https://doi.org/10.29235/1814-6023-2021-18-3-327-339
Views: 636
Email this article 