Mauro Schenone

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 MCA Doppler and its Role in the Evaluation of Fetal Anemia and Fetal Growth Restriction

Doppler velocimetry of the middle cerebral artery (MCA) has played a major role in fetal medicine for the last 23 years, both in intrauterine growth-restricted (IUGR) and anemic fetuses. Its utility in the diagnosis and management of cases of fetal anemia was initially demonstrated in cases of red cell alloimmunization and later extended to other types of anemia. In addition, MCA Doppler studies are crucial in the evaluation of IUGR fetuses. This article is a review of the role of the MCA in these 2 conditions.

Prediction of neonatal respiratory morbidity by quantitative ultrasound lung texture analysis: a multicenter study

BACKGROUND: Prediction of neonatal respiratory morbidity may be useful to plan delivery in complicated pregnancies. The limited predictive performance of the current diagnostic tests together with the risks of an invasive procedure restricts the use of fetal lung maturity assessment. OBJECTIVE: The objective of the study was to evaluate the performance of quantitative ultrasound texture analysis of the fetal lung (quantusFLM) to predict neonatal respiratory morbidity in preterm and early‐term (<39.0 weeks) deliveries. STUDY DESIGN: This was a prospective multicenter study conducted in 20 centers worldwide. Fetal lung ultrasound images were obtained at 25.0–38.6 weeks of gestation within 48 hours of delivery, stored in Digital Imaging and Communication in Medicine format, and analyzed with quantusFLM. Physicians were blinded to the analysis. At delivery, perinatal outcomes and the occurrence of neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, were registered. The performance of the ultrasound texture analysis test to predict neonatal respiratory morbidity was evaluated. RESULTS: A total of 883 images were collected, but 17.3% were discarded because of poor image quality or exclusion criteria, leaving 730 observations for the final analysis. The prevalence of neonatal respiratory morbidity was 13.8% (101 of 730). The quantusFLM predicted neonatal respiratory morbidity with a sensitivity, specificity, positive and negative predictive values of 74.3% (75 of 101), 88.6% (557 of 629), 51.0% (75 of 147), and 95.5% (557 of 583), respectively. Accuracy was 86.5% (632 of 730) and positive and negative likelihood ratios were 6.5 and 0.3, respectively. CONCLUSION: The quantusFLM predicted neonatal respiratory morbidity with an accuracy similar to that previously reported for other tests with the advantage of being a noninvasive technique.

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.

Predicting Fetal Lung Maturity Using the Fetal Pulmonary Artery Doppler Wave Acceleration/Ejection Time Ratio

Objective: To determine whether the acceleration/ejection time ratio of the fetal main pulmonary artery Doppler waveform (PATET) can accurately predict the results of fetal lung maturity testing in amniotic fluid. Methods: We prospectively studied pregnant women attending our ultrasound unit for clinically indicated fetal lung maturity testing. An ultrasound examination that included measurement of the PATET was performed before the results of the amniocentesis were reported. The results of the PATET and the surfactant/albumin ratio were compared, and a receiver operating characteristic curve was used to determine the PATET cutoff with the optimal sensitivity and specificity for predicting surfactant/albumin ratio results. p < 0.05 was considered statistically significant. Results: Forty-three patients were included in this study. The receiver operating characteristic curve demonstrated that a PATET cutoff of 0.3149 provided a specificity of 93% (95% CI 77-98%), a sensitivity of 73% (95% CI 48-89%), a negative predictive value of 87% (95% CI 70-95%), and a positive predictive value of 85% (95% CI 58-96%) for predicting immature surfactant/albumin ratio results. Conclusion: The PATET may provide a noninvasive means of determining fetal lung maturity with acceptable levels of sensitivity, specificity, and predictive values.

Abruptio placentae in the baboon (Papio spp.)

INTRODUCTION Placental abruption is a serious condition that increases perinatal morbidity and mortality. Clinical prevention and treatment options are limited, especially in human preterm deliveries. Knowledge of the mechanisms that keep the placenta in place during pregnancy is critical for developing strategies for the prevention of abruption. Failure of physiological transformation of spiral arteries has been described as a major contributing factor of the placental abruption development. Baboons (Papio spp.) share striking similarities with humans in regard to placental structure, utero-placental blood flow, and fetal development; however, the mode of trophoblast invasion is shallow in baboons. This fact prompted the hypothesis that the incidence of placental abruption will be increased in baboons compared to humans. MATERIAL AND METHODS Baboon placentas were collected between 2002 and 2008. Two independent veterinary pathologists evaluated the slides. A certified physician pathologist performed additional histology. RESULTS Placental abruption was diagnosed in 22 baboons among 2423 live births during the study period (0.9% prevalence). The most common clinical presentations were fetal demise and vaginal bleeding. The most common pathological findings were intraplacental hemorrhages with or without hematoma formation (86.4%). Other findings consisted of neutrophil infiltration (50%), decidual necrosis (22.7%), decidual vascular congestion and inflammation, villous congestion and retroplacental hemorrhage/hematoma (each 18.2%). These pathologic findings were the same for term and preterm deliveries. CONCLUSION This is the first systematic study of placental abruption in non-human primates, analyzing a large colony of baboons. Despite differences in trophoblast invasion, the clinical features observed in placental abruption affecting baboons resembled those reported in humans. The cluster of placental pathological findings in baboons also agreed with clinical reports, but the prevalence of these findings differed between baboons and humans. We discuss a mechanism of anti-abruption forces that offset shallow trophoblast invasion observed in baboons.

Technique for bilateral salpingectomy at the time of Cesarean delivery: a case series

The American Congress of Obstetricians and Gynecologists and the Society of Gynecologic Oncology endorse bilateral salpingectomy for ovarian cancer prevention. We describe a bilateral salpingectomy technique in 23 patients during Cesarean delivery. Operative time, hospital length of stay and complications are reported. Bilateral salpingectomy during Cesarean delivery appears feasible.

Eclampsia Characteristics and Outcomes: A Comparison of Two Eras

Objective. To describe the trends in incidence, characteristics, and outcomes of women with eclampsia. Methods. We reviewed and abstracted data from medical records of all women diagnosed with eclampsia in our institution from August 1998 to April 2011. In addition to overall characteristics and outcomes, the cases were stratified by onset: antenatal versus postnatal and early (<32 weeks of gestation) versus late antenatal cases (≥32 weeks of gestation). Comparisons were made using chi-square, Fishers exact, Mann-Whitney U, and t-tests. A two-sided P < 0.05 was considered statistically significant. Results. We identified 87 eclampsia cases out of 59,388 deliveries; 62 cases were diagnosed before delivery, and 25 had a postnatal onset. Among the 62 antenatal cases, 41 were diagnosed before 32 weeks and 21 at or after 32 weeks of gestation. Antenatal cases had higher systolic (P = 0.03) and diastolic (P = 0.01) blood pressures, more abnormal dipstick-test proteinuria (P = 0.002), and lower platelet counts (P ≤ 0.001) than postnatal cases. Early eclampsia cases were complicated more often with HELLP syndrome than late eclampsia cases (P = 0.007). Conclusion. The occurrence of eclampsia has decreased over time. The earlier the onset is, the worse the outcome appears to be.

Effects of selective reduced uterine perfusion pressure in pregnant rats.

INTRODUCTION To assess the effects of selective reduced uterine perfusion pressure (SRUPP) in pregnant rats. METHODS 20 pregnant Sprague-Dawley rats were allocated either to an intervention group, exposed to SRUPP (n = 10) or a control group, exposed to sham surgery (n = 10). Such procedures were performed on gestational day (GD) 14. The Mean arterial pressure (MAP) was measured on GD14 (before surgery) and GD20. We measured 18 h proteinuria on GD20. On GD21, mean fetal (MFW) and placental (MPW) weights were obtained. Oxidative stress and angiogenic markers were measured in placental tissue and urine. Mann Whitney U or Independent samples T test were used when appropriate. A two-sided P < 0.05 indicated statistical significance. RESULTS MAP on GD20 was higher in the intervention group (109 ± 1.7 mmHg) when compared with the control group (83 ± 1.5 mmHg) (P = 0.002). There was no significant difference in urinary protein excretion (117 ± 3.1 mg/24 h versus 136 mg ± 2.8/24 h, P = 0.18), MFW (4.14 ± 0.05 versus 4.39 ± 0.04 g, P = 0.19) or MPW (0.43 ± 0.008 versus 0.44 ± 0.006 g, P = 0.73) between the intervention and the control groups, respectively. The oxidative stress was increased; whereas, the sFLT1 expression was not increased when the SRUPP group was compared with controls. DISCUSSION SRUPP is associated with an increase in maternal MAP and oxidative stress and therefore it may become a useful tool in the study of pregnancy-related hypertensive disorders.

Parturition in baboons (PAPIO SPP.)

The Old World non-human primates (NHP) - baboons (Papio spp.) share similarities with humans regarding fetal and placental development and some pregnancy-related complications. Information about the mechanism of birth and complications arising during parturition in these species is relatively sparse. In this manuscript, we add information from a series of pathological and observational cases to highlight insights and selected complications of birth in Papio spp, based on video-recording of the delivery process, X-ray, MRI, and ultrasound evaluations in pregnant baboons. Additionally, we abstracted pathology records obtained from perinatal loss in a large baboon colony during a 17 year period. The presented cases provide important information for the management of pregnancy and delivery in Papio spp.