Aleksandra Novakov-Mikic

Inherited Thrombophilia is Associated With Pregnancy Losses That Occur After 12th Gestational Week in Serbian Population

Recurrent fetal loss (RFL) is a significant clinical problem, occurring in 1% to 5% of reproductive females. Inherited or acquired thrombophilia has been diagnosed in 50% to 65% of women with history of unexplained fetal loss. The objective of our study was to determine the prevalence of thrombophilia in women with unexplained RFL in Serbian population and to find out whether the presence of thrombophilia is associated with pregnancy losses that occur later than 12th gestational week. We have examined 147 women with unexplained RFL or intrauterine fetal death and 128 healthy women with at least 1 uncomplicated pregnancy. The antithrombin (AT), protein C (PC), protein S (PS), activated protein C (APC) resistance, factor V (FV) G1691A, factor II (FII) G20210A, and MTHFR C677T were determined. At least 1 inherited thrombophilic defect was found in 54 (36.7%) of 147 women with repeated fetal losses and in 11 (8.59%) of 128 controls (P < .001, OR 6.17, 95% CI 3.06-12.48). The most common thrombophilic abnormalities were homozygosity for MTHFR 677TT, FV Leiden, and FII G20210A. Deficiency of natural anticoagulants occurred in 10 patients, with protein S deficiency being the most frequent one. Thrombophilia was found in 46 of 94 women with RFL that occurred later than the 12th gestational week and in only 8 of 53 with RPL earlier than 12th week (P = .001). Our study has shown the association between the hereditary thrombophilia and RFL that occurred after the 12th gestational week in Serbian population.

Ultrasonographic observations of the maturation of basic movements in guinea pig fetuses

Ultrasonography has not previously been used for studying fetal movements in precocial rodents. The objective of this study was to ultrasonographically determine the sequence of the appearance of basic movements in a guinea pig fetus. The research included eight guinea pig females carrying one fetus each. Fetal movements were observed for 10 minutes each day, from the 25th to 38th day of gestation. The time and sequence of the appearance of movements was observed as follows: whole body flexion (mean 27.6 SD ± 1.68), whole body extension (mean 28.1 SD ± 1.12), head flexion (mean 28.1 SD ± 1.80), head extension (mean 30.5 SD ± 2.67) forelimbs flexion (mean 30.5 SD ± 2.32), forelimbs extension (mean 30.7 SD ± 1.84), trunk rotation (mean 31.9 SD ± 2.23), forelimbs alternating flexion and extension (mean 32.1 SD ± 2.1), hind limbs extension (mean 32.2 SD ± 3.2), hind limbs flexion (mean 32.4 SD ± 3.16), and hind limbs alternating flexion and extension (mean 33.5 SD ± 2.39). The identical sequences of basic movement appearances in guinea pigs, sheep, and rats suggest that the rostrocaudal gradient of basic movement appearance could be a general developmental pattern in mammalian species.

Lipid peroxidation in the first trimester of pregnancy.

Aim: To determine the existence and level of oxidative stress caused by lipid peroxidation in pregnancy. Methods: The research was conducted as prospective examination that included 60 healthy women (age 18–45). The women included in the examination were divided into two groups. The group I (N-31) included women in the first trimester of normal, healthy pregnancy. The group II included healthy nongravid women (N-29). Concentrations of markers of lipid peroxidation malondialdehyde (MDA) and thiobarbituric acid (TBARS) were determined using commercial ELISA tests OxiSelect™ TBARS Assay Kit and OxiSelect™ MDA ELISA Kit. Results: The results of this research indicate that the concentrations of the markers of lipid peroxidation TBARS and MDA are detectable in both groups. Higher mean values of MDA (>20 pmol/mg) were measured in the group of pregnant women, than in the group of nongravid women. The results indicate that mean values of TBARS markers are lower in pregnant women (≤50 µM) than in nongravid women (>100 µM). Conclusion: The marker of lipid peroxidation MDA proved to be a sensitive marker for following lipid peroxidation during pregnancy, therefore it can be considered as a good predictor of possible complications during pregnancy.

Decreased expression of the righting reflex and locomotor movements in breech-presenting newborns in the first days of life

AIM To investigate differences between the infants born in occipital and breech presentation relative to the passive and active motility. METHOD A prospective study was conducted in the period from 2006 to 2007 at the Department of Obstetrics and Gynecology in Novi Sad. Subjects were 50 breech-presenting and 87 occipital-presenting term newborns delivered by elective cesarean section following a regular course of pregnancy, without fetal, newborn, and the pregnant female disease. Outcome measures were popliteal angle; extension of the hip-joint; ventral flexion and dorsal extension in the axis; spontaneous displacement; crawling reflex; righting reaction in vertical and sitting positions; righting reaction in horizontal suspension, the automatic walking investigated on the second and fourth day of life. RESULTS Except for righting reaction in horizontal suspension, the newborns from breech presentation had a significantly lower score for all investigated parameters of active movements at the first and second examination. There was no difference between occipital and breech-group relative to the ventral flexion and dorsal extension in the axis. The popliteal angle was significantly increased, whereas the extension in the hip joint was significantly decreased in the breech group. CONCLUSIONS Investigations showed a significantly decreased expression of active movements in the breech group, which cannot be explained only by postural deformities.

Breech presentation and the cornual-fundal location of the placenta

Aim To investigate the association of cornual-fundal location of the placenta and breech presentation at term delivery. Methods This study was conducted at the Department of Obstetrics and Gynecology, Novi Sad, in 2011. The inclusion criteria were delivery at ≥37 weeks of gestation, singleton gestation, and cornual-fundal location of the placenta determined by ultrasonography at ≥37 weeks of gestation when 3/4 or more of the placenta was in the cornual-fundal region. Results Out of 2750 ultrasound examinations performed, 143 showed cornual-fundal location of the placenta (frequency 5.2%). Eighty six cases had cephalic presentation (60.14%) and 57 (39.86%) had breech presentation. Of the remaining cases with non- cornual-fundal location, 2585 had cephalic presentation and 22 (0.84%) had breech presentation. The difference in the frequency of breech presentation between the cornual-fundal and non-cornual-fundal groups was significant (χ2 = 77.78, P < 0.001). Conclusion Cornual-fundal location of the placenta may be an important clue in resolving the etiology of a number of cases of breech presentation at term delivery.

Antioxidant Status in Normal Pregnancy and Preeclampsia upon Multivitamin-Mineral Supplementation in the Region of Vojvodina

Normal pregnancy is associated with oxidative stress and this is even increased during preeclampsia (PE). The decrease in total antioxidant capacity is the pathophysiological basis for vitamin supplementation during pregnancy, but the beneficial effect of this approach is still unclear. Levels of creatinine, urea, cystatin, malondialdehyde (MDA), superoxide dysmutase activity (SOD), glutathione peroxidase (GSH-Px) activity and acidum ascorbicum were measured in the serums of all women. Mean MDA level in maternal plasma in normal pregnancies was significantly lower than in PE pregnancies (2,78 ±0.78 pmol/mg vs 3.20±0.91 pmol/mg, p< 0.05), as well as mean GSH-Px levels (811 ±206 U/l vs 1350±575 U/l, p< 0.05. Mean ascorbic acid values were significantly higher in normal than in PE pregnancies (9,85 ±2,43 mg/L vs 5.54±1.81 mg/L, p< 0.001), as well as mean SOD values (26.8 ±18.45% vs 12.3±10.3%, p< 0.001). There were no significant differences in normal pregnancy group with and without multivitamin supplementation. MDA levels were significantly lower in PE pregnancies with vitamin supplementation (2.99 ± 0.81 pmol/mg vs 3.42 ± 1.01 pmol/mg, p< 0.05), as well as GSC-Px levels (1200 ± 500 U/l vs 1500 ± 650 U/l, p< 0.05). Ascorbic acid values were significantly higher in the PE group with vitamin supplementation (6.16 ± 1.66 mg/L vs 4.92 ± 1.96 mg/L, p< 0.05), as well as SOD levels (13 ± 11.4 % vs 11.6 ± 9.2%, p< 0.001).

Prenatal diagnosis of varix of the fetal intraabdominal umbilical vein--case report.

Varix of intraabdominal part of fetal umbilical vein is during a prenatal ultrasound scan seen as a hypoechogenic mass between anterior abdominal wall and lower edge of liver, and the diagnosis is confirmed when blood flow is seen during color Doppler examination. A case of prenatal diagnosis of this abnormality is presented, with review of contemporary literature regarding diagnosis and management as well as the outcome of such pregnancies.

APRIL and sTACI could be predictors of multiorgan dysfunction syndrome in sepsis

ABSTRACT Although the role of B cells in sepsis immunoregulation has become an interesting topic, there is lack of data on the role of B cell function regulators in prediction of multiorgan dysfunction syndrome (MODS). The aim of this study was to evaluate the prognostic value of A Proliferation Inducing Ligand (APRIL) and soluble Transmembrane Activator and CAML Interactor Protein (sTACI), the main B cell function regulators, in prediction of MODS development within the first 48 h after admission to intensive care unit, among septic patients. We included 112 patients with sepsis, treated at Clinic for Infectious Diseases and Emergency Center, Clinical Center of Vojvodina, Novi Sad, Serbia. Plasma concentrations of APRIL and sTACI were determined at the admission and potential development of MODS was confirmed in the first 48 h. Concentrations of APRIL (p = 0.003) and sTACI (p<0.001) were higher in patients who developed MODS (n = 30). ROC curve analysis showed that AUC for sTACI (AUC = 0.764) was greater than that for procalcitonin (AUC = 0.719) and APRIL (AUC = 0.673) in MODS development prediction. Multivariate regression analysis showed that sTACI, as an anti-inflammatory biomarker stimulating the apoptosis of B cells, was the only independent predictor of MODS, beside SOFA score. Elevated level of sTACI could be the alarm for the increased B cell apoptosis and development of immune paralysis. Including these biomarkers into predictive scores specific for septic patients may potentially improve their sensitivity and specificity. Measurement of their concentrations dynamics could contribute to better assessment of sepsis evolution and timely introduction of immunomodulatory therapy.

Complement component consumption in sepsis correlates better with hemostatic system parameters than with inflammatory biomarkers

INTRODUCTION The aim of this study was to investigate the role of C3 and C4 complement components in prediction of sepsis outcome. The secondary aim was to determine relationship between complement components and other inflammatory parameters, and parameters of hemostasis. METHODS One-hundred-thirty-seven patients with sepsis (Sepsis-3 criteria) were included in the study. Routine laboratory markers, predictive APACHEII and SOFA scores, concentrations of C3 and C4, activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen, antithrombin (AT), protein C (PC), protein S (PS), endogenous thrombin potential (ETP), thrombomodulin, and D-dimer were available. Concentrations of C3 and C4 were correlated with the disease outcome, predictive scores, inflammatory markers and parameters of hemostasis. Statistical analysis was performed using the non-parametric approach and significance was set at p < 0.05. RESULTS A significant depletion of the complement was observed in non-survivors (AUCROCC3 = 0.692, pC3 < 0.001,AUCROCC4 = 0.672, pC4 = 0.001). There was a significant negative correlation of C3and C4with APACHEII and SOFA (C3-APACHEII ρ = -0.364, p = 0.011, C3-SOFA ρ = -0.460, p < 0.001), aPTT (ρ = -0.407, p < 0.001), PT (ρ = -0.408, p < 0.001), and D-dimer (ρ = -0.274, p = 0.001). A significant positive correlation was observed with natural anticoagulants (C3-AT ρ = 0.493, p < 0.001; C3-PC ρ = 0.450, p < 0.001; C3-PS ρ = 0.345, p < 0.001), fibrinogen (ρ = 0.481, p < 0.001),and ETP (ρ = 0.384, p < 0.001). C3 and C4 correlated significantly only with CRP (ρ = 0.207, p = 0.015), while no significant correlations with procalcitonin and WBC were detected. Results were similar for C4 and C3, although C3 presented higher correlation coefficients. CONCLUSION In septic patients with poorer outcome, a significant depletion of the complement system was observed. Concentrations of complement components demonstrated stronger correlations with coagulation parameters than with inflammatory biomarkers.

The role of TNF-α superfamily members in immunopathogenesis of sepsis

Background Members of TNF&agr; superfamily, A proliferation inducing ligand (APRIL), B‐cell activating factor (BAFF) and Transmembrane activator and calcium cyclophylin interactor (TACI) are main regulators of B‐cell function. The aim of this study was to evaluate concentrations of APRIL, BAFF and soluble TACI (sTACI) receptor in septic patients compared to healthy controls and compare concentrations of these biomarkers depending on sepsis severity and outcome. Materials and methods A total of 115 septic patients and 30 healthy volunteers were included and concentrations of APRIL, BAFF and sTACI were determined in all subjects at the admission (ELISA R&D Systems tests). Concentrations of these biomarkers in function of sepsis severity (sepsis n = 94 and septic shock n = 21) and outcome (lethal n = 40, recovery n = 75) were tested, as well as correlations with APACHE II and SOFA scores, immunoglobulins, complement, PCT and CRP concentrations. Results Concentrations of all three biomarkers were significantly increased in septic patients compared to controls (AUCAPRIL = 0.982, AUCBAFF = 0.873, AUCsTACI = 0.683). Higher concentrations of APRIL and sTACI (p = 0.033, p = 0.037), and lower concentrations of BAFF (p = 0.005) were observed in patients with septic shock compared to sepsis. BAFF concentrations correlated positively with IgM, C3 and C4 levels. sTACI and APRIL were shown to be predictors of lethal outcome (p = 0.003, p = 0.049). Conclusions Concentrations of observed TNF&agr; superfamily members are significantly increased in septic patients, confirming their role in sepsis pathogenesis. Higher concentrations of anti‐inflammatory sTACI receptor correlated with severity of sepsis and poorer prognosis, thus potentially indicating domination of anti‐inflammatory response in septic patients with worse outcome. HighlightsHigh concentrations of TNF‐&agr; superfamily members point to prompt activation of B cells in sepsis.APRIL, BAFF and sTACI are good predictors of septic shock and lethal outcome in sepsis.Their concentrations correlate well with SOFA, but do not correlate with PCT.Lower BAFF and higher sTACI concentrations suggest increased apoptosis of B cells in septic shock.sTACI is an anti‐inflamatory cytokine that had the highest AUC in outcome prediction.