A differentiated approach to pregnancy planning in women with varicose veins of the lower extremities

Close metadata

MATERIAL AND METHODS

To develop a mathematical model for predicting placental insufficiency in patients with varicose veins of the lower extremities, we examined 128 women with chronic diseases of the veins of the lower extremities who applied to prepare for a planned pregnancy, who underwent a comprehensive assessment of clinical and laboratory parameters, including levels of vascular endothelial growth factor (VEGF), endothelin-1, C-reactive protein (CRP), vitamin 25(OH)D, parameters of the hemostatic system.

RESULTS

The following indicators have high prognostic significance: VEGF >25.75 pg/ml (sensitivity 89.4%, specificity 76.5%), endothelial-on-1 >4.75 pg/ml (sensitivity 78.7%, specificity 66.7%), CRP >4.05 mg/l (sensitivity 78.7%, specificity 71.6%), fibrinogen >4.715 g/ml (sensitivity 72.6%, specificity 70.4%), D-dimers >141 ng/ml (sensitivity 72.3%, specificity 67.9%), vitamin D (25-OH vitamin D) <10.5 ng/ml (sensitivity 74.2%, specificity 67, 9%). A mathematical model was developed based on the determination of a set of clinical and laboratory parameters (area under the curve — AUC=0.94, 95% confidence interval 0.842—0.956; p<0.001). The optimal binary classification threshold is a cutoff point of 0.581. The probability of developing of placental insufficiency should be considered high if the specified threshold value is exceeded.

CONCLUSION

The use of the method for determining the probability of developing of placental insufficiency in women with varicose veins of the lower extremities allows, at the stage of preparation for a planned pregnancy, to carry out the most effective therapeutic and preventive measures aimingly in order to improve perinatal outcomes.

Keywords:

clinical class of chronic diseases of the veins of the lower extremities

varicose veins of the lower extremities

placental insufficiency

angiogenic factors

vascular endothelial growth factor

endothelin

Authors:

Mozheiko L.F.

Belarusian State Medical University

Tikhonovich E.V.

Belarusian State Medical University

Received:

09.09.2021

Accepted:

07.10.2021

List of references:

Budzyń M, Iskra M, 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 insufficienc (CVI)-A pilot study. PLoS One. 2018;13:1:e0191902. https://doi.org/10.1371/journal.pone.0191902
Howlader MH, Coleridge Smith PD. Relationship of plasma vascular endothelial growth factor to CEAP clinical stage and symptoms in patients with chronic venous disease. Eur J Vasc Endovasc Surg. 2004;27:1:89-93. https://doi.org/10.1016/j.ejvs.2003.10.002
Mellor RH, Brice G, Stanton AW, French J, Smith A, Jeffery S, Levick JR, Burnand KG, Mortimer PS. Mutations in FOXC2 are strongly associated with primary valve failure in veins of the lower limb. Circulation. 2007;115:14:1912-1920. https://doi.org/10.1161/CIRCULATIONAHA.106.675348
Serra R, Ssempijja L, Provenzano M, Andreucci M. Genetic biomarkers in chronic venous disease. Biomark Med. 2020;14:2:75-80. https://doi.org/10.2217/bmm-2019-0408
García-Honduvilla N, Ortega M, Asúnsolo Á, García-Honduvilla, N, Ortega M, Asúnsolo Á, Álvarez-Rocha M, 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 Pathol. 2018;77:45-53. https://doi.org/10.1016/j.humpath.2018.03.022
Botasheva TL, Rudova OI, Gudz’ EB, Zheleznyakova EV, Babayan KT, Ganikovskaya YuV. Influence of blood flow in veins of lower limbs on the hemodynamic processes in the utero-placental-fetal complex at the various stereofunctional organization of the mother—placenta—fetus system. Sovremenny`e problemy` nauki i obrazovaniya. 2017;5:87-89. (In Russ.).
Fukaya E, Flores AM, Lindholm D. Clinical and genetic determinants of varicose veins. Circulation. 2018;138:25:2869-2880. https://doi.org/10.1161/CIRCULATIONAHA.118.035584
Strizhakov AN, Lipatov IS, Tezikov YuV. Integrated assessment of the severity of chronic placental insufficiency. Akusherstvo i ginekologiya. 2012;3:20-25. (In Russ.).
Herraiz I, Escribano D, Gómez-Arriaga PI, Herníndez-García JM, Herraiz MA, Galindo A. Predictive value of sequential models of the uterine artery Doppler in pregnancy at high risk for preeclampsia. Ultrasound Obstet Gynecol. 2012;40:1:68-74. https://doi.org/10.1002/uog.10147
Liang PY, Diao LH, Huang CY, Lian R-C, Chen X, Li G-G, Zhao J, Li Y-Y, He X-B, Zeng Y. The pro-inflammatory and anti-inflammatory cytokine profile in peripheral blood of women with recurrent implantation failure. Reprod Biomed Online. 2015;31:6:823-826. https://doi.org/10.1016/j.rbmo.2015.08.009
Mureșan D, Rotar IC, Stamatian F. The usefulness of fetal Doppler evaluation in early versus late onset intrauterine growth restriction. Review of the literature. Med Ultrason. 2016;18:1:103-109. https://doi.org/10.11152/mu.2013.2066.181.dop
Association of Phlebologists of Russia. Russian clinical guidelines for the diagnosis and treatment of chronic venous diseases. Flebologiya. 2013;2:2:47. (In Russ.).
Shevchenko YuD, Stoiko YuM, Gudy’movich VG, Nikitina AM. Endothelial dysfunction in development of varicose veins of lower extremities and possibilities of it’s correction. Meditsinskii vestnik Yuga Rossii. 2014;4:113-119. (In Russ.).
Agu O, Hamilton G, Baker DM, Dashwood MR. Endothelin receptors in the aetiology and pathophysiology of varicose veins. Eur J Vasc Endovasc Surg. 2002;23:2:165-171. https://doi.org/10.1053/ejvs.2001.1569
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. J Steroid Biochem Mol Biol. 2017;173:273-279. https://doi.org/10.1016/j.jsbmb.2017.02.003
Friedman J, Hastie T, Tibshirani R. Regularization paths for generalized linear models via coordinate descent. J Stat Softw. 2010;33:1:1-22. https://doi.org/10.18637/jss.v033.i01
Nitesh V. Smote: synthetic minority over-sampling technique. J Artificial Intelligence Res. 2002;16:321-357.
Mosteller F, Tukey J. Data Analysis, Including Statistics. 2nd ed. [Princeton N.J.]: Addison-Wesley. 1968.
Tszukanov YuT, Tszukanov AYu. Varicosis of the lower extremities as a consequence of connective tissue dysplasia. Angiologiya i sosudistaya khirurgiya. 2004;10:2:84-89. (In Russ.).
Ryabova SA, Tezikov IS, Lipatov EV, Zhernakova EV, Tabel`skaya TV. Prediction of fetal pathology in placental insufficiency from the first trimester of pregnancy. Sovremenny`e problemy` nauki i obrazovaniya. 2016;5. (In Russ.).
Shiny applications on the Web. R Studio, PBC. https://www.shinyapps.io

Close metadata