Multicentre study protocol comparing standard NRP to deveLoped Educational Modules for Resuscitation of Neonates in the Delivery Room with Congenital Heart Disease (LEARN-CHD).

INTRODUCTION: Infants born with critical congenital heart defects (CCHDs) have unique transitional pathophysiology that often requires special resuscitation and management considerations in the delivery room (DR). While much is known about neonatal resuscitation of infants with CCHDs, current neonatal resuscitation guidelines such as the neonatal resuscitation programme (NRP) do not include algorithm modifications or education specific to CCHDs. The implementation of CCHD specific neonatal resuscitation education is further hampered by the large number of healthcare providers (HCPs) that need to be reached. Online learning modules (eLearning) may provide a solution but have not been designed or tested for this specific learning need. Our objective in this study is to design targeted eLearning modules for DR resuscitation of infants with specific CCHDs and compare HCP knowledge and team performance in simulated resuscitations among HCPs exposed to these modules compared with directed CCHD readings. METHODS AND ANALYSIS: In a prospective multicentre trial, HCP proficient in standard NRP education curriculum are randomised to either (a) directed CCHD readings or (b) CCHD eLearning modules developed by the study team. The efficacy of these modules will be evaluated using (a) individual preknowledge/postknowledge testing and (b) team-based resuscitation simulations. ETHICS AND DISSEMINATION: This study protocol is approved by nine participating sites: the Boston Children's Hospital Institutional Review Board (IRB-P00042003), University of Alberta Research Ethics Board (Pro00114424), the Children's Wisconsin IRB (1760009-1), Nationwide Children's Hospital IRB (STUDY00001518), Milwaukee Children's IRB (1760009-1) and University of Texas Southwestern IRB (STU-2021-0457) and is under review at following sites: University of Cincinnati, Children's Healthcare of Atlanta, Children's Hospital of Los Angeles and Children's Mercy-Kansas City. Study results will be disseminated to participating individuals in a lay format and presented to the scientific community at paediatric and critical care conferences and published in relevant peer-reviewed journals.

The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth.

The placenta is metabolically active and supports the growth of the fetus. We hypothesize that deficits in the capacity of the placenta to maintain bioenergetic and metabolic stability during pregnancy may result in spontaneous preterm birth (SPTB). To explore this hypothesis, we performed a nested cased control study of metabolomic signatures in placentas from women with SPTB (<36 weeks gestation) compared to normal pregnancies (≥38 weeks gestation). To control for the effects of gestational age on placenta metabolism, we also studied a subset of metabolites in non-laboring preterm and term Rhesus monkeys. Comprehensive quantification of metabolites demonstrated a significant elevation in the levels of amino acids, prostaglandins, sphingolipids, lysolipids, and acylcarnitines in SPTB placenta compared to term placenta. Additional quantification of placental acylcarnitines by tandem mass spectrometry confirmed the significant elevation in SPTB human, with no significant differences between midgestation and term placenta in Rhesus macaque. Fatty acid oxidation as measured by the flux of 3H-palmitate in SPTB placenta was lower than term. Collectively, significant and biologically relevant alterations in the placenta metabolome were identified in SPTB placenta. Altered acylcarnitine levels and fatty acid oxidation suggest that disruption in normal substrate metabolism is associated with SPTB.

Acquiring and Maintaining Technical Skills Using Simulation: Initial, Maintenance, Booster, and Refresher Training.

Simulation-based education has been shown to be an effective tool to mitigate skill decay. However, many of the strategies reported in the literature have overlapping terminology with little consensus on the timing of the strategy to prevent skill decay. In this review, we propose and provide a standardized nomenclature and framework for simulation strategies used to obtain, maintain, or regain skills that are decaying. This framework delineates four types of training: initial, maintenance, booster, and refresher. The framework differentiates these training types based on the learner competency at the time of the training, as well as the frequency and intensity of the training. Initial training is aimed at "novice" learners with the goal to achieve competency. Once competency is achieved, maintenance training prevents skill deterioration through low-dose high-frequency (LDHF) training. Booster training is used when the learner is still proficient, but competency begins to wane. Booster training occurs less frequently than maintenance training but with greater intensity to overcome the skill decay that occurs over time. Refresher training is aimed at re-establishing skill levels after competency has reached unsatisfactory levels. Refresher training is higher intensity than booster and maintenance training. We describe simulation-based strategies reported in the literature that can be used for each type of training. We conclude that there should be an increased emphasis in medical education towards maintenance and booster training in order to preserve skills before competency is lost.

Maternal obesity and prenatal programming.

Obesity is a significant and increasing public health concern in the United States and worldwide. Clinical and epidemiological evidence clearly shows that genetic and environmental factors contribute to the increased susceptibility of humans to obesity and its associated comorbidities; the interplay of these factors is explained by the concept of epigenetics. The impact of maternal obesity goes beyond the newborn period; fetal programming during the critical window of pregnancy, can have long term detrimental effects on the offspring as well as future generations. Emerging evidence is uncovering a link between the clinical and molecular findings in the offspring with epigenetic changes in the setting of maternal obesity. Research targeted towards reducing the transgenerational propagation and developmental programming of obesity is vital in reducing the increasing rates of disease.

A five year retrospective study of short term respiratory support outcomes for infants who received tracheostomy before one year of age.

OBJECTIVES: This study aims to describe respiratory support requirements at the time of hospital discharge for infants who undergo tracheostomy, and to determine whether certain indications for tracheostomy are significantly associated with ventilator or oxygen dependence at the time of discharge. METHODS: Retrospective chart review identified 150 patients who underwent tracheostomy before 1 year of age at a single center from 2007 to 2012 and were discharged alive. Patients were divided into groups based on primary indication for tracheostomy: chronic lung disease (CLD); cardiac; airway anomalies (e.g., tracheomalacia, subglottic stenosis); anatomic anomalies of head, neck and chest; neuro/muscular; mixed group (>1 primary indication). Chi-squared tests were used to compare respiratory support requirements at time of discharge, as well as need for supplemental oxygen. RESULTS: Of the 150 patients included in the study, three were discharged on room air alone. Of those 147 who did require some form of support at discharge, significant differences were found between groups when comparing CPAP to ventilator support. For example, of the patients with CLD, 82% were discharged on ventilator support whereas of those with a primary airway indication nearly 54% were discharged on CPAP. Significant differences were also found among groups when comparing patients discharged on room air vs. supplemental oxygen. Patients with CLD were more likely to be discharged on supplemental oxygen (p=0.001) whereas of the patients with anatomic indication 77% required no supplemental oxygen at the time of discharge. CONCLUSION: Respiratory support needs at the time of discharge for neonates who underwent tracheostomy varied significantly depending on the initial indication for tracheostomy. Information about respiratory requirements of infants who undergo tracheostomy can help clinicians counsel families and anticipate post-discharge needs.

Developmental reprogramming of rat GLUT5 requires glucocorticoid receptor translocation to the nucleus.

Fructose consumption has increased dramatically but little is known about mechanisms regulating the intestinal fructose transporter GLUT5 in vivo. In neonatal rats, GLUT5 can be induced only by luminal fructose and only after 14 days of age, unless the gut is primed with dexamethasone prior to fructose perfusion. To elucidate the mechanisms underlying dexamethasone modulation of GLUT5 development, we first identified the receptor mediating its effects then determined whether those effects were genomic. The glucocorticoid receptor (GR) antagonist RU486 dose-dependently prevented the dexamethasone-mediated effects on body weight, intestinal arginase2 (a known GR-regulated gene) and GLUT5. In contrast, an antagonist of the mineralocorticoid receptor as well as agonists of progesterone (PR) and pregnane-X (PXR) receptors did not block the effects of dexamethasone. These receptor antagonists and agonists had no effect on the intestinal glucose transporter SGLT1. Translocation of the GR into the enterocyte nucleus occurred only in dexamethasone-injected pups perfused with fructose, was accompanied by marked increases in brush border GLUT5 abundance, and was blocked by RU486. A priming duration of approximately 24 h is optimal for induction but actinomycin D injection before dexamethasone priming prevented dexamethasone from allowing luminal fructose to induce GLUT5. Actinomycin D had no effect on dexamethasone-independent fructose-induced increases in glucose-6-phosphatase mRNA abundance, suggesting that it did not prevent fructose-induction of GLUT5, but instead prevented dexamethasone-induced synthesis of an intermediate required by fructose for GLUT5 regulation. In suckling rats < 14 days old, developmental regulation of transporters may involve cross-talk between hormonal signals modulating intestinal maturation and nutrient signals regulating specific transporters.