Gut microbial communities are critical players in the pathogenesis of obesity. Pregnancy is associated with increased bacterial load and changes in gut bacterial diversity. Sparse data exist regarding composition of gut microbial communities in obesity combined with pregnancy.

ABSTRACT Psychological flexibility, a complex concept encompassing both acceptance and action related factors, has been identified as a target for intervention for diabetes management. Research suggests acceptance, self-management, and stress, all factors that influence psychological flexibility, have an impact on adaptation to type 1 diabetes (T1D) by youth independently. However, yet to be explored is individually varying patterns of these variables and how they may relate to diabetes adaptation outcomes. The present study aimed to establish individual variations of patterns of these factors to derive profiles of psychological flexibility, and examine their relations to the adaptation outcomes of glycemic control and health-related quality of life. Youth (N = 162, aged 12–17 years) with T1D completed the Acceptance and Action Diabetes Questionnaire, Diabetes Stress Questionnaire, Self-Care Inventory, and Pediatric Quality of Life-Diabetes Module. Hemoglobin A1c values were abstracted from medical records. Latent profile analysis yielded three profiles: High Acceptance & Adherence/Low Stress, Low Acceptance/Moderate Adherence & Stress, and Low Acceptance & Adherence/High Stress. The High Acceptance & Adherence/Low Stress group displayed significantly higher health-related quality of life and lower HbA1c compared to other groups. Fluid psychological variables, such as acceptance and diabetes stress, and adherence behaviors may be salient targets to increase psychological flexibility for individual psychosocial interventions aimed at improving adaptation to type 1 diabetes in youth.

Objectives:General and diabetes-specific family functioning may be associated with youth’s adaptation to type 1 diabetes (T1D); however, empirically derived patterns of family functioning and diabetes-specific conflict among youth have not been explored in relation to T1D adaptation. Methods:Youth (N = 161, aged 12–18) with T1D and caregivers completed measures of family functioning and diabetes-specific conflict that served as indicators in latent profile analyses. Differences in glycemic control (measured by hemoglobin A1cs [HbA1c] and health-related quality of life [HRQoL]) were compared across profiles. Results:Four profiles that varied by levels of family functioning, diabetes-specific conflict, and congruence between youth and caregiver perspectives emerged and related to T1D adaptation differently. Greater agreement between caregiver and youth and lower diabetes-specific conflict was associated with lower HbA1c and greater HRQoL. Conclusions:Person-centered approaches are useful to quantify how many individuals fit into a particular pattern and determine how specific family dynamics may function together differently in relation to T1D adaptation for various subgroups of the population.

IMPORTANCE Bone accrual during youth is critical to establish sufficient strength for lifelong skeletal health. Children with cancer may develop low bone mineral density (BMD) any time before or after diagnosis. OBJECTIVE To evaluate the ability of low-magnitude, high-frequency mechanical stimulation to enhance BMD among childhood cancer survivors. DESIGN, SETTING, AND PARTICIPANTS Double-blind randomized clinical trial conducted at St Jude Children's Research Hospital from June 1, 2010, to January 22, 2013, using cancer survivors, ages 7 to 17 years, who were previously treated at St Jude Children's Research Hospital, were in remission, and at least 5 years from diagnosis, with whole-body or lumbar spine BMD z scores of -1.0 or lower. Participants were randomized (stratified by sex and Tanner stage) to either a placebo device or low-magnitude, high-frequency mechanical stimulation device, which was used at home. INTERVENTIONS Placebo or low-magnitude, high-frequency mechanical stimulation (0.3 g; 32-37 Hz) for 2 sessions lasting 10 minutes each, 7 days per week for 1 year. All participants were prescribed daily cholecalciferol (vitamin D) and calcium. MAIN OUTCOMES AND MEASURES Changes in areal and volumetric BMD and bone biomarkers were compared by analysis of variance, adjusted for strata. RESULTS Of the 65 participants, 32 were randomized to the intervention group (mean [SD] age was 13.6 [3.7] years, 18 [56.2%] were male, and 27 [84.4%] were white), and 33 were randomized to the placebo group (mean [SD] age was 13.6 [2.9] years, 17 [51.5%] were male, and 26 [78.8%] were white). Forty-eight participants completed the trial, 22 in the intervention group and 26 in the placebo group with median adherence of 70.1% for intervention and 63.7% for placebo groups. With intention-to-treat analysis, mean (SD) whole-body BMD z score by dual x-ray absorptiometry improved by 0.25 (0.78) in the intervention (n = 22), but decreased by -0.19 (0.79) in the placebo group (n = 26, P = .05). Circulating osteocalcin at 12 months correlated with change in total body BMD (r = 0.35, P = .02). Tibial trabecular bone among participants completing 70% or more of the prescribed sessions increased by a mean of 11.2% (95% CI, 5.2 to 17.2%) compared with those completing less than 70% who decreased by a mean of -1.3% (95% CI, -7.3 to 4.7%; P = .02). Change in circulating receptor activator of nuclear factor κ-B ligand was higher in the intervention than in the placebo group (0.06 [0.16] vs -0.04 [0.17] pmol/L) (P = .04). CONCLUSIONS AND RELEVANCE Pediatric cancer survivors with low BMD may benefit from low-magnitude, high-frequency mechanical stimulation as a novel and safe intervention to optimize peak bone mass during youth, alone or in conjunction with other therapies. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01010230.

OBJECTIVES:To determine whether the likelihood of readmission (adjusted for severity on first admission) for pediatric type 1 diabetes (T1D) differs between Medicaid managed care and non-managed care.STUDY DESIGN:De-identified patients were retrospectively selected from the Pediatric Health Information Systems database of the Children's Hospital Association (CHA). The cohort of 42 hospitals across 25 states included discharges between 2008 and 2011 for patients who were receiving Medicaid at the time of service and had T1D as their diagnosis.METHODS:Multiple factors and co-variants for readmission were analyzed by logistic regression, including age, race, gender, severity of illness, and state of admission.RESULTS:Of 14,544 T1D discharges with Medicaid, 4985 were readmitted, including 1792 readmitted for diabetic ketoacidosis (DKA). Despite similar rates of DKA between the managed care and non-managed care cohorts, overall 90-day readmission was 1.12 times more likely for Medicaid patients on non-managed care plans than those on managed care (odds ratio, 1.12; range = 1.04-1.20; both adjusted for severity of illness). Significant contributors were race, age, and gender; the relationship of location (state) and days between readmissions was also significant. The conservative estimate of cost reduction from Medicaid managed care related to lower readmission rate for pediatric T1D across CHA institutions between 2008 and 2011 was $2.6 million.CONCLUSIONS:From the largest, national, defined cohort available for contemporary study, youths with T1D on Medicaid managed care plans were less likely to be readmitted within 90 days of discharge.

Background Children generally do not consume adequate amounts of fruits and vegetables (F/V). Eating more F/V can improve energy density and overall diet quality.Objective Our aim was to investigate whether improvements in F/V consumption were associated with improvements in energy density, total calories, and dietary components related to F/V.Design We performed secondary analyses of dietary data from a successful four-group randomized controlled trial promoting F/V. Data were collected at baseline, immediately after gameplay, and 3 months post intervention.Participants/setting Preadolescent child-parent dyads (n=400) were recruited. Eligibility criteria were 4th- or 5th-grade child (approximately 9 to 11 years old) with Internet access and a parent willing to participate in the intervention. Complete dietary data were collected on 387 of the 400 child participants. The videogame was available online on a secure, password-protected website.Main outcome measures Dietary intake was assessed with three unannounced dietary recalls collected at each data-collection period via telephone by trained staff using Nutrition Data System for Research software. Energy density and F/V, nutrient, and food consumption were calculated.Statistical analysis performed A 4x3 (group by time) repeated measures analysis of covariance with mixed-effect linear models was used. Covariates included child's sex, race/ethnicity, and total energy intake as well as parent's age and household education. Energy was excluded as a covariate in the energy density and energy models.Results Significant changes occurred in energy density. A significant interaction (group by time) was observed (F-6,F-515=2.40; P<0.05) in energy density from food only, while a significant time effect was observed for energy density from all foods and beverages ( F-2,F-388=13.75; P<0.0001). Desirable changes were also observed in F/V-related dietary components.Conclusions Increasing F/V consumption improved energy density and diet quality considerably in preadolescent children.

The objective of this article was to determine (1) the existence of individually varying patterns of physical activity, sedentary behavior, and nutrition intake risk; and (2) how these risk-patterns relate to youth's demographics, Body mass index (BMI) and psychosocial functioning. Participants (N = 9,304) from the 2007 8th Grade Early Childhood Longitudinal Study Cohort completed the revised Self-Description Questionnaire II. Age, sex, height, and weight were used to calculate body mass index (BMI) z scores and percentiles. Three risk profiles emerged via Latent Profile Analyses: “Active + Healthy Diet” (AHD; 16.3% Obese); “Sedentary + Unbalanced Diet” (SUD; 21.3% Obese); and “Screen-Time + Recreational Food” (STRF; 25.0% Obese). Significant differences in BMIs, psychosocial factors, and demographic characteristics were found across the profiles. Differential patterns of physical activity, sedentary behavior, and nutritional choices were found to predict BMI and psychosocial functioning. These findings may be helpful to refine and develop modular-based prevention and weight control intervention programs.

Neural precursor cell expressed developmentally down-regulated protein 4 (Nedd4) is the prototypical protein in the Nedd4 ubiquitin ligase (E3) family, which governs ubiquitin-dependent endocytosis and/or degradation of plasma membrane proteins. Loss of Nedd4 results in embryonic or neonatal lethality in mice and reduced insulin/IGF-1 signaling in embryonic fibroblasts. To delineate the roles of Nedd4 in vivo, we examined the phenotypes of heterozygous knockout mice using a high-fat diet-induced obesity (HFDIO) model. We observed that Nedd4+/- mice are moderately insulin resistant but paradoxically protected against HFDIO. After high-fat diet feeding, Nedd4+/- mice showed less body weight gain, less fat mass, and smaller adipocytes vs the wild type. Despite ameliorated HFDIO, Nedd4+/- mice did not manifest improvement in glucose tolerance vs the wild type in both genders. Nedd4+/- male, but not female, mice displayed significantly lower fasting blood glucose levels and serum insulin levels. Under obesogenic conditions, Nedd4+/- mice displayed elevated stimulated lipolytic activity, primarily through a β2-adrenergic receptor. Combined, these data support novel complex roles for Nedd4 in metabolic regulation involving altered insulin and β-adrenergic signaling pathways.

Emerging data suggest that vitamin D status during childhood and adolescence can affect neurocognitive development. The purpose of this study was to investigate whether gestational 25(OH)D status is associated with early childhood cognitive and receptive language development. The Conditions Affecting Neurocognitive Development and Learning in Early Childhood Study (CANDLE) study enrolled 1503 mother-child dyads during the second trimester of healthy singleton pregnancies from Shelby County TN. Among 1020 participants of the total CANDLE cohort for whom 25(OH)D levels were available, mean gestational 25(OH)D level during the second trimester was 22.3 ng/mL (range 5.9–68.4), with 41.7% of values <20 ng/dL. Cognitive and language scaled scores increased in a stair-step manner as gestational 25(OH)D levels in the second trimester rose from <20 ng/dL, through 20–29.99 ng/dL, to ≥30 ng/dL. When controlling for socioeconomic status, race, use of tobacco products, gestational age of the child at birth, and age at the 2-year assessment, the gestational 25(OH)D was positively related to receptive language development (p < 0.017), but not cognitive or expressive language.

Objective To evaluate the factor structure and measurement invariance of the Diabetes Stress Questionnaire (DSQ), a measure of diabetes-specific stress, across sex, age (<9th grade vs. ≥9th grade), and glycemic control (optimal vs. suboptimal). Methods Data from 318 adolescent participants were pooled from four archival data sets and the ongoing Predicting Resiliency in Youth with Type 1 Diabetes study in which the DSQ was completed. Confirmatory factor and measurement invariance analyses were conducted to confirm the proposed factor structure and measurement invariance across sex, age, and glycemic control. Results The DSQ factor structure was found to have an acceptable fit, which was invariant across sex, age, and glycemic control. Conclusions When using the DSQ, differences in diabetes-related stress with respect to sex, age, or glycemic control can be considered meaningful. This study supports the DSQ as an evidence-based and well-established assessment of perceived diabetes stress in youth with type 1 diabetes.

BackgroundWe sought to improve lumbar spine bone mineral density (LS-BMD) in long-term survivors of childhood acute lymphoblastic leukemia (ALL) using calcium and cholecalciferol supplementation.ProcedureThis double-blind, placebo-controlled trial randomized 275 participants (median age, 17 [9-36.1] years) with age- and gender-specific LS-BMD Z-scores <0 to receive nutritional counseling with supplementation of 1,000mg/day calcium and 800International Unit cholecalciferol or placebo for 2 years. The primary outcome was change in LS-BMD assessed by quantitative computerized tomography (QCT) at 24 months. Linear regression models were employed to identify the baseline risk factors for low LS-BMD and to compare LS-BMD outcomes.ResultsPre-randomization LS-BMD below the mean was associated with male gender (P=0.0024), White race (P=0.0003), lower body mass index (P<0.0001), and cumulative glucocorticoid doses of 5,000mg (P=0.0012). One hundred eighty-eight (68%) participants completed the study; 77% adhered to the intervention. Mean LS-BMD change did not differ between survivors randomized to supplements (0.330.57) or placebo (0.28 +/- 0.56). Participants aged 9-13 years and those 22-35 years had the greatest mean increases in LS-BMD (0.50 +/- 0.66 and 0.37 +/- 0.23, respectively). Vitamin D insufficiency (serum 25[OH]D <30ng/ml) found in 296 (75%), was not associated with LS-BMD outcomes (P=0.78).ConclusionCholecalciferol and calcium supplementation provides no added benefit to nutritional counseling for improving LS-BMD among adolescent and young adult survivors of ALL (93% of whom had LS-BMD Z-scores above the mean at study entry). Pediatr Blood Cancer 2014;61:885-893. (c) 2014 Wiley Periodicals, Inc.

Abstract Introduction This team-based learning (TBL) session examines the impact of type 2 diabetes (T2D) on energy metabolism as covered in first-year basic sciences for medical students. Knowledge of molecular mechanisms in energy metabolism and signal transduction are required. Knowledge of anatomy is integrated to apply anatomical knowledge to T2D. This TBL is intended to take place subsequent to carbohydrate metabolism and abdominal anatomy to reinforce knowledge of these subjects. Methods This TBL includes a readiness assurance test (RAT) and a worksheet that applies basic science knowledge to medical decision making. In addition, there are prereading assignments to provide learners with information on genetics and nutrition. Each of our TBL sessions consists of 84 students in permanent six-person teams plus several faculty facilitators. As an interdisciplinary TBL, the module is facilitated by a medical education professional for the RAT events and teams of basic scientists and clinicians for the application. The RAT assessments are completed within 30 minutes, with the rest of the time devoted to the clinical case and the application questions. A PowerPoint/TurningPoint presentation and a Turning Technologies Response System captures individual RAT (iRAT) responses, and printed sheets and scratch-off Immediate Feedback Assessment Technique (IF-AT) cards capture team RAT (tRAT) responses. These are graded for the course. Teams have cards, and stands are present on team tables for application response simultaneous reveals. The application exercise is not graded or recorded. Results This TBL has been implemented for three entering M1 classes in the first (fall) semester. The results of the RAT overall are consistent from year-to-year. The iRAT scores have steadily increased while the tRAT scores have consistently remained high. Students vote each year on what percentage of their RAT score comes from the iRAT as compared to the tRAT, and each year they have chosen the highest percentage of their score allowed to come from the tRAT (75%), with the iRAT counting 25% of the TBL score. Discussion In this molecular course, TBL has proven to be a flexible active learning experience for M1 students. The curriculum has evolved over the 3 years of implementation, and questions in the RAT and Applications have been changed as part of this process with continued change being likely. The faculty facilitators must be able to respond by updating the content in the TBL as curriculum content and delivery of content evolves.

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.

OBJECTIVE The study seeks to improve access for underserved patients via novel integration of Pedi-Flite (a critical care transport team) and to validate whether this safely enhances diabetes care and effectively expands the endocrine workforce. RESEARCH DESIGN AND METHODS The study retrospectively analyzed pager service use in a cohort of established diabetic patients (n = 979) after inception of Pedi-Flite support. Outcomes included incidence and severity of recurrent diabetic ketoacidosis (DKA) and cost savings generated from reduced referrals to the emergency department (ED) and on-call endocrinologist. We generated descriptive statistics to characterize the study population and ED visits for DKA and constructed logistic regression models to examine associations of pager use and likelihood of ED visitation and nonelective inpatient admission from an ED for DKA. RESULTS Pager users comprised 30% of the patient population. They were younger but had more established diabetes than nonusers. While pager users were 2.75 times more likely than nonusers to visit the ED for DKA (P < 0.0001), their visits were less likely to lead to inpatient admissions (odds ratio 0.58; P < 0.02). More than half (n = 587) of all calls to the pager were resolved without need for further referral. Estimates suggest that 439 ED visits and 115 admissions were avoided at a potential cost savings exceeding 760,000 USD. CONCLUSIONS Integration of a transport service provides a novel, cost-effective approach to reduce disparities in diabetes care. Advantages include scalability, applicability to other disease areas and settings, and low added costs. These findings enrich an emerging evidence base for telephonic care-management models supported by allied health personnel.

Protégé was a phase 3, randomized, double-blind, parallel, placebo-controlled 2-year study of three intravenous teplizumab dosing regimens, administered daily for 14 days at baseline and again after 26 weeks, in new-onset type 1 diabetes. We sought to determine efficacy and safety of teplizumab immunotherapy at 2 years and to identify characteristics associated with therapeutic response. Of 516 randomized patients, 513 were treated, and 462 completed 2 years of follow-up. Teplizumab (14-day full-dose) reduced the loss of C-peptide mean area under the curve (AUC), a prespecified secondary end point, at 2 years versus placebo. In analyses of prespecified and post hoc subsets at entry, U.S. residents, patients with C-peptide mean AUC >0.2 nmol/L, those randomized ≤6 weeks after diagnosis, HbA1c <7.5% (58 mmol/mol), insulin use <0.4 units/kg/day, and 8–17 years of age each had greater teplizumab-associated C-peptide preservation than their counterparts. Exogenous insulin needs tended to be reduced versus placebo. Antidrug antibodies developed in some patients, without apparent change in drug efficacy. No new safety or tolerability issues were observed during year 2. In summary, anti-CD3 therapy reduced C-peptide loss 2 years after diagnosis using a tolerable dose.

Placental mitochondrial stress has been described in maternal obesity, pre-eclampsia, and intrauterine growth restriction. Mitochondrial stress is associated with apoptosis and generation of reactive oxygen species (ROS) through NADPH oxidase (NOX) activity. NOX comprises a group of five enzymes, NOX 1-5. NOX 2 is expressed in the placental Hoffbauer cells and neutrophils. We and others previously described placental infiltration by macrophages and neutrophils in maternal obesity. Objectives of this study were to: 1) assess placental NOX-2 protein expression and activity as well as morphology of endothelial (E), cytotrophoblast (CT), and syncytiotrophoblast (ST) mitochondria; 2) measure placental apoptosis and proliferation in obese and non-obese placentas. Placentas from obese (n=4) and non-obese (n=4) baboons near term were retrieved and processed as previously described (Farley et al., 2009). Placental NOX-2 protein was quantified by Western blot of tissue lysates, localized by immunohistochemistry, and assessed functionally by activity assay. Placental mitochondria were measured on electron micrographs using isometric point intersect method. Placenta was stained with KI-67 to access proliferation and TUNNEL staining was used to evaluate placental apoptosis. NOX-2 protein level directly correlated with placental apoptosis (r=0.80, p<0.05) and with mitochondrial volume in E (but not in CT and ST) (r=0.81, p<0.05). There were no differences in placental NOX-2 activity and protein expression, mitochondrial volume, or placental proliferation/apoptosis between obese and non-obese animals. Placental NOX-2 localizes not only to Hoffbauer cells and neutrophils, but is also shown for the first time within the fetal endothelium of this non-human primate model. Such localization of NOX-2 has been described in human endothelia damaged by atherosclerosis or myocardial infarction. Release of ROS by macrophages/neutrophils may directly influence the fetal vascular system.

Interventions to improve fetal growth are limited. Placental structure and the fetal endocrine system (eg, IGFs, leptin) are critical determinants of fetal growth. Endocannabinoids (ECBs), their receptors (CB1, CB2), and related enzymes (e.g., monoacyl glycerol lipase, or MAGL) remodel tissues. Leptin activates a key ECB-degrading enzyme called fatty acid amide-hydrolase (FAAH) in immunologic and neuronal cells. Relationships between placental ECBs, placental structure, and maternal/fetal leptin have not been reported. This study aimed : 1) to evaluate expression of placental ECBs and their relationships to placental composition and to fetal and maternal leptin status in a baboon model; 2) to sequence baboon CB1 and CB2 receptors for the first phylogenetic comparison to humans. Placentas from eight baboons were collected and processed as described previously (Farley et al., 2009). Placental composition was estimated using computerized stereology on electron micrographs. Immunohistochemistry employed commercial antibodies. Slides were scanned and processed as previously described (Brocato et al., 2012). RT PCR was done with a kit according to manufacturer's instructions. Two-tailed correlation was applied for statistical analysis, P value of <0.05 was used to determine significance. The ratio of fetal endothelium to placental tissue correlated positively with MAGL and FAAH expressions (r=0.79, p<0.05 and r=0.70, p<0.05, respectively). Protein expression of FAAH in syncytiotrophoblast correlated positively with fetal leptin concentration (r=0.98, p<0.0001, Fig. 1A ). CB1 receptors were expressed in fetal endothelial cells, cytotrophoblast, and fibroblasts of villous core (Fig.1)B, displaying 100% homology on the protein level with human receptor. This is the first report regarding possible regulation of placental ECBs by fetal leptin and ECBs association with fetal endothelial remodeling. Placental FAAH may be a promising target for treatment of poor fetal growth.

Mitochondria play an important role in lipid β-oxidation and steroidogenesis. Mutations in mitochondrial tri-functional proteins in humans have been associated with fetal growth restriction and fatty liver of pregnancy. Also, mitochondrial dysfunction has been linked to obesity and pre-eclampsia. Leptin, produced by adipose and placental tissues, regulates mitochondrial metabolism and structure. How the increased levels of maternal leptin in obesity affects placental metabolism is unclear. This study sought to evaluate mitochondrial morphometry in fetal endothelium (MtE) and cytotrophoblast (MtCT) in a baboon model of maternal obesity (Fig. 1A and 1B respectively). Four (4) obese and four (4) non-obese baboons (Papio spp.) were selected for this study (Farley et al., 2009). Placental samples were collected and processed for electron microscopy as previously described (Samson et al., 2011). Two specimens were collected per placenta. Fields of view were randomly and systematically selected at 30,000X magnification. Equatorial widths of 30 MtE and 100 MtCT were measured per specimen. Additionally, circulating maternal and fetal leptin levels and placental fat content were estimated as previously described (Schlabritz-Loutsevitch et al., 2008, Schlabritz-Loutsevitch et al., 2011). There were no differences in MtE and MtCT morphometry between the obese and non-obese groups. The MtE width correlated negatively with maternal leptin concentration (r=-0.73, p=0.043). MtCT width correlated positively with placental fat content (r=0.8, p=0.05). Increased placental fat content may be associated with cytotrophoblast oxidative damage which could lead to the decreased synthesis of syncytiotrophoblasts. The decreased mitochondrial size has been linked to increased mitochondrial functional activity. Thus, increased maternal leptin may be associated with fetal endothelial function through mitochondrial changes.

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.