Stasii Ya.O. Clinical, laboratory and morphological features of the gestational process and childbirth in pregnant women with coronavirus infection COVID-19. Dissertation for obtaining the scientific degree of Doctor of Philosophy in the field of knowledge 22 "Health care" in the specialty 222 "Medicine" - Odesa National Medical University, Ministry of Health of Ukraine, Odesa, 2024. The dissertation provides a theoretical justification and practical solution to a pressing scientific problem regarding the possibility of predicting the condition of a newborn immediately after childbirth in women with COVID-19 infection during pregnancy based on the study of clinical and laboratory features of the gestational process and childbirth, the study of pathohistological and immunohistochemical characteristics of their placentas, in particular, placental expression of markers of endothelial and mitochondrial dysfunction. The aim was to study of clinical and laboratory features of the gestational process and childbirth, pathohistological and immunohistochemical characteristics of their consequences in women who have contracted COVID-19 during pregnancy, in particular, placental expression of markers of endothelial and mitochondrial dysfunction, and substantiation on this basis of the possibility of predicting perinatal disorders. Among pregnant women with COVID-19, there is a significantly higher percentage of people with impaired fat metabolism (43.1% vs. 22.5%,OR=2.61, 95% CI 1.06-6.46). The course of pregnancy in these women is characterized by a higher frequency of impaired function of the amniotic membranes (58.6% vs. 12.5%; p<0.001), the threat of abortion (34.5% vs. 12.50%, p<0.001). The frequency of premature birth is 4.1 times higher (20.68% vs. 5%, F = 0.039, p <0.05), and deliveries by cesarean section are 2.8 times higher (34.48% vs 12.5%, p <0.001). At birth, children have a significantly lower weight (3067.93 620.21) g vs. (3617.25 354.58) g, p<0.01) and body length (50.4 2.91 cm vs. 54.25 2.08, p<0.01), lower Apgar score (6.48±2.39 vs. 8.05±0.54) points, p <0.01). The highest incidence of COVID-19 is observed in the 3rd trimester of pregnancy (6.9%, 25.7% and 67.4%, p<0.01). 12.1% of pregnant women require observation and treatment in the intensive care unit. In 53.4% of women, bilateral polysegmental pneumonia is detected, in 6.9% - left- or right-sided pneumonia, in 1.7% - pneumonitis, in 6.9% - hydropericardium. The presence of a systemic inflammatory response is reflected by a moderately increased concentration of C-reactive protein (14.06±4.4 mg/l), a slight activation of the procoagulant link of the hemostasis system (D-dimer content 1096±913.7 ng/ml) and an increase in liver enzymes (aspartate aminotransferase - in 25.9% of women, alanine aminotransferase - in 29.3%) and bilirubin (8.6%). Histopathologically, "post- In pregnant women who have had COVID-19, morphological maturity of the placenta is observed with a 4.4-fold lower frequency (15.51% versus 67.50%), while dissociated maturation of the chorion is recorded 5.5 times more often (55.17% versus 10%, and pathological immaturity is recorded 1.9 times more often (24.13% versus 12.50%, p<0.001). In "post-COVID" placentas, signs of maternal vascular malformation in the form of pseudoinfarctions, "white" infarcts (53.45% versus 12.5%; p<0.001), agglutination of the villous chorion with a 5.3-fold increase in the number of syncytial nodules 79.31% versus 15%; p<0.001) are detected 4.3 times more often. "Silent" hemorrhages in the placental structures are observed 3.6 times more often (53.45% vs. 15.00%,p<0.001), and impaired vascularization of the villi is found only in "post-covid" samples (8.6%). When immunophenotyping placentas in "post-covid" samples, no differences in the expression of epidermal growth factor are observed, and the expression of progibitin is 6.1 times higher (HR = 9.5; 95% CI 2.423-37.249, p = 0.0005), which may indicate a protective "stress" of mitochondrial respiration. The sensitivity of progibitin determination for assessing impaired functional state of the placenta is 79.2%, specificity - 71.4%.The effect size determined by the Hedges coefficient (g=1.390832, 95% CI 105.77 198.23) reflects the significance of the difference in progibitin expression in relation to placentas from women in the comparison group.
The presence of relationships between the saturation level (X1) in a pregnant woman and short-term variability (STV X2) according to the data of cardiotocographic examination of the fetus with the assessment of the newborn on the Apgar scale at the 1st minute of life (Y) justifies certain prognostic possibilities, which are described by the multiple linear regression equation (Y = 0.89X1 + 0.028 X2 – 79.53). The relationship between progibitin expression (Y) and saturation levels in women is described by the equation (Y=0.05X1 – 3.27), which indicates a possible interaction between mitochondrial disorders
