A NOVEL PREGNANT RAT MODEL FOR LABOR INDUCTION AND AUGMENTATION WITH OXYTOCIN

Background: Despite the widespread use of oxytocin for induction of labor, mechanistic insights into maternal and neonatal wellbeing are lacking because of the absence of an animal model that recapitulates modern obstetric practice. Objective: The objectives of this research were to create and validate a hi-fidelity animal model that mirrors labor induction with oxytocin in parturients and to assess its translational utility. Study Design: The study was performed in timed-pregnant Sprague Dawley dams. The model consisted of a subcutaneously implanted microprocessor-controlled infusion pump on gestational day 18 that was pre-programmed to deliver an escalating dose of intravenous oxytocin on gestational day 21 to induce birth. Once predictable delivery of healthy pups was achieved, we validated the model with molecular biological experiments on the uterine myometrium and telemetry-supported assessment of changes in intrauterine pressure. Finally, we applied this model to test the hypothesis that labor induction with oxytocin was associated with oxidative stress in the newborn brain with a comprehensive array of biomarker assays and oxidative stress gene expression studies. Results: During the iterative model development phase, we confirmed the optimal gestational age for pump implantation, the concentration of oxytocin, and the rate of oxytocin administration. Exposure to anesthesia and surgery during pump implantation was not associated with significant changes in the cortical transcriptome. Activation of pump with oxytocin on gestational day 21 resulted in predictable delivery of pups within 8-12 hours. Increased frequency of change of oxytocin infusion rate was associated with dystocic labor. Labor induction and augmentation with oxytocin was associated with increased expression of the oxytocin receptor gene in the uterine myometrium, decreased expression of the oxytocin receptor protein on the myometrial cell membrane, and cyclical increases in intrauterine pressure. Examination of the frontal cortex of vaginally delivered newborn pups born after oxytocin-induced labor did not reveal an increase in oxidative stress compared to saline-treated control pups. Specifically, there were no significant changes in oxidative stress biomarkers involving both the oxidative stress (reactive oxygen/nitrogen species, 4-hydroxynonenal, protein carbonyl) and the antioxidant response (total glutathione, total antioxidant capacity). In addition, there were no significant differences in the expression of 16 genes emblematic of the oxidative stress response pathway. Conclusions: Collectively, we provide a viable and realistic animal model for labor induction and augmentation with oxytocin. We demonstrate its utility in addressing clinically relevant questions in obstetric practice that could not be mechanistically ascertained otherwise. Based on our findings, labor induction with oxytocin is not likely to cause oxidative stress in the fetal brain. Adoption of our model by other researchers would enable new lines of investigation related to the impact of perinatal oxytocin exposure on the mother-infant dyad.

Intraamniotic Infection Rates after Intrauterine Pressure Catheter with and without Amnioinfusion

Objective This study aimed to examine the rates of intraamniotic infection between intrauterine pressure catheter with amnioinfusion and intrauterine pressure catheter alone. Study Design This was a retrospective cohort study of all women who had an intrauterine pressure catheter placement during labor at a tertiary referral hospital from January 2016 to June 2018. Outcomes were compared between women who had an intrauterine pressure catheter with amnioinfusion and intrauterine pressure catheter placement alone. The primary outcome was the rate of intraamniotic infection. Secondary outcomes included postpartum endometritis, postpartum hemorrhage (blood loss of ≥1,000 mL), quantitative blood loss (mL), and cesarean delivery. Multivariable logistic regression analysis was performed to calculate adjusted odds ratios (aOR) and 95% confidence interval (95% CI), controlling for age, race, body mass index, gestational age, and length of time of rupture of membranes. Results Of 1,268 women with an intrauterine pressure catheter, 298 (23.5%) also had an amnioinfusion. Women who had amnioinfusion through an intrauterine pressure catheter compared with those who had intrauterine pressure catheter alone had similar rates of intraamniotic infection (5.4 vs. 8.0%, crude p = 0.12, aOR 0.69; 95% CI 0.39–1.21), as well as secondary outcomes such as postpartum endometritis (3.0 vs. 2.5%, crude p = 0.61, aOR 1.12; 95% CI 0.49–2.53), postpartum hemorrhage (16.1 vs. 15.8%, crude p = 0.89, aOR 1.07; 95% CI 0.75–1.54), blood loss (479.5 vs. 500 mL, adjusted p = 0.89), and cesarean delivery (40.6 vs. 43.1%, crude p = 0.45, aOR 0.90; 95% CI 0.68–1.19). Conclusion Amnioinfusion was not associated with increased odds of intraamniotic infection compared with intrauterine pressure catheter placement alone. Key Points

Amniodrainage-Induced Circulatory Dysfunction in Women Treated for Twin-To-Twin Transfusion Syndrome

Twin-to-twin transfusion syndrome (TTTS) in monochorionic-diamniotic twin pregnancies usually requires fetoscopic laser ablation (FLA) followed by amniodrainage (AD). Perioperative maternal hemodynamic changes and hemodilution have been observed. Little is known about the underlying pathophysiology. We aimed to evaluate the impact of high volume amniodrainage on intrauterine pressure, placental thickness and maternal blood characteristics. A total of 18 cases of TTTS were included in this prospective pilot study. All patients were treated with FLA and subsequent AD. Intrauterine pressure and placental thickness were assessed before, during and after amniodrainage. Maternal hemoglobin, hematocrit and serum albumin were measured at admission and 24 h after the intervention. Amniodrainage led to a decrease in mean intrauterine pressure (from 30.1 ± 8.1 mmHg to 17.6 ± 3.6 mmHg (p < 0.001)) and an increase in mean placental thickness (from 16.8 ± 6.4 mm to 31.83 ± 8.64 mm (p < 0.001)). There was a positive correlation between changes in placental thickness and the amount of amniodrainage during intervention (Pearson’s Rho 0.73; p = 0.001). Hematocrit decreased from 33.4 ± 3.8 (%) to 28.4 ± 3.5 (%), i.e., an increase in relative blood volume by 18 ± 10.2% (p < 0.001). Albumin decreased from 37.9 ± 0.9 g/L to 30.7 ± 2.2 g/L, i.e., an increase in relative plasma volume by 24 ± 8.1% (p < 0.001). Amniodrainage leads to uterine decompression, increased placental thickness and subsequent maternal hemodilution. We propose the term “amniodrainage-induced circulatory dysfunction” for these specific maternal hemodynamic changes in the treatment of twin-to-twin transfusion syndrome.

Intrauterine Pressure Catheter Use Is Associated with an Increased Risk of Postcesarean Surgical Site Infections

Objective This study aimed to determine if intrapartum placement of an intrauterine pressure catheter (IUPC) is associated with an increased rate of surgical site infections in women undergoing a cesarean delivery. Study Design This was a secondary analysis of the prospective observational Maternal–Fetal Medicine Units Network Vaginal Birth after Cesarean Registry. We compared patients with and without IUPC use. A multivariable logistic regression was performed to evaluate for an association between IUPC use and postcesarean surgical site infections. Results The study included 16,887 women: 7,441 with IUPC use and 9,446 without IUPC use. After adjustment for potential cofounders, IUPC use was associated with an increased risk of postcesarean infections compared with those without IUPC use (adjusted odds ratio: 1.28; 95% confidence interval: 1.10–1.50; p = 0.002). Conclusion IUPC use is associated with an increased risk of postcesarean surgical site infections. This supports the judicious use of IUPC for limited clinical indications and provides a potential area of focus for reduction in postcesarean infections.