Significant correlation between serum biomarkers and outcome in neonatal hypoxic-ischaemic encephalopathy.

AIM: Associations between serum biomarkers S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) in neonates with hypoxic-ischaemic encephalopathy (HIE) offer contradicting data in regard to neurocognitive outcome. The aim of our study was to provide another dataset to answer this question if S100B or NSE correlates to outcome in neonatal HIE. In addition, we investigate whether amplitude-integrated EEG (aEEG) or magnetic resonance imaging (MRI) also has predictive value. METHODS: In neonates with HIE born in Vorarlberg, Austria, (n = 34) from 2012to 2020, NSE and S100B serum levels were measured on day one. aEEG was installed at admission and MRI performed within 7 days. Surviving children (n = 27) were categorised as good or poor outcome by using an age-appropriate neurocognitive test and a standardised neurological follow-up. Positive and negative predictive values and receiver operating characteristic curves were calculated to evaluate the prognostic value. RESULTS: S100B showed best positive and negative predictive value, 72.7% and 90.5%, respectively, and a significant area under the curve of 0.820. NSE showed a positive and a negative predictive value of 43.8% and 81.3% and an area under the curve of 0.757. Severely abnormal aEEG and abnormal MRI significantly correlated with outcome (p = 0.024 and 0.001 respectively). CONCLUSION: S100B and NSE on day one, severely abnormal aEEG and abnormal MRI show a significant correlation and good predictive value for neurocognitive outcome.

Two-year neurodevelopmental outcome in extremely preterm-born children: The Austrian Preterm Outcome Study Group.

AIM: The current study determined the neurodevelopmental outcome of extremely preterm infants at 2 years of age. METHODS: All live-born infants 23-27 weeks of gestation born between 2011 and 2020 in Austria were included in a prospective registry. Neurodevelopmental outcome at 2 years of corrected age was assessed using Bayley Scales of Infant Development for both motor and cognitive scores, along with a neurological examination and an assessment of neurosensory function. RESULTS: 2378 out of 2905 (81.9%) live-born infants survived to 2 years of corrected age. Follow-up data were available for 1488 children (62.6%). Overall, 43.0% had no, 35.0% mild and 22.0% moderate-to-severe impairment. The percentage of children with moderate-to-severe neurodevelopmental impairment decreased with increasing gestational age and was 31.4%, 30.5%, 23.3%, 19.0% and 16.5% at 23, 24, 25, 26 and 27 weeks gestational age (p < 0.001). Results did not change over the 10-year period. In multivariate analysis, neonatal complications as well as male sex were significantly associated with an increased risk of neurodevelopmental impairment. CONCLUSION: In this cohort study, a 22.0% rate of moderate-to-severe neurodevelopmental impairment was observed among children born extremely preterm. This national data is important for both counselling parents and guiding the allocation of health resources.

Outcome in very preterm infants: a population-based study from a regional center in Austria.

Aim: To determine short-term morbidity and mortality rates in the first state-wide Austrian neonatal cohort and comparison to (inter)national data. Methods: Observational, population-based cohort study, analyzing data of preterm infants (<32 + 0 weeks of gestation) born between 2007 and 2020 (n = 501) in an Austrian state who were admitted to the neonatal intensive care unit. Outcome criteria were mortality, neonatal morbidities: bronchopulmonary dysplasia (BPD), severe necrotizing enterocolitis (NEC), severe intraventricular hemorrhage (IVH grades III-IV), severe retinopathy of prematurity (ROP grades III-V) and survival-free of major complications. Results: Overall survival rate was 95%, survival free of major complications was 79%. Prevalence for BPD was 11.2%, surgical NEC 4.0%, severe IVH 4.6%, and for severe ROP 2.6%, respectively. In the extremely low gestational age neonates (ELGAN) born <28 weeks of gestation (n = 158), survival was 88% and survival free of major complications 58.8%. Over time, mortality decreased significantly, predominantly driven by the improvement of infants born <28 week of gestation and survival free of major complications improved. Conclusions: This study demonstrates a very low mortality rate that decreases over time. Short-term morbidities and survival free of major complications do not differ from (inter)national data in a similar group of very preterm infants. Standard operating procedures, simulation trainings and accordance to international trials may improve patient care and surpass center case loads.

Psychomotor and Cognitive Outcome in Very Preterm Infants in Vorarlberg, Austria, 2007-2019.

AIM: The aim of this study was to analyze neurodevelopmental outcome of very and extremely preterm infants in Vorarlberg, Austria, accessed with neurodevelopmental testing, at the corrected age of 24 months. This article also compared these results with (inter)national data and analyzed the impact of perinatal parameters. METHODS: Population-based, retrospective multicenter study with data on very and extremely preterm infants born in Vorarlberg from 2007 to 2019 assessed with Bayley Scales of Infant Development (BSID-II/Bayley-III). RESULTS: Included were 264 infants with a mean age of 29.0 (± 2.1) weeks of gestational age and a mean birth weight of 1177 (± 328.26) g; 172 infants underwent a BSID-II, 92 a Bayley-III assessment. The psychomotor developmental index (PDI) and mental developmental index (MDI) showed mean scores of 99.6 (± 14.4) and 91 (± 20.4), respectively. Adverse outcomes (scores <70) were assessed in 4.2% for PDI and 15.5% for MDI. In the extremely preterm group (n = 79), results for mean PDI were 100.1 (± 16.8) and for mean MDI 88.4 (± 22.4). Accordingly, adverse outcomes were assessed in 5.1% for PDI and in 20.3% for MDI. In addition to bronchopulmonary dysplasia and intraventricular hemorrhage Grade 3-4, head circumference at birth and patent ductus arteriosus were also identified as risk factors for poor outcome. CONCLUSION: This study showed a remarkably good neurodevelopmental outcome in preterm infants with low rates of adverse outcome, similar to (inter)national reports, especially in the group of extremely preterm infants. Research is needed to explore the role of social factors and infants' environment, especially cognitive outcome and language skills.

Eye-tracking during simulated endotracheal newborn intubation: a prospective, observational multi-center study.

BACKGROUND: The aim was to assess health care providers' (HCPs) visual attention (VA) by using eye-tracking glasses during a simulated neonatal intubation. METHODS: HCPs from three pediatric and neonatal departments (Feldkirch and Vienna, Austria, and Edmonton, Canada) completed a simulated neonatal intubation scenario while wearing eye-tracking glasses (Tobii Pro Glasses 2®, Tobii, Stockholm, Sweden) to record their VA. Main outcomes included duration of intubation, success rate, and VA. We further compared orotracheal and nasotracheal intubations. RESULTS: 30 participants were included. 50% completed the intubation within 30 s (M = 35.40, SD = 16.01). Mostly nasotracheal intubations exceeded the limit. Experience was an important factor in reducing intubation time. VA differed between more and less experienced HCPs as well as between orotracheal and nasotracheal intubations. Participants also focused on different areas of interest (AOIs) depending on the intubator's experience. More experience was associated with a higher situational awareness (SA) and fewer distractions, which, however, did not transfer to significantly better intubation performance. CONCLUSION: Half of the intubations exceeded the recommended time limit. Differences in intubation duration depending on type of intubation were revealed. VA differed between HCPs with different levels of experience and depended on duration and type of intubation. IMPACT: Simulated neonatal intubation duration differs between orotracheal and nasotracheal intubation. Visual attention during simulated neonatal intubation shows differences depending on intubation duration, intubator experience, type of intubation, and level of distraction. Intubator experience is a vital parameter for reducing intubation duration and improving intubator focus on task-relevant stimuli.

Video-Recorded In Situ Simulation Before Moving to the New Combined Neonatal/Pediatric Intensive Care Facility: An Observational Study.

OBJECTIVES: Moving an ICU to a new location is a challenge. The objective of this study was to use in situ simulation to identify potential problems and solutions with the new environment before commencing patient care. DESIGN: Planned, observational video-recorded simulation study using four scenarios: delivery room management of term-neonate; delivery room management of extremely low-birth-weight infant; management and transfer of an infant with respiratory syncytial virus bronchiolitis and apnea; and management and transfer of an adolescent with septic shock. SETTING: Academic tertiary neonatal and combined neonatal ICU/PICU. PARTICIPANTS: Sixteen volunteers (eight physicians, eight nurses). INTERVENTIONS: Standardized briefing introduction, with before versus after survey of thoughts about each scenario, and after 8 weeks, debriefing at least 60 minutes and additional video recording. MEASUREMENTS AND MAIN RESULTS: A total of 91 potential problem areas were identified and included issues related to technical aspects ( n = 29), infrastructure ( n = 27), administration ( n = 19), and structure ( n = 16). Fifty-three (58%) of these potential issues could be resolved before the move, including: 15 of 29 technical, 15 of 27 infrastructure, nine of 19 administration, and 14 of 16 structural. The video analysis revealed an additional 13 problem areas (six technical, three infrastructure, two administration, and two structural). Participants felt more confident 8 weeks after the simulations (χ 2 = 12.125; p < 0.002). All 16 participants confirmed the usefulness of the in situ simulation, the majority wanted further introductions to the new ward ( n = 13) and noted a positive impact of the changes on the new ward ( n = 12). CONCLUSIONS: In situ simulation before moving into a new facility identifies numerousness potential problem areas. Survey shows that providers feel better prepared and are more confident. Video recording reveals additional difficulties not addressed in conventional verbal debriefing.

Preclinical Pediatric Care by Emergency Physicians: A Comparison of Trauma and Nontrauma Patients in a Population-Based Study in Austria.

OBJECTIVES: Fewer than 10% of emergency medical system (EMS) calls concern children and adolescents younger than 18 years. Studies have shown that the preclinical care of children differs from that of adults regarding assessment, interventions, and monitoring. The aims of this study were to describe the preclinical care and emergency transport of pediatric patients in Vorarlberg, Austria and to compare trauma and nontrauma cases. METHODS: This is a population-based study, analyzing medical records of EMS calls to children and adolescents. We received all patient records of EMS calls to children and adolescents younger than 18 years (n = 4390 in total) from the 2 local EMS providers, the Red Cross Vorarlberg and the Austrian Mountain Rescue Service (Christophorus 8 and Gallus 1) covering a study period of 7 years, from 2013 to 2019. The record data were extracted by automation with an in-house program and subsequently anonymized. Statistical analyses were performed with SPSS Statistics. RESULTS: During the study period, 7.9% of all EMS calls concerned children and adolescents younger than 18 years. For our study, 3761 records were analyzed and 1270 trauma cases (33.8%) were identified. The most common injuries were injuries of the extremities and traumatic brain injury. The frequency of National Advisory Committee of Aeronautics Scores of 4 or higher was 17.7%, similar for all age groups and for trauma as well as nontrauma patients. Mean Glasgow Coma Scale scores were higher in the trauma group than in the nontrauma group (14.2 vs 11.2). In 62.9% of all patients, 1 or more vital parameters were documented. A majority of these values was in the pathologic range for the respective age group. The rate of pulsoxymetry monitoring during transport was low (42.1% in trauma and 30.3% in nontrauma patients) and decreased significantly with patient age. Moreover, while the placing of intravenous lines and monitoring during transport were significantly more frequent in trauma patients, the administration of medication or oxygen was significantly more frequent in nontrauma patients. CONCLUSIONS: The pediatric population lacks assessments and monitoring in preclinical care, especially the youngest children and nontrauma patients, although emergency severity scores are similar.

Impact of Pediatric Emergency Care Applied Research Network Rules on Admission, Cranial Computed Tomography and Skull X-ray Rates in a Central European Hospital.

OBJECTIVES: Mild head injury is a common cause of pediatric emergency department visits. Cranial computed tomography (CCT) is the diagnostic standard, although it involves inherent radiation risks. Pediatric Emergency Care Applied Research Network (PECARN) clinical prediction rules were developed to reduce the number of CCT scans. They provide a guideline for CCT use in mild head injuries, based on clinical parameters.Our study aims to evaluate the impact of PECARN rules on hospital admission and CCT rate in children with mild head injury. METHODS: In this retrospective study, we investigated 729 children with mild head injury presenting in the pediatric emergency department between 2012 and 2016. We compared 2 groups, before and after implementation of PECARN criteria in clinical routine. RESULTS: Of 729 included patients (417 male; 5.6 ± 4.8 years;) 380 were seen prior to implementation of the PECARN rules, compared to 349 patients afterwards. Overall admissions to the ward decreased significantly from 83.9% (n = 319) to 71.3% (n = 249) (P < 0.001), a 31.3% reduction. Calculated from all pediatric admissions, the rate of patients with mild head injury fell from 6.0% to 4.3% (P < 0.001).We recorded a nonsignificant decrease in the CCT rate, from 14.7% to 13.2% (P = 0.555).No readmissions were recorded. CONCLUSIONS: Our results show a significant reduction in the rate of hospital admission following implementation of the PECARN rules in our hospital. Already low, the CCT rate did not change after implementation.The PECARN rules appear to be safe because no readmissions were recorded.

A critical appraisal of tools for delivery room assessment of the newborn infant.

Assessment of an infant's condition in the delivery room represents a prerequisite to adequately initiate medical support. In her seminal paper, Virginia Apgar described five parameters to be used for such an assessment. However, since that time maternal and neonatal care has changed; interventions were improved and infants are even more premature. Nevertheless, the Apgar score is assigned to infants worldwide but there are concerns about low interobserver reliability, especially in preterm infants. Also, resuscitative interventions may preclude the interpretation of the score, which is of concern when used as an outcome parameter in delivery room intervention studies. Within the context of these changes, we performed a critical appraisal on how to assess postnatal condition of the newborn including the clinical parameters of the Apgar score, as well as selected additional parameters and a proposed new scoring system. The development of a new scoring system that guide clinicians in assessing infants and help to decide how to support postnatal adaptation is discussed. IMPACT: This critical paper discusses the reliability of the Apgar score, as well as additional parameters, in order to improve assessment of a newborn's postnatal condition. A revised neonatal scoring system should account for infant maturity and the interventions administered. Delivery room assessment should be directed toward determining how much medical support is needed and how the infant responds to these interventions.

Effects of an exclusive human-milk diet in preterm neonates on early vascular aging risk factors (NEOVASC): study protocol for a multicentric, prospective, randomized, controlled, open, and parallel group clinical trial.

BACKGROUND: Preterm birth accounts for approximately 11% of all livebirths globally. Due to improvements in perinatal care, more than 95% of these infants now survive into adulthood. Research has indicated a robust association between prematurity and increased cardiovascular risk factors and cardiovascular mortality. While the innate adverse effects of prematurity on these outcomes have been demonstrated, therapeutic strategies on the mitigation of these concerning developments are lacking. The primary objective of the NEOVASC clinical trial is therefore to investigate whether the administration of a prolonged exclusive human-milk diet in preterm infants is capable of alleviating the harmful effects of preterm birth on the early development of cardiovascular risk factors. METHODS: The NEOVASC study is a multicentric, prospective, randomized, controlled, open, and parallel group clinical trial conducted in four Austrian tertiary neonatal care facilities. The purpose of the present trial is to investigate the effects of a prolonged exclusive human-milk-diet devoid of bovine-milk-based food components on cardiovascular and metabolic risk factors at 1, 2, and 5 years of corrected age. Primary outcomes include assessments of fasting blood glucose levels, blood pressure levels, and the distensibility of the descending aorta using validated echocardiographic protocols at 5 years of corrected age. The test group, which consists of 200 preterm infants, will therefore be compared to a control group of 100 term-born infants and a historical control group recruited previously. DISCUSSION: Given the emerging implications of an increased cardiovascular risk profile in the potentially growing population of preterm infants, further research on the mitigation of long-term morbidities in formerly preterm infants is urgently warranted. Further optimizing preterm infants' nutrition by removing bovine-milk-based food components may therefore be an interesting approach worth pursuing. TRIAL REGISTRATION: ClinicalTrials.gov NCT04413994 . Registered on 4 June 2020.

Adherence to Guidelines in the Treatment of Diabetic Ketoacidosis in Children: An Austrian Survey.

BACKGROUND: The aim of this study is to assess the adherence of Austrian physicians to International Society for Pediatric and Adolescent Diabetes guidelines 2009 concerning treatment in diabetic ketoacidosis and whether there is a difference between specialty (endocrinologists or intensivists) or clinical experience. PATIENTS AND METHODS: An online questionnaire was sent to members of the working groups of the Austrian Society of Pediatric and Adolescent Medicine. RESULTS: Of 106 questionnaires, 56 were included in the analysis. The mean ± SD overall adherence was 60 ± 23.5%. Endocrinologists showed a nonsignificant higher result, related to a significant higher adherence regarding the amount of fluids (P < 0.05) and tendency to bicarbonate use (P = 0.052) respectively. No differences were found between participants with different clinical experience. All gave crystalloids, 55% administered initial bolus of 10 to 20 mL/kg per hour, 58% used 1.5 to 2 times fluid maintenance, 87% started insulin after first fluid bolus, 28% gave 0.05 and 0.1 IE/kg per hour to infants and children respectively, and 43% 0.05 IE/kg per hour to all patients. When blood glucose falls, 53% gave glucose and 47% reduced insulin. In cerebral edema, 46% gave at least 2 of 3 recommended measures (fluid reduction, mannitol, or hypertonic saline). In acidosis (pH <6.9), 25% administered bicarbonate (as per guideline) and 52.9% never gave bicarbonate. CONCLUSIONS: Adherence to the actual guidelines is 60% and does neither depend on speciality nor on clinical routine. Essential treatment measures (eg, amount of fluids, consequence of rapid glucose fall, bicarbonate use) are not commonly known.

Chorioamnionitis and neurodevelopmental outcome in very preterm infants from 2007 to 2017-a population-based study.

AIM: The study compares neurodevelopmental outcome at 24 months corrected age of very preterm infants exposed to chorioamnionitis and controls. Peripartal parameters which may influence outcome are also investigated. METHODS: In this observational population-based study, very preterm infants born between 2007 and 2017 were eligible (n = 466) and included if a histological placental examination and a complete neurodevelopmental assessment (Bayley Scale of Infant Development II or III) (n = 168) were performed. Secondary analyses were calculated to identify peripartal factors that significantly influence mental and psychomotor outcome. RESULTS: Included infants showed a mean MDI of 91.2 (SD = 20.7) and a mean PDI of 99.4 (SD = 14.8). Infants with (n = 71) and without (n = 97) chorioamnionitis did not statistically differ either with mean MDI (91.8 vs. 90.3 points; p = 0.29) or mean PDI (98.3 vs. 100.9 points; p = 0.81), even after controlling for gestational age, mean APGAR scores and administration of antenatal steroids. Bronchopulmonary dysplasia was identified as the most influential factor for both MDI (p = .024) and PDI (p = .004). CONCLUSION: We could not find an effect of chorioamnionitis on neurodevelopmental outcome of very preterm infants over an eleven-year period. Analysis shows that postnatal factors have higher impacts than does chorioamnionitis.

Delivery Room Management of Infants with Very Low Birth Weight in 3 European Countries-The Video Apgar Study.

OBJECTIVE: To assess delivery room management of infants born preterm at 4 Level III perinatal centers in 3 European countries. STUDY DESIGN: This was a prospective, multicenter observational study. Management at birth was video-recorded and evaluated (Interact version 9.6.1; Mangold-International, Arnstorf, Germany). Data were analyzed and compared within and between centers. RESULTS: The infants (n = 138) differed significantly with respect to the median (25%, 75%) birth weight (grams) (Center A: 1200 [700, 1550]; Center B: 990 [719, 1240]; Center C: 1174 [835, 1435]; Center D: 1323 [971, 1515] [B vs A, C, D: P < .05]), gestational week (Center A: 28.4 [26.3, 30.0]; Center B: 27.9 [26.7, 29.6]; Center C: 29.3 [26.4, 31.0]; Center D: 30.3 [28.0, 31.9]), Apgar scores, rates of cesarean delivery, and time spent in the delivery room. Management differed significantly for frequency and drying time, rates of electrocardiographic monitoring, suctioning or stimulation, and for fundamental interventions such as time for achieving a reliable peripheral oxygen saturation signal (seconds) (Center A: 97.6 ± 79.3; Center B: 65.1 ± 116.2; Center C: 97.1 ± 67.0; Center D: 114.4 ± 140.5; B vs A, C, D: P < .001) and time for intubation (seconds) (Center A: 48.7 ± 4.2; Center B: 49.0 ± 30.7; Center C: 69.1 ±37.9; Center D: 65.1 ± 23.8; B vs D, P < .025). Mean procedural times did not meet guideline recommendations. The sequence of interventions was similar at all centers. CONCLUSIONS: The Video Apgar Study showed great variability in and between 4 neonatal centers in Europe. The study also showed it is difficult to adhere to published guidelines for recommended times for important, basic measures such as peripheral oxygen saturation measurements and intubation.

A Syrian patient with Steel syndrome due to compound heterozygous COL27A1 mutations with colobomata of the eye.

The joint occurrence of short stature, congenital dislocation of the hip, carpal coalition, dislocation of the radial head, cavus deformity, scoliosis, and vertebral anomalies was first described in 1993 by Steel et al. (OMIM #615155) in 23 children from Puerto Rico. The condition is caused by a deficient matrix protein, collagen type XXVII alpha 1 chain, due to bi-allelic loss of function mutations in the gene COL27A1. Outside of Puerto Rico, only four families have been described, in three of which the patients also had hearing loss. However, structural eye defects have not yet been reported in conjunction with this rare autosomal recessive syndrome. Here, we describe a 9-year-old girl born to nonconsanguineous Syrian parents with the characteristic features of Steel syndrome, including short stature, massive malalignment of large joints, kyphoscoliosis, hearing loss, and typical facial dysmorphism. However, she was also born with bilateral colobomata of the irides and choroido-retinae with unilateral affection of the macula. Whole exome sequencing identified two pathogenic compound heterozygous variants in COL27A1: c.93del, p.(Phe32Leufs*71) and c.3075del, p.(Lys1026Argfs*33). There was no discernible alternative cause for the colobomata. Our findings might indicate an association of this exceptionally rare disorder caused by COL27A1 mutations with developmental defects of the eye from the anophthalmia/microphthalmia/coloboma spectrum.

Incidence of hypoglycemia in newborn infants identified as at risk.

Background: Temporary low plasma glucose concentrations are common in healthy newborns. Although there is no uniform definition of neonatal hypoglycemia, there is a consensus in the current literature that plasma glucose concentrations should be measured in infants at risk. Known risk groups for transient neonatal hypoglycemia include infants of diabetic mothers (IDM), large (LGA) or small (SGA) for gestational age and late preterm (LPT) infants.Objectives: The aim of this retrospective trial was to determine the incidence of hypoglycemia and the impact of the application of a 2011 revised guideline in respect of additional feeding or i.v. glucose administration, admission to a neonatal ward and the number of blood samples taken.Methods: During the period 1 January 2015 to 31 January 2016, the plasma glucose concentrations of all infants at risk were determined. They were screened over a period of 24 hours or until plasma glucose concentration was >45 mg/dL on three occasions. Hypoglycemia was defined as a plasma glucose concentration <40 mg/dL, regardless of the age of the infant.Results: One hundred and thirty-six (13.6%) out of 1017 newborns were identified as at-risk patients, 119 (87.5%) of whom were included in the final data evaluation. Ten study participants had more than one risk factor and 32 (26.9%) newborns (male:female = 1.1:1) had a total of 40 hypoglycemic episodes. Three (9.4%) out of these 32 newborns had to be transferred to the neonatal ward for i.v. glucose treatment. The mean number of blood samples taken was 7.6 ± 2.4.Conclusions: The incidence of hypoglycemia in the studied infants at risk was 27%, and 19.7 blood samples had to be taken to detect one episode of low glucose concentration. Neonatal hypoglycemia can be recognized and avoided in time, which justifies the establishment of a standardized plasma glucose measurement protocol in newborn infants at risk.Brief RationaleFollowing a considerable number of sources, it is recommended that infants at risk be identified, low plasma glucose concentrations prevented and, if necessary, the affected neonates cared for. Our data show that the risk group for neonatal hypoglycemia comprised about one-tenth of all infants at our nursery and hypoglycemia occurred in one-fourth. These results are in accordance with the recommendations to implement this protocol as a screening tool in neonates.

Effect of Sustained Inflations vs Intermittent Positive Pressure Ventilation on Bronchopulmonary Dysplasia or Death Among Extremely Preterm Infants: The SAIL Randomized Clinical Trial.

Importance: Preterm infants must establish regular respirations at delivery. Sustained inflations may establish lung volume faster than short inflations. Objective: To determine whether a ventilation strategy including sustained inflations, compared with standard intermittent positive pressure ventilation, reduces bronchopulmonary dysplasia (BPD) or death at 36 weeks' postmenstrual age without harm in extremely preterm infants. Design, Setting, and Participants: Unmasked, randomized clinical trial (August 2014 to September 2017, with follow-up to February 15, 2018) conducted in 18 neonatal intensive care units in 9 countries. Preterm infants 23 to 26 weeks' gestational age requiring resuscitation with inadequate respiratory effort or bradycardia were enrolled. Planned enrollment was 600 infants. The trial was stopped after enrolling 426 infants, following a prespecified review of adverse outcomes. Interventions: The experimental intervention was up to 2 sustained inflations at maximal peak pressure of 25 cm H2O for 15 seconds using a T-piece and mask (n = 215); standard resuscitation was intermittent positive pressure ventilation (n = 211). Main Outcome and Measures: The primary outcome was the rate of BPD or death at 36 weeks' postmenstrual age. There were 27 prespecified secondary efficacy outcomes and 7 safety outcomes, including death at less than 48 hours. Results: Among 460 infants randomized (mean [SD] gestational age, 25.30 [0.97] weeks; 50.2% female), 426 infants (92.6%) completed the trial. In the sustained inflation group, 137 infants (63.7%) died or survived with BPD vs 125 infants (59.2%) in the standard resuscitation group (adjusted risk difference [aRD], 4.7% [95% CI, -3.8% to 13.1%]; P = .29). Death at less than 48 hours of age occurred in 16 infants (7.4%) in the sustained inflation group vs 3 infants (1.4%) in the standard resuscitation group (aRD, 5.6% [95% CI, 2.1% to 9.1%]; P = .002). Blinded adjudication detected an imbalance of rates of early death possibly attributable to resuscitation (sustained inflation: 11/16; standard resuscitation: 1/3). Of 27 secondary efficacy outcomes assessed by 36 weeks' postmenstrual age, 26 showed no significant difference between groups. Conclusions and Relevance: Among extremely preterm infants requiring resuscitation at birth, a ventilation strategy involving 2 sustained inflations, compared with standard intermittent positive pressure ventilation, did not reduce the risk of BPD or death at 36 weeks' postmenstrual age. These findings do not support the use of ventilation with sustained inflations among extremely preterm infants, although early termination of the trial limits definitive conclusions. Trial Registration: clinicaltrials.gov Identifier: NCT02139800.

Nocturnal asthma is affected by genetic interactions between RORA and NPSR1.

BACKGROUND: Neuropeptide S Receptor 1 ( NPSR1) and Retinoid Acid Receptor-Related Orphan Receptor Alpha (RORA ) interact biologically, are both known candidate genes for asthma, and are involved in controlling circadian rhythm. Thus, we assessed (1) whether interactions between RORA and NPSR1 specifically affect the nocturnal asthma phenotype and (2) how this may differ from other asthma phenotypes. METHODS: Interaction effects between 24 single-nucleotide polymorphisms (SNPs) in RORA and 35 SNPs in NPSR1 on asthma and nocturnal asthma symptoms were determined in 1432 subjects (763 asthmatics [192 with nocturnal asthma symptoms]; 669 controls) from the Multicenter Asthma Genetic in Childhood/International Study of Asthma and Allergies in Childhood studies. The results were validated and extended in children from the Manchester Asthma and Allergy Study (N = 723) and the Children Allergy Milieu Stockholm and Epidemiological cohort (N = 1646). RESULTS: RORA* NPSR1 interactions seemed to affect both asthma and nocturnal asthma. In stratified analyses, however, interactions mainly affected nocturnal asthma and less so asthma without nocturnal symptoms or asthma severity. Results were replicated in two independent cohorts and seemed to remain constant over time throughout youth. CONCLUSION: RORA* NPSR1 interactions appear to be involved in mechanisms specific for nocturnal asthma. In contrast to previous studies focusing on the role of beta 2 receptor polymorphisms in nocturnal asthma as a feature of asthma control or severity in general, our data suggest that changes in circadian rhythm control are associated with nighttime asthma symptoms.

High Prevalence and Incidence of Diabetic Peripheral Neuropathy in Children and Adolescents With Type 1 Diabetes Mellitus: Results From a Five-Year Prospective Cohort Study.

BACKGROUND: In this prospective cohort study, we investigated the prevalence of diabetic peripheral neuropathy at baseline and after five years of follow-up in children and adolescents with type 1 diabetes mellitus using both measurements of nerve conduction velocity and clinical neurological examination. METHODS: A total of 38 patients who underwent insulin pump or intensive insulin therapy were included. The subjects averaged 12.6 ± 2.4 years of age and their diabetes duration averaged 5.6 ± 3.2 years. All patients underwent a detailed physical, neurological, and electrophysiological examination, as well as laboratory testing at their annual checkup. RESULTS: At baseline, the prevalence of diabetic peripheral neuropathy diagnosed using neurological examination was 13.2%, whereas nerve conduction velocity testing revealed diabetic peripheral neuropathy in 31.6%, highlighting a high prevalence of subclinical diabetic peripheral neuropathy. During follow-up, there was a strong increase in the prevalence of clinically diagnosed diabetic peripheral neuropathy, which reached 34.2% (P = 0.039) after five years; the proportion of patients with subclinical diabetic peripheral neuropathy even reached 63.2% (P = 0.002). The most significant changes in electrophysiological parameters were observed in the tibial sensory nerve (P = 0.001). CONCLUSIONS: The prevalence of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus was high, and there was a rapid increase in the prevalence of diabetic peripheral neuropathy during a five-year follow-up interval. Importantly, our data show that a mere clinical evaluation is not sensitive enough to diagnose diabetic peripheral neuropathy in these patients. Nerve conduction velocity measurement, which is regarded as the gold standard for the assessment of diabetic peripheral neuropathy, should be applied more broadly.

Doublesex and mab-3 related transcription factor 1 (DMRT1) is a sex-specific genetic determinant of childhood-onset asthma and is expressed in testis and macrophages.

BACKGROUND: Asthma is a disease affecting more boys than girls in childhood and more women than men in adulthood. The mechanisms behind these sex-specific differences are not yet understood. OBJECTIVE: We analyzed whether and how genetic factors contribute to sex-specific predisposition to childhood-onset asthma. METHODS: Interactions between sex and polymorphisms on childhood asthma risk were evaluated in the Multicentre Asthma Genetics in Childhood Study (MAGICS)/Phase II International Study of Asthma and Allergies in Childhood (ISAAC II) population on a genome-wide level, and findings were validated in independent populations. Genetic fine mapping of sex-specific asthma association signals was performed, and putatively causal polymorphisms were characterized in vitro by using electrophoretic mobility shift and luciferase activity assays. Gene and protein expression of the identified gene doublesex and mab-3 related transcription factor 1 (DMRT1) were measured in different human tissues by using quantitative real-time PCR and immunohistochemistry. RESULTS: Polymorphisms in the testis-associated gene DMRT1 displayed interactions with sex on asthma status in a population of primarily clinically defined asthmatic children and nonasthmatic control subjects (lowest P = 5.21 × 10(-6)). Replication of this interaction was successful in 2 childhood populations clinically assessed for asthma but showed heterogeneous results in other population-based samples. Polymorphism rs3812523 located in the putative DMRT1 promoter was associated with allele-specific changes in transcription factor binding and promoter activity in vitro. DMRT1 expression was observed not only in the testis but also in lung macrophages. CONCLUSION: DMRT1 might influence sex-specific patterns of childhood asthma, and its expression in testis tissue and lung macrophages suggests a potential involvement in hormone or immune cell regulation.