Pulse Pressure and Carotid Artery Doppler Velocimetry as Indicators of Maternal Volume Status: A Prospective Cohort Study.

BACKGROUND: Narrow pulse pressure has been demonstrated to indicate low central volume status. In critically ill patients, volume status can be qualitatively evaluated using Doppler velocimetry to assess hemodynamic changes in the carotid artery in response to autotransfusion with passive leg raise (PLR). Neither parameter has been prospectively evaluated in an obstetric population. The objective of this study was to determine if pulse pressure could predict the response to autotransfusion using carotid artery Doppler in healthy intrapartum women. We hypothesized that the carotid artery Doppler response to PLR would be greater in women with a narrow pulse pressure, indicating relative hypovolemia. METHODS: Intrapartum women with singleton gestations ≥35 weeks without acute or chronic medical conditions were recruited to this prospective cohort study. Participants were grouped by admission pulse pressure as <45 mm Hg (narrow) or ≥50 mm Hg (normal). Maternal carotid artery Doppler assessment was then performed in all patients before and after PLR using a standard technique where carotid blood flow (mL/min) = π × (carotid artery diameter/2) × (velocity time integral) × (60 seconds). The velocity time integral was calculated from the Doppler waveform. The primary outcome was the change in the carotid Doppler parameters (carotid artery diameter, velocity time integral, and carotid blood flow) after PLR. Outcomes were compared between study groups with univariable and multivariable analyses with adjustment for potential confounding factors. RESULTS: Thirty-three women consented to participation, including 18 in the narrow and 15 in the normal pulse pressure groups (mean and standard deviation initial pulse pressure, 38.3 ± 4.4 vs 57.3 ± 4.1 mm Hg). The 2 groups demonstrated similar characteristics except for initial pulse pressure, systolic and diastolic blood pressure, and race. In response to PLR, the narrow pulse pressure group had a significantly greater increase in carotid artery diameter (0.08 vs 0.02 cm; standardized difference, 2.0; 95% confidence interval [CI], 1.16-2.84), carotid blood flow (79.4 vs 16.0 mL/min; standardized difference, 2.23; 95% CI, 1.36-3.10), and percent change in carotid blood flow (47.5% vs 8.7%; standardized difference, 2.52; 95% CI, 1.60-3.43) compared with the normal pulse pressure group. In multivariable analysis with adjustment for potential confounding factors, women with narrow admission pulse pressure had a significantly larger carotid diameter (0.66 vs 0.62 cm; P < .0001) and greater carotid flow (246.7 vs 219.3 cm/s; P = .001) after PLR compared to women with a normal pulse pressure. Initial pulse pressure was strongly correlated with the change in carotid flow after PLR (r = 0.60; P < .0001). CONCLUSIONS: The hemodynamic response of the carotid artery to autotransfusion after PLR is significantly greater in women with narrow pulse pressure. Pulse pressure correlates with the physiological response to autotransfusion and provides a qualitative indication of intravascular volume in term and near-term pregnant women.

A Novel Y-Specific Long Non-Coding RNA Associated with Cellular Lipid Accumulation in HepG2 cells and Atherosclerosis-related Genes.

There is an increasing appreciation for the role of the human Y chromosome in phenotypic differences between the sexes in health and disease. Previous studies have shown that genetic variation within the Y chromosome is associated with cholesterol levels, which is an established risk factor for atherosclerosis, the underlying cause of coronary artery disease (CAD), a major cause of morbidity and mortality worldwide. However, the exact mechanism and potential genes implicated are still unidentified. To date, Y chromosome-linked long non-coding RNAs (lncRNAs) are poorly characterized and the potential link between these new regulatory RNA molecules and hepatic function in men has not been investigated. Advanced technologies of lncRNA subcellular localization and silencing were used to identify a novel intergenic Y-linked lncRNA, named lnc-KDM5D-4, and investigate its role in fatty liver-associated atherosclerosis. We found that lnc-KDM5D-4 is retained within the nucleus in hepatocytes. Its knockdown leads to changes in genes leading to increased lipid droplets formation in hepatocytes resulting in a downstream effect contributing to the chronic inflammatory process that underpin CAD. Our findings provide the first evidence for the implication of lnc-KDM5D-4 in key processes related to fatty liver and cellular inflammation associated with atherosclerosis and CAD in men.

Maternal Pulse Pressure and the Risk of Postepidural Complications: A Randomized Controlled Trial.

OBJECTIVE: To test the hypothesis that increasing the intravenous fluid bolus volume at the time of epidural placement in women with narrow pulse pressure would reduce postepidural fetal heart rate (FHR) abnormalities, hypotension, and resuscitative obstetric interventions. METHODS: We performed a single-center randomized controlled trial. Eligible participants were normotensive with a nonanomalous singleton gestation at or after 35 weeks and with a narrow pulse pressure (less than 45 mm Hg) on admission. Enrolled patients remained eligible for randomization at epidural request if they were within 6 hours of admission and the FHR remained category 1. Patients were allocated to a 500-mL (institutional standard) or 1,500-mL intravenous fluid bolus at epidural placement. A reference group with admission pulse pressure 50 mm Hg or greater was also evaluated. The primary outcome was a category 2 or 3 FHR pattern within 60 minutes after the epidural test dose. Evaluated secondary outcomes included maternal hypotension and composite resuscitative interventions to correct FHR abnormalities or hypotension. We calculated that 276 women (138/group) would provide 80% power to detect a relative 50% reduction in the occurrence of the primary outcome from 27% in the 500-mL group to 13.5% in the 1,500-mL group (two-sided α=0.05). RESULTS: From October 2015 to November 2016, 276 women were allocated to receive a 500-mL (n=139) or 1,500-mL (n=137) fluid bolus. One hundred thirty-eight women were evaluated in the reference group. Demographic, obstetric, and labor characteristics were similar between groups. The 1,500-mL group had significantly fewer postepidural FHR abnormalities (38.0% compared with 51.8%, relative risk 0.73, 95% CI 0.56-0.96, P=.02). Maternal systolic hypotension (10.2% compared with 34.5%, relative risk 0.30, 95% CI 0.17-0.51, P<.001) and composite postepidural interventions (18.3% compared with 44.2%, relative risk 0.42, 95% CI 0.28-0.62, P<.001) were also less frequent in the 1,500-mL group. Fetal heart rate abnormalities remained significantly less frequent in the reference group than among women with a narrow pulse pressure on admission for delivery. CONCLUSION: A 1,500-mL intravenous fluid bolus in women with a narrow pulse pressure decreases the risk of postepidural FHR abnormalities (number needed to treat=7), results in less frequent postepidural hypotension, and reduces the need for resuscitative interventions. Admission pulse pressure may be used to individualize intrapartum fluid management at the time of initiation of neuraxial labor analgesia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02565485.

Detection theory for accurate and non-invasive skin cancer diagnosis using dynamic thermal imaging.

Skin cancer is the most common cancer in the United States with over 3.5M annual cases. Presently, visual inspection by a dermatologist has good sensitivity (> 90%) but poor specificity (< 10%), especially for melanoma, which leads to a high number of unnecessary biopsies. Here we use dynamic thermal imaging (DTI) to demonstrate a rapid, accurate and non-invasive imaging system for detection of skin cancer. In DTI, the lesion is cooled down and the thermal recovery is recorded using infrared imaging. The thermal recovery curves of the suspected lesions are then utilized in the context of continuous-time detection theory in order to define an optimal statistical decision rule such that the sensitivity of the algorithm is guaranteed to be at a maximum for every prescribed false-alarm probability. The proposed methodology was tested in a pilot study including 140 human subjects demonstrating a sensitivity in excess of 99% for a prescribed specificity in excess of 99% for detection of skin cancer. To the best of our knowledge, this is the highest reported accuracy for any non-invasive skin cancer diagnosis method.

The systematic error in the estimation of fetal weight and the underestimation of fetal growth restriction.

Fetal growth restriction (FGR) is associated with an increased risk of perinatal morbidity and mortality and has lifetime implications for the risk of chronic medical conditions. Antenatal diagnosis of FGR remains poor, with the majority of cases remaining undiagnosed. Although several factors contribute to the underdiagnosis of FGR, the error in ultrasound estimation of fetal weight (EFW) generally is not considered in clinical practice. In this commentary, we suggest that the intrinsic, or systematic, error in ultrasound EFW is a significant factor contributing to the underestimation of fetuses predicted to have FGR and should be incorporated into screening and surveillance recommendations. To illustrate this point, we present an analytic model of published data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies characterizing and quantifying the impact of the systematic error in ultrasound EFW on the underdiagnosis of FGR. Independent of the centile at which the risk of adverse outcome related to FGR begins, whether the 10th, 5th or 3rd percentile, our analysis suggests the need to modify to the current paradigm for identifying and responding to fetuses estimated to be at risk.

Comparison of 2- and 3-Dimensional Sonography for Estimation of Birth Weight and Neonatal Adiposity in the Setting of Suspected Fetal Macrosomia.

OBJECTIVES: To compare the accuracy of 2-dimensional (2D) and 3-dimensional (3D) fetal measurements for prediction of birth weight Z score and neonatal adiposity (percent body fat) in the setting of suspected fetal macrosomia. METHODS: We conducted a prospective observational study of term singleton pregnancies with suspected macrosomia. Patients were enrolled on admission to labor and delivery and underwent sonographic examinations. Within 48 hours of delivery, neonatal anthropometric measurements were obtained. RESULTS: Thirty-four neonates were included in the analysis. Mothers were very obese (mean body mass index ± SD, 39.1 ± 7.8 kg/m(2)); 56.5% were white; and 39.1% had diabetes. Neonates were 38% female and had a mean birth weight of 3940.0 ± 496.8 g, percent body fat of 18.5% ± 4.0%, and Ponderal index of 2.8 ± 0.3 g/cm(3). Mean 2D estimated fetal weight was 3973 ± 443 g; mean 3D estimated fetal weight was 3803 ± 528 g; and mean thigh volume was 102.5 ± 19.6 cm(3). Both 2D and 3D measurements accounted for about half the variance in predicted birth weight (R(2) for 2D = 0.53, 71% within 10% of birth weight; R(2) for 3D = 0.47, 65% within 10% of birth weight). Thigh volume Z score was the prenatal parameter most highly correlated with both birth weight Z score (R(2) = 0.52; r = 0.72; 95% confidence interval, 0.54-0.84; P < .001) and percent body fat (R(2) = 0.22; r = 0.47; 95% confidence interval, 0.17-0.69; P = .04). CONCLUSIONS: In our population of fetuses with suspected macrosomia, fractional thigh volume was the best sonographic estimate of neonatal percent body fat and birth weight Z score. Future research on prediction of neonatal weight and adiposity in macrosomic fetuses should include an estimate of fetal soft tissue given the generalized increase in body fat of these fetuses.

Zinc transporters and zinc signaling: new insights into their role in type 2 diabetes.

Zinc is an essential trace element that plays a vital role in many biological processes including growth and development, immunity, and metabolism. Recent studies have highlighted zinc's dynamic role as a "cellular second messenger" in the control of insulin signaling and glucose homeostasis. Accordingly, mechanisms that contribute to dysfunctional zinc signaling are suggested to be associated with metabolic disease states including cancer, cardiovascular disease, Alzheimer's disease, and diabetes. The actions of the proteins that control the uptake, storage, and distribution of zinc, the zinc transporters, are under intense investigation due to their emerging role in type 2 diabetes. The synthesis, secretion, and action of insulin are dependent on zinc and the transporters that make this ion available to cellular processes. This suggests that zinc plays a previously unidentified role where changes in zinc status over time may affect insulin activity. This previously unexplored concept would raise a whole new area of research into the pathophysiology of insulin resistance and introduce a new class of drug target with utility for diabetes pharmacotherapy.

The zinc transporter, Slc39a7 (Zip7) is implicated in glycaemic control in skeletal muscle cells.

Dysfunctional zinc signaling is implicated in disease processes including cardiovascular disease, Alzheimer's disease and diabetes. Of the twenty-four mammalian zinc transporters, ZIP7 has been identified as an important mediator of the 'zinc wave' and in cellular signaling. Utilizing siRNA targeting Zip7 mRNA we have identified that Zip7 regulates glucose metabolism in skeletal muscle cells. An siRNA targeting Zip7 mRNA down regulated Zip7 mRNA 4.6-fold (p = 0.0006) when compared to a scramble control. This was concomitant with a reduction in the expression of genes involved in glucose metabolism including Agl, Dlst, Galm, Gbe1, Idh3g, Pck2, Pgam2, Pgm2, Phkb, Pygm, Tpi1, Gusb and Glut4. Glut4 protein expression was also reduced and insulin-stimulated glycogen synthesis was decreased. This was associated with a reduction in the mRNA expression of Insr, Irs1 and Irs2, and the phosphorylation of Akt. These studies provide a novel role for Zip7 in glucose metabolism in skeletal muscle and highlight the importance of this transporter in contributing to glycaemic control in this tissue.

Caveolin-1 is necessary for hepatic oxidative lipid metabolism: evidence for crosstalk between caveolin-1 and bile acid signaling.

Caveolae and caveolin-1 (CAV1) have been linked to several cellular functions. However, a model explaining their roles in mammalian tissues in vivo is lacking. Unbiased expression profiling in several tissues and cell types identified lipid metabolism as the main target affected by CAV1 deficiency. CAV1-/- mice exhibited impaired hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent oxidative fatty acid metabolism and ketogenesis. Similar results were recapitulated in CAV1-deficient AML12 hepatocytes, suggesting at least a partial cell-autonomous role of hepatocyte CAV1 in metabolic adaptation to fasting. Finally, our experiments suggest that the hepatic phenotypes observed in CAV1-/- mice involve impaired PPARα ligand signaling and attenuated bile acid and FXRα signaling. These results demonstrate the significance of CAV1 in (1) hepatic lipid homeostasis and (2) nuclear hormone receptor (PPARα, FXRα, and SHP) and bile acid signaling.

The fetal cardiovascular response to increased placental vascular impedance to flow determined with 4-dimensional ultrasound using spatiotemporal image correlation and virtual organ computer-aided analysis.

OBJECTIVE: We sought to determine if increased placental vascular impedance to flow is associated with changes in fetal cardiac function using spatiotemporal image correlation and virtual organ computer-aided analysis. STUDY DESIGN: A cross-sectional study was performed in fetuses with umbilical artery pulsatility index >95th percentile (abnormal [ABN]). Ventricular volume (end-systole, end-diastole), stroke volume, cardiac output (CO), adjusted CO, and ejection fraction were compared to those of 184 normal fetuses. RESULTS: A total of 34 fetuses were evaluated at a median gestational age of 28.3 (range, 20.6-36.9) weeks. Mean ventricular volumes were lower for ABN than normal cases (end-systole, end-diastole) with a proportionally greater decrease for left ventricular volume (vs right). Mean left and right stroke volume, CO, and adjusted CO were lower for ABN (vs normal) cases. Right ventricular volume, stroke volume, CO, and adjusted CO exceeded the left in ABN fetuses. Mean ejection fraction was greater for ABN than normal cases. Median left ejection fraction was greater (vs right) in ABN fetuses. CONCLUSION: Increased placental vascular impedance to flow is associated with changes in fetal cardiac function.

The risk of fetal death: current concepts of best gestational age for delivery.

OBJECTIVE: To compare the risk of fetal death (FD) between 34 and 41 weeks' gestational age (GA) with the neonatal mortality rate to examine the best GA for delivery. STUDY DESIGN: Linked birth and infant death data for the US from the National Center for Health Statistics analyzed nonanomalous singleton pregnancies between 2003 and 2005. Pregnancies were classified as high risk or low risk based on preexisting maternal complications. Outcomes of 8,785,132 live births and 12,777 FDs between 34 and 42 completed weeks' gestation were examined. The risk of FD was determined using the following equation: The FD risk of those remaining undelivered was compared with the neonatal death rate for each week of gestation. RESULTS: Between 34 and 40 weeks' gestation, the FD risk of those remaining undelivered for all pregnancies declined and then increased at term. For high risk pregnancies, the FD risk of those remaining undelivered is substantially higher than for low risk pregnancies. The number of FDs that can be avoided by delivery exceeds the neonatal death rate between 37 and 38 weeks' gestation in low risk pregnancies and at 36 weeks' gestation in high risk pregnancies. CONCLUSION: These findings suggest that delivery at 39 weeks' gestation in both high and low risk pregnancies would result in an increased number of perinatal deaths. Decisions regarding the "optimal time for delivery" should include the risk of remaining undelivered.

Zinc transporters, mechanisms of action and therapeutic utility: implications for type 2 diabetes mellitus.

Zinc is an essential trace element that plays a vital role in maintaining many biological processes and cellular homeostasis. Dysfunctional zinc signaling is associated with a number of chronic disease states including cancer, cardiovascular disease, Alzheimer's disease, and diabetes. Cellular homeostasis requires mechanisms that tightly control the uptake, storage, and distribution of zinc. This is achieved through the coordinated actions of zinc transporters and metallothioneins. Evidence on the role of these proteins in type 2 diabetes mellitus (T2DM) is now emerging. Zinc plays a key role in the synthesis, secretion and action of insulin in both physiological and pathophysiological states. Moreover, recent studies highlight zinc's dynamic role as a "cellular second messenger" in the control of insulin signaling and glucose homeostasis. This suggests that zinc plays an unidentified role as a novel second messenger that augments insulin activity. This previously unexplored concept would raise a whole new area of research into the pathophysiology of insulin resistance and introduce a new class of drug target with utility for diabetes pharmacotherapy.

Fetal cardiac ventricular volume, cardiac output, and ejection fraction determined with 4-dimensional ultrasound using spatiotemporal image correlation and virtual organ computer-aided analysis.

OBJECTIVE: The objective of this study was to quantify fetal cardiovascular parameters using spatiotemporal image correlation (STIC) and virtual organ computer-aided analysis (VOCAL). STUDY DESIGN: A cross-sectional study was performed in normal pregnancies (19-42 weeks) to evaluate ventricular volume, stroke volume (SV), cardiac output (CO), and ejection fraction (EF). The CO was also expressed as a function of estimated fetal weight and biometric parameters. RESULTS: The following results were found: (1) 184 STIC datasets; (2) with advancing gestation, ventricular volume, SV, CO, and adjusted CO increased, whereas EF decreased; (3) right ventricular (RV) volume was larger than the left ventricular (LV) volume in systole (0.50 vs 0.27 mL; P < .001) and diastole (1.20 vs 1.03 mL; P < .001); (4) there were no differences between the LV and RV in SV, CO, or adjusted CO; and (5) LV EF was greater than the RV EF (72.2 vs 62.4%; P < .001). CONCLUSION: Normal fetal cardiovascular physiology is characterized by a larger RV volume and a greater LV EF, resulting in similar LV and RV SV and CO.

Nr4a1 siRNA expression attenuates α-MSH regulated gene expression in 3T3-L1 adipocytes.

Several recent investigations have underscored the growing role of melanocortin signaling in the peripheral regulation of lipid, glucose, and energy homeostasis. In addition, the melanocortins play a critical role in the central control of satiety. These observations, and the latest reports highlighting the emerging role of the nuclear hormone receptor (NR) 4A subgroup in metabolism, have prompted us to investigate the cross talk between [Nle(4), d-Phe(7)] (NDP)-α-MSH and Nr4a signaling in adipose. We have shown that NDP-MSH strikingly and preferentially induces the expression of the NR4A subgroup (but not any other members of the NR superfamily) in differentiated 3T3-L1 adipocytes. Utilization of quantitative PCR on custom-designed metabolic TaqMan low-density arrays identified the concomitant and marked induction of the mRNAs encoding Il-6, Cox2, Pdk4, and Pck-1 after NDP-MSH treatment. Similar experiments demonstrated that the mRNA expression profile induced by cAMP and NDP-MSH treatment displayed unique but also overlapping properties and suggested that melanocortin-mediated induction of gene expression involves cAMP-dependent and -independent signaling. Nr4a1/Nur77 small interfering RNA (siRNA) expression suppressed NDP-MSH-mediated induction of Nr4a1/Nur77 and Nr4a3/Nor-1 (but not Nr4a2/Nurr1). Moreover, expression of the siRNA-attenuated NDP-MSH mediated induction of the mRNAs encoding Il-6, Cox2/Ptgs2, and Pck-1 expression. In addition, Nur77 siRNA expression attenuated NDP-MSH-mediated glucose uptake. In vivo, ip administration of NDP-MSH to C57 BL/6J (male) mice significantly induced the expression of the mRNA encoding Nur77 and increased IL-6, Cox2, Pck1, and Pdk4 mRNA expression in (inguinal) adipose tissue. We conclude that Nur77 expression is necessary for MSH-mediated induction of gene expression in differentiated adipocytes. Furthermore, this study demonstrates cross talk between MSH and Nr4a signaling in adipocytes.

Chicken ovalbumin upstream promoter-transcription factor II regulates nuclear receptor, myogenic, and metabolic gene expression in skeletal muscle cells.

We demonstrate that chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) mRNA is more abundantly expressed (than COUP-TFI mRNA) in skeletal muscle C2C12 cells and in (type I and II) skeletal muscle tissue from C57BL/10 mice. Consequently, we have utilized the ABI TaqMan Low Density Array (TLDA) platform to analyze gene expression changes specifically attributable to ectopic COUP-TFII (relative to vector only) expression in muscle cells. Utilizing a TLDA-based platform and 5 internal controls, we analyze the entire NR superfamily, 96 critical metabolic genes, and 48 important myogenic regulatory genes on the TLDA platform utilizing 5 internal controls. The low density arrays were analyzed by rigorous statistical analysis (with Genorm normalization, Bioconductor R, and the Empirical Bayes statistic) using the (integromics) statminer software. In addition, we validated the differentially expressed patho-physiologically relevant gene (identified on the TLDA platform) glucose transporter type 4 (Glut4). We demonstrated that COUP-TFII expression increased the steady state levels of Glut4 mRNA and protein, while ectopic expression of truncated COUP-TFII lacking helix 12 (COUP-TFΔH12) reduced Glut4 mRNA expression in C2C12 cells. Moreover, COUP-TFII expression trans-activated the Glut4 promoter (-997/+3), and ChIP analysis identified selective recruitment of COUP-TFII to a region encompassing a highly conserved SP1 binding site (in mouse, rat, and human) at nt positions -131/-118. Mutation of the SpI site ablated COUP-TFII mediated trans-activation of the Glut4 promoter. In conclusion, this study demonstrates that in skeletal muscle cells, COUP-TFII regulates several nuclear hormone receptors, and critical metabolic and muscle specific genes.

Repeatability and reproducibility of fetal cardiac ventricular volume calculations using spatiotemporal image correlation and virtual organ computer-aided analysis.

OBJECTIVE: The objective of this study was to quantify the repeatability and reproducibility of fetal cardiac ventricular volumes obtained using spatiotemporal image correlation (STIC) and Virtual Organ Computer-Aided Analysis (VOCAL; GE Healthcare, Kretztechnik, Zipf, Austria). METHODS: A technique was developed to compute ventricular volumes using the subfeature Contour Finder: Trace. Twenty-five normal pregnancies were evaluated for the following: (1) to compare the coefficient of variation (CV) of ventricular volumes obtained using 15 degrees and 30 degrees rotation; (2) to compare the CV between 3 methods of quantifying ventricular volumes: (a) Manual Trace, (b) Inversion Mode, and (c) Contour Finder: Trace; and (3) to determine repeatability by calculating agreement and reliability of ventricular volumes when each STIC was measured twice by 3 observers. Reproducibility was assessed by obtaining 2 STICs from each of 44 normal pregnancies. For each STIC, 2 ventricular volume calculations were performed, and agreement and reliability were evaluated. Additionally, measurement error was examined. RESULTS: (1) Agreement was better with 15 degrees rotation than 30 degrees (15 degrees: 3.6%; 95% confidence interval [CI], 3.0%-4.2%; versus 30 degrees: 7.1%; 95% CI, 5.8%-8.6%; P < .001); (2) ventricular volumes obtained with Contour Finder: Trace had better agreement than those obtained using either Inversion Mode (Contour Finder: Trace: 3.6%; 95% CI, 3.0%-4.2%; versus Inversion Mode: 6.0%; 95% CI, 4.9%-7.2%; P < .001) or Manual Trace (10.5%; 95% CI, 8.7%-12.5%; P < .001); (3) ventricular volumes were repeatable with good agreement and excellent reliability for both intraobserver and interobserver measurements; and (4) ventricular volumes were reproducible with negligible differences in agreement and good reliability. In addition, bias between STIC acquisitions was minimal (<1%; mean percent difference, -0.4%; 95% limits of agreement, -5.4%-5.9%). CONCLUSIONS: Fetal echocardiography using STIC and VOCAL allows repeatable and reproducible calculation of ventricular volumes with the subfeature Contour Finder: Trace.