Copeptin concentration in cord blood in infants with early-onset sepsis, chorioamnionitis and perinatal asphyxia

Background Vasopressin is one of the most important physiological stress and shock hormones. Copeptin, a stable vasopressin precursor, is a promising sepsis marker in adults. In contrast, its involvement in neonatal diseases remains unknown. The aim of this study was to establish copeptin concentrations in neonates of different stress states such as sepsis, chorioamnionitis and asphyxia. Methods Copeptin cord blood concentration was determined using the BRAHMS kryptor assay. Neonates with early-onset sepsis (EOS, n = 30), chorioamnionitis (n = 33) and asphyxia (n = 25) were compared to a control group of preterm and term (n = 155) neonates. Results Median copeptin concentration in cord blood was 36 pmol/l ranging from undetectable to 5498 pmol/l (IQR 7 - 419). Copeptin cord blood concentrations were non-normally distributed and increased with gestational age (p < 0.0001). Neonates born after vaginal compared to cesarean delivery had elevated copeptin levels (p < 0.0001). Copeptin correlated strongly with umbilical artery pH (Spearman's Rho -0.50, p < 0.0001), umbilical artery base excess (Rho -0.67, p < 0.0001) and with lactate at NICU admission (Rho 0.54, p < 0.0001). No difference was found when comparing copeptin cord blood concentrations between neonates with EOS and controls (multivariate p = 0.30). The highest copeptin concentrations were found in neonates with asphyxia (median 993 pmol/l). Receiver-operating-characteristic curve analysis showed that copeptin cord blood concentrations were strongly associated with asphyxia: the area under the curve resulted at 0.91 (95%-CI 0.87-0.96, p < 0.0001). A cut-off of 400 pmol/l had a sensitivity of 92% and a specifity of 82% for asphyxia as defined in this study. Conclusions Copeptin concentrations were strongly related to factors associated with perinatal stress such as birth acidosis, asphyxia and vaginal delivery. In contrast, copeptin appears to be unsuitable for the diagnosis of EOS.

Nasopharyngeal microbiota in infants with acute otitis media

Interspecies interactions of the nasopharyngeal microbiota are likely to be involved in the pathogenesis of acute otitis media (AOM). Capturing the breadth of microbial interactions requires a detailed description of the microbiota during health and AOM.

Retrospective analysis of stored dried blood spots from children with cystic fibrosis and matched controls to assess the performance of a proposed newborn screening protocol in Switzerland

Newborn screening (NBS) for Cystic Fibrosis (CF) has been introduced in many countries, but there is no ideal protocol suitable for all countries. This retrospective study was conducted to evaluate whether the planned two step CF NBS with immunoreactive trypsinogen (IRT) and 7 CFTR mutations would have detected all clinically diagnosed children with CF in Switzerland.

Impact of sepsis on neurodevelopmental outcome in a Swiss National Cohort of extremely premature infants

Neonatal sepsis causes high mortality and morbidity in preterm infants, but less is known regarding the long-term outcome after sepsis. This study aimed to determine the impact of sepsis on neurodevelopment at 2 years' corrected age in extremely preterm infants.

Surfactant replacement therapy in preterm infants: a European survey

Exogenous surfactant is an undisputed treatment for neonatal respiratory distress syndrome but its efficacy is highly dependent on the treatment strategy. International guidelines have published recommendations on the optimal surfactant replacement strategy.

Interobserver variability in assessment of cranial ultrasound in very preterm infants

Cranial ultrasound (cUS) findings help doctors in the clinical management of preterm infants and in their discussion with parents regarding prediction of outcome. cUS is often used as outcome measure in clinical research studies. Accurate cUS performance and interpretation is therefore required.

Prediction of codeine toxicity in infants and their mothers using a novel combination of maternal genetic markers

Substantial variation exists in response to standard doses of codeine ranging from poor analgesia to life-threatening central nervous system (CNS) depression. We aimed to discover the genetic markers predictive of codeine toxicity by evaluating the associations between polymorphisms in cytochrome P450 2D6 (CYP2D6), UDP-glucuronosyltransferase 2B7 (UGT2B7), P-glycoprotein (ABCB1), mu-opioid receptor (OPRM1), and catechol O-methyltransferase (COMT) genes, which are involved in the codeine pathway, and the symptoms of CNS depression in 111 breastfeeding mothers using codeine and their infants. A genetic model combining the maternal risk genotypes in CYP2D6 and ABCB1 was significantly associated with the adverse outcomes in infants (odds ratio (OR) 2.68; 95% confidence interval (CI) 1.61-4.48; P(trend) = 0.0002) and their mothers (OR 2.74; 95% CI 1.55-4.84; P(trend) = 0.0005). A novel combination of the genetic and clinical factors predicted 87% of the infant and maternal CNS depression cases with a sensitivity of 80% and a specificity of 87%. Genetic markers can be used to improve the outcome of codeine therapy and are also probably important for other opioids sharing common biotransformation pathways.

Physiological parameters after nonpharmacological analgesia in preterm infants: a randomized trial

To compare the influence of three different nonpharmacological interventions on cortical activation, heart rate and peripheral oxygen saturation (SaO2 ) after heelstick in preterm infants.

A prospective study of the impact of air pollution on respiratory symptoms and infections in infants

Rationale: There is increasing evidence that short-term exposure to air pollution has a detrimental effect on respiratory health, but data from healthy populations, particularly infants, are scarce. Objectives: To assess the association of air pollution with frequency and severity of respiratory symptoms and infections measured weekly in healthy infants. Methods: In a prospective birth cohort of 366 infants of unselected mothers, respiratory health was assessed weekly by telephone interviews during the first year of life (19,106 total observations). Daily mean levels of particulate matter (PM10), nitrogen dioxide (NO2), and ozone (O3) were obtained from local monitoring stations. We determined the association of the preceding week's pollutant levels with symptom scores and respiratory tract infections using a generalized additive mixed model with an autoregressive component. In addition, we assessed whether neonatal lung function influences this association and whether duration of infectious episodes differed between weeks with normal PM10 and weeks with elevated levels. Measurements and Main Results: We found a significant association between air pollution and respiratory symptoms, particularly in the week after respiratory tract infections (risk ratio, 1.13 [1.02-1.24] per 10 μg/m(3) PM10 levels) and in infants with premorbid lung function. During times of elevated PM10 (>33.3 μg/m(3)), duration of respiratory tract infections increased by 20% (95% confidence interval, 2-42%). Conclusions: Exposure to even moderate levels of air pollution was associated with increased respiratory symptoms in healthy infants. Particularly in infants with premorbid lung function and inflammation, air pollution contributed to longer duration of infectious episodes with a potentially large socioeconomic impact.

Newborn screening for cystic fibrosis in Switzerland - Consequences after analysis of a 4 months pilot study

BACKGROUND: Switzerland introduced newborn screening (NBS) for CF in 2011, using an IRT/DNA/IRT protocol. This paper describes the results of the first year and compares two versions of the protocol with different IRT cut-offs, particularly effects on recall rate, sensitivity and specificity. METHODS: IRT cut-offs were >45ng/ml (99.0th percentile) in period 1 (months 1-4) and >50ng/ml (99.2nd percentile) in period 2 (months 5-12). In period 2 we abstained from recalls when none of the 7 most common CF mutations were detected and IRT was <60ng/ml. RESULTS: In periods 1 and 2, 26,535 and 56,663 tests were performed. Recall rates were 0.94% and 0.48%, respectively (p<0.001), PPV increased from 23% to 47% (p=0.024) and sensitivity was 90% and 100%. CONCLUSIONS: Raising initial IRT cut-off from the 99.0th to the 99.2nd percentile and abstaining from recalls for children with an IRT<60ng/ml and carrying no major CFTR mutation significantly reduced the recall rate without affecting sensitivity.

Correlation properties of spontaneous motor activity in healthy infants: a new computer-assisted method to evaluate neurological maturation

Qualitative assessment of spontaneous motor activity in early infancy is widely used in clinical practice. It enables the description of maturational changes of motor behavior in both healthy infants and infants who are at risk for later neurological impairment. These assessments are, however, time-consuming and are dependent upon professional experience. Therefore, a simple physiological method that describes the complex behavior of spontaneous movements (SMs) in infants would be helpful. In this methodological study, we aimed to determine whether time series of motor acceleration measurements at 40-44 weeks and 50-55 weeks gestational age in healthy infants exhibit fractal-like properties and if this self-affinity of the acceleration signal is sensitive to maturation. Healthy motor state was ensured by General Movement assessment. We assessed statistical persistence in the acceleration time series by calculating the scaling exponent α via detrended fluctuation analysis of the time series. In hand trajectories of SMs in infants we found a mean α value of 1.198 (95 % CI 1.167-1.230) at 40-44 weeks. Alpha changed significantly (p = 0.001) at 50-55 weeks to a mean of 1.102 (1.055-1.149). Complementary multilevel regression analysis confirmed a decreasing trend of α with increasing age. Statistical persistence of fluctuation in hand trajectories of SMs is sensitive to neurological maturation and can be characterized by a simple parameter α in an automated and observer-independent fashion. Future studies including children at risk for neurological impairment should evaluate whether this method could be used as an early clinical screening tool for later neurological compromise.

Outcome at two years of age in a Swiss national cohort of extremely preterm infants born between 2000 and 2008

Background While survival rates of extremely preterm infants have improved over the last decades, the incidence of neurodevelopmental disability (ND) in survivors remains high. Representative current data on the severity of disability and of risk factors associated with poor outcome in this growing population are necessary for clinical guidance and parent counselling. Methods Prospective longitudinal multicentre cohort study of preterm infants born in Switzerland between 240/7 and 276/7 weeks gestational age during 2000–2008. Mortality, adverse outcome (death or severe ND) at two years, and predictors for poor outcome were analysed using multilevel multivariate logistic regression. Neurodevelopment was assessed using Bayley Scales of Infant Development II. Cerebral palsy was graded after the Gross Motor Function Classification System. Results Of 1266 live born infants, 422 (33%) died. Follow-up information was available for 684 (81%) survivors: 440 (64%) showed favourable outcome, 166 (24%) moderate ND, and 78 (11%) severe ND. At birth, lower gestational age, intrauterine growth restriction and absence of antenatal corticosteroids were associated with mortality and adverse outcome (p < 0.001). At 360/7 weeks postmenstrual age, bronchopulmonary dysplasia, major brain injury and retinopathy of prematurity were the main predictors for adverse outcome (p < 0.05). Survival without moderate or severe ND increased from 27% to 39% during the observation period (p = 0.02). Conclusions In this recent Swiss national cohort study of extremely preterm infants, neonatal mortality was determined by gestational age, birth weight, and antenatal corticosteroids while neurodevelopmental outcome was determined by the major neonatal morbidities. We observed an increase of survival without moderate or severe disability.