Interleukin (IL)-6: A Friend or Foe of Pregnancy and Parturition? Evidence From Functional Studies in Fetal Membrane Cells.

OBJECTIVE: Protection of the fetus within the amniotic sac is primarily attained by remodeling fetal membrane (amniochorion) cells through cyclic epithelial to mesenchymal and mesenchymal to epithelial (EMT and MET) transitions. Endocrine and paracrine factors regulate EMT and MET during pregnancy. At term, increased oxidative stress forces a terminal state of EMT and inflammation, predisposing to membrane weakening and rupture. IL-6 is a constitutively expressed cytokine during gestation, but it is elevated in term and preterm births. Therefore, we tested the hypothesis that IL-6 can determine the fate of amnion membrane cells and that pathologic levels of IL-6 can cause a terminal state of EMT and inflammation, leading to adverse pregnancy outcomes. METHODS: Primary amnion epithelial cells (AECs) were treated with recombinant IL-6 (330, 1,650, 3,330, and 16,000 pg/ml) for 48 h (N = 5). IL-6-induced cell senescence (aging), cell death (apoptosis and necrosis), and cell cycle changes were studied using flow cytometry. Cellular transitions were determined by immunocytochemistry and western blot analysis, while IL-6 signaling (activation of signaling kinases) was measured by immunoassay. Inflammatory marker matrix metalloproteinase (MMP9) and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations were measured using a Fluorokine E assay and ELISA, respectively. Amniotic membranes collected on gestational day (D) 12 and D18 from IL-6 knockout (KO) and control C57BL/6 mice (N = 3 each) were used to determine the impact of IL-6 on cell transitions. Fold changes were measured based on the mean of each group. RESULTS: IL-6 treatment of AECs at physiologic or pathologic doses increased JNK and p38MAPK activation; however, the activation of signals did not cause changes in AEC cell cycle, cellular senescence, apoptosis, necrosis, cellular transitions, or inflammation (MMP9 and GM-CSF) compared to control. EMT markers were higher on D18 compared to D12 regardless of IL-6 status in the mouse amniotic sac. CONCLUSION: Physiologic and pathologic concentrations of IL-6 did not cause amnion cell aging, cell death, cellular transitions, or inflammation. IL-6 may function to maintain cellular homeostasis throughout gestation in fetal membrane cells. Although IL-6 is a good biomarker for adverse pregnancies, it is not an indicator of an underlying pathological mechanism in membrane cells.

Quality Improvement Initiative to Reduce Time from Regional Anesthesia Placement to Delivery for Cesarean Delivery.

OBJECTIVE: Our objective was to evaluate the impact of a quality improvement (QI) initiative on the regional anesthesia placement-to-infant delivery time during cesarean delivery (CD). STUDY DESIGN: We performed a quality improvement trial. Before June 18, 2018, the preoperative protocol was as follows: the anesthesiologist administered regional anesthesia in the operating room then the nurse placed the Foley's catheter, clipped pubic hair, precleaned the abdomen, and abdominal preparation. On June 18, 2018, the protocol changed and all the preoperative preparation (Foley's clip and preclean) were performed prior to the arrival in the operating room. The records of patients who underwent scheduled or nonemergency CD between May 1 and July 15, 2018, were reviewed. Our primary outcome was time between the placements of regional anesthesia to infant delivery at the time of CD. Bivariate and multivariable analyses were performed. RESULTS: A total of 194 patients were included, 124 before and 70 after the process change. The change in process leads to a significant reduction in anesthesia-to-delivery time, even after adjusting for number of prior CD and body mass index (BMI). Other times were also significantly impacted by the change. CONCLUSION: Our QI initiative significantly decreased the time from anesthesia placement to delivery of the fetus. Performing preoperative preparation activities, such as Foley's placement and shaving, after regional anesthesia for CD, increase the risk of fetal exposure to maternal hypotension. We evaluated the impact of a QI initiative on regional anesthesia placement to infant delivery time during CD.

The impact of low-dose versus high-dose antibiotic prophylaxis regimens on surgical site infection rates after cesarean delivery.

OBJECTIVE: The objective of this study was to determine if high-dose antibiotic prophylaxis with cefazolin decreases the risk of surgical site infection (SSI) after a cesarean delivery. METHODS: We performed a retrospective cohort study of women who underwent a cesarean section. Two preoperative antibiotic regimens were compared: low dose versus high dose. The primary outcome was SSI. A sample size of 343 patients per group was calculated for a 50% reduction in risk for SSI. RESULTS: Seven hundred and thirty women were included with an incidence of SSI of 5%. Women who received the high-dose antibiotic regimen had lower rates of risk factors for SSI. The only exception was skin incision closure with staples. The rate of SSI did not differ between the low-dose and high-dose groups, even after adjusting for confounding variables [aOR 1.78, 95% CI (0.82-3.9)]. CONCLUSIONS: Higher doses of antibiotic prophylaxis did not decrease the rates of SSI after cesarean delivery.

Performance of Risk Assessment Models for Peripartum Thromboprophylaxis.

OBJECTIVE: There is no consensus on which risk stratification approach to use for thromboprophylaxis in pregnancy, and most available risk assessment models (RAMs) for venous thromboembolism (VTE) events have not been validated in pregnancy. Our objective was to compare the performance of some of the most commonly used VTEs RAMs in our patient population in the peripartum period. STUDY DESIGN: This is a retrospective cohort of women who delivered at our institution in 2015 and 2016. We excluded patients with history of prior or current VTEs or those already receiving anticoagulants. Antepartum, intrapartum, and postpartum records were reviewed. Data were collected on known risk factors for VTEs in order to calculate scores for 3 RAMs on admission for delivery: Padua, Caprini, and Royal College of Obstetricians and Gynaecologists (RCOG). The primary objective was to the estimate the performance of the various RAMs in preventing postpartum VTEs. We calculated the proportion of women who would have been high risk, determined the number of VTEs cases within high- and low-risk categories, as well as calculated the number needed to treat (NNT) for each RAM. We performed analyses using different RAM scores cutoffs, VTEs outcome rates, and effectiveness of anticoagulation to prevent VTEs. The P value <.05 was considered statistically significant. RESULTS: A total of 6094 women were included. Three women had VTEs for an overall rate of 0.04% (N = 3; 95% confidence interval [CI]: 0.01-0.15). The proportion of women categorized as high risk for VTEs were 62% (95% CI: 61-64) for RCOG, 0.8% (95% CI: 0.6-1.0) for Padua, and 94% (95% CI: 94-95) for Caprini. Of the 3 VTEs, the RCOG model classified 1 woman as high risk and Padua model classified 3 women as high risk; whereas the Caprini did not identify any women as high risk. Assuming 100% effectiveness of thromboprophylaxis, the observed NNT was 3838 using RCOG, not able to calculate using Padua (no VTEs cases occurred in the high-risk group, thus none were prevented), and 1927 using Caprini. CONCLUSION: The rates of VTEs in pregnancy are very low and the available RAMs do not identify most of them. The RCOG and Caprini RAMs would categorize a large proportion of women as high risk and are associated with high NNTs. The Padua RAM appears to have the lowest NNT but missed all the VTEs in our cohort.