A Broad-Spectrum Chemokine Inhibitor Blocks Inflammation-Induced Myometrial Myocyte–Macrophage Crosstalk and Myometrial Contraction

Prophylactic administration of the broad-spectrum chemokine inhibitor (BSCI) FX125L has been shown to suppress uterine contraction, prevent preterm birth (PTB) induced by Group B Streptococcus in nonhuman primates, and inhibit uterine cytokine/chemokine expression in a murine model of bacterial endotoxin (LPS)-induced PTB. This study aimed to determine the mechanism(s) of BSCI action on human myometrial smooth muscle cells. We hypothesized that BSCI prevents infection-induced contraction of uterine myocytes by inhibiting the secretion of pro-inflammatory cytokines, the expression of contraction-associated proteins and disruption of myocyte interaction with tissue macrophages. Myometrial biopsies and peripheral blood were collected from women at term (not in labour) undergoing an elective caesarean section. Myocytes were isolated and treated with LPS with/out BSCI; conditioned media was collected; cytokine secretion was analyzed by ELISA; and protein expression was detected by immunoblotting and immunocytochemistry. Functional gap junction formation was assessed by parachute assay. Collagen lattices were used to examine myocyte contraction with/out blood-derived macrophages and BSCI. We found that BSCI inhibited (1) LPS-induced activation of transcription factor NF-kB; (2) secretion of chemokines (MCP-1/CCL2 and IL-8/CXCL8); (3) Connexin43-mediated intercellular connectivity, thereby preventing myocyte–macrophage crosstalk; and (4) myocyte contraction. BSCI represents novel therapeutics for prevention of inflammation-induced PTB in women.

EHG-Based Preterm Delivery Prediction Algorithm Driven by Transfer Learning

Preterm delivery is currently a global concern of maternal and child health, which directly affects infants’ early morbidity, and even death in several severe cases. Therefore, it is particularly important to effectively monitor the uterine contraction of perinatal pregnant women, and to make effective prediction and timely treatment for the possibility of preterm delivery. Electromyography (EHG) signal, an important measurement to predict preterm delivery in clinical practice, shows obvious consistency and correlation with the frequency and intensity of uterine contraction. This paper proposed a deep convolution neural network (DCNN) model based on transfer learning. Specifically, it is based on the VGGNet model, combined with recurrence plot (RP) analysis and transfer learning techniques such as “Fine-tune”, marked as VGGNet19-I3. Optimized with the clinical measured term-preterm EHG database, it showed good auxiliary prediction performances in 78 training and test samples, and achieved a high accuracy of 97.00% in 100 validation samples.

PERFORMANCE OF A MATERNAL ABDOMINAL SURFACE ELECTRODE SYSTEM FOR FETAL HEART RATE AND UTERINE CONTRACTION MONITORING FROM 34-37 WEEKS

Objective: Compare performance of a maternal surface electrode patch with ultrasound- and tocodynamometer-based monitoring to detect fetal heart rate and uterine contractility in late preterm labors. Study design: Thirty women between 340/7 and 366/7 weeks’ gestation were monitored simultaneously with a Doppler/tocodynamometer system and a wireless fetal-maternal abdominal surface electrode system. Fetal and maternal heart rate and uterine contraction data from both systems were compared. Reliability was measured by the success rate and percent agreement. Deming regression and Bland-Altman analysis estimated the concordance between the systems. Uterine contractions were assessed by visual interpretation of monitor tracings. Results: The success rate for the surface electrode system was 89.5 (95% CI 85.7,93.3)% and for ultrasound 88.4 (84.9,91.9)%; p=0.73, with a percent agreement of 88.1 (84.2,92.8)%. Results were uninfluenced by the subjects’ body mass. The mean Deming slope was 1.0 and the y-intercept -3.0 bpm. Bland-Altman plots also showed a close relationship between the methods, with limits of agreement <10 bpm. The percent agreement for maternal heart rate was 98.2 (97.4,98.8)% and for uterine contraction detection was 89.5 (85.5,93.4)%. Conclusions: Fetal heart rate and uterine contraction monitoring at 34-366/7 weeks using abdominal surface electrodes was not inferior to Doppler ultrasound-tocodynamometry for fetal-maternal assessment. Registration: clinicaltrials.gov/February 20, 2017/ Identifier NCT03057275

Programmed intermittent epidural bolus in comparison with continuous epidural infusion for uterine contraction pain relief after caesarean section: a randomised, double-blind clinical trial

Objective Programmed intermittent epidural bolus (PIEB) was reported to provide superior maintenance of labour analgesia with better pain relief, and less motor block than continuous epidural infusion (CEI). Whether this is also evident for uterine contraction pain relief after caesarean section remains unknown. Design Randomised, double blind, positive-control trial. Setting Guangzhou Women and Children’s Medical Center, China Population Parturients scheduled for elective caesarean section under combined spinal-epidural anaesthesia were enrolled. Methods At the end of the surgery, after a similar epidural loading dose given, patients received either PIEB (6 mL every hour) or CEI (6 mL/h) of 0.1% ropivacaine. Main outcome measures The primary outcome was the effectiveness of uterine contraction pain relief during breastfeeding assessed with visual analog scale score (VAS-UD) at the postoperative 36 h. Secondary main outcome was lower extremity motor block (defined as Bromage score > 0). Results One hundred and twenty parturients were studied (PIEB, 60; CEI, 60). The VAS-UD at the postoperative 36 h was significantly lower in the PIEB group than in the CEI group [median (IQR), 30 (20 to 40) mm] compared with the CEI group [40 (30 to 50) mm], with an estimated difference of -10 mm (95% CI -15 to -5 mm; P=0.001). Motor block was higher in the CEI group than in the PIEB group during the study period except 2 h (all P<0.05). Conclusions PIEB provides more effective uterine contraction pain relief and less motor block after caesarean section than CEI.

The Effect of Citral on Aquaporin 5 and Trpv4 Expressions and Uterine Contraction in Rat—An Alternative Mechanism

Aquaporins (AQPs) are expressed in the uterus, playing a physiological role during pregnancy. An osmotic pathway—through AQP5—may modify the transient potential vanilloid 4 (TRPV4) function and uterine contraction. Our aim was to determine the role of TRPV4 antagonist citral in the regulation of pregnant uterine contraction. In vitro uterine contractions were evoked by KCl and the response was modified with citral. The expressions of TRPV4 and AQP5 were measured by RT-PCR and Western blot techniques. The lengths of gestational periods were determined in normal and LPS-induced preterm births after citral treatment, in vivo. Citral significantly decreased the uterine contraction on day 22 of pregnancy. AQP5 expression significantly increased after citral incubation; however, TRPV4 expression did not show significant changes. After citral pretreatment, the gestational period was extended both in normal and LPS-induced preterm births. Our results suppose that the downregulation of AQP5 may initiate hypertonic stress, activating TRPV4 the uterine contraction on the last day of the gestational period. The putative cooperation between AQP5 and TRPV4 may open a novel target to treat or prevent preterm birth.

Efficacy of intravenous flurbiprofen axetil with epidural analgesia for post-cesarean section analgesia: a multi-center, prospective, randomized, blinded trial

BackgroundEpidural analgesia provided satisfactory analgesic effects of incision pain after cesarean section. However, uterine contraction pain is also a common complication that cannot be relieved despite adequate levels of sensory blockade by epidural analgesia. This study evaluates the effect of flurbiprofen axetil with patient-controlled epidural analgesia on incision pain and uterine contraction pain after cesarean section.MethodsA multi-center, prospective, randomized, blinded trial was performed. 1000 obstetric patients scheduled for cesarean delivery were randomized to receive epidural analgesia with intravenous flurbiprofen axetil (group EF) or placebo (group E) postoperatively. The primary outcomes were incision pain and uterine contraction pain score 48 hours after a cesarean section. Secondary outcomes were the PCEA attempts, the incidence of complication, satisfaction scores, and return of gastrointestinal (GI) function.ResultsBaseline characteristics were similar between groups. The VAS of uterine contraction pain was significantly lower in group EF than in group E from 12 hours to 48 hours after cesarean delivery (P < 0.01). The VAS of incision pain at rest and on movement was lower in group EF than in group E from 12 hours to 48 hours after cesarean delivery. While sitting or walking, the VAS of incision pain was lower in group EF compared with that in group E. GI function recovered faster in group EF than that in group E (15 ± 6 vs. 25 ± 12, 95%CI 5.7 to 8.7, P < 0.01). The satisfaction scores are higher in group EF than that in group E (3.2 ± 0.5 vs. 2.9 ± 0.5, 95%CI -0.36 to -0.11, P < 0.01).ConclusionCombination flurbiprofen axetil with PCEA provides more effective analgesia for uterine contraction pain and incision pain after cesarean section, with a higher quality of recovery and better satisfaction scores.Trials RegistrationThis study was approved by the Institutional Review Board of Guangzhou Women and Children’s Medical Center (IRB2017062201) and written informed consent was obtained from his or her parents or legal guardians for each pediatric patient in the trial. The trial was registered before patient enrollment at chictr.org.cn (ChiCTR-IOR-17011956, Principal investigator: Ying-Jun She, Date of registration: 2017.07.12). Written informed consent was obtained from patients in the study.

Various modalities of induction of labour and its feto-maternal outcomes: An observational study

: In order for induction to be successful, it should result in labour with adequate uterine contraction and progressive dilatation of cervix with the outcome of a vaginal delivery with minimal risk to both mother and foetus. Primary outcome of the current study was to compare various modalities of Induction of Labour, alone or in combination & to evaluate the different outcomes of mother and baby.: History, general, obstetrical, vaginal examination to record Modified Bishop score, basic investigations and recent obstetric ultrasound was noted of 200 pregnant mothers and the results were analyzed. Foetal monitoring was done in all except those with confirmed IUFD cases. Methods used were Dinoprostone, Misoprostol, Oxytocin, Amniotomy and Mechanical Dilatation with Foley’s catheter; single or in combination with each other.: Among the 200 mothers, 118(59%) delivered vaginally and 82 (41%) mothers underwent LSCS. Dinoprostone gel was the dominant method used followed by misoprostol and oxytocin respectively. NICU admissions were required in 21.7%, 25,8% & 33.3% of the mothers who were induced with Dinoprostone, Misoprostol and Oxytocin respectively. 14 babies were diagnosed with IUFD, all delivered vaginally, out of which 10 were induced with misoprostol and 4 were induced with mechanical dilatation. Majority of the patients who underwent induction with dinoprostone alone delivered by LSCS (63.4%) but Dinoprostone with ARM & oxytocin for induction had a better outcome. Induction with Dinoprostone followed by misoprostol lead to more LSCS than SVD and there were 1%(2 babies) of perinatal mortality due to Meconium Aspiration Syndrome.: Misoprostol and Mechanical induction were the most preferred method in cases of IUFD. Induction with a combination of Dinoprostone with ARM or Oxytocin lead to more vaginal delivery than Dinoprostone alone, so this should be preferred. Induction with Dinoprostone followed by misoprostol lead to more LSCS and perinatal mortality so a combination of them should be given cautiously.

Practical guidance on the use of uterine contraction and haemostatic agents

Practical instructions regarding the use of agents that reduce the uterus and hemostatic are given by Strata (Zntrb. F. G., 1924, No. 1-2) on the basis of his long-term observations.