The Role of High Concentrations of Homocysteine for the Development of Fetal Growth Restriction.

Lazzat Balash,Akylbek Tussupkaliyev,Andrey Gaiday

doi:10.1055/s-0042-1743093

Abstract

To assess homocysteine (Hcy) levels in the three trimesters of pregnancy in women with fetal growth restriction (FGR) and to evaluate the role of Hcy as a possible predictor of FGR. A total of 315 singleton pregnant women were included in the present prospective cohort study and were monitored since the 1st trimester of pregnancy before delivery. Newborns were monitored for the first 7 days of life. Patients who had risk factors for FGR were excluded. Fetal growth restriction was defined according to uterine fundal height (< 10 percentile), ultrasound fetometry (< 5 percentile), and anthropometry of newborns (< 5 percentile). The concentrations of Hcy were detected at between 10 and 14, between 20 and 24, and between 30 and 34 weeks of pregnancy by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristics (ROC) curve test and diagnostic odds ratio (DOR) were performed to evaluate the results of ELISA. The concentration of Hcy in patients with FGR was 19.65 umol/L at between 10 and 14 weeks, compared with 9.28 umol/L in patients with normal fetal growth (p < 0.0001). The optimal cut-off level for Hcy in the 1st trimester of pregnancy was > 13.9 umol/L with AUC 0.788, sensitivity of 75%, specificity of 83.6%, and DOR of 15.2. Assessment of serum Hcy concentration may be used as a predictor of FGR, with the highest diagnostic utility in the 1st trimester of pregnancy.

Highlights

Assessment of serum Hcy concentration may be used as a predictor of Fetal growth restriction (FGR), with the highest diagnostic utility in the 1st trimester of pregnancy
The remodeling of the spiral arteries occurs, while the cytotrophoblast increases the expression of vascular endothelial growth factor (VEGF) and placental growth factor (PLGF)
Serum biomarkers are increasingly preferred for the prediction and diagnosis of FGR, of which the most commonly used are pregnancyassociated plasma protein-A (PAPP-A), α-fetoprotein (AFP), placental growth factor (PLGF), and soluble fms-like tyrosine kinase-1.6,9–13

Summary

Introduction

Fetal growth restriction (FGR) occurs when the fetus does not reach its intrauterine potential for growth and development as a result of compromise in placental function. According to various sources, the incidence of FGR is between 5 and 10% worldwide, and is the second cause of perinatal mortality. The risk of death of newborns with FGR increases between 2 and 4 times, and the negative outcomes of childbirth are manifested in newborns as hypothermia, hypoglycemia, hyperglycemia, persistent pulmonary hypertension, pulmonary hemorrhage, polycythemia, stillbirth, and intranatal asphyxia.2In the process of growth, the fetus produces hemodynamic and metabolic changes, in which an adequate trophoblast invasion is an important component, and endothelial and subendothelial changes can contribute to their violation. Today, it is known that the underlying causes of FGR are genetic, placental, fetal, and maternal factors.2,5,6An important physiological process that ensures normal perfusion of the placenta is the invasion of trophoblast villi and the reshuffle of the cytotrophoblast from the epithelial to the endothelial phenotype, which is called pseudovasculogenesis. Subsequently, the remodeling of the spiral arteries occurs, while the cytotrophoblast increases the expression of vascular endothelial growth factor (VEGF) and placental growth factor (PLGF). Nowadays, serum biomarkers are increasingly preferred for the prediction and diagnosis of FGR, of which the most commonly used are pregnancyassociated plasma protein-A (PAPP-A), α-fetoprotein (AFP), placental growth factor (PLGF), and soluble fms-like tyrosine kinase-1 (sFlt-1). Along with well-known biomarkers, in the last decade, studies indicated the possibility of using serum homocysteine (Hcy) for the prediction and diagnosis of preeclampsia (PE) and FGR; there are no studies available from the Kazakhstan population. Fetal growth restriction (FGR) occurs when the fetus does not reach its intrauterine potential for growth and development as a result of compromise in placental function.. In the process of growth, the fetus produces hemodynamic and metabolic changes, in which an adequate trophoblast invasion is an important component, and endothelial and subendothelial changes can contribute to their violation.. It is known that the underlying causes of FGR are genetic, placental, fetal, and maternal factors.. The remodeling of the spiral arteries occurs, while the cytotrophoblast increases the expression of vascular endothelial growth factor (VEGF) and placental growth factor (PLGF).. Serum biomarkers are increasingly preferred for the prediction and diagnosis of FGR, of which the most commonly used are pregnancyassociated plasma protein-A (PAPP-A), α-fetoprotein (AFP), placental growth factor (PLGF), and soluble fms-like tyrosine kinase-1 (sFlt-1).. Injury to endothelial cells is associated with HHcy, which leads to changes in the coagulation system, platelet activation, and thrombogenesis.

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Conclusion