Placental factors in pregnant women with isolated heart disease of the fetus

Abstract

The placenta, as a unique and transient organ in humans, ensures the development and protection of the fetus, the expression of angiogenic and antiangiogenic factors and their receptors. The integrity of the fetoplacental endothelial barrier is critical for the development of fetal organs, especially the cardiovascular system. Placental growth factor (PLGF) regulates the morphologic and functional development of the uteroplacental vasculature and can vary with gestational age and in various pathologic conditions of the pregnant woman. Since there is a differential expression of PLGF and soluble form of fms-like tyrosine kinase (sFlt-1) at different gestational ages and their competitive interaction, it is advisable to study their level in the blood of a pregnant woman as indicators of regulation of the placental vascular system in pathological conditions of the woman and fetus.

Purpose - to determine the levels of placental factors, namely PLGF and sFlt-1, in the serum of pregnant women with isolated congenital heart disease (CHD) in the fetus to increase the effectiveness of diagnostics and the ability to predict heart diseases.

Materials and methods. The work was based on a prospective clinical study of a hospital sample, using the case-control study method, with the evaluation of some clinical and laboratory data in 30 pregnant women with isolated fetal CHD (study group) and 60 pregnant women with a healthy fetus (control group). In order to minimize the influence of various risk factors for fetal heart disease, the criteria for selecting pregnant women with non-syndromic forms of CHD and the control group were defined. Clinical, laboratory and statistical methods were used in the study. The level of angiogenesis indicators in blood serum of pregnant women of both groups was determined by enzyme-linked immunosorbent assay in units of pg/ml in the third trimester of pregnancy. The statistical analysis was carried out using the R software package. ROC analysis and AUC (area under the ROC curve) were used for quantitative interpretation. Differences with p<0.05 were considered statistically significant.

Results. According to the results of the study, the age of the women in the study group ranged from 17 to 39 years with a mean of 28.36±5.12, and the age of the women in the control group was 29.63±5.39 (p=0.239). The mean gestational age of women in the study group at enrollment was 28.26±8.45 weeks. The mean PLGF level was 93.73±77.32 pg/mL in the study group and 198.63±168.27 pg/mL in the control group (p=0.002). The average level of sFlt-1 in the blood serum of the women in the study group was 9779.44±5407.53 pg/ml, while in the pregnant women in the control group it was 3124.6±1624.53 (p<0.001). The sFlt/PlGF ratio was 180.9±151.1 in the study group and 15.76±14.7 in the control group (p<0.001).

Conclusions. The obtained results in the form of a decrease of the placental growth factor in the blood of pregnant women with congenital heart defects in the fetus and an increase of the antiangiogenic factor in this group in the III trimester compared to a healthy fetus indicate a violation of angiogenesis in the fetoplacental system. Analysis of data on the age of pregnant women of both groups did not reveal a statistically significant difference between them. Due to the usage of multifactor logistic regression model, was created the CHD “risk calculator” which, using the placental factors of the pregnant woman, calculates the probability of the occurrence of a heart defect in fetus.

The study was conducted in accordance with the tenets of the Declaration of Helsinki. The local ethics committee approved the study protocol for all participants. Informed consent was obtained from patients.

No conflict of interests was declared by the author.