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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Cross-sectional study to evaluate the longitudinal development of child and adolescent psychiatric diagnoses of inpatients in Vorarlberg, Austria.

Clinical experience has repeatedly shown evidence for continuity between mental disorders in children and adolescents and mental disorders in adulthood. Up to now, Austria has had no epidemiologic data on psychiatric diseases in children and adolescents and their development into adulthood. How often do children and adolescents with psychiatric diseases have psychiatric diseases in adulthood? Is there any association between psychiatric diagnoses in childhood/adolescence and adulthood? Electronic medical records provided us with data on 2210 children and adolescents who were admitted to any hospital in the State of Vorarlberg, Austria, between 1997 and 2012 because of psychiatric diseases. In this cross-sectional study, diagnoses were coded according to ICD-10 and ICD-9 criteria. The three main reasons for admission of children and adolescents were substance abuse, emotional disorders and conduct disorders. Of the admitted children and adolescents, 9.8 % were readmitted to a psychiatric institution in adulthood. The main reason for readmission in adulthood appears to be disorders due to psychoactive substances (42.1 %). Of young patients with psychoactive substance use, 9.7 % were rehospitalized in adulthood, 70.8 % of them showed a diagnosis in the same category (F1) on admission. Children and adolescents admitted for schizophrenia, schizotypal, and delusional disorders (F2) were significantly more likely to be readmitted in adulthood (40.9 %) compared to any other child psychiatric diagnosis. CONCLUSION: This study once again shows the continuity of psychiatric disorders from childhood and adolescence to adulthood. It also gives further information about the transmission of diagnoses when patients reached the age of 18 years and their outcome. WHAT IS KNOWN: Until now, there is hardly any information about the outcome of children and adolescents with psychiatric diagnoses in Austria. WHAT IS NEW: We want to bring up more knowledge on that issue. Research findings may improve prevention and clinical assessment of children and adolescents with mental health problems.

Neonatal assessment in the delivery room--Trial to Evaluate a Specified Type of Apgar (TEST-Apgar).

BACKGROUND: Since an objective description is essential to determine infant's postnatal condition and efficacy of interventions, two scores were suggested in the past but weren't tested yet: The Specified-Apgar uses the 5 items of the conventional Apgar score; however describes the condition regardless of gestational age (GA) or resuscitative interventions. The Expanded-Apgar measures interventions needed to achieve this condition. We hypothesized that the combination of both (Combined-Apgar) describes postnatal condition of preterm infants better than either of the scores alone. METHODS: Scores were assessed in preterm infants below 32 completed weeks of gestation. Data were prospectively collected in 20 NICU in 12 countries. Prediction of poor outcome (death, severe/moderate BPD, IVH, CPL and ROP) was used as a surrogate parameter to compare the scores. To compare predictive value the AUC for the ROC was calculated. RESULTS: Of 2150 eligible newborns, data on 1855 infants with a mean GA of 28(6/7) ± 2(3/7) weeks were analyzed. At 1 minute, the Combined-Apgar was significantly better in predicting poor outcome than the Specified- or Expanded-Apgar alone. Of infants with a very low score at 5 or 10 minutes 81% or 100% had a poor outcome, respectively. In these infants the relative risk (RR) for perinatal mortality was 24.93 (13.16-47.20) and 31.34 (15.91-61.71), respectively. CONCLUSION: The Combined-Apgar allows a more appropriate description of infant's condition under conditions of modern neonatal care. It should be used as a tool for better comparison of group of infants and postnatal interventions. TRIAL REGISTRATION: clinicaltrials.gov Protocol Registration System (NCT00623038). Registered 14 February 2008.

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.

Severe growth retardation, delayed bone age, and facial dysmorphism in two patients with microduplications in 2p16 → p22.

Interstitial duplications of the short arm of chromosome 2 have been rarely described. Here, we report on two unrelated patients with overlapping chromosome 2p16 → p22 de novo microduplications found by SNP-array analysis. The affected individuals were an 8-year-3-month-old boy with a direct duplication of approximately 14.6 Mb harboring 63 genes, and a 12-year-old girl with a direct duplication of around 9.6 Mb harboring 48 genes. Both patients have severe growth retardation, delayed bone age, prominent veins on trunk and extremities, total IGF1 level in the low range, mild developmental delay, and facial dysmorphism such as relative macrocephaly, a broad and prominent forehead, and a large anterior fontanelle. Comparison with patients previously reported in the literature and in the DECIPHER 5.1 and ECARUCA databases indicates a common region of interest of around 1.9 Mb responsible for most of the features. Two candidate genes (EPAS and RHOQ), may be particularly relevant for the marked growth retardation and developmental delay.

Different FCER1A polymorphisms influence IgE levels in asthmatics and non-asthmatics.

BACKGROUND: Recently, three genome-wide association studies (GWAS) demonstrated FCER1A, the gene encoding a ligand-binding subunit of the high-affinity IgE receptor, to be a major susceptibility locus for serum IgE levels. The top association signal differed between the two studies from the general population and the one based on an asthma case-control design. In this study, we investigated whether different FCER1A polymorphisms are associated with total serum IgE in the general population and asthmatics specifically. METHODS: Nineteen polymorphisms were studied in FCER1A based on a detailed literature search and a tagging approach. Polymorphisms were genotyped by the Illumina HumanHap300Chip (6 polymorphisms) or MALDI-TOF MS (13 polymorphisms) in at least 1303 children (651 asthmatics) derived from the German International Study of Asthma and Allergies in Childhood II and Multicentre Asthma Genetics in Childhood Study. RESULTS: Similar to two population-based GWAS, the peak association with total serum IgE was observed for SNPs rs2511211, rs2427837, and rs2251746 (mean r(2) > 0.8), with the lowest p-value of 4.37 × 10(-6). The same 3 polymorphisms showed the strongest association in non-asthmatics (lowest p = 0.0003). While these polymorphisms were also associated with total serum IgE in asthmatics (lowest p = 0.003), additional polymorphisms (rs3845625, rs7522607, and rs2427829) demonstrated associations with total serum IgE in asthmatics only (lowest p = 0.01). CONCLUSIONS: These data suggest that FCER1A polymorphisms not only drive IgE levels in the general population but that specific polymorphisms may also influence IgE in association with asthma, suggesting that disease-specific mechanisms in IgE regulation exist.

Mild head injury in pediatrics: algorithms for management in the ED and in young athletes.

Mild head injury is of interest because of a history of under diagnosis and underestimated clinical importance. Half of the patients with mild head injuries or concussions have sport-related injuries. Knowledge of symptoms and appropriate management can be improved and is a matter of practical interest. Several algorithms exist for discharge, admission or for cranial computed tomography (CT).These employ different risk factors and calculate their sensitivity of correctly identifying children with traumatic brain injury (TBI). In contrast, a multicenter, prospective study in the United States developed a prediction model to diagnose the absence of intracranial injury when certain symptoms are missing (negative prediction value). An acute concussion presents with a combination of physical, cognitive, and emotional symptoms, which are usually self-limited. In young athletes, a second impact before full recovery from the first may have deleterious consequences and should be avoided by strict "return to play" rules. Recent research suggests that repetitive minor hits may cause delayed brain damage (dementia pugilistica, "punch-drunk syndrome"). A link to neurodegenerative diseases such as dementia, Alzheimer's disease and parkinsonism (tauopathies) is described by amyloid ß plaques in the brain of such patients. A genetic predisposition (apolipoprotein) is discussed. This review focuses on the rules attempting to determine the need for cranial CT in the emergency department and the impact of mild head injuries in young athletes. We describe in detail standardized guidelines for appropriate diagnosis and treatment and discuss the association between repetitive minor injuries and chronic traumatic encephalopathy and neurodegenerative diseases.

Genetic variants in Protocadherin-1, bronchial hyper-responsiveness, and asthma subphenotypes in German children.

BACKGROUND: Recently, Protocadherin-1 (PCDH1) was reported as a novel susceptibility gene for bronchial hyper-responsiveness (BHR) and asthma. PCDH1 is located on chromosome 5q31-33, in the vicinity of several known candidate genes for asthma and allergy. To exclude that the associations observed for PCDH1 originate from the nearby cytokine cluster, an extensive linkage disequilibrium (LD) analysis was performed. Effects of polymorphisms in PCDH1 on asthma, BHR, and related phenotypes were studied comprehensively. METHODS: Genotype information was acquired from Illumina HumanHap300Chip genotyping, MALDI-TOF MS genotyping, and imputation. LD was assessed by Haploview 4.2 software. Associations were investigated in a population of 1454 individuals (763 asthmatics) from two German study populations [MAGICS and International Study of Asthma and Allergies in Childhood phase II (ISAAC II)] using logistic regression to model additive effects. RESULTS: No relevant LD between PCDH1 tagging polymorphisms and 98 single nucleotide polymorphisms within the cytokine cluster was detected. While BHR was not associated with PCDH1 polymorphisms, significant associations with subphenotypes of asthma were observed. CONCLUSION: Protocadherin-1 polymorphisms may specifically affect the development of non-atopic asthma in children. Functional studies are needed to further investigate the role of PCDH1 in BHR and asthma development.