First-trimester ductus venosus velocity ratio as a marker of major cardiac defects.

OBJECTIVES: To examine ductus venosus (DV) flow in fetuses with and those without a cardiac defect and to evaluate different phases of DV flow in addition to the standard assessment of DV pulsatility index for veins (PIV) and the a-wave. METHODS: This was a retrospective study of singleton pregnancies that underwent first-trimester ultrasound screening, which included DV flow assessment, at the University of Tübingen (between 2010 and 2017) or the University of Cologne (between 2013 and 2016). The study population comprised normal fetuses and fetuses with major cardiac defects at a ratio of 10:1. For each fetus, the following parameters of the DV waveform were evaluated: qualitative assessment of the a-wave, PIV measurement and ratios of flow velocities during the S-wave (S) or D-wave (D) and the a-wave (a) or v-wave (v). Reproducibility of DV-PIV and DV flow ratios was evaluated in 30 fetuses in which the DV flow was assessed twice. RESULTS: Our study population included 480 anatomically normal fetuses and 48 with a cardiac defect. Median fetal nuchal translucency (NT) in the normal and in the affected group was 1.9 mm and 2.6 mm, respectively. In five (1.0%) of the normal and 18 (37.5%) of the affected cases, fetal NT thickness was above the 99th centile. In the normal group, the DV a-wave was reversed in 15 (3.1%) cases and the DV-PIV was above the 95th centile in 25 (5.2%). In the cases with cardiac defects, the a-wave was reversed and the DV-PIV measurement was above the 95th centile in 26 (54.2%). The reproducibility of measurement of the ratios of DV flow velocities was similar to that of the DV-PIV. Most cardiac defects were associated with an abnormal a/S or a/D ratio. If the cut-off for these two ratios was set at the 5th centile of the normal distribution, the detection rate of fetal cardiac anomalies would be 62.5%. This compares favorably with the DV-PIV, which detects 26 (54.2%) of the affected fetuses for the same threshold. CONCLUSION: In the first trimester, the a/S ratio has the potential to detect approximately 60% of congenital cardiac defects for a false-positive rate of 5%. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Infrahepatic inferior caval and azygos vein formation in mammals with different degrees of mesonephric development.

Controversies regarding the development of the mammalian infrahepatic inferior caval and azygos veins arise from using topography rather than developmental origin as criteria to define venous systems and centre on veins that surround the mesonephros. We compared caudal-vein development in man with that in rodents and pigs (rudimentary and extensive mesonephric development, respectively), and used Amira 3D reconstruction and Cinema 4D-remodelling software for visualisation. The caudal cardinal veins (CCVs) were the only contributors to the inferior caval (IVC) and azygos veins. Development was comparable if temporary vessels that drain the large porcine mesonephros were taken into account. The topography of the CCVs changed concomitant with expansion of adjacent organs (lungs, meso- and metanephroi). The iliac veins arose by gradual extension of the CCVs into the caudal body region. Irrespective of the degree of mesonephric development, the infrarenal part of the IVC developed from the right CCV and the renal part from vascular sprouts of the CCVs in the mesonephros that formed 'subcardinal' veins. The azygos venous system developed from the cranial remnants of the CCVs. Temporary venous collaterals in and around the thoracic sympathetic trunk were interpreted as 'footprints' of the dorsolateral-to-ventromedial change in the local course of the intersegmental and caudal cardinal veins relative to the sympathetic trunk. Interspecies differences in timing of the same events in IVC and azygos-vein development appear to allow for proper joining of conduits for caudal venous return, whereas local changes in topography appear to accommodate efficient venous perfusion. These findings demonstrate that new systems, such as the 'supracardinal' veins, are not necessary to account for changes in the course of the main venous conduits of the embryo.

Hemodynamic studies of isolated absent ductus venosus.

OBJECTIVE: The objective of this article is to evaluate hemodynamic changes among fetuses with isolated absent ductus venosus (IADV) diagnosed by prenatal ultrasonography. PATIENTS AND METHODS: Fetuses with prenatal diagnosis of IADV were recruited and followed. Hemodynamic assessment was performed in all cases, including measurement of cardiac dimensions, shortening fraction, myocardial performance index, preload index in the inferior vena cava and the presence of venous pulsations in the umbilical vein (UV). RESULTS: Nine fetuses of IADV were assessed, including six cases with extra-hepatic UV drainage and three with intra-hepatic drainage. All fetuses with extra-hepatic UV drainage showed an elevated preload index in the inferior vena cava, venous pulsations in the UV and cardiomegaly. Of them, four had hydrops, two showed poor cardiac function and three resulted in perinatal mortality. Three cases with intra-hepatic drainage had continuous flow in the UV, normal in all hemodynamic parameters and all survived. CONCLUSION: Hemodynamic assessment of fetuses with IADV was helpful in predicting the development of hydrops and perinatal mortality. The poor prognostic factors included cardiac overload, cardiomegaly, poor myocardial performance, increased preload, the presence of venous pulsations and extra-hepatic UV drainage. © 2015 John Wiley & Sons, Ltd.

Development of the human infrahepatic inferior caval and azygos venous systems.

Differences in opinion regarding the development of the infrahepatic inferior caval and azygos venous systems in mammals centre on the contributions of 'caudal cardinal', 'subcardinal', 'supracardinal', 'medial and lateral sympathetic line' and 'sacrocardinal' veins. The disagreements appear to arise from the use of topographical position rather than developmental origin as criterion to define separate venous systems. We reinvestigated the issue in a closely spaced series of human embryos between 4 and 10 weeks of development. Structures were visualized with the Amira(®) reconstruction and Cinema4D(®) remodelling software. The vertebral level and neighbouring structures were used as topographic landmarks. The main results were that the caudal cardinal veins extended caudally from the common cardinal vein between CS11 and CS15, followed by the development of the subcardinal veins as a plexus sprouting ventrally from the caudal cardinal veins. The caudal cardinal veins adapted their course from lateral to medial relative to the laterally expanding lungs, adrenal glands, definitive kidneys, sympathetic trunk and umbilical arteries between CS15 and CS18, and then became interrupted in the part overlaying the regressing mesonephroi (Th12-L3). The caudal part of the left caudal cardinal vein then also regressed. The infrarenal part of the inferior caval vein originated from the right caudal cardinal vein, while the renal part originated from subcardinal veins. The azygos veins developed from the remaining cranial part of the caudal cardinal veins. Our data show that all parts of the inferior caval and azygos venous systems developed directly from the caudal cardinal veins or from a plexus sprouting from these veins.

Lineage tree for the venous pole of the heart: clonal analysis clarifies controversial genealogy based on genetic tracing.

RATIONALE: Genetic tracing experiments and cell lineage analyses are complementary approaches that give information about the progenitor cells of a tissue. Approaches based on gene expression have led to conflicting views about the origin of the venous pole of the heart. Whereas the heart forms from 2 sources of progenitor cells, the first and second heart fields, genetic tracing has suggested a distinct origin for caval vein myocardium, from a proposed third heart field. OBJECTIVE: To determine the cell lineage history of the myocardium at the venous pole of the heart. METHODS AND RESULTS: We used retrospective clonal analyses to investigate lineage segregation for myocardium at the venous pole of the mouse heart, independent of gene expression. CONCLUSIONS: Our lineage analysis unequivocally shows that caval vein and atrial myocardium share a common origin and demonstrates a clonal relationship between the pulmonary vein and progenitors of the left venous pole. Clonal characteristics give insight into the development of the veins. Unexpectedly, we found a lineage relationship between the venous pole and part of the arterial pole, which is derived exclusively from the second heart field. Integration of results from genetic tracing into the lineage tree adds a further temporal dimension to this reconstruction of the history of venous myocardium and the arterial pole.

Reference ranges for ductus venosus velocity ratios in pregnancies with normal outcomes.

OBJECTIVES: The purpose of this study was to establish reference ranges for ductus venosus velocity ratios. METHODS: Singleton pregnancies from 11 to 38 weeks with exactly established gestational ages (GAs) were recruited for the study. Pregnancies with fetal anomalies, growth abnormalities, maternal medical complications, stillbirth, birth weight below the 10th or above the 90th percentile, and neonatal anomalies were excluded. The ductus venosus pulsatility index for veins (PIV) and velocity ratios (S/v, S/D, v/D, S/a, v/a, and D/a, where S indicates ventricular systole [s-wave], v, ventricular end-systolic relaxation [v-descent], D, passive diastolic ventricular filling [D-wave], and a, active ventricular filling during atrial systole [a-wave]) were calculated. Separate regression models were fitted to estimate the mean and standard deviation at each GA for each ratio. RESULTS: A total of 902 velocity wave ratios and ductus venosus PIVs were used for reference ranges. The S/v, S/D, and v/D ratios were not changed with GA (P > .05 for all). The PIV and S/a, v/a, and D/a ratios were reduced with GA (P < .0001 for all). Significant reductions in the means and standard deviations of the PIV and S/a, v/a, and D/a ratios were observed between 17 and 18 weeks' gestation. Therefore, nomograms were separately created between 11 and 17 weeks and 18 and 38 weeks. CONCLUSIONS: We created reference ranges for ductus venosus velocity ratios between 11 and 38 weeks' gestation in normal pregnancies. These reference ranges may prove beneficial for evaluation of fetal conditions that are associated with cardiovascular abnormalities.

A reference for ductus venosus blood flow at 11-13+6 weeks of gestation.

OBJECTIVE: To establish reference ranges for ductus venosus (DV) blood flow assessment obtained transabdominally at 11-13(+6) weeks of gestation. METHODS: A cross-sectional study was conducted on singleton pregnancies with a crown-rump length (CRL) ranging from 45 to 84 mm, normal fetus, and subsequent newborn birth weight appropriate for gestational age. Measurements of DV Doppler variables were performed by experienced sonographers: peak velocity during ventricular systole (S-wave) and diastole (D-wave), nadir during atrial contraction (A-wave), time-averaged maximum velocity (TAmax), pulsatility index for veins (PIV), and peak velocity index for veins (PVIV). RESULTS: A total of 304 fetuses were included. The mean CRL was 60.7 ± 7.2 mm (range: 45.9-75.5). The mean nuchal translucency measurement was 1.4 ± 0.4 mm. The S-wave, D-wave, A-wave, and TAmax values varied significantly with gestational age (p < 0.05) and regression models were constructed for each variable. The remaining variables, systolic/atrial wave ratio, preload index, PVIV, and PIV, did not vary significantly with gestational age within this CRL range. CONCLUSION: Reference ranges for DV Doppler assessment were established in normal fetuses. These ranges may be a useful tool for evaluation of anueploidy and fetal cardiac function.

Ultrasound of the fetal veins part 1: the intrahepatic venous system.

Advances in high-resolution ultrasound combined with color Doppler and three-dimensional (3 D) rendering have contributed to an increasing understanding of the fetal venous circulation in recent years. Still the sonographic evaluation of the venous system in the fetus remains difficult. This article reviews the normal and abnormal intrahepatic venous system. Normal anatomy and abnormal findings of the umbilical vein (UV), the ductus venosus (DV), portal veins, hepatic veins and the inferior vena cava are demonstrated by grayscale, color Doppler and 3D ultrasound and explained by numerous schemes. Typical variants and abnormalities such as agenesis of the DV and portal venous system, persistence of the right UV, UV varix are explained and the clinical value of normal and abnormal Doppler findings in the DV is discussed. Many of these abnormal findings can be detected by a targeted examination of the intrahepatic vasculature with means of color Doppler.

The clinical anatomy of the inferior vena cava: a review of common congenital anomalies and considerations for clinicians.

Anomalies in the course and drainage of the Inferior Vena Cava (IVC) may complicate normal functioning, correct diagnosis, and therapeutic interventions within the abdomen. Development of the IVC occurs during the 4th to 8th week of gestation, and due to its developmental complexity, there are many opportunities for malformations to occur. Although most IVC anomalies are clinically silent and are usually discovered incidentally on abdominal imaging, aberrations may be responsible for formation of thrombosis, back pain, and anomalous circulation of blood to the heart. In this review, we will discuss the most common variations and abnormalities of the IVC, which include the posterior cardinal veins, the subcardinal veins, the supracardinal veins, persistent left IVC, IVC duplication, situs inversus, left retroaortic renal vein, left circumaortic renal collar, scimitar syndrome, and IVC agenesis. For each abnormality outlined above, we aim to discuss relevant embryology and potential clinical significance with regards to presentation, diagnosis, and treatment as is important for radiologists, surgeons, and clinicians in current clinical practice.

Regional differences in the umbilical vein and ductus venosus at different stages of normal human development.

During the fetal period, oxygenated blood from the placenta flows through the umbilical vein (UV), portal sinus, ductus venosus (DV), and inferior vena cava (IVC) to the heart. This venous route varies regionally in many aspects. Herein, we sought to characterize the venous route's morphological features and regional differences during embryonic and early-fetal periods. Twenty-nine specimens were selected for high-resolution digitized imaging; 18 embryos were chosen for histological analysis. The venous route showed a primitive, large, S-shaped curved morphology with regional narrowing and dilation at Carnegie stage (CS) 15. Regional differences in vessel-wall differentiation became apparent from approximately CS20. The vessel wall was poorly developed in most DV parts; local vessel-wall thickness at the inlet was first detected at CS20. The lumen of the venous route changed from a nonuniform shape to a relatively round and uniform morphology after CS21. During the early-fetal period, two large bends were observed around the passage of the umbilical ring and at the inlet of the liver. The length ratio of the extrahepatic UV to the total venous route increased. The sectional area gradually increased during embryonic development, whereas differences in sectional area between the DV, UV, and IVC became more pronounced in the early-fetal period. Furthermore, differences in the sectional area between the narrowest part of the DV and other hepatic veins and the transverse sinus became more pronounced. In summary, the present study described morphological, morphometric, and histological changes in the venous route throughout embryonic and early-fetal development, clarifying regional characteristics.

[Computerized three-dimensional reconstruction of the retrohepatic segment of inferior vena cava of a 20 mm human embryo]. / Reconstruction tridimensionnelle informatisée du segment rétrohépatique de la veine cave inférieure d'un embryon humain de 20mm.

The subdiaphragmatic venous drainage of the embryo is provided by the two caudal cardinal veins to which is added the subcardinal vein system, draining the mesonephros, the perispinal supracardinal veins and the umbilical and vitelline venous system. The anastomosis of certain segments of the embryonic venous structures and the disappearance of others are at the origin of the inferior vena cava. Since the 19th century, three-dimensional reconstruction of solid models from histological sections were developed. At present, the development of computerized three-dimensional reconstruction techniques allowed to operate a multitude of techniques of image processing and modeling in space. Three-dimensional reconstruction is a tool for teaching and research very useful in embryological studies because of the obvious difficulty of dissection and the necessity of introducing time as the fourth dimension in the study of organogenesis. This method represents a promising alternative compared to previous three-dimensional reconstruction techniques including Born technique. The aim of our work was to create a three-dimensional computer reconstruction of the retrohepatic segment of the inferior vena cava of a 20mm embryo from the embryo collection of Saints-Pères institute of anatomy (Paris Descartes university, Paris, France) to specify the path relative to the liver and initiate a series of computerized three-dimensional reconstruction that will follow the evolution of this segment of the inferior vena cava and this in a pedagogical and morphological research introducing the time as the fourth dimension.

Congenital anomalies of the inferior vena cava.

Congenital anomalies of the inferior vena cava (IVC) and its tributaries are increasingly recognized in asymptomatic patients due to the more frequent use of cross-sectional imaging and computed tomography (CT) in particular. IVC development is a complex process involving formation of anastomoses between three pairs of embryonic veins in the 4th to 8th week of gestation. Various permutations occur in the basic venous plan of the abdomen and pelvis resulting in variants such as isolated left IVC, double IVC, and retroaortic left renal vein. The majority of these anomalies are asymptomatic but occasionally present clinically with thromboembolic complications. However, awareness of their existence is important to avoid important diagnostic pitfalls and in preoperative surgical and interventional radiological planning.

Missing ductus venosus: a case report.

BACKGROUND: The ductus venosus is a short vessel, present in the newborn infant on the dorsal surface of the liver, connecting the portal and umbilical circulation with the inferior vena cava. Agenesis of the duct is a rare anomaly. CASE: A 28-year-old woman was referred to our department for the first trimester ultrasound evaluation. Detailed scanning revealed agenesis of the duct. Fetal echocardiography showed cardiac disproportion at the level of the ventricles. CONCLUSION: Agenesis of the duct can be related to either cardiac or congenital abnormalities.

Hemodynamics of fetal breathing movements: the inferior vena cava.

OBJECTIVE: Based on the hypothesis that fetal breathing movements (FBM) enhance sections of the circulation to meet the needs of gas transport, we studied the effects of FBM on the fetal inferior vena cava (IVC), which transports blood with the lowest oxygen saturation in the fetal body. METHODS: One-hundred and ten women with low-risk singleton pregnancies were included in a longitudinal study during the second half of pregnancy. Inner diameter, peak systolic velocity and time-averaged maximum blood velocity were measured in the IVC below the ductus venosus outlet during rest and FBM. Volume flow and pressure gradient were estimated in 55 observations of forced inspiratory movements at 36 weeks of gestation. The results are presented as mean and 95% CI of the mean. RESULTS: Based on 585 observations obtained during fetal rest and FBM, we found no difference in diameter, 0.42 (95% CI, 0.41-0.43) cm vs. 0.41 (95% CI, 0.39-0.42) cm, respectively, apart from during high-amplitude inspiratory movement, when the diameter was 0.15 (95% CI, 0.13-0.17) cm. The peak systolic velocity was different during rest and FBM, 34.0 (95% CI, 32.7-35.3) cm/s vs. 81.5 (95% CI, 76.2-87.5) cm/s, respectively, and correspondingly for time-averaged maximum velocity, 19.7 (95% CI, 18.9-20.5) cm/s vs. 37.2 (95% CI, 34.9-39.9) cm/s, respectively. Forced inspiratory movements at 36 weeks significantly reduced flow in the IVC compared with rest, 63.6 (95% CI, 44.4-88.1) mL/min vs. 186.0 (95% CI, 142.8-238.1) mL/min, respectively. The pressure gradient increased 14-fold during forced inspiration, from 0.64 to 8.76 mmHg. CONCLUSIONS: High-amplitude fetal inspiration substantially constricts the abdominal IVC and creates a negative pressure in the chest. The IVC constriction withholds abdominal blood, thus temporarily giving way to other flows.

Congenital retroperitoneal vascular anomalies: impact on pelvic surgery.

PURPOSE: Congenital anomalies of the inferior vena cava (IVC) are not commonly recognized since they generally do not cause symptoms. METHODS: Preoperative cross-sectional imaging can identify anomalies of vascular structures that are highly relevant to the pelvic surgeon. The clinical impact of congenital vascular variations of IVC, especially on paraaortic lymphadenectomy, is investigated. RESULTS: In case the surgeon is unaware of these anomalies, impending differential diagnostic confusion (paraaortic adenopathy), intraoperative blood loss and the need for transfusion may occur. The development of IVC is a complex process concerning the formation of several anastomoses between three paired embryonic veins (posterior cardinal, subcardinal, supracardinal veins). In double IVC, the left IVC typically ends at the level of the left renal vein, in an anastomosis which crosses anterior to the aorta to join the normal right IVC. CONCLUSION: Anomalies of IVC are present in 0.4-3.5% of women. As different aberrations of IVC have important clinical implications, awareness of retroperitoneal abnormal vessels is crucial to avoid diagnostic pitfalls and intraoperative complications.

Size and location of the kidneys during the fetal period.

PURPOSE: The aim of this study was to determine the morphometric development and location of the kidneys during the fetal period. METHODS: Three hundred and forty-four fetal kidneys, obtained from 172 human fetuses and aged between 9 and 40 weeks, were used in this study. Fetuses were divided into four groups according to the gestational weeks: first trimester, second trimester, third trimester, and full-term gestation. First, the anterior abdominal wall was dissected. Topographic localization of the kidneys in the abdominal cavity was then assessed. The distance between the inferior pole of the kidney and iliac crest was measured. The vertebral levels of the superior and the inferior poles and relations to ribs of the kidneys were determined. The distances between hilum of the kidneys and inferior vena cava, abdominal aorta, and midline of the vertebral column were determined. The dimensions (width, length, and thickness), weight, and volume of kidneys were measured. RESULTS: The results showed that the distance between the inferior poles of the kidneys and the iliac crest increases with gestational age. The vertebral levels of the superior and inferior poles of the kidneys increased during the fetal period. The level of the left kidney was higher than the level of the right kidney in the fetal period. The posterior surface relations to the ribs showed certain ascendance during gestation, corresponding to vertebral levels. However, fetal kidneys do not reach the same level as adults at full term. The kidneys move farther apart from the midline of the body during the fetal period. The dimensions, weight, and volume of the kidneys increased with gestational age during the fetal period. The ratio between kidney weights and fetal body weights were determined, and we observed that the ratio decreased during the fetal period. There were no sex or laterality differences in any parameter. CONCLUSIONS: The morphometric parameters and the location of the fetal kidneys were determined by the present study. This will also contribute to imaging of fetal kidneys and detection of kidney abnormalities in the intrauterine period. We hope that the present results can provide some useful findings for radiological (ultrasound and MR) studies.

Ductus venosus velocimetry in acute fetal acidemia and impending fetal death in a sheep model of increased placental vascular resistance.

We investigated whether hypoxemia without acidemia affects ductus venosus (DV) blood velocity waveform pattern in sheep fetuses with intact placenta and whether worsening acidemia and impending fetal death are related to changes in DV velocimetry in fetuses with increased placental vascular resistance. A total of 34 fetuses were instrumented at 115-136/145 days of gestation. Placental embolization was performed in 22 fetuses on the fourth postoperative day, 24 h before the experiment. The control group was comprised of 12 fetuses with intact placenta. The experimental protocol consisted of fetal hypoxemia that was induced by replacing maternal inhaled oxygen with medical air. To further deteriorate fetal oxygenation and blood-gas status, uterine artery volume blood flow was reduced by maternal hypotension. Fetuses that underwent placental embolization were divided into two groups according to fetal outcome. Group 1 consisted of 12 fetuses that completed the experiment, and group 2 comprised 10 fetuses that died during the experiment. DV pulsatility index for veins (PIV) and fetal cardiac outputs (COs) were calculated. Placental volume blood flow, fetal blood pressures, and acid base and lactate values were monitored invasively. On the experimental day, the mean gestational age did not differ significantly between the groups. In groups 1 and 2, the baseline mean DV PIV and fetal COs were not statistically significantly different from the control group. In the control group, the DV PIV values increased significantly with hypoxemia. In groups 1 and 2, the DV PIV values did not change significantly, even with worsening acidemia and imminent fetal death in group 2. During the experiment, the fetal COs remained unchanged. We conclude that fetal hypoxemia increases the pulsatility of DV blood velocity waveform pattern. In fetuses with elevated placental vascular resistance, DV pulsatility does not increase further in the presence of severe and worsening fetal acidemia and impending fetal death.

Screening for twin-twin transfusion syndrome at 11-14 weeks of pregnancy: the key role of ductus venosus blood flow assessment.

OBJECTIVES: A discrepancy in crown-rump length (CRL) and/or nuchal translucency thickness (NT) between monochorionic twins has been found to be associated with an increased risk of twin-twin transfusion syndrome (TTTS). As one of the most plausible mechanisms for increased NT is hemodynamic imbalance and cardiac dysfunction, indirectly manifested by abnormal blood flow in the ductus venosus (DV), we aimed to clarify the role of DV blood flow assessment in identifying those monochorionic twins more prone to develop TTTS. METHODS: We present 99 cases of monochorionic diamniotic twin pregnancies in which CRL, NT and DV blood flow were evaluated at 11-14 weeks' gestation. RESULTS: Discrepant values of CRL were not predictive of TTTS development. Intertwin NT discrepancy >or= 0.6 mm had a sensitivity of 50.0% and a specificity of 92.0%. The presence of at least one abnormal blood flow waveform in the DV was associated with a relative risk for developing TTTS of 11.86 (95% CI, 3.05-57.45), with a sensitivity of 75.0% and a specificity of 92.0%. The combination of abnormal DV blood flow with NT discrepancy >or= 0.6 mm yielded a relative risk for the development of TTTS of 21 (95% CI, 5.47-98.33). CONCLUSIONS: Both intertwin discrepancy in NT and abnormal flow in the DV in monochorionic twins may represent early manifestations of hemodynamic imbalance between donor and recipient. In these pregnancies, in addition to NT measurement at 11-14 weeks, the Doppler assessment of DV blood flow significantly increases the performance of screening for those at risk of developing TTTS.

Nuchal fold thickness, nasal bone absence or hypoplasia, ductus venosus reversed flow and tricuspid valve regurgitation in screening for trisomies 21, 18 and 13 in the early second trimester.

OBJECTIVE: To investigate the performance of nuchal fold thickness, nasal bone hypoplasia, reversed flow in the ductus venosus and tricuspid valve regurgitation in the prediction of fetal aneuploidies in the early second trimester. METHODS: This was a prospective study of 870 fetuses at 14 + 0 to 17 + 6 weeks of gestation, performed from 2005 to 2007. In all cases we assessed classical structural anomalies, second-trimester markers of aneuploidy including nuchal fold thickness and nasal bone length, as well as ductus venosus blood flow pattern and tricuspid valve regurgitation. RESULTS: The study group included 37 fetuses with trisomy 21, eight with trisomy 18 and four with trisomy 13. Nasal bone hypoplasia was the single most sensitive parameter to identify fetuses with trisomy 21. Independent from maternal age, screening by assessment of nuchal fold and nasal bone identified 64.9% of cases with trisomy 21 and 66.7% of cases with trisomy 18/13 (false-positive rate (FPR), 5.8%). By including ductus venosus and tricuspid flow evaluation, the detection rate increased to 75.7% for trisomy 21 and 83.3% for trisomy 18/13 (FPR, 10.8%). Identification of fetuses with structural abnormalities combined with assessment of all four markers under investigation raised the detection rate of trisomy 21 to 83.9% and that of trisomy 18/13 to 100%. The sensitivity of classical second-trimester markers was 62.2% for trisomy 21 and 70.6% for other autosomal aneuploidies (FPR, 11.3%). CONCLUSION: The combination of assessment of nuchal fold thickness, nasal bone hypoplasia, ductus venosus reversed flow and tricuspid regurgitation in the early second trimester is associated with a higher detection rate of autosomal trisomies compared with classical second-trimester marker screening.