Multimodal Pain Management for Cesarean Delivery: A Double-Blinded, Placebo-Controlled, Randomized Clinical Trial.

OBJECTIVE: Our objective was to evaluate the efficacy of perioperative multimodal pain management in reducing opioid use after elective cesarean delivery (CD). STUDY DESIGN: A single-center, double-blinded, placebo-controlled randomized trial of women undergoing elective CD. Participants were allocated 1:1 to receive the multimodal protocol or matching placebos. The multimodal protocol consisted of a preoperative dose of intravenous acetaminophen, preincision injection of subcutaneous bupivacaine, and intraoperative injection of intramuscular ketorolac. Primary outcome was total opioid intake at 48 hours postoperatively. Secondary outcomes were pain scores, time to first opioid intake, neonatal outcomes, and total outpatient opioid intake on postoperative day (POD) 7. Data were analyzed using parametric and nonparametric tests and quantile regression as appropriate. RESULTS: A total of 242 women were screened with 120 randomized, 60 to the multimodal group and 60 to control group. There was no significant difference in the primary outcome of opioid use nor in the secondary outcomes. Smokers and patients with a history of drug use had higher median postoperative opiate use and earlier administration. On POD 7, only 40% of prescribed opioids had been used, and there was no difference between the groups. CONCLUSION: This perioperative multimodal pain regimen did not reduce opioid use in 48 hours after CD. Patients who smoke or with a history of drug use required more opioids in the postoperative period. Providers significantly overprescribed opioids after CD.

Maternal obesity is associated with chorioamnionitis and earlier indicated preterm delivery among expectantly managed women with preterm premature rupture of membranes.

OBJECTIVE: To determine the association between maternal obesity and delivery due to chorioamnionitis prior to labor onset, among expectantly managed women with preterm premature rupture of membranes (pPROM). METHODS: This was a secondary analysis of a multicenter randomized trial of magnesium sulfate versus placebo to prevent cerebral palsy or death among offspring of women with anticipated delivery at 24-31-week gestation. After univariable analysis, Cox proportional hazard evaluated the association between maternal obesity and chorioamnionitis, while Laplace regression investigated how obesity affects the gestational age at delivery of the first 20% of women developing the outcome of interest. RESULTS: A total of 164 of the 1942 women with pPROM developed chorioamnionitis prior to labor onset. Obese women had a 60% increased hazard of developing such complication (adjusted HR 1.6, 95%CI 1.1-2.1, p = .008), prompting delivery 1.5 weeks earlier, as the 20th survival percentile was 27.2-week gestation (95%CI 26-28.6) among obese as opposed to 28.8 weeks (95%CI 27.4-30.1) (p = .002) among nonobese women. CONCLUSIONS: Maternal obesity is a risk factor for chorioamnionitis prior to labor onset. Future studies will determine if obesity is important enough to change the management of latency after pPROM according to maternal BMI.

Amnion epithelial cell-derived exosomes induce inflammatory changes in uterine cells.

BACKGROUND: Fetal endocrine signals are generally considered to contribute to the timing of birth and the initiation of labor. Fetal tissues under oxidative stress release inflammatory mediators that lead to sterile inflammation within the maternal-fetal interface. Importantly, these inflammatory mediators are packaged into exosomes, bioactive cell-derived extra cellular vesicles that function as vectors and transport them from the fetal side to the uterine tissues where they deposit their cargo into target cells enhancing uterine inflammatory load. This exosome-mediated signaling is a novel mechanism for fetal-maternal communication. OBJECTIVE: This report tested the hypothesis that oxidative stress can induce fetal amnion cells to produce exosomes, which function as a paracrine intermediary between the fetus and mother and biochemically signal readiness for parturition. STUDY DESIGN: Primary amnion epithelial cells were grown in normal cell culture (control) or exposed to oxidative stress conditions (induced by cigarette smoke extract). Exosomes were isolated from cell supernatant by sequential ultracentrifugation. Exosomes were quantified and characterized based on size, shape, and biochemical markers. Myometrial, decidual, and placental cells (BeWo) were treated with 2 × 105, 2 × 107, and 2 × 109 control or oxidative stress-derived amnion epithelial cell exosomes for 24 hours. Entry of amnion epithelial cell exosomes into cells was confirmed by confocal microscopy of fluorescent-labeled exosomes. The effect of amnion epithelial cell exosomes on target cell inflammatory status was determined by measuring production of interleukin-6, interleukin-8, interleukin-1ß, tumor necrosis factor-α, and prostaglandin E2 by enzyme-linked immunosorbent assay and inflammatory gene transcription factor (nuclear factor-κß) activation status by immunoblotting for phosphorylated RelA/p65. Localization of NANOG in term human myometrium and decidua obtained from women before labor and during labor was performed using immunohistochemistry. Data were analyzed by Wilcoxon-Mann-Whitney test to compare effects of exosomes from control and oxidative stress-treated amnion epithelial cells on inflammatory status of target cells. RESULTS: Amnion epithelial cells released ∼125 nm, cup-shaped exosomes with ∼899 and 1211 exosomes released per cell from control and oxidative stress-induced cells, respectively. Amnion epithelial cell exosomes were detected in each target cell type after treatment using confocal microscopy. Treatment with amnion epithelial cell exosomes increased secretion of interleukin-6, interleukin-8, and PGE2 and activation of NF-κß (each P < .05) in myometrial and decidual cells. Exosome treatments had no effect on interleukin-6 and PGE2 production in BeWo cells. NANOG staining was higher in term labor myometrium and decidua compared to tissues not in labor. CONCLUSION: In vitro, amnion epithelial cell exosomes lead to an increased inflammatory response in maternal uterine cells whereas placental cells showed refractoriness. Fetal cell exosomes may function to signal parturition by increasing maternal gestational cell inflammation.

Gestational tissue inflammatory biomarkers at term labor: A systematic review of literature.

Parturition at term is characterized by inflammatory overload in both feto-maternal tissues. Despite the large number of individual studies on changes in inflammatory biomarkers linked to labor, a comprehensive profile of them in each of the uterine compartments is not available to better understand their mechanistic contributions to labor. This systematic review investigated the pro- and anti-inflammatory biomarkers reported in intra-uterine tissues (amnion, chorion, decidua, placenta, and myometrium) at term labor. We conducted a systematic review of studies on pro- and anti-inflammatory biomarkers (mRNA and/or protein) reported in feto-maternal tissues during normal human term labor, published in English (1980-2016), in 3 electronic data bases. From a total of 3712 citations, 172 were included for final review. Each tissue expresses a unique set of biomarkers at the time of term labor, but there is significant overlap between tissues. All tissues had IL-6, IL-8, IL-1ß, COX-2, PGE-2, TNF-α, and hCAP18 in common at term labor. Common and unique inflammatory biomarkers are expressed in various feto-maternal compartments at term labor. Increase in pro-inflammatory markers in all gestational tissue signifies their harmonious functional role in promoting labor. Anti-inflammatory markers at term labor are hardly reported.

Differences in Women Who Choose Subdermal Implants Versus Intrauterine Devices.

Objective: To determine if there are any differences in the patient populations that choose subdermal implants versus intrauterine devices (IUDs) for contraceptive purposes. Study Design: Retrospective chart review. Electronic medical records of women who presented to the University of Texas Medical Branch in Galveston's Regional Maternal Child Health Program Clinics in southeast Texas from March 2011 to March 2013 and received a subdermal implant or IUD were reviewed. Differences in characteristics of women who chose either form of contraception were determined. Results: A total of 356 charts were reviewed. Of those, 188 (53%) women chose the subdermal implant and 168 (47%) chose an IUD. Patients who chose subdermal implants were more likely to have had a long-acting reversible contraceptive (LARC) method previously (p<0.01), previous vaginal deliveries (p<0.001), and an interval from delivery to LARC placement of >1 year (p<0.001). LARC choice was race-specific in that, when compared to Caucasian women, African-American women were significantly more likely to choose an IUD, while Hispanic women were significantly more likely to choose subdermal implants (p=0.002). Conclusion: Different populations choose subdermal implants versus IUDs for contraception. Further research is needed to determine etiologies for these differences.