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Glucose-6-phosphate dehydrogenase (G6PD) deficiency and polymorphism in uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) were associated with significant neonatal hyperbilirubinemia (NHB) and increased risk for kernicterus. However, quantitative screening tests for G6PD enzyme activity proved unsatisfactory in estimating the risk for significant NHB, especially in heterozygous females that could present phenotype overlap between normal homozygotes, heterozygotes, and deficient homozygotes, resulting in a continuum of intermediate G6PD activity. Objective: To examine the association of genotype and phenotype in newborns with decreased G6PD activity and its relation to NHB. Study design: Quantitative G6PD enzyme activities were measured on umbilical cord blood samples. After accepting parental consent, samples were analyzed for G6PD mutations and UGT1A1 gene polymorphisms (number of TA repeats in the UGT1A1 promoter). The associations to quantitative G6PD activity and bilirubin levels were assessed. Results: 28 females and 27 males were studied. The Mediterranean mutation (NM_001360016.2(G6PD): c.563C>T (p.Ser188Phe)) was responsible for most cases of G6PD deficiency (20 hemizygous males, 3 homozygous and 16 heterozygous females). The association between this mutation, decreased G6PD activity and higher bilirubin levels was confirmed. Heterozygosity to 6/7 TA repeats in the UGT1A1 promoter was associated with increased NHB, especially in female newborns with G6PD deficiency. However, it seems that the interaction between G6PD deficiency, UGT1A1 promoter polymorphism, and NHB is more complex, possibly involving other genetic interactions, not yet described. Despite genotyping females with G6PD deficiency, the overlap between the upper range of borderline and the lower range of normal G6PD activity could not be resolved. Conclusions: The results of this study highlight the possibility for future implementation of molecular genetic screening to identify infants at risk for significant NHB, especially UGT1A1 polymorphism in heterozygous females with borderline G6PD deficiency. However, further studies are needed before such screening could be applicable to daily practice.

Objectives This study aimed to compare time to full feeding (TFF) between continuous gastric feeding (CGF) and bolus feeding (BF) in very low birth weight (VLBW) infants supported with noninvasive ventilation (NIV) and to evaluate feasibility and identify methodological pitfalls for future large-scale studies. Study Design This study is a randomized controlled, prospective, pilot study. VLBW premature infants, supported with NIV, were randomized while still on trophic feeding Results Overall, 32 infants were included in this analysis, 17 in the CGF group and 15 in the BF group. Infants in the CGF group were significantly younger than the BF group (mean ± standard deviation [SD] gestational age [GA] 26.9 ± 1.2 vs. 28.9 ± 1.5 weeks, respectively). TFF was comparable with median (interquartile range [IQR]) for the two groups, 10.0 (10.0, 19.0) days in the BF group versus 12.0 (9.0, 13.0) days in the CGF group (p = 0.59). Feeding length was not found to significantly affect TFF in multivariate analysis correcting for GA. Groups were comparable in weight gain, gastrointestinal complications, length of NIV, bronchopulmonary dysplasia incidence, and age at discharge. Most infants from both groups (60% of BF and 70% of CGF) required changes in feeding length. Conclusion In this pilot study, among VLBW infants supported with NIV, TFF was comparable between the BF and CGF groups. These results should be interpreted with caution due to the small sample size and despite the multivariate analysis correcting for the different GA. Interestingly, most infants required changes in feeding length regardless of their allocation. This feasibility study emphasizes the need for careful attention to randomization and strict feeding protocols including criteria for switching allocation in future large-scale studies aimed at determining the preferred feeding length during NIV in VLBW infants. Key Points

Intrapartum antibiotics are widely used and may potentially affect bilirubin levels and neurotoxicity in the newborn. The aim of this study was to examine the effect of intrapartum antibiotic exposure on neonatal jaundice. We retrospectively collected data from 972 neonates born to 963 mothers. Five hundred forty-five mothers (56.6%) received intrapartum antibiotics. There were no statistically significant differences in maximum bilirubin level (7.82 ± 3.65 vs 7.63 ± 3.71, P = .43) or need for phototherapy (9 [1.62%] vs 4 [0.94%], P = .52) between exposed and non-exposed newborns. The rate of phototherapy was significantly higher only in the group of infants born to mothers who received broad-spectrum antibiotics at 2 to 3.9 hours prior to delivery (χ2 = 10.453, P = .015) and was not higher in the group of exposure >4 hours, which may represent a short transient effect of antibiotics exposure on bilirubin turnover. Further studies are needed to validate this finding.

Despite in-depth discussions regarding professional identity of doctors, there is still a gap in our understanding of how this professional identity actually evolves.To outline some major mechanisms involved in formation of medical students' professional identity.A qualitative study based on thematic analysis. 296 diary entries, written by eight medical students as part of the three-year course 'Becoming a Physician,' were reviewed. The course, conducted in small groups, gradually exposes students to the clinical field, and emphasizes awareness to marginalized populations, and interpersonal communication skills.Following the social constructivist learning theory, where learners individually and socially construct meaning attributed to their experiences, we identified three major mechanisms based on students' written reflections. These include linking current experiences to past; comparing different types or aspects of knowledge, doctors or medicine; and future perspective taking.This study sheds light on the possible mechanisms used by medical students in forming their professional identity prior to their clinical training. Knowing these mechanisms can help medical educators better understand and support their students in formation of their professional identities. Conducting reflective writing could serve as an effective tool for learners to comprehend the meanings of their experiences.

Transthyretin (TTR), also known as prealbumin, has been suggested as an indicator of protein and nutritional status.The aim of this study was to examine the maternal and umbilical cord (UC) TTR in relation to intrauterine growth, and the serum TTR of preterm infants in relation to nutritional status and growth.After application of exclusion criteria, 49 preterm infants (mean gestational age and birth-weight 32.9±2.9 weeks and 1822±556 g) were included in the study. Transthyretin was sampled at birth and on days 14, 28, and at discharge with growth parameters and nutritional laboratory test results.Mean UC and maternal TTR were positively correlated (8.5±2.4 mg/dL and 20.4±7.0 mg/dL, r=0.31, P=0.07). Umbilical cord TTR was neither an index of maturity nor of intrauterine growth. Umbilical cord TTR was higher in females (9.4±2.6 versus 7.6±1.8 mg/dL, P=0.015). Maternal TTR was lower in twin pregnancies (16.8±4.9 versus 22.5±7.3 mg/dL, P=0.007). Although TTR levels gradually increased over time in correlation with post-menstrual and chronological ages (r=0.24, P=0.011 and r=0.40, P0.001, respectively), there was no correlation to weight gain (r=0.10, P=0.41), nutritional status, protein intake, or nutritional laboratory test results. The only significant correlations were between TTR and glucose and triglycerides levels (r=0.51, P0.001 for both).Although TTR levels increased over time, we could not demonstrate significant correlations between TTR and indices of the nutritional status in preterm infants at birth or during the neonatal course.

PURPOSE: To describe the experience and perceptions of physicians involved in group mentoring of undergraduate pre-clinical medical students. METHOD: We conducted a cross-sectional questionnaire-based survey on perceptions of mentors regarding their motivation, personal development, reflective experience, and burnout. All the participants were mentors to undergraduate pre-clinical medical students in the course “Becoming a Physician.” This unique course focuses on various aspects of medical professionalism and aims to increase awareness and sensitivity to patients, especially of disadvantaged populations, and to promote sensitive effective communication skills. Mentors in the course are expected to serve as role models to their students. RESULTS: Of 36 mentors, 33 (91.7%) responded. The most frequent motivations to join the course were to contribute to students’ personal, social, and professional development and to contribute to educating more compassionate physicians. The topics discussed most in the groups were the meaning of being a physician and ethical dilemmas. Mentors expressed that they gained professional growth and opportunities to reflect on the complexity of physicians’ training and work. They perceived their highest success as being able to serve as role models for their students and provide them broad perspectives. Mentors stated that they failed in trying to facilitate content learning, and were disturbed by students’ lack of punctuality. Group mentors scored relatively low on the Maslach Burnout Inventory for Physicians. DISCUSSION: This study provides insights on the experience of mentorship of medical school students, and on mentors’ perceptions regarding their teaching experience and personal and professional development. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-020-01146-1.

Objective To compare coronary flows between premature infants with and without hemodynamically significant patent ductus arteriosus (hsPDA) and to determine if coronary flow is influenced by medical PDA treatment. Design Prospective, observational pilot study. Forty-three infants

To investigate the association between delivery mode and necrotizing enterocolitis (NEC) in very preterm (24-31 weeks' gestational age (GA)) very-low-birth-weight (VLBW) (≤1500 g) infants.Population-based observational study using univariate and multivariable logistic regression analyses.The Israel National VLBW infant database 1995-2015.20,223 VLBW infants, 11,832 singletons and 8391 multiples.The association of NEC occurrence to delivery by cesarean section (CS) in singletons and multiples VLBW very preterm infants.NEC occurred in 7.6% of singletons and 6.4% of multiples. 71.5% were delivered by CS (64.7% of singletons, 80.9% of multiples). CS delivery was not significantly associated with NEC stages 2-3 in singletons; but multiple births CS were associated with significantly higher odds for NEC (OR 1.31, 95% CI 1.01-1.69). Odds for NEC were greater with lower GA, small for GA (SGA) and patent ductus arteriosus (PDA) in both singletons and multiples, and lower in multiples with antenatal corticosteroids.We demonstrated association between deliveries by CS and increased risk for NEC only in multiple pregnancies.

The coronavirus disease-2019 (COVID-19) pandemic forced drastic changes in all layers of life. Social distancing and lockdown drove the educational system to uncharted territories at an accelerated pace, leaving educators little time to adjust.To describe changes in teaching during the first phase of the COVID-19 pandemic.We described the steps implemented at the Technion-Israel Institute of Technology Faculty of Medicine during the initial 4 months of the COVID-19 pandemic to preserve teaching and the academic ecosystem.Several established methodologies, such as the flipped classroom and active learning, demonstrated effectiveness. In addition, we used creative methods to teach clinical medicine during the ban on bedside teaching and modified community engagement activities to meet COVID-19 induced community needs.The challenges and the lessons learned from teaching during the COVID-19 pandemic prompted us to adjust our teaching methods and curriculum using multiple online teaching methods and promoting self-learning. It also provided invaluable insights on our pedagogy and the teaching of medicine in the future with emphasis on students and faculty being part of the changes and adjustments in curriculum and teaching methods. However, personal interactions are essential to medical school education, as are laboratories, group simulations, and bedside teaching.

Background Little is known about the impact of social interactions on iatrogenesis and lapses in patient safety. Methods This field-based experience-sampling study of primarily nurses in a general hospital explored the impact of rudeness on patient safety performance, state depletion (that is, exhaustion of mental energy for reflective behavior), and team processes (for example, information sharing). Objective measures of performance were compliance with hand hygiene and medication preparation protocols, as well as archival reports of adverse events. Data were analyzed by department shift (480 shifts [15 days] in 16 departments). Results A total of 231 rudeness incidents were reported in 98 shifts, most stemming from a patient or family. Compliance with hand hygiene was significantly lower up to 24 hours after rudeness exposure (p = 0.03). Rudeness significantly increased team members' state depletion (p = 0.002) and was associated with decreased information sharing (p = 0.046) but was not directly associated with adverse events or level of compliance with medication and hand hygiene protocols. However, the adverse indirect effect of shifts' temporal proximity to rudeness on poor compliance with medication preparation and team members' information sharing via state depletion was significant. Rudeness exposure was also associated with increased rate of adverse events in the subsequent 24 hours, although this association was not statistically significant. Conclusion Rudeness exposure was associated with reduced team member compliance with infection control and medication protocols via greater team member state depletion and diminished information sharing.

International audience

ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Venous access

ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition : Iron and trace minerals

Exposure to pain in early life was associated with long term consequences, therefore strategies for minimizing painful procedures in newborns should be employed. The utility and reliability of cord blood CBC was demonstrated before, however data regarding use of cord blood in healthy infants at risk for polycythemia are lacking.A single-center, paired-sampling prospective laboratory study including all healthy asymptomatic infants born after 36 weeks gestation who were SGA (2500 g), LGA (4000 g), or born to mothers with diabetes in pregnancy. Blood count indices were compared between umbilical and neonatal capillary or venous blood samples. In order to predict cut-off values for neonatal polycythemia using umbilical hematocrit, receiver operator curves (ROC) were plotted.Paired samples were collected from 433 infants. Mean gestational age and birth-weight were 39.0 ± 1.3 weeks and 3489 ± 682 g. Hemoglobin, hematocrit and WBC values were lower in cord blood compared to neonatal, but PLT count was higher. Pearson r showed only modest correlation between peripheral capillary and umbilical or venous Hct - 0.35 (p 0.001), and 0.44 (p 0.001), respectively. In order to try and capture clinically significant polycythemia ROC was plotted for hematocrit70% and40%. In our cohort, using the calculated cutoff values (51% and35%) could have resulted in a decrease of 72% of neonatal blood draws.This analysis should be interpreted with caution, as currently it cannot support the routine use of umbilical samples' hematocrits for making treatment decision in newborns at risk for polycythemia. Further larger studies are needed.

The incidence of gestational diabetes mellitus (GDM) is increasing in parallel to the worldwide obesity and type 2 diabetes pandemic. Both GDM and pre-gestational diabetes mellitus (PGDM) are associated with short- and long-term consequences in the offspring. There are few recent studies addressing outcomes of newborns born to women diagnosed with GDM and PGDM in Israel.To assess perinatal complications in offspring of women with GDM and PGDM.The authors conducted a single-center retrospective case-control study of outcomes of all newborns whose mothers had been diagnosed with diabetes in pregnancy compared to randomly assigned controls born on the same date, whose mothers had no diabetes.In the study period 2015-2017, 526 mothers diagnosed with GDM or PGDM and their newborn infants were identified. The authors randomly assigned 526 control infants. The rate of women with diabetes in pregnancy was 5.0%. Mothers with GDM and PGDM had higher rates of pre-eclampsia, multiple pregnancies, and preterm deliveries. Mothers with PGDM had significantly higher rates of intrauterine fetal demise (4.3%), congenital anomalies (12.8%), and small-for-gestational-age neonates (10.6%) compared to controls (0%, 3.2%, and 4.2%, respectively, P0.001). The risks for preterm or cesarean delivery, large-for-gestational-age neonate, respiratory morbidity, hypoglycemia, and polycythemia were increased in offspring of mothers with diabetes, especially PGDM.Despite all the advancements in prenatal care, diabetes in pregnancy, both PGDM and GDM, is still associated with significant morbidities and complications in offspring. Better preconception and inter-pregnancy care might reduce these risks.

Importance Use of cannulas with long and narrow tubing (CLNT) has gained increasing popularity for applying noninvasive respiratory support for newborn infants thanks to ease of use, perceived patient comfort, and reduced nasal trauma. However, there is concern that this interface delivers reduced and suboptimal support. Objective To determine whether CLNT is noninferior to short binasal prongs and masks (SPM) when providing nasal intermittent positive pressure ventilation (NIPPV) in preterm infants. Design, Setting, and Participants This randomized controlled, unblinded, prospective noninferiority trial was conducted between December 2017 and December 2019 at 2 tertiary neonatal intensive care units. Preterm infants born between 24 weeks’ and 33 weeks and 6 days’ gestation were eligible if presented with respiratory distress syndrome with the need for noninvasive ventilatory support either as initial treatment after birth or after first extubation. Analysis was performed by intention to treat. Interventions Randomization to NIPPV with either CLNT or SPM interface. Main Outcomes and Measures The primary outcome was the need for intubation within 72 hours after NIPPV treatment began. Noninferiority margin was defined as 15% or less absolute difference. Results Overall, 166 infants were included in this analysis, and infant characteristics and clinical condition (including fraction of inspired oxygen, Pco2, and pH level) were comparable at recruitment in the CLNT group (n = 83) and SPM group (n = 83). The mean (SD) gestational age was 29.3 (2.2) weeks vs 29.2 (2.5) weeks, and the mean (SD) birth weight was 1237 (414) g vs 1254 (448) g in the CLNT and SPM groups, respectively. Intubation within 72 hours occurred in 12 of 83 infants (14%) in the CLNT group and in 15 of 83 infants (18%) in the SPM group (risk difference, −3.6%; 95% CI, −14.8 to 7.6 [within the noninferiority margin], χ2 P = .53). Moderate to severe nasal trauma was significantly less common in the CLNT group compared with the SPM group (4 [5%] vs 14 [17%];P = .01). There were no differences in other adverse events or in the course during hospitalization. Conclusions and Relevance In this study, CLNT was noninferior to SPM in providing NIPPV for preterm infants, while causing significantly less nasal trauma. Trial Registration ClinicalTrials.gov Identifier:NCT03081611

Phototherapy has been reported to reduce coronary blood flow in neonates but without affecting gross measures of cardiac function. The aim of our current study was to evaluate earlier, more sensitive changes in cardiac function during phototherapy.Nineteen neonates with jaundice treated with phototherapy had Doppler echocardiographic evaluation, before, during and after phototherapy and were compared to 25 matched controls. Sensitive measures for cardiac performance in this study included left ventricular dimension, ventricular Doppler parameters and regional function assessment.Phototherapy was associated with a significant increase in heart rate. In addition, atrioventricular valve closure to opening interval decreased significantly during phototherapy while ventricular ejection times tended to decrease. However, left and right ventricular filling parameters and outflow velocity parameters, longitudinal tissue-Doppler annular velocities and myocardial performance indices were not affected by phototherapy and were similar to those in controls. Coronary blood velocities and integrals decreased significantly during phototherapy.Our study found no differences in early and sensitive measures of cardiac performance including the diastolic and systolic function, despite modestly lower flow in coronary arteries among healthy neonates during phototherapy.

The recognition of the newborn as a separate patient with special unique needs and rights began relatively late compared to other medical disciplines. This process occurred concomitantly with the development of modern neonatology in the country and the establishment of special care nurseries. The process included organization of skilled teams, standardization of treatment methods, introduction of standardized language and practices, and teamwork optimization. The importance of providing support to a newborn in distress after birth - in the first minute, and as needed for the first hour of his life, coined as "The Golden Hour", is highlighted in the training sessions in the program. These principles are conveyed today in multiple simulation-based training courses of multidisciplinary teams taking place in most Israeli hospitals, based on the recommendations of the leading organizations in the field and following the consensus statements outlined by the International Liaison Committee for Resuscitation (ILCOR). This article describes the processes that enabled present achievements, and the goals for further future improvements in the outcomes of newborn resuscitation in Israel.

We acknowledge all the authors of the ESPGHAN/ESPR/ESPEN/CSPEN pediatric parenteral nutrition guidelines for their contributions and vote (Christian Braegger, University Children’s Hospital, Zurich, Switzerland; Jiri Bronsky, University Hospital Motol, Prague, Czech Republic; Cristina Campoy, Department of Paediatrics, School of Medicine, University of Granada, Granada, Spain; Magnus Domellof, Department of Clinical Sciences, Pediatrics, Umeå University, Sweden; Nicholas Embleton, Newcastle University, Newcastle upon Tyne, UK; Mary Fewtrell, UCL Great Ormond Street Institute of Child Health, London, UK; Natasa Fidler, University Medical Centre Ljubljana, Ljubljana, Slovenia; Axel Franz, University Children’s Hospital, Tuebingen, Germany; Oliver Goulet, University Sordonne-Paris-Cite; Paris-Descartes Medical School, Paris, France; Corina Hartmann, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel and Carmel Medical Center, Israel; Susan Hill, Great Ormond Street Hospital for Children, NHS Foundation Trust and UCL Institute of Child Health, London, UK; Iva Hojsak, Children’s Hospital Zagreb, University of Zagreb School of Medicine, University of J. J. Strossmayer School of Medicine Osijek, Croatia; Sylvia Iacobelli, CHU La Reunion, Saint Pierre, France; Frank Jochum, Ev. Waldkrankenhaus Spandau, Berlin, Germany; Koen Joosten, Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus MC Sophia Children’s Hospital, Rotterdam, The Netherlands; Sanja Kolacek, Children’s Hospital, University of Zagreb School of Medicine, Zagreb, Croatia; Alexandre Lapillone, Paris-Descartes University, Paris, France; Szimonetta Lohner, Department of Pediatrics, University of Pecs, Pecs, Hungary; Dieter Mesotten, KU Leuven, Leuven, Belgium; Walter Mihatsch, Ulm University, Ulm, and Helios Hospital, Pforzheim, Germany; Francis Mimouni, Department of Pediatrics, Division of Neonatology, The Wilf Children’s Hospital, the Shaare Zedek Medical Center, Jerusalem, and the Tel Aviv University, Tel Aviv, Israel; Christian Molgaard, Department of Nutrition, Exercise and Sports, University of Copenhagen, and Paediatric Nutrition Unit, Rigshospitalet, Copenhagen, Denmark; Sissel Moltu, Oslo University Hospital, Oslo, Norway; Antonia Nomayo, Ev. Waldkrankenhaus Spandau, Berlin, Germany; John Puntis, The General Infirmary at Leeds, Leeds, UK; Arieh Riskin, Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel; Miguel Saenz de Pipaon, Department of Neonatology, La Paz University Hospital, Red de Salud Materno Infantil y Desarrollo e SAMID, Universidad Autonoma de Madrid, Madrid, Spain; Raanan Shamir, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel; Tel Aviv University, Tel Aviv, Israel; Peter Szitanyi, General University Hospital, First Faculty of Medicine, Charles University in Prague, Czech Republic; Merit Tabbers, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands; Chris van den Akker, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands; Hans van Goudoever, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, The Netherlands; Sacha Verbruggen, Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands; Cai Wei, Shanghai Jiao Tong University, Shanghai, China; Weihui Yan, Department of Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China) and the members of the ESPR Section on Nutrition, Gastroenterology and Metabolism (Fredrik Ahlsson, Uppsala University Children’s Hospital and Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden; Sertac Arslanoglu, Division of Neonatology, Department of Pediatrics, Istanbul Medeniyet University, Istanbul, Turkey; Wolfgang Bernhard, Department of Neonatology, Children’s Hospital, Faculty of Medicine, Eberhard-Karls- University, Tübingen, Germany; Janet Berrington, Newcastle Neonatal Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Signe Bruun, Hans Christian Andersen Hospital for Children and Adolescents, Odense University Hospital, Odense, Denmark; Christoph Fusch, Department of Pediatrics, Paracelsus Medical School, General Hospital of Nuremberg, Nuremberg, Germany; Shalabh Garg, South Tees Hospitals, Middlesborough, UK; Maria Gianni, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Ann Hellstrom, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Claus Klingenberg, Department of Pediatrics and Adolescence Medicine, University Hospital of North Norway, Tromsø, Norway; Helen Mactier, Neonatal Unit, Princess Royal Maternity Hospital, Glasgow, UK; Neena Modi, Section of Neonatal Medicine, Department of Medicine, Chelsea and Westminster Campus, Imperial College London, London, UK; Niels Rochow, Division of Neonatology, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada; Paola Rogerro, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Umberto Simeoni, Division of Pediatrics, CHUV & University of Lausanne, Lausanne, Switzerland; Atul Singhal, Paediatric Nutrition, UCL Great Ormond Street Institute of Child Health, London, UK.; Ulrich Thome, Department of Neonatology, Universitatsklinikum Leipzig, Leipzig, Germany; Anne Twomey, Department of Neonatology, The National Maternity Hospital, Dublin, Ireland; Mireille Vanpee, Karolinska University Hospital, Stockholm, Sweden; Gitte Zachariassen, Hans Christian Andersen Hospital for Children and Adolescents, Odense University Hospital, Odense, Denmark) for their vote., Parenteral nutrition is used to treat children that cannot be fully fed by the enteral route. While the revised ESPGHAN/ ESPEN/ESPR/CSPEN pediatric parenteral nutrition guidelines provide clear guidance on the use of parenteral nutrition in neonates, infants, and children based on current available evidence, they have helped to crystallize areas where research is lacking or more studies are needed in order to refine recommendations. This paper collates and discusses the research gaps identified by the authors of each section of the guidelines and considers each nutrient or group of nutrients in turn, together with aspects around delivery and organization. The 99 research priorities identified were then ranked in order of importance by clinicians and researchers working in the field using a survey methodology. The highest ranked priority was the need to understand the relationship between total energy intake, rapid catch-up growth, later metabolic function, and neurocognitive outcomes. Research into the optimal intakes of macronutrients needed in order to achieve optimal outcomes also featured prominently. Identifying research priorities in PN should enable research to be focussed on addressing key issues. Multicentre trials, better definition of exposure and outcome variables, and long-term metabolic and developmental follow-up will be key to achieving this.

Background Most infants with congenital cytomegalovirus (cCMV) have no overt manifestations at birth, yet may later develop CMV-related sensorineural hearing loss (SNHL). With targeted screening, many asymptomatic neonates are missed and lose the opportunity for timely anti-viral treatment to ameliorate SNHL. Saliva is the preferred screening specimen given its ease of collection. Objectives Assess a pooled saliva CMV DNA detection technique for cCMV screening of healthy full-term neonates. Study design We conducted a prospective laboratory CMV PCR screening study in a secondary hospital from March-June 2019. Saliva specimens were obtained from 1000 newborns two-four hours after birth. Specimens were analyzed for CMV DNA with a real-time PCR platform (Altona) in pools of 10 and individually (40 μL and 400 μL, respectively). Neonates with positive saliva CMV DNA detection required urine CMV PCR testing to confirm cCMV diagnosis. Results From the 1000 saliva samples, there were 6 urine-confirmed cCMV cases, yielding a prevalence rate of 0.6 %. The specificity was high for both pooled and individual saliva sampling (99.9 % and 98.1 %, respectively). The positive predictive value of the pooled sample was 85.7 %, compared to 24.0 % for a single saliva sample. Conclusions Pooling saliva of healthy newborns appears to be a reliable method to identify asymptomatic cCMV infection when positive results are confirmed by urine CMV DNA. Pooling in sizes appropriate to the cCMV prevalence rate may improve the laboratory workflow and decrease costs. Further studies should evaluate the clinical implications of this widespread cCMV pooled screening technique.

Mother's own human milk is the best nutrition for infants, especially preterm very-low-birth-weight (VLBW) (≤1,500 g) infants, because of its immune-modulatory constituents that strengthen the infant's host defense, provide protection against infections, and decrease the risk of necrotizing enterocolitis (NEC). When mother's own milk is unavailable or insufficient, donor human milk is considered the best alternative, especially for preterm VLBW infants. However, to assure biological safety, donor milk must be pasteurized. This results in partial or complete inactivation of some of the immunomodulatory constituents of human milk, which confer host defense. This review summarizes the current evidence regarding the effects of pasteurization on the different immunological constituents of donor milk, and their clinical significance, especially in relation to prevention of NEC.

ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Lipids

ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Energy

ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition : Standard versus individualized parenteral nutrition

The goals of early nutrition in preterm infants are to provide all the necessary vital nutrients, achieve extra-uterine growth rates similar to fetuses of the same gestational age, and support functional neurodevelopmental outcomes that are comparable to those of infants born at term. It is vital to provide nutrition that will maximally support brain growth and development, but over-feeding with accelerated growth, fat accumulation and long-term metabolic consequences should also be avoided. Because the morbidity associated with prematurity increases nutritional and energetic demands, the basic approach is of providing early intensive nutrition. Protein is the main driving force for growth and brain development. Since deficits in protein occur from the first day of extra-uterine life, sufficient quantities of parenteral amino acids should be provided from the first hours of life. With protein and carbohydrates, enough energy should also be provided, via concomitant early administration of intravenous lipid emulsions. Early initiation of enteral feeding with advancement to full enteral nutrition is associated with better maturation of the gut and better neuro-developmental outcomes. Human milk is the best food for preterm babies, although enrichment may be needed.

International audience; Background: Previous guidelines on Paediatric Parenteral Nutrition (PN) were published in 2010, by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), supported by the European Society of Paediatric Research (ESPR) were published. The aim of the present paper was to provide up-to-date evidence for health professionals working with infants, children and adolescents receiving PN. Methods: The current document is a revision of the 2005 guidelines produced by the same 3 organizations (ESPEN, ESPGHAN, ESPR) together with the Chinese Society of Parenteral and Enteral Nutrition (CSPEN). Experts participating in the guideline updating process were all professionals with extensive experience in managing PN from a wide range of European countries, Israel and China. The guideline development process was coordinated by a guideline steering committee. Each chapter of the guideline was prepared by a separate author group. These author groups were responsible for screening titles and abstracts identified by a systematic literature search for inclusion, for conducting additional expert searches (including secondary sources such as other published valid guidelines), for evaluating the quality of studies included in the given chapter and assigning evidence levels to the literature. Based on the evidence level of included studies experts formulated and graded recommendations. A consensus conference was held in February 2015. All chapter manuscripts were revised following the recommendations of the consensus conference and then reviewed and edited by the project steering committee. Final consensus on each individual guideline and its individual recommendations was achieved and assessed by online voting. This process lasted until January 2018. Funding for the consensus conference (including travel expenses for participants) was provided by all participating societies. No other funding was received for the guideline updating process and participants received no payment. Support was provided by the Hungarian Cochrane organization. Results/conclusions: The present document provides guideline for the use of PN across the wide range of pediatric patients, ranging from extremely premature infants up to teenagers weighing up to and over 100 kg [1]. It covers their individual macro- and micronutrient needs [2], [3], [4], [5], [6], [7], [8], fluid requirements [9], venous access [10], organizational aspects [11], home parenteral nutrition [12], standardized vs. individualized PN [13], and last but not least a wide range of safety considerations for prevention and management of complications such central line associated bloodstream infections (CLABSI)

Objective To evaluate the recommendations based on the early-onset sepsis (EOS) calculator in the first 2 years of its implementation in Israel. Study design Prospective 2-year surveillance of a cohort of infants born at gestational age of ≥34 weeks in Bnai Zion Medical Center, who were evaluated using the EOS calculator because of peripartum risk factors. Results We evaluate 1146 newborns with peripartum risk factors using the EOS calculator. The percentage of infants who had laboratory evaluation decreased to 4.6%, and the EOS calculator recommended empiric antibiotic therapy in only 2.2%. During the study period, there were 4 early-onset infections (EOS incidence of 0.6 in 1000 live births). Three had group B streptococcus (GBS) and one had Escherichia coli infection. Only 2 of these infants had perinatal risk factors and the EOS calculator identified them and recommended laboratory evaluation and empiric antibiotics. However, 2 infants with GBS EOS had no perinatal risk factors or clinical symptoms at delivery, and were discovered clinically at older ages. Conclusions The Israeli EOS calculator-based guidelines seem to be appropriate and are associated with less laboratory evaluations, and little use of empiric antibiotics. Concerns are related to the current recommendation of no GBS universal screening in Israel, and the inability of the calculator-based approach to identify GBS EOS in infants born to mothers with unknown GBS who have no peripartum risk factors before presentation of clinical symptoms.

Competency-based medical education (CBME) is a model aimed to address certain challenges and shortcomings attributed to the contemporary models of medical education and the medical profession in general. The CBME model has been used mainly in the education of undergraduate medical students with no continuation to residency, fellowship, or independent practice. In this review, we present a program based on the CBME model for the design and implementation of a new fellowship program in neonatology in Israel. As part of the program, we propose a mentorship program as a means to facilitate the implementation and acceptance of the program in the different wards. We designed assessment tools that can help the mentor track the fellow's development over time as well as to examine the impact of the proposed program on performance and on all stakeholders' satisfaction over time. We aim to evaluate the benefits and effectiveness of this CBME training not only on the fellows' abilities and performance outcomes, but also on the accompanying general organizational changes that can lead to general improvement in the neonatal profession in Israel.

BACKGROUND AND OBJECTIVES: Exposure to negative social interactions (such as rudeness) has robust adverse implications on medical team performance. However, little is known regarding the effects of positive social interactions. We hypothesized that expressions of gratitude, a prototype of positive social interaction, would enhance medical teams’ effectiveness. Our objective was to study the performance of NICU teams after exposure to expressions of gratitude from alternative sources. METHODS: Forty-three NICU teams (comprising 2 physicians and 2 nurses) participated in training workshops of acute care simulations. Teams were randomly assigned to 1 of 4 conditions: (1) maternal gratitude (in which the mother of a preterm infant expressed gratitude to NICU teams, such as the one that treated her child), (2) expert gratitude (in which a physician expert expressed gratitude to teams for participating in the training), (3) combined maternal and expert gratitude, or (4) control (same agents communicated neutral statements). The simulations were evaluated (5-point Likert scale: 1 = failed and 5 = excellent) by independent judges (blind to team exposure) using structured questionnaires. RESULTS: Maternal gratitude positively affected teams’ performances (3.9 ± 0.9 vs 3.6 ± 1.0; P = .04), with most of this effect explained by the positive impact of gratitude on team information sharing (4.3 ± 0.8 vs 4.0 ± 0.8; P = .03). Forty percent of the variance in team information sharing was explained by maternal gratitude. Information sharing predicted team performance outcomes, explaining 33% of the variance in diagnostic performance and 41% of the variance in therapeutic performance. CONCLUSIONS: Patient-expressed gratitude significantly enhances medical team performance, with much of this effect explained by enhanced information sharing.

ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition : Home parenteral nutrition

ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition : Fluid and electrolytes

The efficacy of inhaled steroids in spontaneously breathing infants with established bronchopulmonary dysplasia (BPD) is debatable. The inhaled steroid hydrofluoalkane-beclomethasone dipropionate (QVAR) is unique in its small particle size that results in higher lung deposition. Our objective was to determine if inhaled QVAR could decrease respiratory rehospitalizations of infants with established BPD.Double-blind, randomized placebo-controlled, multicenter pilot study. Preterm infants with moderate-to-severe BPD were randomized to inhaled QVAR 100 μg per dose or placebo twice daily via Aerochamber with face mask. Treatment was administered daily from recruitment at 36 weeks post menstrual age until 3 months post discharge. Analysis was carried out by intention to treat.The QVAR (n=18) and placebo (n=20) groups were comparable in birth and recruitment characteristics. Length of stay (108.5±26.3 vs 108.7±36.0 days) and infants requiring oxygen at discharge (5/17 vs 6/19) or at study end (0/17 vs 2/19) were comparable. Respiratory rehospitalizations/infant (0.1±0.5 vs 0.4±0.6), rehospitalization days (0.5±1.5 vs 4.1±10.3), and post-discharge additive inhaled (0.3±0.9 vs 6.4±21.5 days), systemic (0.7±2.8 vs 1.0±1.4 days) and combined (inhaled/systemic) steroids (1.0±2.9 vs 7.8±25.8 days) tended to be lower in the QVAR compared with the placebo group. Blood pressure, height and weight gain, and urine cortisol/creatinine ratio at study end were comparable between groups.Our study was unable to detect a significant effect of inhaled QVAR on the respiratory course of established BPD. The study was underpowered. Possible benefits of QVAR could be masked by a tendency toward higher use of additional steroids in the placebo group.

Objective Although its incidence is declining with the widespread use of intrapartum antibiotics, early-onset sepsis (EOS) continues to be associated with high morbidity and mortality. Maternal, infant, and peripartum risk factors, as well as infant's laboratory tests, have been used to try and identify asymptomatic newborns at risk. In this study, we reevaluate the management of newborns at risk for EOS by comparing our outcomes using two different approaches. Study Design Comparison of clinical data and outcomes of newborns at risk for EOS between two study periods, in which we have used two different protocols for their evaluation and management. Results Although outcomes were not different, adoption of the criteria suggested in the 2012 American Academy of Pediatrics guidelines in the second era resulted in increased utilization of diagnostic laboratory tests and increased use of empiric antibiotic treatments with less yield in a population with a low incidence of EOS (< 0.3/1,000 live births), such as ours. Conclusion In asymptomatic newborns at risk for EOS, careful assessment of a set of maternal, infant, and peripartum risk factors and their severity combined with careful clinical observation, judicious use of laboratory evaluations, and empiric antibiotic treatment only in selected cases seem to be appropriate.

Healthy social-emotional development in early childhood is important as an indicator of general well-being and for positive outcome in later childhood. Therefore, screening for potential social emotional problems is valuable. Accurate, usable, and affordable screening tools have been especially difficult to develop. The cross cultural validity of a screening instrument should be assessed. The aim of the current study was to investigate the reliability and validity of the Greenspan social–emotional growth chart (GSEGC) in Israeli children of three diagnostic groups: (1) Autistic spectrum disorder (ASD) (2) Developmental language disorder (DLD) and (3) Developmental motor delay (DMD). An internal reliability of alpha of 0.95 for the GSEGC standardized for age score and of 0.78 for the sensory processing sub scores was found. A confirmatory factor analysis (CFA) using a 5-factor model confirmed an acceptable fit. Positive (62.86%) and negative (94.73%) predictive values also support the clinical usefulness of the GSEGC in identifying children at low risk for ASD. Conclusions:The GSEGC appears to be a promising tool for the screening of social emotional problems in early childhood. Further studies in different cultures are warranted.

Background: Phototherapy has been reported to alter blood flow to various tissues. We hypothesized that during phototherapy the coronary blood flow will decrease because of a ‘steal effect' to the periphery. Objectives: To evaluate the effects of phototherapy on coronary blood flow in healthy, jaundiced, term neonates. Methods: Flow velocity [peak diastolic velocity (Vd)] and flow measures [diastolic time velocity integral (TVId) and flow index (FI)] in the left main (LM) and left anterior descending (LAD) coronary arteries were prospectively studied with 2D/pulsed Doppler ultrasound before, during and after phototherapy in 19 healthy term, jaundiced neonates (study group) and in matched nonjaundiced controls (25 neonates). Significance was set at p < 0.05. Results: The neonates' characteristics were comparable in both groups. Sequential studies in the study group showed no significant decrease in measures of velocity and flow during phototherapy; however, there was a significant increase in some of these measures (Vd and TVId in the LM coronary artery, and Vd in the LAD coronary artery) after phototherapy. Velocity (Vd) and flow measures (TVId and FI) in the LAD coronary artery, but not in the LM coronary artery, were significantly lower when comparing the study group during phototherapy with the controls. In a multivariate model, phototherapy was an independent variable affecting Vd and TVId in LAD coronary arteries. Measures of cardiac output did not change significantly throughout the study. Conclusions: While part of our findings may suggest a modestly lower flow in coronary arteries during phototherapy, we conclude that no clinically significant alteration in coronary arterial flow occurs during phototherapy in healthy term neonates.

Background: Previous guidelines on Paediatric Parenteral Nutrition (PN) were published in 2010, by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), supported by the European Society of Paediatric Research (ESPR) were published. The aim of the present paper was to provide up-to-date evidence for health professionals working with infants, children and adolescents receiving PN. Methods: The current document is a revision of the 2005 guidelines produced by the same 3 organizations (ESPEN, ESPGHAN, ESPR) together with the Chinese Society of Parenteral and Enteral Nutrition (CSPEN). Experts participating in the guideline updating process were all professionals with extensive experience in managing PN from a wide range of European countries, Israel and China. The guideline development process was coordinated by a guideline steering committee. Each chapter of the guideline was prepared by a separate author group. These author groups were responsible for screening titles and abstracts identified by a systematic literature search for inclusion, for conducting additional expert searches (including secondary sources such as other published valid guidelines), for evaluating the quality of studies included in the given chapter and assigning evidence levels to the literature. Based on the evidence level of included studies experts formulated and graded recommendations. A consensus conference was held in February 2015. All chapter manuscripts were revised following the recommendations of the consensus conference and then reviewed and edited by the project steering committee. Final consensus on each individual guideline and its individual recommendations was achieved and assessed by online voting. This process lasted until January 2018. Funding for the consensus conference (including travel expenses for participants) was provided by all participating societies. No other funding was received for the guideline updating process and participants received no payment. Support was provided by the Hungarian Cochrane organization. Results/conclusions: The present document provides guideline for the use of PN across the wide range of pediatric patients, ranging from extremely premature infants up to teenagers weighing up to and over 100 kg [1]. It covers their individual macro- and micronutrient needs [2], [3], [4], [5], [6], [7], [8], fluid requirements [9], venous access [10], organizational aspects [11], home parenteral nutrition [12], standardized vs. individualized PN [13], and last but not least a wide range of safety considerations for prevention and management of complications such central line associated bloodstream infections (CLABSI)

ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Carbohydrates