Preeclampsia (PE) is a leading cause of maternal complications and is diagnosed by clinical manifestation. The aim of the study was to evaluate changes of cell-free DNA (cfDNA) and cell-free foetal DNA (cffDNA) concentration during uncomplicated pregnancy and PE in one group of women, and define the predictive value for PE. A total of 580 women were prospectively evaluated, 20 of them developed PE and were included in laboratory analysis, and 22 healthy pregnant with uncomplicated pregnancy were included as the laboratory control group. We determined cfDNA and cffDNA in maternal blood at 11–14, 24–26, and 30–32 weeks. Level of cfDNA was evaluated by determining the RASSF1A gene using PCR analysis, cffDNA—by determining the hypermethylated part of RASSF1A gene. The concentration of cfDNA did not differ in the first and second trimesters but significantly increased at 30–32 weeks in both groups. During uncomplicated pregnancy, median cffDNA level increased from 14.15 GE/ml to 24.87 GE/ml (p = 0.002) and 32.62 GE/ml (p = 0.005). In the PE group, an elevation in cffDNA level was significant only in the second half of pregnancy (from 54.85 to 96.72 (p > 0.05) and 158.30 GE/ml (p = 0.031) at 11–14, 24–26, and 30–32 weeks, respectively). At all studied periods, cffDNA level in the PE group was significantly higher compared to uncomplicated pregnancy (р < 0.001). ROC analysis showed that a cut-off value of cffDNA concentration 22.54 GE/ml in maternal blood at 11–14 weeks of pregnancy had the greatest predictive value for PE prediction, with 85.0% sensitivity and 81.8% specificity. CffDNA is a promising marker for PE prediction from the first trimester of pregnancy.
We evaluated the content of cell-free fetal DNA in maternal blood and expression of ZBP-1 receptors in the placental tissue of women with uncomplicated pregnancy, preeclampsia, and preterm labor. The study included 16 women with preeclampsia (early and late-onset preeclampsia, 8 cases each), 16 women with preterm labor, and 21 women with uncomplicated pregnancy. The concentration of cell-free fetal DNA was measured by PCR by detecting hypermethylated region of the RASSF1A gene. Immunohistochemistry was performed on paraffin-embedded sections of the placenta samples using primary polyclonal antibodies to ZBP-1. Significant increase in the level of cell-free fetal DNA was found in women with preeclampsia (both early and late-onset form) in comparison with uncomplicated pregnancy. The concentration of cell-free fetal DNA in preterm labor group did not differ from the control group; however, it was significantly lower than in early-onset preeclampsia, but not late preeclampsia. Immunohistochemical study showed higher expression of ZBP-1 in the villus syncytiotrophoblast in early-onset preeclampsia in comparison with that in preterm labor group (p=0.006). Fragments of damaged placental cells, predominantly trophoblast, enter maternal circulation and are the source of cell-free fetal DNA and a potential ligand for ZBP-1, which leads to further cell damage and the formation of a vicious circle. The increase in the content of cell-free fetal DNA in maternal blood and ZBP-1 expression in the syncytiotrophoblast in preeclampsia are interrelated processes reflecting impaired morphofunctional state of the placenta.
The aim of the study was to compare the efficacy and safety of tocolytic agents - atosiban and hexoprenaline.Patients and methods: The study included 119 pregnant women with threatening preterm labour between 28 to 34 weeks of gestation. Sixty two pregnant received 62 tocolysis by hexoprenaline and fifty seven - atosiban. There were no differences in the clinical condition of pregnant women and features of preterm labour among groups before start of the tocolysis.The degree of effectiveness is determined by the duration of the pregnancy prolongation (48 hours, 7 days, more than 14 days).Results: 9 women of 62 that received hexoprenaline tocolysis (22,6%), and 2 – atosiban (3.5%) failed to prolong the pregnancy for more than 48 hours (p < 0,05). Additionally, 5 women of the hexoprenaline group had premature labour within the first week from the treatment start and eight within 7-14 days. In the group of women with an effective atosiban tocolysis all births took place in a range of more than 7 days from the beginning of tocolysis. Four woman in hexoprenaline group received one repeated course of therapy with this drug (without a loading dose) for 24 hours. In atosiban group full repeated course was conducted in the two cases. Full-term gestation births occurred in 14 women (22.6%) after hexoprenaline tocolysis and in 19 (33.3%) – atosiban (p > 0,05%). On average, atosiban tocolysis allowed to prolong pregnancy by 6.5 days longer than hexoprenaline (p < 0,05).Conclusion: The results of study has shown that atosiban is more effective than hexoprenaline in pregnancy prolongation for more than 48 hours in threatening preterm labor.