Maternal and fetal outcomes in a retrospective cohort of obstetrical patients that used an insulin pump paired with a continuous glucose monitor.

OBJECTIVE: To assess maternal and neonatal outcomes in pregnant pregestational diabetic patients using a continuous subcutaneous insulin infusion (CSII) pump paired with a continuous glucose monitor (CGM). METHODS: This retrospective cohort study included 55 patients who delivered within one healthcare system from October 2019 to October 2022 with pregestational diabetes managed using CSII pumps paired with CGM. Maternal blood glucose (BG) data were analyzed for the two-week period preceding delivery. The percentage of time spent at a BG level of less than 140 mg/dL was recorded and compared between patients with and without obstetric and neonatal morbidities. RESULTS: Patients who delivered with severe preeclampsia (S. PreE) had a significantly lower mean percentage of time spent at BG < 140 mg/dL than those who did not (S. PreE 15/55, 63.1% ± 19.0 vs. 40/55, 73.6% ± 13.8; p = 0.03). Mothers who had a preterm birth (PTB) had a significantly lower mean percentage of time spent at BG < 140 mg/dL than those who delivered at term (PTB 35/55, 66.4% ± 16.4 vs 20/55, 78.3% ± 11.9; p = 0.006). The mean percentage of time spent at a BG < 140 mg/dL among mothers of neonates with respiratory distress syndrome (RDS) was significantly lower than those without RDS (RDS present 13/55, 59.7% ± 20.4 vs 42/55, 74.1% ± 12.7; p = 0.003). There was a significant correlation between a greater neonatal birth weight percentile and worse time spent at BG < 140 mg/dL (r = - 0.31; p = 0.02). No other significant differences were observed between the groups. CONCLUSION: Improved blood glucose levels in pregestational diabetic patients using a CSII pump and CGM is associated with reduced maternal and neonatal morbidity as well as lower birth weight percentile neonates. Future studies are needed to clarify how much time each day a patient needs to spend below a given blood sugar, how long this blood glucose should be maintained, and what specific blood glucose target should be selected.

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.

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.

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.

Evidence of the involvement of caspase-1 under physiologic and pathologic cellular stress during human pregnancy: a link between the inflammasome and parturition.

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 (IL)-1 beta, 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 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 IAI (median 41.4 pg/mL, range 0.0-515.0) had a significantly higher median amniotic fluid caspase-1 concentration than those without IAI 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 0.0-199.5); 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-1 beta processing and secretion, is a candidate pathway leading to the activation of the common pathway of parturition.

Premature labor: a state of platelet activation?

OBJECTIVE: This study was undertaken to determine whether premature labor is associated with changes in the maternal plasma concentration of soluble CD40 ligand (sCD40L), a marker of platelet activation. METHODS: A cross-sectional study included patients in the following groups: 1) non-pregnant (n=21); 2) normal pregnancy (n=71); 3) normal pregnancy at term with (n=67) and without labor (n=88); 4) preterm labor (PTL) with intact membranes (n=136) that was divided into the following sub-groups: 4a) PTL who delivered at term (n=49); 4b) PTL without intra-amniotic infection and/or inflammation (IAI) who delivered preterm (n=54); and 4c) PTL with IAI who delivered preterm (n=33). sCD40L concentrations were measured by ELISA. RESULTS: The median maternal plasma sCD40L concentration was higher in pregnant than non-pregnant women (P=0.017). Patients with PTL had a higher median maternal plasma sCD40L concentration than women with normal pregnancies, regardless of the presence or absence of IAI and gestational age at delivery (P<0.001 for all comparisons). IAI was not associated with a higher median maternal plasma concentration of sCD40L. CONCLUSIONS: 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.

Visfatin/Pre-B cell colony-enhancing factor in amniotic fluid in normal pregnancy, spontaneous labor at term, preterm labor and prelabor rupture of membranes: an association with subclinical intrauterine infection in preterm parturition.

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 (n=75); 2) term not in labor (n=27); 3) term in spontaneous labor (n=51); 4) patients with preterm labor with intact membranes (PTL) without MIAC who delivered at term (n=35); 5) patients with PTL without MIAC who delivered preterm (n=52); 6) patients with PTL with MIAC (n=25); 7) women with preterm PROM without MIAC (n=26); and 8) women with preterm PROM with MIAC (n=26). Non-parametric statistics were used for analysis. RESULTS: 1) The median AF concentration of visfatin was significantly higher in patients at term than in mid-trimester; 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.

Exodus-1 (CCL20): evidence for the participation of this chemokine in spontaneous labor at term, preterm labor, and intrauterine infection.

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 intra-amniotic infection/inflammation (IAI). METHODS: A cross-sectional study was conducted including the following groups: (1) mid-trimester of pregnancy (n=65); (2) term not in labor (TNL; n=22); (3) term in labor (TIL; n=47); (4) spontaneous preterm labor (PTL) who delivered at term (n=57); (5) spontaneous PTL without IAI who delivered preterm (n=71); and (6) spontaneous PTL with IAI (n=38). 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.

Four-dimensional sonography of the fetal heart with spatiotemporal image correlation directed at the interventricular septum.

OBJECTIVE: The purpose of this report is to describe a new technique to visualize the fetal interventricular cardiac septum in its entirety in a uniform fashion. METHODS: Using spatiotemporal image correlation, a technique of volume data manipulation is described to produce standard long-axis, short-axis, and "face-on" views of the interventricular septum. RESULTS: Using the detailed description of volume data manipulation, examples of large and small ventricular septal defects are presented. CONCLUSIONS: By using a standardized technique of volume manipulation, complete assessment of the interventricular septum is accomplished. Incorporating the technique into routine fetal heart evaluation is easily accomplished and may aid in the fetal diagnosis of ventricular septal defects.

Prenatal diagnosis and management of fetal anemia secondary to a large chorioangioma.

BACKGROUND: Chorioangiomas are benign vascular tumors of the placenta. Complications occur when their size exceeds 5 cm. CASE: We report the use of peak systolic velocity in the middle cerebral artery, fetal hemoglobin levels in maternal circulation, and maternal serum alpha-fetoprotein levels in the diagnosis and management of fetal anemia in a patient with a large placental chorioangioma. CONCLUSION: Fetal hemoglobin levels in maternal circulation and abrupt elevations of middle cerebral artery peak velocity may be useful in detecting fetal anemia.