Achieved Oxygenation Saturations and Outcome in Extremely Preterm Infants.

Infants in the Neonatal Oxygenation Prospective Meta-analysis trials were randomized to SpO2 targets of 85% to 89% or 91% to 95%. Group allocation was masked. Different outcomes are likely partially attributable to differences in achieved SpO2. Infants randomized to the lower range had higher than intended readings. SpO2 distributions of infants in the low-range group of the Benefits of Oxygen Saturation Targeting II UK trial who died or developed necrotizing enterocolitis were centered around 90% to 92%. These achieved SpO2 distributions caution against using lower SpO2 target ranges early or throughout the clinical course in extremely preterm infants.

Pulse Oximeter Saturation Targeting and Oximeter Changes in the Benefits of Oxygen Saturation Targeting (BOOST)-II Australia and BOOST-II UK Oxygen Trials.

Infants in the Australian and UK Benefits of Oxygen Saturation Targeting-II trials treated using revised oximeters spent more time within their planned pulse oximeter saturation target ranges than infants treated using the original oximeters (P < .001). This may explain the larger mortality difference seen with revised oximeters. If so, average treatment effects from the Neonatal Oxygen Prospective Meta-analysis trials may be underestimates.

Whole blood gene expression profiling of neonates with confirmed bacterial sepsis.

Neonatal infection remains a primary cause of infant morbidity and mortality worldwide and yet our understanding of how human neonates respond to infection remains incomplete. Changes in host gene expression in response to infection may occur in any part of the body, with the continuous interaction between blood and tissues allowing blood cells to act as biosensors for the changes. In this study we have used whole blood transcriptome profiling to systematically identify signatures and the pathway biology underlying the pathogenesis of neonatal infection. Blood samples were collected from neonates at the first clinical signs of suspected sepsis alongside age matched healthy control subjects. Here we report a detailed description of the study design, including clinical data collected, experimental methods used and data analysis workflows and which correspond with data in Gene Expression Omnibus (GEO) data sets (GSE25504). Our data set has allowed identification of a patient invariant 52-gene classifier that predicts bacterial infection with high accuracy and lays the foundation for advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis.

Identification of a human neonatal immune-metabolic network associated with bacterial infection.

Understanding how human neonates respond to infection remains incomplete. Here, a system-level investigation of neonatal systemic responses to infection shows a surprisingly strong but unbalanced homeostatic immune response; developing an elevated set-point of myeloid regulatory signalling and sugar-lipid metabolism with concomitant inhibition of lymphoid responses. Innate immune-negative feedback opposes innate immune activation while suppression of T-cell co-stimulation is coincident with selective upregulation of CD85 co-inhibitory pathways. By deriving modules of co-expressed RNAs, we identify a limited set of networks associated with bacterial infection that exhibit high levels of inter-patient variability. Whereas, by integrating immune and metabolic pathways, we infer a patient-invariant 52-gene-classifier that predicts bacterial infection with high accuracy using a new independent patient population. This is further shown to have predictive value in identifying infection in suspected cases with blood culture-negative tests. Our results lay the foundation for future translation of host pathways in advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis.

The twists and turns of neonatal oxygen therapy.

Although supplemental oxygen is one of the commonest treatments in neonatal medicine, the evidence base for deciding which newborns need it, and what is the appropriate dose remains weak. Clinical research in this area is difficult because it requires clinicians to depart from established practice and, in the case of oxygen therapy, the stakes seem far higher to them than for other investigational treatments. Consequently, beyond the knowledge that extreme hyperoxia and hypoxia are harmful, the middle ground remains uncertain for both preterm and term infants.

Provision of servo-controlled cooling during neonatal transport.

INTRODUCTION: Therapeutic hypothermia is a time critical intervention for infants who have experienced a hypoxic-ischaemic event. Previously reported methods of cooling during transport do not demonstrate the same stability achieved in the neonatal unit. The authors developed a system which allowed provision of servo-controlled cooling throughout transport, and present their first year's experience. METHODS: Retrospective review of routinely collected patient data. RESULTS: 14 out-born infants were referred for cooling during a 12-month period. Nine infants were managed with the servo-controlled system during transport. Cooling was commenced in all infants before 6 h of life. Median time from team arrival to the infant having a temperature in the target range (33-34°C) was 45 min. Median temperature during transfer was 33.5°C (range 33-34°C). Temperature on arrival at the cooling centre ranged from 33.4°C to 33.8°C. CONCLUSION: Servo-controlled cooling during transport is feasible and provides an optimal level of thermal control.

Normative values of substance P and neurokinin A in neonates.

BACKGROUND: Substance P (SP) and neurokinin A (NKA) are neuropeptides that have been researched as pain markers in adults, as they are involved in transmission and modulation of pain signals. There is a potential role for them as neurochemical markers of pain in neonates, but this has never previously been investigated. AIM: To establish normative values of SP and NKA in neonates. METHODS: Longitudinal once-daily morning blood samples were collected over two weeks from 142 neonates, gestation 23-40 weeks. Peptides were extracted, and then quantified using an in-house radioimmunoassay. Infants with presumed painful conditions were excluded. RESULTS: SP concentrations ranged from <0.98 to 11.2 pmol/L (median 1.7 pmol/L) and NKA concentrations from <1.95 to 74.6 pmol/L (median 6.0 pmol/L). Gestation and birth weight had no significant correlation with peptide concentrations. Postnatally, there was a gradual rise in median SP during the first three days, which decreased again by day 14. Median NKA showed a similar rise, but was not statistically significant. This postnatal rise and fall were more apparent in preterm infants < or = 32 weeks gestation. CONCLUSIONS: This is the first description of normative values of SP and NKA in neonates. SP and NKA show changes with postnatal age, which are more marked in preterm infants.

Respiratory strategies for preterm infants at birth.

Neonatologists treating extremely premature infants in the delivery room are faced with many dilemmas, not least how best to support their breathing. A balance must be struck between helping those infants who need it and not applying potentially harmful treatments to infants who might not need them. Crucial to this process is being able to identify infants who might benefit.

Quantitative assessment of human whole blood RNA as a potential biomarker for infectious disease.

Infection remains a significant cause of morbidity and mortality especially in newborn infants. Analytical methods for diagnosing infection are severely limited in terms of sensitivity and specificity and require relatively large samples. It is proposed that stringent regulation of the human transcriptome affords a new molecular diagnostic approach based on measuring a highly specific systemic inflammatory response to infection, detectable at the RNA level. This proposition raises a number of as yet poorly characterised technical and biological variation issues that urgently need to be addressed. Here we report a quantitative assessment of methodological approaches for processing and extraction of RNA from small samples of infant whole blood and applying analysis of variation from biochip measurements. On the basis of testing and selection from a battery of assays we show that sufficient high quality RNA for analysis using multiplex array technology can be obtained from small neonatal samples. These findings formed the basis of implementing a set of robust clinical and experimental standard operating procedures for whole blood RNA samples from 58 infants. Modelling and analysis of variation between samples revealed significant sources of variation from the point of sample collection to processing and signal generation. These experiments further permitted power calculations to be run indicating the tractability and requirements of using changes in RNA expression profiles to detect different states between patient groups. Overall the results of our investigation provide an essential first step toward facilitating an alternative way for diagnosing infection from very small neonatal blood samples, providing methods and requirements for future chip-based studies.

Initial ventilation strategies during newborn resuscitation.

Ventilation alone is usually effective in most neonatal resuscitation episodes. A review of the evidence underpinning recommendations for methods and devices for providing initial ventilation during newborn resuscitation was conducted. Self-inflating bags, flow-inflating (anesthesia) bags, and T-piece devices all may be used to provide effective ventilation after birth, with none clearly superior. Whichever method is used, ventilation is likely to be delivered more consistently if a pressure-monitoring device is incorporated. The best indication of successful ventilation is a prompt increase in heart rate. The role of positive end-expiratory pressure during resuscitation requires further research, particularly in preterm infants, in whom it may protect against lung injury.