Browsing by Author "Mikovic, Zeljko (7801694296)"

There are no more than 20 antenatally diagnosed aorto-left ventricular tunnel cases reported in the literature. In most of them the diagnosis was made indirectly and only after multiple fetal scans based on findings such as thick and dilated left ventricle and grossly dilated ascending aorta. We present a patient in whom a direct tunnel visualization and aorto-left ventricular tunnel diagnosis was made at the 30th gestation week after a single fetal scan using the recently introduced “cockade sign”. Clinical implications of antenatal diagnosis on postnatal treatment and outcome are also discussed. © 2017, Turkish Journal of Pediatrics. All rights reserved.

Recurrent pregnancy loss (RPL) is a heterogeneous condition affecting up to 5% of women of reproductive age. Inherited thrombophilia have been postulated as one of the causes of RPL. Here we examined the prevalence of nine thrombophilic gene polymorphisms among women with history of recurrent miscarriages and fertile controls. The study included 70 women with history of at least three early pregnancy losses and 31 fertile controls with no miscarriages. We investigated mutations in genes responsible for clotting and fibrinolysis, including factor V (FV) Leiden, FV H1299R, factor II (FII) G20210A, methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C, factor XIII (FXIII) V34L, plasminogen activator inhibitor-1 (PAI-1) 4G/5G and endothelial protein C receptor (EPCR) H1 and H3 haplotypes using reverse polymerase chain reaction ViennaLab cardiovascular disease StrippAssays. Our results showed no significant increase in prevalence of tested polymorphisms in women with RPL. However, relative risk for PRL among women heterozygous for FXIII V34L was 2.81 times increased (OR 2.81, 95% CI 1.15-6.87, P=0.023). Haplotype analysis showed that combined presence of high-risk genotypes for FXIII and PAI-1 significantly increases risk for RPL (OR 13.98, CI 95% 1.11-17.46, P=0.044). This is the first study in Serbian population that investigated prevalence of FVR2, A1298C, FXIII V34L and EPCR gene variants. Compound heterozygosity for FXIII V34L and PAI-1 4G is significant risk factor for recurrent miscarriage. Our results should be viewed in context of small case-control study, so further large prospective studies are need for confirmation of our findings. © 2019 Society of Medical Biochemists of Serbia and Montenegro.

Recurrent pregnancy loss (RPL) is a heterogeneous condition affecting up to 5% of women of reproductive age. Inherited thrombophilia have been postulated as one of the causes of RPL. Here we examined the prevalence of nine thrombophilic gene polymorphisms among women with history of recurrent miscarriages and fertile controls. The study included 70 women with history of at least three early pregnancy losses and 31 fertile controls with no miscarriages. We investigated mutations in genes responsible for clotting and fibrinolysis, including factor V (FV) Leiden, FV H1299R, factor II (FII) G20210A, methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C, factor XIII (FXIII) V34L, plasminogen activator inhibitor-1 (PAI-1) 4G/5G and endothelial protein C receptor (EPCR) H1 and H3 haplotypes using reverse polymerase chain reaction ViennaLab cardiovascular disease StrippAssays. Our results showed no significant increase in prevalence of tested polymorphisms in women with RPL. However, relative risk for PRL among women heterozygous for FXIII V34L was 2.81 times increased (OR 2.81, 95% CI 1.15-6.87, P=0.023). Haplotype analysis showed that combined presence of high-risk genotypes for FXIII and PAI-1 significantly increases risk for RPL (OR 13.98, CI 95% 1.11-17.46, P=0.044). This is the first study in Serbian population that investigated prevalence of FVR2, A1298C, FXIII V34L and EPCR gene variants. Compound heterozygosity for FXIII V34L and PAI-1 4G is significant risk factor for recurrent miscarriage. Our results should be viewed in context of small case-control study, so further large prospective studies are need for confirmation of our findings. © 2019 Society of Medical Biochemists of Serbia and Montenegro.

Background and Objectives: The aim of the present work was to compare the characteristics of delta and omicron variants of COVID-19 infection in pregnant women, the association of infection with comorbidity, clinical manifestation of the disease, type of delivery, and pregnancy outcome. Material and Methods: The study was designed as an observational, retrospective study of a single center. The analysis included the cohort of women who had SARS-CoV-2 infection during pregnancy and/or childbirth in the period from 1 March 2020 to 30 June 2023. Results: Out of a total of 675 pregnant women with SARS-CoV-2 infection, 130 gave birth with the delta and 253 with the omicron variant. In our retrospective analysis, pregnant women with both SARS-CoV-2 variants had a mild clinical history in most cases. In the omicron period, a significantly lower incidence of pregnancy loss (p < 0.01) and premature birth (p = 0.62) admission of mothers and newborns to the intensive care unit (p < 0.05) was recorded. Conclusions: In our retrospective analysis, pregnant women with COVID-19 infection generally exhibited a milder clinical manifestation with both variants (delta and omicron) of the viral infection. During the delta-dominant period, ten percent of affected pregnant women experienced a severe clinical history. However, during the omicron-dominant period infection, a significantly lower incidence of complications, pregnancy loss, preterm delivery, and admission of mothers and neonates to the intensive care unit was recorded. This can be partly explained by the greater presence of pregnant women with natural or induced vaccine immunity. © 2024 by the authors.

The study was conducted to evaluate the effect of anticoagulant therapy in women with thrombophilia and to detect the possible differences among carriers of mutations (factor V [FV] Leiden and FIIG20210) and those with natural anticoagulant deficiency. The 4-year prospective investigation included 85 pregnant women, with a history of recurrent fetal loss (RFL). They were treated with prophylactic doses of low-molecular-weight heparin (nadroparin) starting from 6 to 8 weeks of gestation. Pregnancy outcomes were evaluated based on the thrombophilia type. Carriers of thrombophilic mutations had a live birth rate of 93%, compared to 41.6% for women with natural anticoagulant deficiencies. Significant differences between the groups were also observed for intrauterine fetal death, intrauterine growth restriction, and postpartum thrombosis. The optimal therapy for women with natural anticoagulant deficiency and RFL remains unclear and future prospective study with a large number of patients is required to determine the best treatment for these severe thrombophilic conditions. © The Author(s) 2013.

Objective: To determine if there is any difference in amniotic fluid erythropoietin (EPO) concentration between fetuses small for gestational age (SGA) and appropriate for gestational age (AGA), and between the constitutionally small (CSF) and growth-restricted (GRF) fetuses. Methods: EPO concentrations in the amniotic fluid samples were determined by EpoELISA test in 38 pregnancies with SGA and 15 pregnancies with AGA fetuses. In the SGA group we measured Ponderal index (PI) and skin-fold thickness (SFT). If PI and/or SFT were below 10th percentile the neonate was GRF. If both PI and SFT were above 10th percentile the neonate was CSF. Results: Higher levels of EPO were detected in the SGA in comparison to the AGA fetuses (p<0.01). EPO concentration was higher in GRF compared to CSF (p<0.05). The EPO cut-off level between SGA and AGA was 6.81IU/L (sensitivity 92.3%; specificity 73.3%), and between GRF and CSF was 9.8IU/L (sensitivity 81%; specificity 80%). Conclusion: The preliminary results of this study suggest that amniotic fluid erythropoietin concentration is elevated in growth-restricted fetuses and could potentially be used for distinction between growth restricted and constitutionally small fetuses. Confirmation of these results on a larger group of pregnant women is needed. © 2014 Informa UK Ltd.

Introduction: Haemostatic balance shifted towards hypercoagulability in normal pregnancy is even more pronounced in pre-eclampsia (P-EC). The aim of this study was to analyse haemostatic disturbances and fibrin clot properties in women with pre-eclampsia and to investigate their association with maternal and foetal outcomes. Methods: Forty-six pregnant women diagnosed with pre-eclampsia were included in the study, with blood sampling done on the morning following admission to hospital, as well as after delivery (mean duration 4.8 days). Two global haemostatic assays—endogenous thrombin potential (ETP) and assay of overall haemostatic potential (OHP)—were employed, including fibrin clot turbidity measurements and scanning electron microscopy (SEM) of representative samples. Results: Three thrombin generation parameters (ETP, t_lag and peak height) and OHP were significantly increased in pre-eclampsia compared with controls, whereas overall fibrinolytic potential (OFP—determined as a parameter of the OHP assay) had significantly lower values. Clot lysis time was significantly prolonged in patients with pre-eclampsia. In the pre-eclamptic group after delivery, we observed a significant elevation in the peak height and a reduction in the time to peak and OFP compared with values before delivery. Pre-eclamptic patients with renal complications had significantly higher values for ETP, peak height and D-dimer. Turbidity measurements and SEM revealed dense fibrin structure in patients with pre-eclampsia. Conclusion: Patients with pre-eclampsia have enhanced coagulation and impaired fibrinolysis before, and even after, delivery. In particular, the presence of multi-organ dysfunction, such as renal dysfunction, may be associated with increased thrombin generation in pre-eclampsia. © 2020 John Wiley & Sons Ltd

Introduction: Haemostatic balance shifted towards hypercoagulability in normal pregnancy is even more pronounced in pre-eclampsia (P-EC). The aim of this study was to analyse haemostatic disturbances and fibrin clot properties in women with pre-eclampsia and to investigate their association with maternal and foetal outcomes. Methods: Forty-six pregnant women diagnosed with pre-eclampsia were included in the study, with blood sampling done on the morning following admission to hospital, as well as after delivery (mean duration 4.8 days). Two global haemostatic assays—endogenous thrombin potential (ETP) and assay of overall haemostatic potential (OHP)—were employed, including fibrin clot turbidity measurements and scanning electron microscopy (SEM) of representative samples. Results: Three thrombin generation parameters (ETP, t_lag and peak height) and OHP were significantly increased in pre-eclampsia compared with controls, whereas overall fibrinolytic potential (OFP—determined as a parameter of the OHP assay) had significantly lower values. Clot lysis time was significantly prolonged in patients with pre-eclampsia. In the pre-eclamptic group after delivery, we observed a significant elevation in the peak height and a reduction in the time to peak and OFP compared with values before delivery. Pre-eclamptic patients with renal complications had significantly higher values for ETP, peak height and D-dimer. Turbidity measurements and SEM revealed dense fibrin structure in patients with pre-eclampsia. Conclusion: Patients with pre-eclampsia have enhanced coagulation and impaired fibrinolysis before, and even after, delivery. In particular, the presence of multi-organ dysfunction, such as renal dysfunction, may be associated with increased thrombin generation in pre-eclampsia. © 2020 John Wiley & Sons Ltd

Introduction: Follicular and serum vitamin D are considered potential markers of the oocyte and embryos' quality and predictors of in vitro fertilization (IVF) outcomes. Methods: This retrospective cross-sectional study correlated vitamin D in sera and follicular fluid of women with unexplained infertility mutually and with IVF outcomes. ELISA was used for measuring vitamin D. Results: The results show positive correlation only between follicular and serum levels of vitamin D (Rho = 0.615, p = 0.025), and between follicular levels of vitamin D and the percentage of embryo fragmentation (Rho = 0.544; p = 0.036). Conclusions: The results suggest that serum and follicular fluid vitamin D measurements could be complementary tools to the routine assessment of embryos. © 2021 Termedia & Banach.

Introduction: Temperature, glycemia and respiration make neonatal energy triangle (NET). In growth retardation (IUGR) neonates pathological metabolic adaptation exists in transient neonatal period. Aim: The of this study was to examine the occurrence of pathological NET and check its impact on perinatal asphyxia during the transient period in IUGR neonates. Material and methods: One hundred and fifty-nine neonates with IUGR were classified into early preterm, late preterm and term neonates. By the presence of hypothermia, hypoglycemia and hypoxia in the first hour after birth neonates were classified into: group of pathological NET, group of unstable NET and group of stable NET. We analyzed distribution per body mass, gestational age, type of IUGR, gender and the frequency of perinatal asphyxia between the groups. Results: The late preterm neonates were the most frequent in the group of pathological NET. Perinatal asphyxia was diagnosed in 52 (32.7%) neonates, with highest frequency in the group of pathological NET. Univariate binary logistic regression analysis showed that pathological NET in neonates with IUGR is significant predictor for perinatal asphyxia occurrence (OR = 8.57; CI = 4.05-18.12; p < 0.001 R2 = 0.27). Conclusion: Poor metabolic adaptation in neonates with IUGR in the first hour after birth is significant risk factor for the perinatal asphyxia. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

Purpose: We aimed to evaluate if ovarian stimulation with individualized dosing of recombinant follicle-stimulating hormone (rec-FSH) with follitropin delta compared with standard gonadotropin dosing reduce occurrence of follicular asynchrony in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF). Methods: Matched case–control study analyzed occurrence of follicular growth asynchrony during ovarian stimulation and IVF outcomes in women with PCOS. Follicular growth was considered to be asynchronous when one or two leading follicles were at least 4 mm larger in diameter than the rest of the cohort on day 5 and 9 of stimulation. Analysis encompassed 44 women stimulated with individualized rec-FSH dosing, and 88 women treated with standard dosing. The patients were matched in terms of age, Anti-Müllerian hormone levels and body weight. Results: Early and late follicular asynchrony were present less frequently in individualized dosing compared to standard dosing group (4.5% vs 17%, p = 0.04 and 2.3% vs 37.5%, p < 0.001, on stimulation day 5 and 9, respectively). Multivariate logistic regression on follicular asynchrony revealed that individualized dosing significantly decreases the occurrence and chances for late follicular asynchrony (Odds Ratio 0.28, p < 0.001). Shorter duration of stimulation (9.6 vs 10.4 days, p = 0.001), lower total gonadotropin dose (1118 vs 1940 IU, p < 0.001), higher number of metaphase II oocytes (7.1 + 4.3 vs 5.4 ± 3.0, p = 0.001), good quality embryos (3.8 vs 2.0, p < 0.001), and implantation rates (31.0 vs 23.4, p = 0.04) were observed in the individualized dosing group. Conclusion: Individualized rec-FSH dosing reduces asynchronous follicular growth and improves ovarian stimulation efficiency in women with PCOS undergoing IVF. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.

Background: Pre-eclampsia (P-EC) is associated with systemic inflammation, endothelial dysfunction and hypercoagulability. The role of extracellular vesicles (EVs) in coagulation disturbances affecting the development and severity of P-EC remains elusive. We aimed to evaluate the concentration of EVs expressing phosphatidylserine (PS) and specific markers in relation to the thrombin and fibrin formation as well as fibrin clot properties, in pregnant women with P-EC in comparison to healthy pregnant women of similar gestational age. Methods: Blood samples of 30 pregnant women diagnosed with P-EC were collected on the morning following admission to hospital and after delivery (mean duration 5 days). The concentration of the PS-exposing EVs (PS+ EVs) from platelets (CD42a+, endothelial cells (CD62E+), and PS+ EVs expressing tissue factor (TF) and vascular cell adhesion molecule 1 (VCAM-1) were measured by flow cytometry. Further phenotyping of EVs also included expression of PlGF. Markers of maternal haemostasis were correlated with EVs concentration in plasma. Results: Preeclamptic pregnancy was associated with significantly higher plasma levels of PS+ CD42a+ EVs and PS+ VCAM-1+ EVs in comparison with normotensive pregnancy. P-EC patients after delivery had markedly elevated concentration of PS+ CD42a+ EVs, CD62E+ EVs, TF+ EVs, and VCAM-1+ EVs compared to those before delivery. Inverse correlation was observed between EVs concentrations (PS+, PS+ TF+, and PlGF+) and parameters of overall haemostatic potential (OHP) and fibrin formation, while PS+ VCAM-1+ EVs directly correlated with FVIII activity in plasma. Conclusion: Increased levels of PS+ EVs subpopulations in P-EC and their association with global haemostatic parameters, as well as with fibrin clot properties may suggest EVs involvement in intravascular fibrin deposition leading to subsequent microcirculation disorders. Copyright © 2021 Lalic-Cosic, Dopsaj, Kovac, Mandic-Markovic, Mikovic, Mobarrez and Antovic.

Introduction: Preeclampsia (PE) is a pregnancy-associated, multi-organ, life-threatening disease that appears after the 20th week of gestation. The aim of this study was to perform a systematic review and meta-analysis to determine whether women with PE have disrupted miRNA expression compared to women who do not have PE. Methods: We conducted a systematic review and meta-analysis of studies that reported miRNAs expression levels in placenta or peripheral blood of pregnant women with vs. without PE. Studies published before October 29, 2021 were identified through PubMed, EMBASE and Web of Science. Two reviewers used predefined forms and protocols to evaluate independently the eligibility of studies based on titles and abstracts and to perform full-text screening, data abstraction and quality assessment. Standardized mean difference (SMD) was used as a measure of effect size. Results: 229 publications were included in the systematic review and 53 in the meta-analysis. The expression levels in placenta were significantly higher in women with PE compared to women without PE for miRNA-16 (SMD = 1.51,95%CI = 0.55–2.46), miRNA-20b (SMD = 0.89, 95%CI = 0.33–1.45), miRNA-23a (SMD = 2.02, 95%CI = 1.25–2.78), miRNA-29b (SMD = 1.37, 95%CI = 0.36–2.37), miRNA-155 (SMD = 2.99, 95%CI = 0.83–5.14) and miRNA-210 (SMD = 1.63, 95%CI = 0.69–2.58), and significantly lower for miRNA-376c (SMD = –4.86, 95%CI = –9.51 to –0.20). An increased level of miRNK-155 expression was found in peripheral blood of women with PE (SMD = 2.06, 95%CI = 0.35–3.76), while the expression level of miRNA-16 was significantly lower in peripheral blood of PE women (SMD = –0.47, 95%CI = –0.91 to –0.03). The functional roles of the presented miRNAs include control of trophoblast proliferation, migration, invasion, apoptosis, differentiation, cellular metabolism and angiogenesis. Conclusion: miRNAs play an important role in the pathophysiology of PE. The identification of differentially expressed miRNAs in maternal blood creates an opportunity to define an easily accessible biomarker of PE. Copyright © 2021 Cirkovic, Stanisavljevic, Milin-Lazovic, Rajovic, Pavlovic, Milicevic, Savic, Kostic Peric, Aleksic, Milic, Stanisavljevic, Mikovic, Garovic and Milic.

Introduction: Preeclampsia (PE) is a pregnancy-associated, multi-organ, life-threatening disease that appears after the 20th week of gestation. The aim of this study was to perform a systematic review and meta-analysis to determine whether women with PE have disrupted miRNA expression compared to women who do not have PE. Methods: We conducted a systematic review and meta-analysis of studies that reported miRNAs expression levels in placenta or peripheral blood of pregnant women with vs. without PE. Studies published before October 29, 2021 were identified through PubMed, EMBASE and Web of Science. Two reviewers used predefined forms and protocols to evaluate independently the eligibility of studies based on titles and abstracts and to perform full-text screening, data abstraction and quality assessment. Standardized mean difference (SMD) was used as a measure of effect size. Results: 229 publications were included in the systematic review and 53 in the meta-analysis. The expression levels in placenta were significantly higher in women with PE compared to women without PE for miRNA-16 (SMD = 1.51,95%CI = 0.55–2.46), miRNA-20b (SMD = 0.89, 95%CI = 0.33–1.45), miRNA-23a (SMD = 2.02, 95%CI = 1.25–2.78), miRNA-29b (SMD = 1.37, 95%CI = 0.36–2.37), miRNA-155 (SMD = 2.99, 95%CI = 0.83–5.14) and miRNA-210 (SMD = 1.63, 95%CI = 0.69–2.58), and significantly lower for miRNA-376c (SMD = –4.86, 95%CI = –9.51 to –0.20). An increased level of miRNK-155 expression was found in peripheral blood of women with PE (SMD = 2.06, 95%CI = 0.35–3.76), while the expression level of miRNA-16 was significantly lower in peripheral blood of PE women (SMD = –0.47, 95%CI = –0.91 to –0.03). The functional roles of the presented miRNAs include control of trophoblast proliferation, migration, invasion, apoptosis, differentiation, cellular metabolism and angiogenesis. Conclusion: miRNAs play an important role in the pathophysiology of PE. The identification of differentially expressed miRNAs in maternal blood creates an opportunity to define an easily accessible biomarker of PE. Copyright © 2021 Cirkovic, Stanisavljevic, Milin-Lazovic, Rajovic, Pavlovic, Milicevic, Savic, Kostic Peric, Aleksic, Milic, Stanisavljevic, Mikovic, Garovic and Milic.

[No abstract available]

Objective: The objective of this study was to analyze if the addition of simple cardiac scan in cases with increased nuchal translucency (NT) and/or abnormal ductus venosus (DV) blood flow, and/or tricuspid regurgitation (TCR) can improve detection of congenital heart defects (CHD) in chromosomally normal fetuses without non-cardiac defects at 11-13 + 6 gestational weeks in a population of singleton pregnancies. Methods: During the 10 years period, all singleton pregnancies at 11-13 + 6 weeks were routinely scanned for NT, DV blood flow and TCR assessment and, if a single of these parameters was abnormal, simple cardiac scan with 2D gray scale and color and/or directional power Doppler in 4-chamber (4-CV) and 3 vessel and trachea views (3VTV) was performed. Results: The sensitivity and specificity of NT ≥ 95th + DV R/A a-wave + TCR in detecting CHD were 77% and 97%, respectively, and of simple cardiac scan, 67% and 98%, respectively. Area under the curve of receiver operating characteristic curve of NT ≥ 95th + DV R/A a-wave + TCR was 0.838, and of NT ≥ 95th + DV R/A a-wave + TCR + simple cardiac scan was 0.915. Conclusions: In chromosomally normal fetuses without non-cardiac anomalies, addition of simple cardiac scan to the combined first trimester screening parameters improves detection of major CHD during first trimester. © 2019 Wiley Periodicals, Inc.

Objective: The aim of this study was to evaluate the screening performances of abnormal ductus venosus (DV) blood flow for the detection of heart defects in chromosomally normal fetuses with increased nuchal translucency (NT) thickness at 11-13+6weeks' gestational in a population of singleton pregnancies. Methods: During an 8-year period, all singleton pregnancies from 11+0 to 13+6weeks were scanned for NT and DV blood flow assessment. Two groups of cases with abnormal NT were evaluated: NT≥95th and NT≥99th centile. DV waveforms were considered to be abnormal if the a-wave was reversed or absent (R/A). Results: Addition of DV R/A a-wave to either NT≥95th or NT≥99th percentile increased specificity (p<0.001 and p<0.001, respectively), but not screening performances in detection of major heart defects (p=0.73 and p=0.91, respectively). Combination of DV R/A a-wave with NT≥95th or NT≥99th centile correlated with right heart defects (p=0.024 and p=0.013, respectively). Conclusions: In chromosomally normal fetuses, addition of abnormal DV a-wave to increased NT does not improve screening performances of NT in detection of major hearts defects in first trimester. However, there is correlation of such parameter with right heart defects and AV septal defects. What's already known about this topic? Measurement of NT thickness in first trimester is a standard clinical practice of prenatal screening for heart defects. There are conflicting results whether the addition of qualitative assessment of ductus venosus flow improves screening performances of increased NT for heart defects. What does this study add? Addition of reduced or absent DV a-wave to increased NT improves its specificity for detection of major heart defects during the first trimester. Reduced or absent a-wave of DV flow in combination with increased NT correlates with increased risk of right heart defects and AV septal defects. © 2015 John Wiley & Sons, Ltd.

Introduction: Small supernumerary marker chromosomes (sSMCs) are infrequent findings in prenatal diagnostics, however they pose a great challenge for prenatal genetic counseling. Methods: We report prenatal 12 sSMC cases detected in a single center during 10 years period, their molecular characterization by fluorescence in situ hybridization (FISH) or chromosomal microarray (CMA). Those cases were found among 9620 prenatal diagnostic analyzes by GTG-banding technique. In selected cases, additional UPD testing was also done. Results: Incidence of sSMCs in our study was 0.12%. sSMC characterization was done by FISH in 9 cases, in the remainder of three CMA was employed. The most common sSMC shape was centric minute, followed by inverted duplication and one case with ring conformation. sSMCs originating from acrocentric chromosomes (chromosomes 14, 21 and 22), sex chromosomes (X, Y) and non-acrocentric autosomal chromosomes (chromosome 4 and 18) were confirmed in 3 cases each; no result could be obtained in 3 further cases. Discussion: No anomalies were detected by prenatal ultrasound in any of the cases. In 58% of the cases, outcome was reported as normal at birth, while anomalies at birth were described in one case. Only two patients opted for pregnancy termination. Preterm labor occurred in case of twin pregnancy resulting in stillbirth and early neonatal death of twins. Overall, our study highlights the importance of a sSMC characterization by molecular cytogenomic methods in order to make appropriate genotype-phenotype correlations and ensure adequate genetic counseling. Copyright © 2024 Joksic, Toljic, Milacic, Stankovic, Karadzov Orlic and Mikovic.

Introduction: Small supernumerary marker chromosomes (sSMCs) are infrequent findings in prenatal diagnostics, however they pose a great challenge for prenatal genetic counseling. Methods: We report prenatal 12 sSMC cases detected in a single center during 10 years period, their molecular characterization by fluorescence in situ hybridization (FISH) or chromosomal microarray (CMA). Those cases were found among 9620 prenatal diagnostic analyzes by GTG-banding technique. In selected cases, additional UPD testing was also done. Results: Incidence of sSMCs in our study was 0.12%. sSMC characterization was done by FISH in 9 cases, in the remainder of three CMA was employed. The most common sSMC shape was centric minute, followed by inverted duplication and one case with ring conformation. sSMCs originating from acrocentric chromosomes (chromosomes 14, 21 and 22), sex chromosomes (X, Y) and non-acrocentric autosomal chromosomes (chromosome 4 and 18) were confirmed in 3 cases each; no result could be obtained in 3 further cases. Discussion: No anomalies were detected by prenatal ultrasound in any of the cases. In 58% of the cases, outcome was reported as normal at birth, while anomalies at birth were described in one case. Only two patients opted for pregnancy termination. Preterm labor occurred in case of twin pregnancy resulting in stillbirth and early neonatal death of twins. Overall, our study highlights the importance of a sSMC characterization by molecular cytogenomic methods in order to make appropriate genotype-phenotype correlations and ensure adequate genetic counseling. Copyright © 2024 Joksic, Toljic, Milacic, Stankovic, Karadzov Orlic and Mikovic.

Background: Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the SERPINC1 gene. The most common clinical presentation in AT deficient patients includes venous thrombosis and pulmonary embolism, while the association of AT deficiency and its effect on the development of pregnancy complications has been less studied. The aim of our research was to evaluate the effect of AT deficiency types, determined by genotyping, on pregnancy outcomes. Methods: A retrospective cohort study included 28 women with AT deficiency, and their 64 pregnancies were analyzed. Results: With regard to live birth rate, a significant difference was observed among women who were carriers of different SERPINC1 mutations, as the rate varied from 100% in cases of type I to the extremely low rate of 8% for women with type II HBS (AT Budapest 3) in the homozygous variant, P = 0.0005. All pregnancies from the type I group, even untreated ones, resulted in live births. In women with AT Budapest 3 in homozygous variant the overall live birth rate increased to 28.5% in the treated pregnancies. In this group the highest incidence of fetal death was observed of 62%; repeated fetal losses in 30%; fetal growth restriction in 22% and placental abruption in 7% of all pregnancies. Conclusion: Our study results indicate a difference between type I and type II AT deficiency. The risk of pregnancy related VTE was equally present in both groups, except for AT Budapest 3 in the heterozygous variant, while adverse pregnancy outcomes were strictly related to type II, especially AT Budapest 3 in the homozygous variant. © 2018 Elsevier Ltd