Video recording in the delivery room: current status, implications and implementation.

Many factors determine the performance and success of delivery room management of newborn babies. Improving the quality of care in this challenging surrounding has an important impact on patient safety and on perinatal morbidity and mortality. Video recording (VR) offers the advantage to record and store work as done rather than work as recalled. It provides information about adherence to algorithms and guidelines, and technical, cognitive and behavioural skills. VR is feasible for education and training, improves team performance and results of research led to changes of international guidelines. However, studies thus far have not provided data regarding whether delivery room video recording affects long-term team performance or clinical outcomes. Privacy is a concern because data can be stored and individuals can be identified. We describe the current state of clinical practice in high- and low-resource settings, discuss ethical and medical-legal issues and give recommendations for implementation with the aim of improving the quality of care and outcome of vulnerable babies. IMPACT: VR improves performance by health caregivers providing neonatal resuscitation, teaching and research related to delivery room management, both in high as well low resource settings. VR enables information about adherence to guidelines, technical, behavioural and communication skills within the resuscitation team. VR has ethical and medical-legal implications for healthcare, especially recommendations for implementation of VR in routine clinical care in the delivery room. VR will increase the awareness that short- and long-term outcomes of babies depend on the quality of care in the delivery room.

Low mortality and short-term morbidity in very preterm infants in Austria 2011-2016.

AIM: The current study determined survival, short-term neonatal morbidity and predictors for death or adverse outcome of very preterm infants in Austria. METHODS: This population-based cohort study included 5197 very preterm infants (53.3% boys) born between 2011 and 2016 recruited from the Austrian Preterm Outcome Registry. Main outcome measures were gestational age-related mortality and major short-term morbidities. RESULTS: Overall, survival rate of all live-born infants included was 91.6% and ranged from 47.1% and 73.4% among those born at 23 and 24 weeks of gestation to 84.9% and 88.2% among infants born at 25 and 26 weeks to more than 90.0% among those with a gestational age of 27 weeks or more. The overall prevalence of chronic lung disease, necrotising enterocolitis requiring surgery, intraventricular haemorrhage Grades 3-4, and retinopathy of prematurity Grades 3-5 was 10.0%, 2.1%, 5.5%, and 3.6%, respectively. Low gestational age, low birth weight, missing or incomplete course of antenatal steroids, male sex, and multiple births were significant risk predictors for death or adverse short-term outcome. CONCLUSION: In this national cohort study, overall survival rates were high and short-term morbidity rate was low.

Childhood asthma is associated with mutations and gene expression differences of ORMDL genes that can interact.

BACKGROUND: Genomewide association studies identified ORMDL3 as a plausible asthma candidate gene. ORMDL proteins regulate sphingolipid metabolism and ceramide homeostasis and participate in lymphocyte activation and eosinophil recruitment. Strong sequence homology between the three ORMDL genes and ORMDL protein conservation among different species suggest that they may have shared functions. We hypothesized that if single nucleotide polymorphisms (SNPs) in ORMDL3 alter its gene expression and play a role in asthma, variants in ORMDL1 and ORMDL2 might also be associated with asthma. METHODS: Asthma associations of 44 genotyped SNPs were determined in at least 1303 subjects (651 asthmatics). ORMDL expression was evaluated in peripheral blood mononuclear cells (PBMC) from 55 subjects (eight asthmatics) before and after allergen stimulation, and in blood (n = 60, 5 asthmatics). Allele-specific cis-effects on ORMDL expression were assessed. Interactions between human ORMDL proteins were determined in living cells. RESULTS: Sixteen SNPs in all three ORMDLs were associated with asthma (14 in ORMDL3). Baseline expression of ORMDL1 (P = 1.7 × 10(-6) ) and ORMDL2 (P = 4.9 × 10(-5) ) was significantly higher in PBMC from asthmatics, while induction of ORMDLs upon stimulation was stronger in nonasthmatics. Disease-associated alleles (rs8079416, rs4795405, rs3902920) alter ORMDL3 expression. ORMDL proteins formed homo- and heterooligomers and displayed similar patterns of interaction with SERCA2 and SPT1. CONCLUSIONS: Polymorphisms in ORMDL genes are associated with asthma. Asthmatics exhibit increased ORMDL levels, suggesting that ORMDLs contribute to asthma. Formation of heterooligomers and similar interaction patterns with proteins involved in calcium homeostasis and sphingolipid metabolism could indicate shared biological roles of ORMDLs, influencing airway remodeling and hyperresponsiveness.

Fine-mapping of IgE-associated loci 1q23, 5q31, and 12q13 using 1000 Genomes Project data.

BACKGROUND: Genome-wide association studies (GWAS) repeatedly identified 1q23 (FCER1A), 5q31 (RAD50-IL13 and IL4), and 12q13 (STAT6) as major susceptibility loci influencing the regulation of total serum IgE levels. As GWAS may be insufficient to capture causal variants, we performed fine-mapping and re-genotyping of the three loci using 1000 Genomes Project datasets. METHODS: Linkage disequilibrium tagging polymorphisms and polymorphisms of putative functional relevance were genotyped by chip technology (24 polymorphisms) or MALDI-TOF-MS (40 polymorphisms) in at least 1303 German children (651 asthmatics). The effect of polymorphisms on total serum IgE, IgE percentiles, and atopic diseases was assessed, and a risk score model was applied for gene-by-gene interaction analyses. Functional effects of putative causal variants from these three loci were studied in silico. RESULTS: Associations from GWAS were confirmed and extended. For 1q23 and 5q31, the majority of associations were found with mild to moderately elevated IgE levels, while in the 12q13 locus, single-nucleotide polymorphisms (SNPs) were associated with strongly elevated IgE levels. Gene-by-gene interaction analyses suggested that the presence of mutations in all three loci increases the risk for elevated IgE up to fourfold. CONCLUSION: This fine-mapping study confirmed previous associations and identified novel associations of SNPs in 1q23, 5q31, and 12q13 with different levels of serum IgE and their concomitant contribution to IgE regulation.

A role of FCER1A and FCER2 polymorphisms in IgE regulation.

BACKGROUND: Both FCER2 and FCER1A encode subunits of IgE receptors. Variants in FCER1A were previously identified as major determinants of IgE levels in genome-wide association studies. METHODS: Here we investigated in detail whether FCER2 polymorphisms affect IgE levels alone and/or by interaction with FCER1A polymorphisms. To cover the genetic information of FCER2, 21 single-nucleotide polymorphisms (SNPs) were genotyped by Illumina HumanHap300 BeadChip (5 SNPs) and the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS; 14 SNPs) in at least 1303 Caucasian children (651 asthmatics) (ISAAC II/ MAGICS population); genotypes of two SNPs were imputed. RESULTS: SNP rs3760687 showed the most consistent effect on total serum IgE levels (b [SE] = -0.38 [0.16]; P = 0.016), while FCER2 polymorphisms in general were predominantly associated with mildly-to-moderately increased IgE levels (50th and 66th percentiles). Gene-by-gene interaction analysis suggests that FCER2 polymorphism rs3760687 influences IgE levels mainly in individuals not homozygous for the risk allele of FCER1A polymorphism rs2427837, which belongs to the major IgE-determining tagging bin in the population. CONCLUSION: FCER2 polymorphism rs3760687 affects moderately elevated total serum IgE levels, especially in the absence of homozygosity for the risk allele of FCER1A SNP rs2427837.

The burden of pneumococcal meningitis in Austrian children between 2001 and 2008.

UNLABELLED: The present study was conducted to evaluate the burden of pneumococcal meningitis in Austrian children between 2001 and 2008. Clinical outcome was retrospectively analyzed both on discharge and on follow-up investigations. This study was based on a prospective multicentre surveillance study on hospitalized invasive pneumococcal infections in Austrian children with a total annual "study population" of about 399,000 children aged below 5 years per year. Between 2001 and 2008, 74 cases of pneumococcal meningitis were identified in children aged below 5 years. The mean annual incidence rate for pneumococcal meningitis was 2.3 per 100,000 children in this age group. In 57/74 children (mean age on admission 14.5 ± 13.3 months), outcome data on hospital discharge were available: 5 deaths (8.8%), 20 children (35.1%) with sequelae and 32 children (56.1%) without sequelae were observed. Sequelae on discharge included motor impairment in 8 children (14.0%), hearing impairment in 9 children (15.8%) and/or other complications in 14 children (24.6%). In 7/8 children with motor deficits, matching cerebral lesions were identified by neuroimaging: cerebral infarction in five children, cerebral vasculitis and cerebral abscess in one child each. In 40/57 children, long-term outcome (18.9 ± 20.2 months after discharge) could be assessed: 1 child (2.5%) died 9 months after hospital discharge, 11 children (27.5%) had one or two long-term sequelae and 28 children (70.0%) had no sequelae. Long-term sequelae included motor impairment in three children (7.5%), hearing impairment in nine children (22.5%) and other deficits in two children (5.0%). CONCLUSION: Our study confirms that pneumococcal meningitis causes high mortality and severe long-term sequelae. On long-term follow-up, we observed improvements of motor impairment, but not of hearing impairment.

Hypoglycemia in newborn infants at risk.

UNLABELLED: Infants of diabetic mothers (IDM), large (LGA) or small (SGA) for gestational age and late preterm (LPT) infants are at risk for hypoglycemia. We report the incidence, the consequences and the impact of a recently implemented guideline. From 1 January to 31 December 2012 we screened infants at risk. The first blood glucose was done within 90 min after birth, 30 min after the first feeding and had to be repeated before each feeding. Hypoglycemia was defined as blood glucose below 40 mg/dL independent of age; all babies remained in the study for at least 24 h or until at least 3 glucose measurements were >40 mg/dL. RESULTS: We identified 259 out 1 074 (24.1%) infants and included 145 (56.0%) of these infants in a retrospective analysis. 17 (11.7%) infants (male:female=1:1.1) showed 19 episodes of hypoglycemia. 3 of them had more than one risk factor, 2 were LGA at term. 6 (35%) out of 17 infants had to be transferred, one due to clinical signs and 5 according to the protocol. Mean number of blood glucose measurement was 6.9±1.9. The number of procedures performed to detect one episode of hypoglycemia was 54. CONCLUSION: The incidence of hypoglycemia in infants at risk is low and does not justify screening such a large risk group, which may harm them by requiring a disproportionately large number of blood withdrawals.

Compliance with guidelines recommending the use of simulation for neonatal and infant resuscitation training in Austria.

BACKGROUND: Current international resuscitation guidelines recommend simulation for the training of neonatal and infant resuscitation. We aimed at assessing compliance rates with these recommendations in Austria. METHOD: We performed a national questionnaire survey among 31 neonatal institutions in Austria. RESULTS: 25 questionnaires (80.6%) were analyzed. 22/25 institutions (88%) used simulation as an instructional modality. 8 institutions (32%) had access to medical simulation centers, with 6/8 being used for neonatal and infant resuscitation training. Simulation equipment was available at 17/25 institutions (68%), with a median of 1 part-task trainer (0-2), 2 low-fidelity resuscitation mannequins (0-10), and 0 high-fidelity patient simulators (0-7). Resuscitation training frequency varied widely, ranging from one training per month to one training per year. 5 simulation centers utilized interdisciplinary resuscitation training with other medical specialties and team training including physicians and nursing staff. Of the 17 institutions with simulation equipment at their disposal, 8 (47.1%) carried out interdisciplinary training and 13 (76.5%) performed team-oriented training sessions. DISCUSSION/CONCLUSION: The majority of surveyed institutions adopted simulation for neonatal and infant resuscitation training according to current guidelines and had simulation equipment at their disposal. However, educational practice varied widely, especially in regard to training frequency. Therefore, we suggest a national consensus agreement on best practices in simulation-based neonatal and infant resuscitation training.

Polymorphisms in the IRF-4 gene, asthma and recurrent bronchitis in children.

BACKGROUND: Interferon-regulatory factors (IRFs) play a crucial role in immunity, not only influencing interferon expression but also T cell differentiation. IRF-4 was only recently recognized as a further major player in T cell differentiation. OBJECTIVE: As IRF-1 polymorphisms were shown to be associated with atopy and allergy, we comprehensively investigated effects of IRF-4 variants on allergy, asthma and related phenotypes in German children. METHODS: Fifteen tagging single nucleotide polymorphisms (SNPs) in the IRF-4 gene were genotyped by MALDI-TOF MS in the cross-sectional ISAAC phase II study population from Munich and Dresden (age 9-11; N = 3099). Replication was performed in our previously established genome-wide association study (GWAS) data set (N = 1303) consisting of asthma cases from the Multicenter Asthma Genetic in Childhood (MAGIC) study and reference children from the ISAAC II study. RESULTS: SNPs were not significantly associated with asthma but with bronchial hyperresponsiveness, atopy and, most interestingly, with recurrent bronchitis in the first data set. The IRF-4 variant rs9378805 was associated with recurrent bronchitis in the ISAAC population and replicated in the GWAS data set where further SNPs showed associations with recurrent bronchitis and asthma. CONCLUSIONS: We found genetic associations in IRF-4 to be associated with recurrent bronchitis in our two study populations. Associated polymorphisms are localized in a putative regulatory element in the 3'UTR region of IRF-4. These findings suggest a putative role of IRF-4 in the development of bronchitis.

Therapy in pediatric stroke.

The aim of this review is to summarize the existing literature on therapy and management of cerebrovascular insults in children and adolescents. As data sources, studies were identified by MEDLINE, PubMed, Cochrane Library, and relevant bibliographies for the topic "pediatric stroke." We also reviewed guidelines for "stroke in adults." As a result, pediatric stroke is underestimated. The annual incidence for all stroke entities (cerebral venous thrombosis and hemorrhagic and arterial ischemic stroke) is as high as for pediatric brain tumors, 3-15/100.000 children per year. A distinct etiology can be determined only in a minority of them. Underlying risk factors are multiple, mainly vasculopathies, congential heart diseases, coagulopathies, lipometabolic disorders, and sickle cell anemia. Current recommendations for therapy are based on adult studies, are preliminary, and discussed controversially. Antithrombotic therapy is uniformly recommended for the acute stage of pediatric stroke; no consensus exists on antiplatelet therapy with acetylsalicylic acid (ASA, aspirin) (5 mg/d), with ultra-fractionated or low-molecular-weight heparin. Thrombolysis using recombinant tissue plasminogen activator is not advised, despite the fact that current practice takes a different approach. None of the guidelines specify the duration of ASA for secondary prevention. Additional supportive therapy measures are osmotherapy and decompressive craniectomy. Oxygen in the absence of hypoxemia, intensive insulin therapy, antiepileptic drugs in the absence of clinical or electrographic seizures, corticosteroids, and GP-IIb/IIIa-receptor antagonists should not be used outside clinical trials. In conclusions, current therapeutic guidelines for pediatric stoke are still based on consensus and expert and society opinions and differ between countries. Consensus prevails on the need for acute anticoagulation using either antiplatelets or heparin. Long-term treatment with acetylsalicylic acid in all or only high-risk patients and for how long remains the subject of debate. Lifelong secondary prevention has never been investigated in children or adults. All guidelines agree that there is no indication for thrombolysis in children outside clinical trials, although clinical practice in large centers differs.

[Evaluation of a child protecting team by an independent cooperation partner - suggestions for an optimized procedure]. / Evaluation einer Kinderschutzgruppe bei einem unabhängigen Kooperationspartner - Vorschläge für eine Optimierung der Vernetzung.

UNLABELLED: Cooperation between different institutions in cases of child abuse is essential for the children and their families. The aim of this study is to evaluate the cooperation between the Child Protection Team (CPT) and the Youth Welfare Agency (YWF) in an academic teaching hospital. ISSUES: Is the child or the family already be known to the YWF? Was the suspicion of child abuse confirmed by the CPT? What impact did the CPT's report to the YWF have on the situation of the children, their families, and the members of the YWF?Between 1999 and 2009 196 cases were investigated by the CPT; 80 of them had been reported to the YWF. In 45 of the 80 cases, structured interviews were completed by the YWF social workers. In the remaining 35, the questionnaires were not fully completed (n=15), the responsible social workers not present (n=6), or data were not available due to change of -residence (n=14).Maltreatment was suspected in 21/45 (47%), child abuse in 7 (16%), child neglect in 12 (26%), and a combination of the above in 5 (11%) children. Of the children, 26/45 (58%) were already known to the YWF before being contacted by the CPT, and in 34/45 (75%) children either institutions reported the case to the criminal prosecution authorities. Positive changes were seen in 35/45 (78%) children and in 19/45 (42%) families and the CPT's report was considered helpful for the social workers in 41/45 (91%) children.A CPT is able to correctly identify new cases of child abuse. The activity of the CPT has a positive influence on the situation of affected children, their families, and the respective staff members of the YWF.

Free asymmetric dimethylarginine (ADMA) is low in children and adolescents with classical phenylketonuria (PKU).

INTRODUCTION: Free asymmetric dimethylarginine (ADMA) is a competitive inhibitor of the nitric oxide synthases (NOS). Suppression of nitric oxide (NO) synthesis increases the risk of atherosclerosis. Nevertheless, in the condition of oxidative stress, NOS blockade by ADMA may exert protective effects. Protein metabolism is altered in patients with phenylketonuria (PKU) on dietary treatment and as shown recently, oxidative stress is high in PKU. Since free ADMA concentrations are determined by both protein metabolism and oxidative stress we hypothesized, that free ADMA levels may be elevated in PKU patients. DESIGN: Sixteen patientswith PKU on dietary treatment (mean age 10.1 ± 5.2 yrs), and 91 healthy children (mean age 11.6 ± 3.7 yrs) participated in a cross sectional study. RESULTS: ADMA, total homocysteine (tHcy) and blood glucose were lower and the L-arginine/ADMA ratio was higher in PKU patients compared to controls. No significant correlation was present between phenylalanine (Phe) concentrations, protein intake, and lipid profile, history of cardiovascular disease or ADMA. DISCUSSION: In contrast to our hypothesis, ADMAwas lower and the L-arginine/ADMA ratio was higher in PKU patients. Therefore, in PKU patients, the regulating function of ADMA on NO synthesis is altered and may thus contribute to oxidative stress.

Compliance to clinical guidelines determines outcome in glutaric aciduria type I in the era of newborn screening.

We report on a 4.5-year-old patient diagnosed with Glutaric aciduria type I (GAI), an autosomal recessive inborn error of lysine, hydroxylysine and tryptophan metabolism. Enzymatic assay in cultivated skin fibroblasts revealed complete absence of glutaryl-CoA dehydrogenase activity. All 11 Exons of the GCDH-Gen were sequenced and homozygosity for a yet undescribed mutation was identified. The patient was treated following the recently published guidelines for GA-I. Following this treatment regimen, the child developed normally without any manifest clinical crises. Our patient provides evidence that early commencement and strict adherence to treatment improves clinical outcome even in patients with complete absence of enzyme activity.

Resuscitation after severe hypoxia in a young child: temporary isoelectric EEG and loss of BAEP components.

EEG and multimodality evoked potentials are currently used to ascertain brain death. We have observed electrocerebral silence (ECS) and loss of wave IV and V in BAEP in a 28-month-old child, 2 h after resuscitation from severe hypoxia, followed by reappearance of EEG activity and of waves IV and V (latencies and amplitudes within normal range) 18 h later. Temporary loss of EEG activity has been observed occasionally, while rapid reoccurrence of BAEP waves IV and V was unexpected and in contrast to the common observation, that rostro-caudal loss of BAEP waves is irreversible. This observation suggests that temporary loss of BAEP waves IV and V may occur and that caution is necessary in the interpretation of BAEP recorded immediately after a resuscitation.

Changes in left ventricular function in shocked newborns.

OBJECTIVE: To assess whether the change in cardiac output after volume replacement is due to elevation of stroke volume or heart rate and to determine the effect of mechanical ventilation on the hemodynamic situation. DESIGN: Prospective study. SETTING: A ten-bed neonatal intensive care unit (level III) at a university hospital. PATIENTS: 15 consecutive newborns with blood pressure below the 10th percentile related to age and weight. INTERVENTIONS: Volume replacement with Ringer's lactate 20 ml/kg body weight. MEASUREMENTS AND RESULTS: Before and after volume replacement, arterial pressure recordings, blood gas analysis, and an echocardiographic study were carried out. Left ventricular and aortic diameters were measured by the two-dimensional M-mode technique and velocity time integral of aortic flow by the pulsed color Doppler technique. From these data, stroke volume and cardiac output were calculated. Cardiac output (703 +/- 204 vs 826 +/- 166 ml/ min, p < 0.005) and cardiac index (267 +/- 69 vs 302 +/- 55 ml/min per kg body weight, p < 0.01) changed significantly due to an appreciable elevation in stroke volume (5.2 +/- 1.7 vs 5.8 +/- 1.7 ml, p < 0.05), whereas heart rate was unaltered (140 +/- 12 vs 142 +/- 20 beats/min; NS). The change in blood pressure (32 +/- 5 vs 38 +/- 8 mm Hg, p < 0.01) was also significant. Cardiac index before and after volume replacement showed a significant inverse correlation with the severity of respiratory disease expressed as alveolar-arterial oxygen difference (A-aDO2) (A-aDO2 vs cardiac index before volume replacement: r = -0.77, p < 0.001; after volume replacement: r = -0.73, p < 0.005) or oxygenation index (oxygenation index vs cardiac index before volume replacement: r = -0.73, p < 0.005; after volume replacement: r = -0.73, p < 0.005). Changes in left ventricular diastolic diameter, left ventricular systolic diameter, and fractional shortening were not significant. CONCLUSIONS: These results indicate that the major regulator of left ventricular output in newborns with hypovolemic or cardiogenic shock is stroke volume and not heart rate and that cardiac output depends on the severity of the respiratory disease.

Neonatal lupus erythematosus with congenital heart block and severe heart failure due to myocarditis and endocardititis of the mitral valve.

We report a case of neonatal lupus erythematosus (NLE) with congenital heart block and severe myocardial failure, which was followed from the 25th week of gestation because of fetal bradycardia. The child was delivered at the 37th week of gestation by elective cesarean section because of echocardiographically documented heart enlargement, pericardial effusion and moderate insufficiency of the mitral and tricuspid valves. In spite of immediate pacing, intubation and supportive treatment, the newborn developed progressive heart failure. Echocardiography showed endocarditis of the mitral valve and diffuse myocarditis. The heart failure resolved under steroid treatment. Our experience supports the early use of steroids in treating myocarditis due to NLE. Intrauterine steroid treatment in the presence of fetal hydrops and congenital heart block is discussed.

Comparison of different modes of high-frequency ventilation in surfactant-deficient rabbits.

Various modes of high-frequency ventilation (HFV) have been developed to avoid the disadvantages of conventional mechanical ventilation. In the present study, we examined the hypothesis that high-frequency oscillation (HFO) is superior to high-frequency positive pressure ventilation (HPPV) and combined high-frequency ventilation (CHFV) in surfactant-deficient rabbits. The aim of the ventilator strategy was to adjust the mean airway pressure to 2 cm above critical opening pressure of the inflation limb of the respiratory system pressure volume (P/V) curve, achieve a normal tidal volume (VT) (5 ml/kg body weight) and apply repeated sustained inflations. We studied the effect of these HFV modes on oxygenation, lung mechanics and lung histology in 15 New Zealand White rabbits during a 6-hour experiment. Statistically, the HFO group demonstrated significantly better oxygenation (P < 0.05), lung mechanics (lung stability index: P < 0.05), and better lung tissue histology compared to the HPPV and CHFV groups. In contrast to the HPPV and CHFV groups, the P/V curves of the HFO group showed significant recovery over the 6-hour period after lavage. The lungs of the HFO-treated group had a more uniform distribution of alveoli and less overdistention than the HPPV group (P < 0.002), and less atelectasis than the CHFV group (P < 0.05). The HFO group had less lung injury than the CHFV groups (P < 0.01) and its lungs contained significantly less water than both other groups (P < 0.05). We conclude that the relationship between mean and end-expiratory pressures impacts strongly on both oxygenation and the progression of injury during HFV at the same mean airway pressures. The HFO group showed less acute lung injury than the other ventilatory groups.