Angiogenic imbalance as a starting point for the development of placental dysfunction and pregnancy complications in patients with pathology of the fetal environment

Abstract

In recent years, scientific views on perinatal protection of fetus have shifted to earlier periods of pregnancy – to the I trimester, because from this stage the formation of the fetoplacental complex and laying of organs and tissues take place, which in most cases determines the further course of pregnancy.  The objective: to clarify the role of the imbalance of angiogenic growth factors as one of the pathogenetic mechanisms in the development of placental dysfunction, and to conduct a postnatal macromorphometric study of placenta and umbilical cord in women with pathology of the fetal environment.  Materials and methods.  The object of the study were 80 pregnant women (the main group) with a singleton pregnancy, selected from the cohort of patients from the risk group for the development of preeclampsia and miscarriage. Among them, at 30–32 weeks of gestation oligohydramnios was diagnosed in 40 patients (the first group) and polyhydramnios – in 40 women (the second group). The control group included 30 somatically healthy pregnant women with a normal volume of amniotic fluid and a physiological course of pregnancy.The concentrations of placental growth factor (PlGF), vascular endothelial growth factor-1 (VEGF-1), and an anti-angiogenic marker of neovasculogenesis, soluble fms-like tyrosine kinase (sFlt-1), were performed at 12–16 and 28–32 weeks of pregnancy by enzyme immunoassay method. The study of the structural and functional features of the placenta and umbilical cord included sonographic and organometric methods. The variational statistical method of analysis of the obtained results was carried out using the «STATISTICA for Windows®-6.0» package.Results. In the women of the main group in the I trimester the ultrasound signs of pathology of the embryo and extraembryonic structures were significantly more often observed: low placement of the fertilized egg (33.8 %), its deformation (27.5 %), and partial detachment of the chorion (28.5 %). At 12–16 weeks of pregnancy, a pronounced vascular imbalance was established with a 2.5-fold decrease in the concentration of PlGF in the case of oligohydramnios compared to control data, a 1.8-fold decrease in the level of free VEGF-1 (in the case of oligohydramnios), and an increased level of antiangiogenic growth factors (sFlt-1).The postnatal examination of the placenta and umbilical cord showed that in the pregnant women of the main group a predominance of abnormal forms of placenta (16.3 %), a predominance of eccentric and marginal types of attachment of the umbilical cord (53.8 %), main and intermediate types of vascular branching (63.7 %), changes in the diameter of the umbilical cord (17.5 %), a combination of these features in a third of cases (31.3 %) were found. In the women of the main group, there was a decrease of the placental-fetal coefficient compared to the individuals of the control group, which was especially pronounced in pregnant women with oligohydramnios (up to 0.11±0.01 units compared to control data - 0.16±0.01 units).Conclusions. In the period of 12–16 weeks of pregnancy a vascular imbalance was established at the stage of placentation in patients who were diagnosed pathology of the perinatal environment at 30–32 weeks. In particular, by oligohydramnios there is a 2.5-fold decrease in the concentration of PlGF compared to the control data, a 1.8-fold decrease in the level of VEGF-1, and an increased antiangiogenic growth factor (sFlt-1), which became a prerequisite for the development of placental dysfunction.The results of the postnatal examination of the placenta and umbilical cord became an indirect reflection of placentation conditions. They demonstrated the predominance of abnormal forms, the predominance of the eccentric and marginal type of attachment of the umbilical cord, the main and intermediate type of vascular branching, an increased rate of umbilical cord pathology (Warton’s jelly deficiency, anomalies of the umbilical cord vessels) and a decreased placental-fetal ratio in women with amniotic fluid pathology, which was it is especially pronounced with oligohydramnios.