Objective To quantify fetal cardiovascular parameters with Spatio-Temporal Image Correlation (STIC) and Virtual Organ Computed-aided AnaLysis (VOCAL™) utilizing the sub-feature: “Contour Finder: Trace”. Study Design A cross-sectional study was designed consisting of patients with normal pregnancies between 19 and 40 weeks of gestation. After STIC datasets were acquired, analysis was performed offline (4DView) and the following cardiovascular parameters were evaluated: ventricular volume in end systole and end diastole, stroke volume, cardiac output, and ejection fraction. To account for fetal size, cardiac output was also expressed as a function of head circumference, abdominal circumference, or femoral diaphysis length. Regression models were fitted for each cardiovascular parameter to assess the effect of gestational age and paired comparisons were made between the left and right ventricles. Results 1) Two hundred and seventeen patients were retrospectively identified, of whom 184 had adequate STIC datasets (85% acceptance); 2) ventricular volume, stroke volume, cardiac output, and adjusted cardiac output increased with gestational age; whereas, the ejection fraction decreased as gestation advanced; 3) the right ventricle was larger than the left in both systole (Right: 0.50 ml, IQR: 0.2 – 0.9; vs. Left: 0.27 ml, IQR: 0.1 – 0.5; p<0.001) and diastole (Right: 1.20 ml, IQR: 0.7 – 2.2; vs. Left: 1.03 ml, IQR: 0.5 – 1.7; p<0.001); 4) there were no differences between the left and right ventricle with respect to stroke volume, cardiac output, or adjusted cardiac output; and 5) the left ventricular ejection fraction was greater than the right (Left: 72.2%, IQR: 64 – 78; vs. Right: 62.4%, IQR: 56 – 69; p<0.001). Conclusion Fetal echocardiography, utilizing STIC and VOCAL™ with the sub-feature: “Contour Finder: Trace”, allows assessment of fetal cardiovascular parameters. Normal fetal cardiovascular physiology is characterized by ventricular volumes that are larger on the right and ejection fractions that are greater for the left ventricle resulting in similar left and right ventricular stroke volume and cardiac output.

OBJECTIVE Caspase-1 is a component of the NALP3 inflammasome, a cytosolic multiprotein complex that mediates the processing of pro-inflammatory caspases and cytokines. The inflammasome represents the first line of defense against cellular stress and is a crucial component of innate immunity. Caspase-1 is the enzyme responsible for the cleavage and activation of interleukin-1β, which is a potent pro-inflammatory cytokine, and plays a central role in the mechanisms leading to labor (preterm and term) particularly in the context of intrauterine infection/inflammation. In addition, Caspase-1 cleaves IL-18 and IL-33. The objectives of this study were to determine whether there is a relationship between amniotic fluid concentrations of caspase-1 and gestational age, parturition (term and preterm) and intra-amniotic infection/inflammation (IAI). STUDY DESIGN A cross-sectional study was conducted including 143 pregnant women in the following groups: 1) mid-trimester of pregnancy (n=18); 2) term not in labor (n=25); 3) term in labor (n=28); 4) preterm labor (PTL) who delivered at term (n=23); 5) PTL without intra-amniotic infection and/or inflammation (IAI) who delivered preterm (n=32); 6) PTL with IAI who delivered preterm neonates (n=17). Caspase-1 concentrations in amniotic fluid were determined by a specific and sensitive immunoassay. Non-parametric statistics were used for analysis. RESULTS 1) Caspase-1 was detected in amniotic fluid of women at term, but in none of the mid-trimester samples; 2) Patients in labor at term had a significantly higher median amniotic fluid concentration of caspase-1 than women at term not in labor [term in labor: 10.5 pg/ml, range (0.0–666.0) vs. term not in labor: 5.99 pg/ml, range (0.0–237.4); p<0.05]; 3) Among patients with spontaneous PTL, those with intra-amniotic infection and/or inflammation [median 41.4 pg/ml; range: (0.00–515.00)] had a significantly higher median amniotic fluid caspase-1 concentration than those without intra-amniotic infection and/or inflammation who delivered preterm [median 0.0 pg/ml; range: (0.0–78.4)] and than those who delivered at term [median 0.0 pg/ml, range (0.00–199.5)], (p<0.001 for both comparisons). CONCLUSIONS 1) The presence and concentration of caspase-1 in the amniotic fluid varies as a function of gestational age; 2) Women with spontaneous labor at term had a higher median caspase-1 amniotic fluid concentration than women at term without labor. This suggests that the inflammasome may be activated in spontaneous parturition at term. Since most women with labor do not have intra-amniotic infection, we propose that cellular stress during labor accounts for activation of the inflammasome; 3) Preterm labor associated with infection/inflammation was also associated with a high concentration of caspase-1, suggesting that infection may induce caspase-1 production and activation of the inflammasome; 4) The sequential activation of the inflammasome and caspase-1, leading to interleukin-1β processing and secretion, is a candidate pathway leading...