Biomarkers of placental dysfunction. Clinical experience

Abstract

The objective: to determine the diagnostic value of biomarkers of placental dysfunction at different stages of gestation.Materials and methods. The research was carried out in 2015–2022 on the basis of the municipal non-commercial enterprise “Maternity House No.5” of the Odesa City Council.We analyzed the course and clinical outcomes of pregnancies in 118 women (the main group) who developed and established placental dysfunction (PD) during pregnancy at different stages of gestation. The control group included 78 healthy women whose pregnancies occurred without PD.In women of both groups the frequency of detection of risk factors for PD was assessed by analyzing the content of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) biomarkers in blood serum, Pregnancy-Associated Plasma Protein A (PAPP-A) and β-subunit of chorionic gonadotropin (hCG).Fetal growth retardation was determined by deviations of fetal metric indicators (abdominal circumference, head circumference, biparietal size, thigh length, estimated fetal weight) below the 10th percentile.Statistical processing of the obtained results was carried out using Statistica 14.0 software (TIBCO, USA).Results. Among the examined women of both groups, cases where the pregnancy occurred at the age of 30 years or more and was the first pregnancy that did not end in abortion prevailed. The average age of women in the main group was 33.4±2.3 years, the control group – 29.3±1.4 years.The main group had more women with a history of multiple abortions (odds ratio (OR)=5.6, 95% confidence interval (CI): 1.9–18.8). Disorders of the menstrual cycle in history were found in 39 (33.1%) women of the main group and in 18 (23%) women of the control group (OR=1.6, 95% CI: 0.9–3.2). Concomitant gynecological diseases were represented by uterine fibroids – in 16 (13.6%) pregnant women of the main group and in 8 (10.2%) women of the control group (OR=1.4, 95% CI: 0.6–3.4), benign ovarian tumors – in 13 (11.0%); OR=20.1, 95% CI: 1.2–343.1), mastopathy – in 19 (16.1%; OR=30.8, 95% CI: 1.8–517.6) women of the main group.A significant number of women in the main group had a hypertrophic nutritional status – the body mass index (BMI) at the time of pregnancy was on average 26.7±0.9 kg/m2, women in the control group were represented by the normotrophic type (BMI – 22.2±0.3 kg/m2), in 4 women the indicator was more 30 kg/m2.In the vast majority of pregnant women (68 persons – 57.6%) of the main group the signs of placental malperfusion were registered up to 34 weeks. In 12 (10.2%) cases a primary PD was established.The content of PIGF in women of the main group at the 20th week of pregnancy decreased to 83±4 pg/ml, which is significantly less than the reference values (≥100 pg/ml). On the other hand, in the control group the PIGF concentration was 147±8 pg/ml (p<0.05). The sFlt-1 amount in the main group corresponded to the level of 3395±62 pg/ml. Therefore, the ratio of sFlt-1/PlGF was equal to 40.8±0.4, which is prognostically unfavorable.The PAPP-A indicator, according to monitoring data at the 20th week of pregnancy, was 0.77±0.08 mU/l. In pregnant women with lower values in the future PD occurred earlier. As for the indicators of the β-subunit of hCG, the levels of this hormone in most cases corresponded to the normative values, amounting to an average of 4.7±0.1 IU/l in a pregnancy with a male fetus and 8133±21 IU/l in a pregnancy with a female fetus.Signs of preeclampsia were determined in 22 (18.6%) pregnant women of the main group. The value of the sFlt-1/PlGF ratio in these pregnant women exceeded 50.0.Conclusions. In the vast majority of pregnant women of the main group (68 – 57.6%) the signs of placental malperfusion were found up to 34 weeks. In 22 (18.6%) pregnant women with placental dysfunction (PD) the signs of preeclampsia were detected, the development of which increases when the sFlt-1/PlGF ratio exceeds 50, starting from the II trimester of pregnancy, which is an early biomarker of PD.