Comparison of prenatal functional markers of retardation of fetal growth and delayed fetal development with expression of vascular growth factors in the placenta

Abstract

AIM: The study aimed to investigate and compare Doppler metric indicators in the main arteries of the functional system of the mother, placenta, and fetus as well as the parameters of the activity–rest cycle in fetuses with vascular endothelial growth factor (VEGF) expression and placenta growth factor (PlGF) in the presence of physiological pregnancy and placental insufficiency to analyze morphofunctional parallels between these indicators in the third trimester of pregnancy.

MATERIALS AND METHODS: Twenty-nine women on the 34–35 weeks of pregnancy (period of physiological maturity of the activity–rest cycle in the fetus) were screened. The main group consisted of 19 patients. The inclusion criteria were as follows: single-fetal pregnancy, fetometric indicators below the 10th percentile, and presence of blood flow disorders in the main vessels of the mother–placenta–fetus functional system. The comparison group included 10 relatively healthy women. The criteria for inclusion in the comparison group were as follows: single-fetal physiological pregnancy, fetometric indicators above the 10th percentile, and absence of Doppler disorders of placental blood flow. Fetometry and Doppler studies of the placental blood flow in the main arteries of the functional system of the mother, placenta, fetus were performed using the Voluson 730 Expert ultrasound device (GE, USA). The activity–rest cycle in the fetus was evaluated using Sonicaid Team Care fetal monitor (Oxford, UK). Placental tissue was taken from the central placental area for immunohistochemical analysis of VEGF and PlGF expression with primary monoclonal antibodies of the main women group and comparison group after childbirth (1:100, Abcam, UK).

RESULTS: A direct correlation between the expression of VEGF in the central zone of the placenta and index resistance (IR), ripple index (RI) in the uterine arteries, as well as the cerebroplacental relationship — CPR (r₁=0.487; p₁=0.035; r₂=0.487; p₂=0.035; r₃=0.578; p₃=0.030, respectively) in women of the main group was found. A direct correlation was established between the expression of VEGF in the central zone of the placenta and IR in the umbilical artery (r=0.49; p=0.033) in patients of the main group. The analysis of the rest–activity cycle in fetuses of women of the main group showed that at 34–35 weeks 73% of them do not form it: the behavior of fetuses is represented only by the activated state. An inverse relationship was found between VEGF expression and the motor-cardiac reflex amplitude (r=–0.866; p=0.05) as well as the heart rate oscillation amplitude (r=–0.866; p=0.05) in fetuses of women of the main group.

CONCLUSIONS: The identified morphofunctional parallels will allow to develop non-invasive pathogenetic prognostic models for prenatal diagnosis of fetal development delay with different degrees of growth restriction.

Keywords

retardation of fetal growth and delayed fetal development / placental blood flow Doppler / activity–rest cycle / vascular endothelial growth factor / placental growth factor

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