[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
clinicaltrials.gov Protocol Registration System (NCT00623038). Registered 14 February 2008.
[Show abstract][Hide abstract] ABSTRACT: Invasivemeningococcal disease (IMD) is a leading cause of meningitis and severe sepsis in children and adolescents.Genetic factors are important in determining susceptibility to and outcome of IMD. Recently, a genome-wide association study from the UK showed significant associations of single nucleotide polymorphisms (SNPs) within complement factor H (CFH) (rs1065489) and in CFH-related protein 3 (CFHR3) (rs426736) with susceptibility of IMD. We report data of a genetic replication study in Central-European children.
The study was conducted as a retrospective case-reference study involving 248 patients with confirmed diagnosis of IMD from Austria and Germany and 835 healthy reference individuals from a multi-center German birth cohort.
Carriers of the minor alleles of rs1065489 and rs426736 were at lower risk of IMD (allelic odds ratio = 0.60 [0.44-0.82]; p=0.001 and 0.61 [0.45-0.83]; p=0.001). Also, two major haplotypes (GT and TC) derived from the two SNPs were significantly associated with IMD (p=0.001 and p=0.003, respectively).
The consistency of the resultsbetween the genome wide association study and our study population strengthens the association of CFH polymorphisms to the susceptibility of IMD. Our results support the conclusion that CFH is a critical determinant in acquiring meningococcal disease.
[Show abstract][Hide abstract] ABSTRACT: Background
Genome-wide association studies identified ORMDL3 as a plausible asthma candidate gene. ORMDL proteins regulate sphingolipid metabolism and ceramide homeostasis, participate in lymphocyte activation and eosinophil recruitment. Strong sequence homology between the three ORMDL genes and ORMDL protein conservation amongst 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 1,303 subjects (651 asthmatics). ORMDLs expression was evaluated in peripheral blood mononuclear cells (PBMC) from 55 subjects (8 asthmatics) before and after allergen stimulation, and in blood (n=60, 5 asthmatics). Allele-specific cis-effects on ORMDLs expression were assessed. Interactions between human ORMDL proteins were determined in living cells.ResultsSixteen 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 non-asthmatics. 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.This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: 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.
We performed a national questionnaire survey among 31 neonatal institutions in Austria.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: 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%).
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.
European Journal of Pediatrics 01/2014; 173(7). DOI:10.1007/s00431-013-2260-8 · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
FCER2 polymorphism rs3760687 affects moderately elevated total serum IgE levels, especially in the absence of homozygosity for the risk allele of FCER1A SNP rs2427837.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the prevalence of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus and examine whether the neurological examination validly diagnoses diabetic peripheral neuropathy as compared with the gold standard of nerve conduction velocity in these patients. Nerve conduction velocity was measured in an unselected consecutive series of patients aged 8-18 years who had been suffering from type 1 diabetes mellitus for at least 1 year. For the neurological examination, neuropathy disability scores and neuropathy sign scores were used. Of the 39 patients, six (15%) had clinically evident diabetic peripheral neuropathy, whereas nerve conduction velocity testing revealed diabetic peripheral neuropathy in 15 (38%) patients. Sensitivity and specificity of the neurological examination for the diagnosis of diabetic peripheral neuropathy were 40% and 100%, respectively. The corresponding positive and negative predictive values were 100% and 72.7%, respectively. This conclusions from this study are that in children and adolescents with type 1 diabetes mellitus, diabetic peripheral neuropathy is highly prevalent, but in the majority of patients it is subclinical. Sensitivity and negative predictive values of the neurological examination are low. Therefore, routine nerve conduction velocity measurement for the assessment of diabetic peripheral neuropathy appears to be warranted in these patients.
[Show abstract][Hide abstract] ABSTRACT: 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. ResultsSimilar 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 4.37x10(-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.
[Show abstract][Hide abstract] ABSTRACT: 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 β 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.
The American journal of emergency medicine 05/2013; 31(7). DOI:10.1016/j.ajem.2013.04.007 · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.