Brian Brocato

Endocannabinoid crosstalk between placenta and maternal fat in a baboon model (Papio spp.) of obesity

INTRODUCTION Maternal obesity (MO) remains a serious obstetric problem with acute and chronic morbidities for both mothers and offspring. The mechanisms underlying these adverse consequences of MO remain unknown. Endocannabinoids (ECB) are neuromodulatory lipids released from adipocytes and other tissues. Metabolic crosstalk between placenta and adipocytes may mediate sequelae of MO. The goal of this study was to elucidate placental and systemic ECB in MO. MATERIAL AND METHODS Placentas, sera, and subcutaneous fat were collected at Cesarean sections performed near term (0.9 G) in four non-obese (nOB) and four obese (OB) baboons (Papio spp.). Concentrations of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured by liquid chromatography coupled to tandem mass spectrometry. AEA and 2-AG pathways were characterized in placentas by Q-RT-PCR, Western blot and immunohistochemistry. RESULTS Placental 2-AG levels were lower and maternal fat AEA levels were higher in OB (1254.1 ± 401.3 nmol/kg and 17.3 ± 4 nmol/kg) vs. nOB (3124.2 ± 557.3 nmol/kg and 3.1 ± 0.6 nmol/kg) animals. Concentrations of 2-AG correlated positively between maternal fat and placenta (r = 0.82, p = 0.013), but correlated negatively with maternal leptin concentrations (r = -0.72, p = 0.04 and r = -0.83, p = 0.01, respectively). CONCLUSION This is the first study to demonstrate differential ECB pathway regulation in maternal fat and placenta in MO. Differential regulation and function exist for AEA and 2-AG as the major ECB pathways in placenta.

The Effect of Cesarean Delivery Skin Incision Approach in Morbidly Obese Women on the Rate of Classical Hysterotomy

Objective. To assess the risk of classical hysterotomy and surgical morbidity among women with a body mass index (BMI) greater than 40 kg/m2 who underwent a supraumbilical incision at the time of cesarean delivery. Methods. We conducted a retrospective cohort study in women having a BMI greater than 40 kg/m2 who underwent a cesarean delivery of a live, singleton pregnancy from 2007 to 2011 at a single tertiary care institution. Intraoperative and postoperative outcomes were compared between patients undergoing supraumbilical vertical (cohort, n = 45) or Pfannenstiel (controls, n = 90) skin incisions. Results. Women undergoing supraumbilical incisions had a higher risk of classical hysterotomy (OR, 24.6; 95% CI, 9.0–66.8), surgical drain placement (OR, 6.5; 95% CI, 2.6–16.2), estimated blood loss greater than 1 liter (OR, 3.4; 95% CI, 1.4–8.4), and longer operative time (97 ± 38 minutes versus 68 ± 30 minutes; P < .001) when compared to subjects with Pfannenstiel incisions (controls). There was no difference in the risk of wound complication between women undergoing supraumbilical or Pfannenstiel incisions (OR, 2.7; 95% CI, 0.9–8.0). Conclusion. In women with a BMI above 40 kg/m2, supraumbilical incision at the time of cesarean delivery is associated with a greater risk of classical hysterotomy and operative morbidity.

A Novel Translational Model of Percutaneous Fetoscopic Endoluminal Tracheal Occlusion - Baboons (Papio spp.)

Introduction: Percutaneous fetoscopic endoluminal reversible tracheal occlusion (FETO) was developed to prevent the pulmonary complications of fetal congenital diaphragmatic herniation. There is an urgent need to establish the closest to human translational model of FETO in order to improve fetal outcomes and to determine new clinical approaches and applications. Material and Methods: Seven non-human primates underwent two subsequent surgeries: the first, the FETO in the experimental group (n = 3) or sham operation in the control animals (S-FETO, n = 4) at 132-142 days of gestation (dGA); the second, the reversal of occlusion or sham operation at 162 ± 5 dGA. Maternal stress axis, complete blood count, and biochemical parameters were evaluated and newborn tracheal radiography was performed. Results: The average pregnancy duration and neonatal weights in the FETO group did not differ from the animals in the S-FETO group. There was no bleeding or premature fetal membrane rupture during the procedures in any of the baboons. The maximal tracheal width was 7.02 ± 0.6 mm in the FETO versus 5.46 ± 0.6 mm in S-FETO group. Discussion: This is the very first report of a successful FETO model in non-human primates. Similarities to human tracheomegaly were for the first time documented in any model studied.

195: Critical enzymes for endocannabinoid metabolism in a baboon model of maternal obesity

baboon model of maternal obesity Brian Brocato, Zorica Janjetovich, Andrzej Slominski, Mari Giancarlo, Gene Hubbard, Edward Dick University of TN Health Science Center, Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Memphis, TN, University of TN Health Science Center, Pathology, Memphis, TN, University of Texas Health Science Center at San Antonio, Pathology, San Antonio, TX, Texas Biomedical Research Institute, Pathology, San Antonio, TX OBJECTIVE: Maternal obesity is a risk factor for adverse fetal outcomes including fetal loss and abnormal growth. It has been suggested that the increase in endocannabinoid (ECB) system tone found in obesity may cause early fetal loss. We hypothesized that expression of ECB degrading enzymes (FAAH, MAGL and DAGL) will be altered in placentas of obese baboons. STUDY DESIGN: Four obese and four non-obese baboons (Papio spp) were studied as previously described. Placenta was retrieved during C-section and was flashfrozen and stored at 80°. RNA was isolated using Trizol. 5 g RNA was used for cDNA synthesis (Roche, Basel Switzerland). Primate specific primers and TagMan probes (Roche Universal probes library) were used for Real-time PCR performed on a Roche Light Cycler 480. The amounts were compared to a reference gene ( actin) using a comparative CT method. All reactions were performed in triplicate with the appropriate controls. Relative gene expression data were calculated using Ct method. Data are expressed as mean SEM. Two-tailed t-Student test was used to compare the variables; p 0.05 was considered significant. RESULTS: There were no differences in the relative expression of gene transcripts between obese and non-obese animals. The expression of FAAH was 0.55 0.1 in obese (Ob) vs. 0.76 0.2 in non-obese (nOb) animals, DAGL 0.69 0.2 (Ob) vs. 0.75 0.04 (nOb) and MAGL 5.9 0.9 (Ob) vs. 5.62 0.4 (nOb). CONCLUSION: This is the first report regarding the expression of ECB enzyme gene transcripts in term non-human primate placentas. The detected 38% decrease in FAAH expression seen in the placenta of obese baboons was not statistically significant. Further studies are necessary to determine whether placental ECB metabolizing enzymes might serve as a potential target for intervention to possibly improve poor fetal outcomes associated with maternal obesity.

The Effect on Latency Beyond 24 Weeks of Gestation Based on Cerclage Indication

INTRODUCTION: Cervical insufficiency is characterized by recurrent painless cervical dilation and spontaneous midtrimester delivery. Diagnosis is clinical and retrospective, often ending in poor obstetric outcomes. Management involves cerclage, which is placed based on history of recurrent spontaneous preterm birth or midtrimester loss. Other indications are evidence of cervical shortening and midtrimester dilation determined by sonographic or physical examination. Although previous studies demonstrate the benefits of history-indicated cerclages, there are few studies defining outcomes of ultrasound examination–indicated and physical examination–indicated cerclages as compared with history-indicated cerclages. METHODS: We reviewed records of patients undergoing cerclage at a single center between January 1, 2008 and January 1, 2013. Cases consisted of women with ultrasound examination–indicated or physical examination–indicated cerclages and women in a control group compromised women with history-indicated cerclages. The primary outcome measured was latency beyond 24 weeks of gestation. Statistical analysis was done using commercially available software. Categorical variables were analyzed using &khgr;2 test and continuous variables were analyzed using Students t test or Fishers exact test where appropriate. P=.05 was considered significant. RESULTS: Sixty patients were included. There were no differences in maternal demographics among the women in the case group and those in the control group. The women in the control group were more likely to have had a cerclage in a prior pregnancy. Mean latency beyond 24 weeks of gestation in women in the case group and those in the control group was 7 and 8 weeks, respectively (P=.49). CONCLUSIONS: In pregnancies that reach 24 weeks of gestation, there is no difference in latency between those with history-indicated cerclages and ultrasound examination–indicated or physical examination–indicated cerclages. This information can be used to better counsel women with cervical insufficiency on expected outcomes.

Cardiovascular changes in IUGR

Despite a plethora of publications existing in the literature, there is still confusion about the definition and management of intrauterine growth-restricted fetuses. A second source of confusion lies in the fundamental misunderstanding that all growth-restricted fetuses are the same and all will progress to cardiovascular failure following a similar time frame. Once intrauterine growth restriction is identified, obstetrical management is focused on assuring safety while the fetus continues to mature within a potentially hostile intrauterine environment. In the United States, the approach to management and delivery of the premature growth-restricted fetus is often based on serial biophysical profile evaluations, whereas in Europe it is usually based on the result of the cardiotocography. However, there is no single test that seems superior to the other available tests for timing the delivery of the growth-restricted fetus. Therefore, the decision to deliver a fetus, especially at <32 weeks, remains mostly on the basis of empirical management. The staging system may allow comparison of outcome data for IUGR fetuses and may be valuable in determining more timely delivery for these high-risk fetuses. Most investigators agree that Doppler ultrasonography of the umbilical artery and the middle cerebral arteries, in combination with biometry provides the best tool to identify small fetuses at risk for adverse outcomes. The umbilical artery and the middle cerebral artery are the two vessels that have been extensively studied. Recent studies have looked into the analysis of the fetal venous system and the association between changes in this system with the fetal outcome.