The role of the factors of angiogenesis and hormones of pregnancy in pregnant women with hypertension has been studied inadequately and their interaction in such patients is not fully elucidated at present time. Aim. To detect peculiarities of angiogenesis factors and placental hormones in pregnant women with arterial hypertension I and II grades in comparison with results of healthy pregnant women. Materials and methods. Conducting a prospective study of 88 pregnant women, which included: analysis of clinical and anamnestic characteristics and study of the peculiarities of pregnancy in women with chronic hypertension in the first trimester of pregnancy (11-12 weeks). The open prospective controlled study involved 61 pregnant women with chronic arterial hypertension (CAH) 1-2 degree, who were included in the first - the main group. The second control group included 27 healthy pregnant women with physiological pregnancies. Among the angiogenesis indices, the placental growth factor (PlGF), as a pro-angiogenic factor and placental soluble fms-like tyrosine kinase (sFlt-1) was determined as an anti-angiogenic factor, sFlt-1/PlGF ratio was also estimated. Statistical analysis was done by using «STATISTICA® for Windows 6.0» (Stat Soft Inc., № AXXR712D833214FAN5). Results. In the first trimester of pregnancy (11-12 weeks of gestation) in women with CAH is determined by a shift in the balance between pro- and antiangiogenic factors, manifested by statistically significant (p˂0.05) increase in sFlt-1 levels (1700, 9 pg / ml) and a decrease in PlGF levels in3.7 times (9.1 pg / ml) and, accordingly, an increase in the levels of the coefficient K in 5.3 times (sFlt-1 / PlGF) (184.5). The mean values of estradiol, progesterone and chorionic gonadotropin levels in pregnant women with CAH did not differ statistically significantly from those of the control group (p˃0.05). These changes indicate the presence of angiogenesis disorders in pregnant women with chronic hypertension, starting from the first trimester of gestation. Conclusions. Pregnant women with CAH in І trimester have disturbances in balance between pro-angiogenic and anti-angiogenic factors with prevalence of sFlt-1 and reducing of PlGF in serum plasma. Due to such disbalance in pregnant women with CAH of 1 and 2 grade changed cooperation between angiogenesis factors and hormones from direct to inverse. It may lead to development of placental insufficiency in future. That’s why treatment/prophylaxis of it should be administered to pregnant women with CAH in 1 trimester.

The role of angiogenesis factors and hormonal profile in pregnant women with arterial hypertension has not been detailed studied, and their interaction in such patients has not been determined at present time.The objective: to determine the features of angiogenesis factors and hormonal profile in pregnant women with arterial hypertension of the 1and 2 grade. Materials and methods. A prospective study was conducted in 88 pregnant women, which included: analysis of clinical and anamnestic characteristics and the study of pregnancy characteristics in women with chronic arterial hypertension (CAH) in the I trimester of pregnancy (11–12 weeks). The open prospective controlled study involved 61 pregnant women with CAH of the 1 and 2 stages which consisted the main group. The control group included 27 healthy pregnant women with physiological pregnancy. Concentrations of human chorionic gonadotropin (hCG), progesterone (PG), estradiol (E) and markers of angiogenesis – placental growth factor (PlGF) as a proangiogenic factor and soluble fms-like tyrosine kinase (sFlt-1) as an antiangiogenic factor were determined in the blood serum of all patients, sFlt-1/PGF ratio was also estimated (K). Statistical analysis was performed using «STATISTICA® for Windows 13.0».Results. In the I trimester of pregnancy in women with CAH, a shift in the balance between pro- and anti-angiogenic factors is determined, which is manifested by a statistically significant (p<0.05) increase sFlt-1 level (1700.9 pg/ml) and a decrease PlGF level in 3.7 times (9.1 pg/ml) and, accordingly, an increase K coefficient (sFlt-1/PlGF) by 5.3 times (184.5). The mean concentrations of E, PG and hCG in pregnant women of the main group did not differ statistically significantly from those in the control group. However, according to the results of the correlation analysis, PlGF and PG indicators have feedback in pregnant women with CAH (r=-0.29; p<0.05). When calculating the correlation of PlGF and hormones, it was found that in pregnant women with CAH there is their growth according to the control group, namely the indicator hCG correlates with PlGF (51.8 units vs. 14.8 units) 3.5 times, E correlates with PlGF (309.7 units vs. 70.0 units) 4.4 times and PG correlates with PlGF (4.8 units vs. 1.0 units) 4.8 times (p<0.001 for all indicators). These changes indicate the presence of angiogenesis disorders in pregnant women with chronic hypertension, starting from the I trimester of gestation.Conclusions. Pregnant women with CAH in the I trimester have disturbances in balance between pro-angiogenic and anti-angiogenic factors with prevalence of sFlt-1 and decrease of PlGF in blood serum. Because of such imbalance in pregnant women with CAH of the 1 and 2 grade, the interaction of angiogenesis factors and hormones changed from direct to inverse. It may lead to the development of placental dysfunction in the future, so treatment and prevention should be provided for the pregnant women with CAH in the I trimester.

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The objective: to assess and establish the relationships between Doppler blood flow indicators in the uterine arteries, angiogenesis factors and hormones of the mother-placenta-fetus system in pregnant women with arterial hypertension I-II degree.Materials and methods. A prospective study of 88 pregnant women at 11–12 weeks of gestation was carried out: 61 pregnant women with chronic arterial hypertension (CH) of the I–II degree (main group) and 27 healthy pregnant women with physiological pregnancy (control group). All patients have been examined: blood flow Doppler in the left and right uterine arteries – pulsation index (PI), resistance index (IR) and systolic-diastolic ratio (SDR). Chorionic gonadotropin (HCG), progesterone (PG), estradiol (E) and angiogenesis indices (placental growth factor (PlGF) as a pro-angiogenic factor) and placental-soluble fms-like tyrosine kinase (sFlt-1) as an anti-angiogenic factor and the ratio of sFlt-1/PlGF) were determined in blood. Statistical analysis was performed using the program “STATISTICA 13”.Results. There was no statistically significant difference in SDR and IP indicators between the groups. PI values in the right uterine artery in pregnant women of the main group were significantly higher than the indicator of healthy pregnant women (1.73 (1.65; 1.8) units versus 1.33 (1.1; 1.49) units, respectively). The PI values in the left uterine artery in pregnant women with CAH also significantly differed from those in women with the physiological course of pregnancy (1.7 (1.66; 1.79) units and 1.35 (1.22; 1.51) units, respectively). A significant correlation between SDR indicators and markers of angiogenesis and hormonal profile in women of the main group has not been established. In pregnant women with CAH, an inverse relationship was observed between PI and PlGF (mean strength R=-0.34 for PI in the right uterine artery and R= -0.41 for PI in the left uterine artery), respectively, between PI and sFlt-1/PlGF – direct relationship (average strength R=+ 0.37 for PI in the right uterine artery and R=+0.43 for PI in the left uterine artery). In women with the physiological course of pregnancy and childbirth, the PI value in the right uterine artery correlated with the sFlt-1/PlGF ratio (direct relationship) and PlGF level (feedback). PI in the left uterine artery had a direct relationship with the value of the sFlt-1/PlGF ratio. In pregnant women with CAH, the PlGF level decreases, while the PI value, on the contrary, increases.Conclusions. The significant differences between the indicators of SDS and IR in pregnant women with CAH and pregnant women without CAH have not been established. In women with CAH, significantly higher PI values were found in the right and left uterine arteries compared to those in women without CAH. The course of pregnancy in women with CAH is accompanied by a shift in the balance between pro- and anti-angiogenic factors, as evidenced by a statistically significant increase in sFlt-1 level against the background of a decrease in PlGF level, as well as a corresponding increase in the sFlt-1/PlGF ratio as compared with pregnant women without CAH. There are no correlations between indicators of SDR and IR in the uterine arteries, markers of angiogenesis and hormonal profile in pregnant women with and without CAH. Nevertheless, PI values in the right and left uterine arteries correlate with the PlGF level (feedback) and the sFlt-1/PlGF ratio (direct relationship) in pregnant women with CAH. This indicates the presence of disorders in this contingent of women in the I trimester of pregnancy.

During intrauterine life a fetus with growth restriction does hemodynamic, metabolic and hormonal adjustments to cope with the adverse uterine environment, and these changes can become permanent and irreversible. Despite the progress in the knowledge of delayed fetal development, the biomarkers are able to identify this pathology at an early stage and stratify its severity, both before and after childbirth, are still not determined. The objective: to evaluate the prognostic value of the angiogenesis marker level, hormonal profile and Doppler examination for fetal growth restriction (FGR) in pregnant women with chronic arterial hypertension (CAH).Materials and methods. A prospective examination of 61 pregnant women with CAH 1-2 degrees was conducted, which included an analysis of the clinical and anamnestic characteristics and the study of the pregnancy course in the first trimester (11-12 weeks). To determine the level of risk factors for the FGR development the examined pregnant women were divided into groups: women with CAH with FGR (n=10), and pregnant women with CAH without FGR (n=51).Human chorionic gonadotropin (CHG), progesterone (PG) and estradiol (E) were determined in blood serum. Angiogenesis markers – placental growth factor (P1GF) as a pro-angiogenic factor and soluble fms-like tyrosine kinase (sFlt-1) as an anti-angiogenic factor were studied, the ratio of sFlt-1/PLGF (coefficient K) was calculated. All patients had Doppler examination of vascular blood flow in the left and right uterine arteries (pulsation index – PI, resistance index – RI and systolic-diastolic ratio – SDR). The ultrasound examination was done with the ultrasound machine “Mylab Six System”. Statistical analysis was performed using program Statistica® for Windows 13.0. A single-factor logistic regression analysis and a method of building logistics regression, which was evaluated by means of receive operating characteristic curve (ROC-curve) according to the area under the curve (AUC) were used to determine the prognostic level of markers, the 95 % confidence interval was calculated. Results. In the first trimester of pregnancy in women with CAH the PLGF level was < 8.2 pg/ml (sensitivity – 80.0 %, specificity – 60.78 %), area under the ROC curve (AUC) – 0.697 (95 % CI: 0.566–0.808; p =0.0128), which indicate an increased risk of FGR development. The growth of sFl-1 > 1802.59 ng/ml (sensitivity – 70.0 %, specificity – 64.71 %), area under the ROC-curve (AUC) 0.678 (95 % CI: 0.547–0.792; p=0.05) increase the risk of FGR development. The coefficient K in 11-12 weeks of pregnancy was ≥ 95.36 units (sensitivity – 100.0 %, specificity – 43.14 %), area under ROC-curve (AUC) – 0.735 (95 % CI: 0.607–0.840; p=0.0128), which indicate an increase the risk of FGR development. PG/PlGF ratio is 7.21 (sensitivity – 70.0 %, specificity – 70.59 %) and area under the ROC-curve (AUC) 0.702 (95 % CI: 0.571–0.812; p = 0.0118) also indicate the increase the risk of FGR development, as well as the value of the ratio of E/PLGF > 138.53 (sensitivity – 100.0 %, specificity – 35.29 %) and area under the ROC-curve (AUC) 0.640 (95 % CI: 0.507– 0,759). Doppler results in pregnant women with CAH, in the presence of risk factors for FGR development, demonstrate that the CDR was not likely to differ in all groups of patients: 3.62±0.09 units in the persons with CAH and FGR (n=10) and 3.71±0.05 units in the pregnant women with CAG without FGR (n=51) in the right uterine artery; 3.63 ± 0.09 units and 3.71 ± 0.05 units in the left uterine artery, respectively (p<0.05 for all values). However, if PI in the right uterine artery is more than 1.84 units and more than 1.82 units in the left uterine artery, the FGR will further develop. Conclusions. According to the results of the study, it was found that pregnant women with CAH 1-2th degrees with FGR development in the future, in the first trimester of gestation (11-12 weeks) have a decrease PlGF level, sFlt-1and the coefficient K increase. These indicators in the 11–12 weeks of pregnancy were: PlGF ≤ 8.2 pg/ml, sFlt-1 > 1802.59 ng/ml, coefficient K ≥ 95.36 units, and PG/PlGF > 7.21 units, E/PlGF > 138.53 units and CHG/PlGF ≥ 30.14 units.In the pregnant women with CAG, in whom FGR risk will subsequently determine, the significant changes in the CDR and RI at 11-12 weeks of pregnancy are not established, but with an increase of PI more than 1.84 units in the right uterine artery and more than 1.82 units in the left uterine artery FGR will further develop.