Expanding the phenotypic spectrum of MPDZ gene variants: A case report with prenatally detected Dandy-Walker malformation and single ventricle heart.

A 19-year-old gravida underwent genetic counseling at the 26th week of gestation due to sonographically detected fetal anomalies, including Dandy-Walker malformation, characterized by cerebellar vermis hypoplasia and an enlarged cisterna magna, and single ventricle heart. Following amniocentesis at the 27th week, after the normal quantitative fluorescence polymerase chain reaction and chromosomal microarray results, trio clinical exome sequencing was performed, revealing a novel homozygous pathogenic variant in the MPDZ gene, c.4576G>T (NM_001378778.1). So far, homozygous and compound heterozygous variants in MPDZ have been strongly linked to congenital hydrocephalus type 2 with or without accompanying brain or eye anomalies. The reported variant, absent in control databases, resulted in premature termination of protein synthesis, consistent with pathogenicity predictions. Both parents were identified as heterozygous carriers. Pregnancy termination was chosen post-diagnosis. Postmortem findings correlated with prenatal ultrasound. Our case broadens the prenatal phenotypic spectrum associated with MPDZ variants, necessitating further studies for comprehensive understanding of molecular mechanisms beneath the clinical manifestations.

Expression of miRNAs and proinflammatory cytokines in pregnant women with gestational diabetes mellitus.

Altered microRNAs (miRNAs1) and cytokines expression levels are associated with several pregnancy-induced complications. We evaluated the profile of circulating miRNAs (miR-17, miR-29a and miR-181a) and proinflammatory cytokines (TNF-α, IL-1ß, IL-6 and IL-17) in women with gestational diabetes mellitus (GDM2), as well as their potential use as GDM biomarkers. The case-control study included 65 pregnant women divided into 2 groups - GDM and control. Expression levels of miRNAs in plasma samples and cytokines mRNA isolated from peripheral blood buffy coat were analyzed by quantitative real-time PCR (qPCR3). Significant miR-29a downregulation was found in GDM compared to the control group, and was even more significant after adjustments for covariates. miR-17 and miR-181a expression levels did not differ between the examined groups. Expression levels of IL-1ß were significantly higher in GDM group compared to controls, while TNF-α, IL-6 and IL-17 did not show significant changes in expression between the two groups. As jugded from the ROC curve analysis, miR-29a and IL-1ß had a significant capacity to discriminate between CG and GDM. Additionally, a positive correlation was established between IL-1ß and TNF-α in the GDM group. GDM appeared to be associated with altered levels of miR-29a and IL-1ß making them markers of this condition.

A placenta-on-a-chip model to determine the regulation of FKBPL and galectin-3 in preeclampsia.

Preeclampsia is a pregnancy-specific cardiovascular disorder, involving significant maternal endothelial dysfunction. Although inappropriate placentation due to aberrant angiogenesis, inflammation and shallow trophoblast invasion are the root causes of preeclampsia, pathogenic mechanisms are poorly understood, particularly in early pregnancy. Here, we first confirm the abnormal expression of important vascular and inflammatory proteins, FK506-binding protein-like (FKBPL) and galectin-3 (Gal-3), in human plasma and placental tissues from women with preeclampsia and normotensive controls. We then employ a three-dimensional microfluidic placental model incorporating human umbilical vein endothelial cells (HUVECs) and a first trimester trophoblast cell line (ACH-3P) to investigate FKBPL and Gal-3 signaling in inflammatory conditions. In human samples, both circulating (n = 17 controls; n = 30 preeclampsia) and placental (n ≥ 6) FKBPL and Gal-3 levels were increased in preeclampsia compared to controls (plasma: FKBPL, p < 0.0001; Gal-3, p < 0.01; placenta: FKBPL, p < 0.05; Gal-3, p < 0.01), indicative of vascular dysfunction in preeclampsia. In our placenta-on-a-chip model, we show that endothelial cells are critical for trophoblast-mediated migration and that trophoblasts effectively remodel endothelial vascular networks. Inflammatory cytokine tumour necrosis factor-α (10 ng/mL) modulates both FKBPL and Gal-3 signaling in conjunction with trophoblast migration and impairs vascular network formation (p < 0.005). Our placenta-on-a-chip recapitulates aspects of inappropriate placental development and vascular dysfunction in preeclampsia.

Small supernumerary marker chromosomes in prenatal diagnosis-molecular characterization and clinical outcomes.

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.

Maternal plasma proteome profiling of biomarkers and pathogenic mechanisms of early-onset and late-onset preeclampsia.

Preeclampsia is still the leading cause of morbidity and mortality in pregnancy without a cure. There are two phenotypes of preeclampsia, early-onset (EOPE) and late-onset (LOPE) with poorly defined pathogenic differences. This study aimed to facilitate better understanding of the mechanisms of pathophysiology of EOPE and LOPE, and identify specific biomarkers or therapeutic targets. In this study, we conducted an untargeted, label-free quantitative proteomic analyses of plasma samples from pregnant women with EOPE (n = 17) and LOPE (n = 11), and age, BMI-matched normotensive controls (n = 18). Targeted proteomics approach was also employed to validate a subset of proteins (n = 17). In total, there were 26 and 20 differentially abundant proteins between EOPE or LOPE, and normotensive controls, respectively. A series of angiogenic and inflammatory proteins, including insulin-like growth factor-binding protein 4 (IGFBP4; EOPE: FDR = 0.0030 and LOPE: FDR = 0.00396) and inter-alpha-trypsin inhibitor heavy chain H2-4 (ITIH2-4), were significantly altered in abundance in both phenotypes. Through validation we confirmed that ITIH2 was perturbed only in LOPE (p = 0.005) whereas ITIH3 and ITIH4 were perturbed in both phenotypes (p < 0.05). Overall, lipid metabolism/transport proteins associated with atherosclerosis were highly abundant in LOPE, however, ECM proteins had a more pronounced role in EOPE. The complement cascade and binding and uptake of ligands by scavenger receptors, pathways, were associated with both EOPE and LOPE.

Can Thyroid Screening in the First Trimester Improve the Prediction of Gestational Diabetes Mellitus?

This study aimed to evaluate the clinical utility of the subclinical hypothyroidism (SCH) marker, elevated thyroid-stimulating hormone (TSH) and thyroid antibodies in their ability to predict subsequent gestational diabetes mellitus (GDM). In a prospective clinical trial, 230 pregnant women were screened for thyroid function during the first trimester of pregnancy. Increased TSH levels with normal free thyroxine (fT4) were considered SCH. The titers of thyroid peroxidase antibody (anti TPO Ab) at >35 IU/mL and thyroglobulin antibody (anti Tg Ab) at >115 IU/mL were considered as antibodies present. According to the OGTT results, the number of pregnant women with GDM showed the expected growth trend, which was 19%. Two groups of pregnant women were compared, one with GDM and the other without. Increased TSH levels and the presence of thyroid antibodies showed a positive correlation with the risk of GDM. TSH levels were significantly higher in pregnant women with GDM, p = 0.027. In this study, 25.6% of pregnant women met the diagnostic criteria for autoimmune thyroiditis. Hashimoto's thyroiditis was significantly more common in GDM patients, p < 0.001. Through multivariate logistic regression, it was demonstrated that patient age, TSH 4 IU/mL, and anti TPO Ab > 35 IU/mL are significant predictors of gestational diabetes mellitus that may improve first-trimester pregnancy screening performance, AUC: 0.711; 95% CI: 0.629−0.793.

Antioxidant status in hypertensive disorders of pregnancy.

OBJECTIVE: Pregnancy can be associated with maternal hypertension leading to possible complications in pregnancy outcome. Antioxidant status may be proned to changes during pregnancy with hypertension. The aim of our study was to estimate antioxidant status through high-risk pregnancies. METHODS: Seventy-nine pregnant women with high-risk for preeclampsia development were included and 46 of them developed some hypertensive disorder in pregnancy. Superoxide-dismutase (SOD) and paraoxonase 1 (PON1) activities and relative proportion of PON1 activiity on different HDL subclasses were determined in 1st, 2nd, and 3rd trimester and prior to delivery. RESULTS: SOD activity was significantly lower in 2nd and 3rd trimesters when compared to 1st trimester (P˂0.001) whereas PON1 activity was significantly higher in 3rd than in 1st trimester (P˂0.05) in group of hypertensive women. This group had significantly higher SOD and PON1 activities and relative proportion of PON1 on HDL3c subclasses in the 1st trimester, significantly increased PON1 in the 3rd trimester and prior to delivery and significantly higher PON1 activity on HDL3c subclasses (P˂0.05) than nonhypertensive group. In 1st trimester and prior to delivery, total PON1 activity and relative proportion of PON1 on HDL3c subclasses exhibited significant ability to mark out hypertension in pregnancy (P˂0.05). CONCLUSIONS: SOD activity decreased whereas total PON1 activity increased during pregnancy with hypertension. Pregnant women with hypertension had higher activities of PON1 and SOD and relative proportion of PON1 on HDL3c subclasses than nonhypertensive ones. PON1 activity and relative proportion of PON1 on HDL3c subclasses exhibited significant association with hypertension in pregnancy.

Cholesterol homeostasis is dysregulated in women with preeclampsia.

INTRODUCTION: The link between preeclampsia and dyslipidemia has been established. Even though lipid profile parameters have been intensively investigated in the pathology of preeclampsia, their accurate molecular mechanisms of action have not been fully decoded. OBJECTIVES: We aimed to identify the specifics of cholesterol metabolism in women affected by late-onset preeclampsia and single out potential biomarkers associated with late-onset syndrome. PATIENTS AND METHODS: A total of 90 pregnant women with a priori risk for preeclampsia were monitored at 4 time points during gestation and, based on the outcome of pregnancy, they were classified into the high-risk group (70 women) and the preeclampsia group (20 women). Cholesterol metabolic profiling was done using liquid chromatography-tandem mass spectrometry. RESULTS: The only significant change in the preeclampsia group was an increase in the lathosterol level (P = 0.001). The first-trimester lathosterol level was higher in the preeclampsia group compared with the high-risk group (P = 0.02). Further, in the preeclampsia group, positive correlations were found between desmosterol and ß-sitosterol (ρ = 0.474; P = 0.03) in the third trimester, desmosterol and campesterol changes between the second and the first (ρ = 0.546; P = 0.02), and the third and first trimesters (ρ = 0.754; P <⁠0.001), as well as between the desmosterol and ß-sitosterol differences between the third and first trimesters (ρ = 0.568; P = 0.01). No similar correlations were found in the high-risk group. CONCLUSIONS: Late-onset preeclampsia could be associated with an altered lipid profile. By studying the quantitative metabolic signatures of cholesterol, we might assume that both cholesterol synthesis and absorption are increased, that is, there is an imbalance in the cholesterol homeostasis regulation in women affected by the disease.

The role of resistin in early preeclampsia prediction.

Resistin might be involved with general inflammation and endothelial dysfunction observed in preeclampsia. We aimed to investigate longitudinal changes in resistin concentrations during high-risk pregnancies and evaluate their significance in preeclampsia development. Ninety-one patients were recruited at 11-14 weeks of gestation. They were followed towards the end of each trimester and before their deliveries. Of the 91 pregnant women, 21 developed preeclampsia, while 70 women did not develop preeclampsia despite being at risk. Compared to the 1st trimester, resistin concentration significantly increased during the 2nd trimester (p<.001). When women were divided into groups of those who developed preeclampsia and those who did not develop preeclampsia, we noticed a significant difference only in women who did not develop preeclampsia (p<.001). Moreover, resistin concentration in the 1st trimester was statistically higher in women who developed preeclampsia when compared to those who did not develop preeclampsia (p<.001). The analysis of the Receiver Operating Characteristics (ROC) curves indicated that inclusion of triglycerides (TG), high-sensitivity C-reactive protein (CRP), and resistin (AUC = 0.870) improved diagnostic accuracy of the basic model including demographic and clinical parameters (AUC = 0.777) for preeclampsia prediction (p<.05). If the concentration of resistin is high in the 1st trimester, such pregnancy at risk is likely to develop preeclampsia as a complication, indicating that resistin concentration in the 1st trimester might contribute to existing predictive and prognostic models for preeclampsia. A multi-marker model, possibly including also resistin and other clinical, metabolic, and inflammatory parameters, seems to be the best approach in late-onset preeclampsia prediction.

Use of FMF algorithm for prediction of preeclampsia in high risk pregnancies: a single center longitudinal study.

OBJECTIVE: This study aimed to assess the accuracy of The Fetal Medicine Foundation (FMF) screening algorithm for the prediction of preeclampsia.METHODS: Out of 138 women with high-risk pregnancies prospectively followed, 30 developed preeclampsia. The clinical examination and biochemical measurements were performed at first, second, early and late third trimester.RESULTS: A lower PAPP-A levels were found in the first trimester, while sFlt/PlGF was increased in the second and early third trimester in preeclampsia (p>0.05). FMF algorithm presented higher specificity (>70%), but had a drawback of lower sensitivity (35-77%).CONCLUSION: FMF algorithm had modest performance in the prediction of preeclampsia for high-risk pregnancies.

Unraveling the role of oxidative stress and lipid status parameters in the onset of preeclampsia.

OBJECTIVE: The aim of the study was to assess the potential role of oxidative stress and lipid status in the onset of preeclampsia.METHODS: 138 high-risk pregnant women were prospectively followed. Assessment of oxidative stress (TAS, TOS, AOPP and SH groups) and lipid status (t-C, LDL-C, HDL-C, TGC, APO-A1, APO-B) was carried out during the pregnancy.RESULTS: 30 women developed preeclampsia. TGC, atherogenic index of plasma, TAS and SH levels were higher in women who subsequently developed preeclampsia (p<0.05).CONCLUSION: Oxidative stress and lipid status disturbance have a potential role in the onset of preeclampsia in high risk pregnancies.

Characterisation of cardiac health in the reduced uterine perfusion pressure model and a 3D cardiac spheroid model, of preeclampsia.

BACKGROUND: Preeclampsia is a dangerous cardiovascular disorder of pregnancy that leads to an increased risk of future cardiovascular and metabolic disorders. Much of the pathogenesis and mechanisms involved in cardiac health in preeclampsia are unknown. A novel anti-angiogenic protein, FKBPL, is emerging as having a potential role in both preeclampsia and cardiovascular disease (CVD). Therefore, in this study we aimed to characterise cardiac health and FKBPL regulation in the rat reduced uterine perfusion pressure (RUPP) and a 3D cardiac spheroid model of preeclampsia. METHODS: The RUPP model was induced in pregnant rats and histological analysis performed on the heart, kidney, liver and placenta (n ≥ 6). Picrosirius red staining was performed to quantify collagen I and III deposition in rat hearts, placentae and livers as an indicator of fibrosis. RT-qPCR was used to determine changes in Fkbpl, Icam1, Vcam1, Flt1 and Vegfa mRNA in hearts and/or placentae and ELISA to evaluate cardiac brain natriuretic peptide (BNP45) and FKBPL secretion. Immunofluorescent staining was also conducted to analyse the expression of cardiac FKBPL. Cardiac spheroids were generated using human cardiac fibroblasts and human coronary artery endothelial cells and treated with patient plasma from normotensive controls, early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE); n = 3. FKBPL and CD31 expression was quantified by immunofluorescent labelling. RESULTS: The RUPP procedure induced significant increases in blood pressure (p < 0.001), collagen deposition (p < 0.001) and cardiac BNP45 (p < 0.05). It also induced a significant increase in cardiac FKBPL mRNA (p < 0.05) and protein  expression  (p < 0.01). RUPP placentae also exhibited increased collagen deposition and decreased Flt1 mRNA expression (p < 0.05). RUPP kidneys revealed an increase in average glomerular size (p < 0.05). Cardiac spheroids showed a significant increase in FKBPL expression when treated with LOPE plasma (p < 0.05) and a trend towards increased FKBPL expression following treatment with EOPE plasma (p = 0.06). CONCLUSIONS: The rat RUPP model induced cardiac, renal and placental features reflective of preeclampsia. FKBPL was increased in the hearts of RUPP rats and cardiac spheroids treated with plasma from women with preeclampsia, perhaps reflective of restricted angiogenesis and inflammation in this disorder. Elucidation of these novel FKBPL mechanisms in cardiac health in preeclampsia could be key in preventing future CVD.

Combined presence of coagulation factor XIII V34L and plasminogen activator inhibitor 1 4G/5G gene polymorphisms significantly contribute to recurrent pregnancy loss in Serbian population.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Placenta-specific plasma miR518b is a potential biomarker for preeclampsia.

INTRODUCTION: MicroRNAs have a significant role in the pathogenesis of preeclampsia. Circulating microRNAs could represent a potential biomarker for preeclampsia. The aim of this study was to evaluate plasma miR210-3p and miR518b in preeclampsia and healthy pregnancy for the first time by digital droplet PCR (ddPCR). METHODS: Thirty-six pregnant women (seventeen healthy pregnancies, nineteen preeclampsia patients) were involved from the Clinic for Gynaecology and Obstetrics "Narodni front" in Belgrade, Serbia. Plasma miR210-3p, miR518b and cel-miR-39 as a spike-in control were measured by ddPCR. RESULTS: MiR518b was significantly elevated in preeclampsia compared to a healthy pregnancy (P = 0.034; 0.302(0.217-0.421) vs. 0.171(0.110-0.266)). MiR210-3p showed no significant difference between the two groups (P = 0.951). The adjustment of miR518b was made for a gestational age and smoking status and the difference between the preeclampsia and healthy pregnancy group was more significant (P = 0.026; 0.300(0.216-0.419) vs. 0.172(0.121-0.245)). Plasma miR-518b was significantly higher in the group of preeclampsia patients with proteinuria above the 75th percentile for the group (P = 0.033), in women who smoked (P = 0.039), and was positively related to uric acid in preeclampsia (P = 0.018, r = 0.536). Plasma miR518b was able to significantly discriminate between preeclampsia and healthy pregnancy, yielding AUC of 0.712 (95%CI:0.539-0.891), P = 0.028. CONCLUSIONS: In this study plasma microRNA were measured for the first time in preeclampsia and healthy pregnancies with ddPCR. Placenta-specific miR-518b could serve as a potential biomarker for discriminating preeclampsia and healthy pregnancy, which should be confirmed on a larger study population. This study has failed to confirm the same potential for miR210-3p.

Screening performance of congenital heart defects in first trimester using simple cardiac scan, nuchal translucency, abnormal ductus venosus blood flow and tricuspid regurgitation.

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.

Increased oxidative stress and cytokinesis-block micronucleus cytome assay parameters in pregnant women with gestational diabetes mellitus and gestational arterial hypertension.

We investigated whether gestational diabetes mellitus (GDM) and gestational arterial hypertension (GH) are associated with increased oxidative stress and DNA damage. Study included 3 groups of pregnant women (GDM, GH and control). DNA damage biomarkers (micronuclei MNi, nucleoplasmic bridges NPBs and nuclear buds NBUDs) were assessed by cytokinesis-block micronucleus cytome assay. Oxidative stress levels were evaluated by analyzing malondialdehyde equivalents (TBARS) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Genotoxic effect of methyldopa, drug used to treat GH, was evaluated in in vitro experiment. TBARS levels, MNi, NPBs and NBUDs frequencies were significantly increased in both GDM and GH group. Concentrations of 8-OHdG were significantly higher in GDM than in other groups. Since methyldopa did not affect MNi, NPBs and NBUDs frequencies, nor TBARS and 8-OHdG levels, we concluded that methyldopa has no genotoxic effect. Thus, even when hyperglycemia or hypertension are present only during pregnancy they induce oxidative stress, DNA damage and chromosomal aberrations.

Major risk factors of maternal adverse outcome in women with two or more previous cesarean sections.

Background/Aim: Maternal morbidity is defined as any condition that is attributed to or aggravated by pregnancy and childbirth that has a negative impact on the woman's wellbeing. In recent years, a growing trend of cesarean section rates can be seen throughout the world. The aim of this study was to assess factors that might have major impact on maternal adverse outcome in women with two or more previous cesarean sections. Methods: This retrospective study included women with single term pregnancy after two or more cesarean deliveries in a 10-year period (2004−2013) in the University Clinic "Narodni front" in Belgrade, Serbia. Medical records were reviewed for clinical data for maternal intraoperative and early postoperative complications regarding gestational age at delivery, the number of previous cesarean sections and mode of surgery (elective or emergency). Results: A total of 551 patients were included in the study. At 37 completed weeks delivered 14.1%, at 38 delivered 45.2% and at 39 completed weeks 40.7% patients. Women younger than 35 years more often delivered after 39 completed weeks compared with those over 35 years (69.2% vs 30.8%, p < 0.05). The overall rate of maternal complications in the study group was 16.5% with no statistical difference by gestational age at delivery. The overall rate of maternal adverse outcome was significantly less in the patients with three as compared with those with four or more cesareans (10.4% vs 66.7%, p < 0.05). There was a statistically significant difference between these groups of women regarding complications: scar dehiscence, the presence of adhesions, blood transfusion and admission in intensive care unit. Elective cesarean delivery was with less maternal complications compared with emergency cesarean deliveries (12.9% vs 27.3%, p < 0.05). Conclusion: Termination of pregnancy before completed 39 weeks does not decrease maternal morbidity. The major impact on maternal complications has the number of previous cesarean deliveries (≥ 3), as well as emergency cesarean section. Patients should be informed about potential risks for maternal health with increasing number of cesarean deliveries, especially after the first cesarean section when counseling in elective repeat cesarean vs trial of labor.

Screening performances of abnormal first-trimester ductus venosus blood flow and increased nuchal translucency thickness in detection of major heart defects.

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 + 6 weeks' gestational in a population of singleton pregnancies. METHODS: During an 8-year period, all singleton pregnancies from 11 + 0 to 13 + 6 weeks 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.