Dynamic monitoring of the endothelium function in pregnant women at high risk of preeclampsia during pathogenetic prevention of its development

BACKGROUND: Today, preclinical diagnosis of preeclampsia presents significant difficulties. In widespread practice, it is diagnosed based on existing clinical signs and laboratory and functional research methods. Most of them are invasive and expensive, which makes it difficult to use them in widespread clinical practice for diagnosis and, especially, for monitoring the effectiveness of therapy over the dynamics of the disease. It is known that the pathogenesis of preeclampsia can have two independent development paths, converging in a common resulting link — the formation of endothelial dysfunction. Methods for studying endothelial function include determining markers of its imbalance in blood samples and non-invasive functional tests. Non-invasive diagnosis of endothelial dysfunction using the EndoPAT test allows us to quantify endothelium-mediated changes in vascular tone during 5-minute occlusion of the brachial artery.

AIM: The aim of this study was to evaluate the method for determining the endothelium function in the first, second and third trimesters of pregnancy during ongoing pathogenetic prevention of preeclampsia.

MATERIALS AND METHODS: This interventional uncontrolled study of the effectiveness of preventing preeclampsia using non-invasive assessment of vascular endothelial dysfunction during pregnancy was conducted at the Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott, St. Petersburg, Russia. The study involved 108 pregnant women at high risk of developing preeclampsia. All pregnant women underwent a cuff test to determine endothelial dysfunction using the peripheral arterial tonometry technique on the Endo-PAT 2000 device. The dynamic study was carried out in the first, second and third trimesters of pregnancy. As a result of the study, when endothelial dysfunction was detected [logarithmic transformation of reactive hyperemia peripheral arterial tonometry index (LnRHI) less 0.51], a complex glycosaminoglycan was additionally added to the basic prophylaxis with acetylsalicylic acid at a dosage of 250 MU (one capsule three times a day for eight weeks), then a cuff test was monitored after 6–12 weeks. Statistical analysis was performed using the IBM SPSS Statistics 20 software. All tests for significance were two-tailed, and differences were considered significant at p < 0.05.

RESULTS: Endothelial dysfunction was detected in the first trimester in 59 (55%) patients, then during ongoing complex therapy in the second trimester (n = 72) in 46 (64%) patients and in the third trimester (n = 46) in 4 (1%) patients. Moderate preeclampsia in the third trimester (35–39 weeks of gestation) developed in 28 (25.9%) patients out of 108. At the same time, at the start of the study, 15 patients with endothelial dysfunction received complex therapy, and 13 individuals only took acetylsalicylic acid. Among 46 patients who observed the dynamics of the entire pregnancy, only 4 (8.7%) women developed preeclampsia. After complex treatment prescribed based on the first trimester parameters, out of 36 patients who discontinued complex therapy and did not undergo a functional test subsequently, preeclampsia developed in 16 (44.4%) women. In the second trimester, out of 26 patients who stopped complex therapy, preeclampsia developed in 8 (30.8%) people. Thus, constant monitoring and complex therapy reduced the frequency of preeclampsia. In the group with a history of preeclampsia, the disease developed in 13 (39.4%) women. In the group with a high risk of preeclampsia according to the results of combined prenatal screening in the first trimester, with the exception of a history of preeclampsia (blood pressure test, placental growth factor level in the blood serum, lowest uterine artery pulsatility index value calculated to assess the individual risk of preeclampsia with a titer less than 1 : 100), preeclampsia occurred in 4 (13.3%) women. In the group with extragenital pathology associated with the risk of preeclampsia, including obesity, pregestational diabetes mellitus, chronic arterial hypertension, and chronic kidney disease, with the exception of a history of preeclampsia and a high risk of preeclampsia according to the results of perinatal screening, preeclampsia occurred in 11 (24.4%) women. In the high–risk groups for preeclampsia, we identified the highest-risk group, namely, one with the presence of preeclampsia in the anamnesis.

CONCLUSIONS: The effectiveness of the functional method for determining endothelial dysfunction in the first, second and third trimesters of pregnancy during pathogenetic prevention of preeclampsia has been proven.