Prediction of the development of fetal growth retardation in pregnant women with chronic arterial hypertension

Abstract

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.