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...

Objective: Visfatin, a novel adipokine originally discovered as a pre-B-cell colony enhancing factor, is expressed by amniotic epithelium, cytotrophoblast, and decidua and is over-expressed when fetal membranes are exposed to mechanical stress and/or pro-inflammatory stimuli. Visfatin expression by fetal membranes is dramatically up-regulated after normal spontaneous labor. The aims of this study were to determine if visfatin is detectable in amniotic fluid (AF) and whether its concentration changes with gestational age, spontaneous labor, preterm prelabor rupture of membranes (preterm PROM) and in the presence of microbial invasion of the amniotic cavity (MIAC). Methods: In this cross-sectional study, visfatin concentration in AF was determined in patients in the following groups: 1) mid-trimester (ns75); 2) term not in labor (ns27); 3) term in spontaneous labor (ns51); 4) patients with preterm labor with intact membranes (PTL) without MIAC who delivered at term (ns35); 5) patients with PTL without MIAC who delivered preterm (ns52); 6) patients with PTL with MIAC (ns25); 7) women with preterm PROM without MIAC (ns26); and 8) women with preterm PROM with MIAC (ns26). Non-parametric statistics were used for analysis. Results: 1) The median AF concentration of visfatin was significantly higher in patients at term than in midtrimester; 2) Among women with PTL who delivered preterm, the median visfatin concentration was significantly higher in patients with MIAC than those without MIAC; 3) Similarly, patients with PTL and MIAC had a higher median AF visfatin concentration than those with PTL who delivered at term; 4) Among women with preterm PROM, the median AF visfatin concentration was significantly higher in patients with MIAC than those without MIAC. Conclusions: 1) Visfatin is a physiologic constituent of AF; 2) The concentration of AF visfatin increases with advancing gestational age; 3) AF visfatin concentration is elevated in patients with MIAC, regardless of the membrane status, suggesting that visfatin participates in the host response against infection.Keywords: Microbial invasion of the amniotic cavity (MIAC); pre-B cell colony-enhancing factor (PBEF); preterm labor; preterm prelabor rupture of membranes (preterm PROM); visfatin.

Aim: CCL20, also known as MIP-3 alpha, is a chemokine that participates in chemotaxis of immature dendritic cells, effector/memory T-cells, and B-lymphocytes. The objectives of this study were to determine whether CCL20 can be detected in amniotic fluid (AF) and if AF concentration of this chemokine changes with advancing gestational age, parturition (term and preterm), and intraamniotic infection/inflammation (IAI). Methods: A cross-sectional study was conducted including the following groups: (1) mid-trimester of pregnancy (ns65); (2) term not in labor (TNL; ns22); (3) term in labor (TIL; ns47); (4) spontaneous preterm labor (PTL) who delivered at term (ns57); (5) spontaneous PTL without IAI who delivered preterm (ns71); and (6) spontaneous PTL with IAI (ns38). AF CCL20 concentrations were determined using ELISA. Results: (1) The median AF CCL20 concentration in TNL was higher than that of mid-trimester patients; (2) Women in spontaneous labor at term had a higher median AF concentration of CCL20 than patients at term not in labor; (3) Patients with spontaneous PTL and IAI had a significantly higher median AF concentration of CCL20 than those without IAI who delivered preterm and those who delivered at term. Moreover, women with spontaneous PTL without IAI who delivered preterm had a significantly higher median AF concentration than those with PTL who subsequently delivered at term. Conclusions: (1) CCL20 is a physiologic constituent of AF and its concentration increases as term approaches; (2) spontaneous labor (term and preterm) in the absence of IAI is associated with increased bioavailability of AF CCL20 suggesting that an increase in CCL20 is part of the common pathway of human parturition; (3) patients with IAI had dramatic elevations in the AF CCL20 concentrations suggesting that this chemokine participates in the host response to infection or other stimuli associated with intra-amniotic infection.

Objective To quantify the repeatability and reproducibility of fetal cardiac ventricular volumes obtained utilizing STIC and VOCAL™. Methods A technique was developed to compute ventricular volumes using the sub-feature: Contour Finder: Trace. Twenty-five normal pregnancies were evaluated for the following: (1) to compare the coefficient of variation (CV) in ventricular volumes between 15° and 30° rotation; (2) to compare the CV between three 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 two 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° rotation than 30° (15°: 3.6%, 95% CI: 3.0 – 4.2 versus 30°: 7.1%, 95% CI: 5.8 – 8.6; p<0.001); (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 < 0.001) or Manual Trace (10.5%, 95% CI 8.7 – 12.5; p < 0.001); (3) ventricular volumes were repeatable with good agreement and excellent reliability for both intra-observer and inter-observer measurements; and 4) ventricular volumes were reproducible with negligible difference 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 utilizing STIC and VOCAL allows repeatable and reproducible calculation of ventricular volumes with the sub-feature Contour Finder: Trace.

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Normal pregnancy is a state in which there is a physiologic increase of sCD40L. PTL was associated with an increased median maternal plasma sCD40L concentration that could not be accounted for by IAI. Thus, our findings suggest that platelet activation occurs during an episode of preterm labor.

Fetal hemoglobin levels in maternal circulation and abrupt elevations of middle cerebral artery peak velocity may be useful in detecting fetal anemia.