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BACKGROUND: Bronchopulmonary dysplasia (BPD), an inflammatory-mediated chronic lung disease, is common in extremely preterm infants born before 28 weeks' gestation and is associated with an increased risk of adverse neurodevelopmental and respiratory outcomes in childhood. Effective and safe prophylactic therapies for BPD are urgently required. Systemic corticosteroids reduce rates of BPD in the short term but are associated with poorer neurodevelopmental outcomes if given to ventilated infants in the first week after birth. Intratracheal administration of corticosteroid admixed with exogenous surfactant could overcome these concerns by minimizing systemic sequelae. Several small, randomized trials have found intratracheal budesonide in a surfactant vehicle to be a promising therapy to increase survival free of BPD. The primary objective of the PLUSS trial is to determine whether intratracheal budesonide mixed with surfactant increases survival free of bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age (PMA) in extremely preterm infants born before 28 weeks' gestation. METHODS: An international, multicenter, double-blinded, randomized trial of intratracheal budesonide (a corticosteroid) mixed with surfactant for extremely preterm infants to increase survival free of BPD at 36 weeks' postmenstrual age (PMA; primary outcome). Extremely preterm infants aged < 48 h after birth are eligible if (1) they are mechanically ventilated, or (2) they are receiving non-invasive respiratory support and there is a clinical decision to treat with surfactant. The intervention is budesonide (0.25 mg/kg) mixed with poractant alfa (200 mg/kg first intervention, 100 mg/kg if second intervention), administered intratracheally via an endotracheal tube or thin catheter. The comparator is poractant alfa alone (at the same doses). Secondary outcomes include the components of the primary outcome (death, BPD prior to or at 36 weeks' PMA), and potential systemic side effects of cort

BACKGROUND: Bronchopulmonary dysplasia (BPD), an inflammatory-mediated chronic lung disease, is common in extremely preterm infants born before 28 weeks' gestation and is associated with an increased risk of adverse neurodevelopmental and respiratory outcomes in childhood. Effective and safe prophylactic therapies for BPD are urgently required. Systemic corticosteroids reduce rates of BPD in the short-term but are associated with poorer neurodevelopmental outcomes if given to ventilated infants in the first week after birth. Intratracheal administration of corticosteroid admixed with exogenous surfactant could overcome these concerns by minimizing systemic sequelae. Several small, randomized trials have found intratracheal budesonide in a surfactant vehicle to be a promising therapy to increase survival free of BPD. METHODS: An international, multicenter, double-blinded, randomized trial of intratracheal budesonide (a corticosteroid) mixed with surfactant for extremely preterm infants to increase survival free of BPD at 36 weeks' postmenstrual age (PMA; primary outcome). Extremely preterm infants aged < 48 h after birth are eligible if: (1) they are mechanically ventilated, or (2) they are receiving non-invasive respiratory support and there is a clinical decision to treat with surfactant. The intervention is budesonide (0.25 mg/kg) mixed with poractant alfa (200 mg/kg first intervention, 100 mg/kg if second intervention), administered intratracheally via an endotracheal tube or thin catheter. The comparator is poractant alfa alone (at the same doses). Secondary outcomes include the components of the primary outcome (death, BPD prior to or at 36 weeks' PMA), potential systemic side effects of corticosteroids, cost-effectiveness, early childhood health until 2 years of age, and neurodevelopmental outcomes at 2 years of age (corrected for prematurity). DISCUSSION: Combining budesonide with surfactant for intratracheal administration is a simple intervention that may r

A portable test to rapidly determine levels of levodopa, the drug used to treat Parkinson's disease, can improve clinical management of the disease. In this study, screen-printed electrodes (SPEs) were modified with polymers to facilitate the electrochemical detection of levodopa. Cyclic voltammetry was used to deposit a thin layer of polyaniline on the electrode surface. Scanning electron microscopy revealed high surface coverage, which did not impact the electrode's conductivity. Differential pulse voltammetry measurements with the polyaniline-modified electrodes enabled the measurement of levodopa at physiologically relevant concentrations with discrimination between a common interferent (ascorbic acid) and a structurally similar compound (L-tyrosine). However, the use of the polymer layer did not permit differentiation between levodopa and dopamine; the only difference in these molecules is that levodopa has an amino acid moiety whereas dopamine has a free amine group. Density functional theory calculations demonstrated that aniline formed a hydrogen bond between the amino group of the monomer and the meta-hydroxyl group, which is present in both levodopa and dopamine, with similar binding energies (−53.36 vs −50.08 kJ mol−1). Thus, the polymer-functionalised SPEs are a valuable tool to measure compounds important in Parkinson's disease, but further refinement is needed to achieve selective detection.

BACKGROUND: Our aim was to report perinatal characteristics of very preterm births before arrival (BBAs) at a hospital, and perinatal and infant mortality rates up to one year, comparing BBAs with births in a hospital. MATERIALS AND METHODS: A population-based cohort study of 22-31 weeks' gestation births in the state of Victoria, Australia from 1990-2009. BBAs were defined as unintentional births at home or on route to hospital. Perinatal data were obtained from the Department of Health and Human Services, Victoria. Perinatal and infant mortality data comparing BBAs with births in hospitals were analysed by logistic regression, adjusted for gestational age, birthweight and sex. RESULTS: One hundred and thirty-three BBAs were recorded: 51 (38%) stillbirths and 82 (62%) livebirths. Compared with births in a hospital, BBAs were less mature (26.3 weeks (SD 2.9) vs 27.7 weeks (SD 2.8), P < 0.001) and a higher proportion were born to teenagers: 13% versus 5% (adjusted odds ratio (aOR) 2.86, P < 0.001). BBAs were significantly more likely to be stillborn (aOR 2.13, 95% confidence interval (CI) 1.41, 3.23, P < 0.001) die within 28 days of livebirth (aOR 2.97, 95% CI 1.54, 5.73, P = 0.001) or die within a year of livebirth (aOR 2.87, 95% CI 1.51, 5.46, P = 0.001) compared with hospital births. Overall, 54 BBAs survived to one year (41% all BBAs, 67% liveborn BBAs), compared with 69% of hospital births (87% of livebirths). CONCLUSIONS: Very preterm birth before arrival is more common in teenagers and is associated with significantly increased risks of perinatal and infant mortality compared with birth in a hospital.

AIM: Neonatal clinicians may be asked to review X-ray images when unable to directly access the original image. Transmitting an X-ray image to a smartphone is a technique increasingly being used by clinicians in a number of settings. Minimal data exist on its use in the neonatal setting. Our aim was to compare the ability of neonatal clinicians to correctly diagnose a pneumothorax from a chest radiograph (CXR) viewed on a smartphone, paralleled with the same image viewed on a computer screen. METHODS: We investigated the accuracy, sensitivity, specificity, positive predictive value and negative predicative value of two methods of viewing CXR images to diagnose pneumothorax, compared with a gold standard radiologist report. Clinicians were presented with 40 CXR images on two occasions, at least 1 week apart. Images were viewed once on a smartphone and once on a computer screen. Both the viewing method and viewing order of the images were randomised. The clinical details of the infant at the time the CXR was taken were provided, and participants were asked if a pneumothorax was present. RESULTS: Twenty-one clinicians viewed all CXR images using both viewing methods (840 paired observations). There was no difference in accuracy of detecting pneumothorax between viewing methods, 81% correctly identified a pneumothorax using the smartphone, versus 80% using the computer screen (P = 0.40 (95% CI), difference -4 to 1.5%). CONCLUSION: Diagnosis of neonatal pneumothorax was as accurate using a smartphone as viewing CXR images displayed on a computer screen when clinicians were presented with X-rays with diagnosis of pneumothorax.

AIM: To determine the rate of nonpublication and discontinuation of randomised controlled trials (RCTs) in newborns. METHODS: This was a retrospective, cross-sectional study of RCTs registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR) between 2008 and 2012. RESULTS: Fifty trials were identified, of which 23 (46%) were retrospectively registered. Thirty trials (60%) were published. After a median follow-up of 8.0 (range 4.6-17.4) years from Research Ethics Committee approval, 15 of 41 completed trials (37%) remained unpublished, representing 5422 neonatal trial participants. Nine trials (18%) were discontinued, including four that were published. The most frequent reason for discontinuation was poor recruitment (n = 4). Sample size discrepancies between registration and publication were found in 17 (65%) of the 26 completed, published trials. In nine (35%) of these trials, the calculated sample size in the method section of the published article differed from the planned sample size in the trial registry (relative difference -20% to +33%). CONCLUSION: Nonpublication and discontinuation of RCTs conducted in newborns is common. Additional efforts are needed to minimise the number of neonatal trial participants that are exposed to interventions without subsequent publication.

OBJECTIVE: To compare the physiological stress responses of infants born <30 weeks' gestational age when undergoing clustered nursing cares with standardised neurobehavioural assessments in neonatal nurseries. DESIGN/METHODS: Thirty-four infants born <30 weeks' gestation were recruited from a tertiary neonatal intensive care unit. Heart rate (HR) and oxygen saturation were recorded during clustered nursing cares and during standardised neurobehavioural assessments (including the General Movements Assessment, Hammersmith Neonatal Neurological Examination and Premie-Neuro Assessment). Two assessors extracted HR and oxygen saturations at 5 s intervals, with HR instability defined either as tachycardia (HR >180 beats per minute (bpm)) or bradycardia (HR <100 bpm). Oxygen desaturations were defined as SpO2<90%. Physiological stability was compared between nursing cares and neurobehavioural assessments using linear (for continuous outcomes) and logistic (HR instability and oxygen desaturation) regression. RESULTS: Compared with clustered nursing cares HR was lower (mean difference -5.9 bpm; 95% CI -6.5 to 5.3; P<0.001) and oxygen saturation higher (mean difference 2.4%; 95% CI 2.1% to 2.6%; P<0.001) during standardised neurobehavioural assessments. Compared with clustered nursing cares neurobehavioural assessments were also associated with reduced odds of tachycardia (OR 0.44, 95% CI 0.22 to 0.86), HR instability (OR 0.43, 95% CI 0.22 to 0.85) and oxygen desaturation (OR 0.43, 95% CI 0.26 to 0.70). CONCLUSIONS: Standardised neurobehavioural assessments are associated with less physiological stress than clustered nursing cares in infants aged 29-32 weeks' postmenstrual age, and are therefore possible without causing undue physiological disturbance in medically stable infants.

AIM: We tested whether operators using manometers attached to self-inflating bags could accurately deliver set targeted peak inspiratory pressures (PIPs) compared to the Neopuff(™) T-piece resuscitator (TPR). METHODS: Participants provided positive pressure ventilation to a leak-free neonatal test lung at a rate of 60 inflations/min and a flow of 8 L/min. Participants used three manometers attached to self-inflating bags and a Neopuff(™) TPR to target PIPs of 20, 30 and 40 cmH2 O on each device. Mean PIPs delivered with each manometer were compared to the 'gold standard' Neopuff(™) TPR. RESULTS: In total, 13 991 inflations delivered by 20 participants were analysed. At all target PIPs, the mean PIP delivered using the Mercury Medical manometer attached to a Laerdal self-inflating bag was significantly higher by 5 cmH2 O (p < 0.01) than the Neopuff(™) TPR. The PIP delivered using both the Ambu(™) and Parker Healthcare manometers attached to their respective devices was similar to that delivered by the Neopuff(™) TPR at all targeted PIPs. CONCLUSION: Accurately targeted PIPs can be achieved when a manometer specifically designed for use on a self-inflating bag is used during manual ventilation. This may be useful in settings where access to a Neopuff(™) TPR or a gas flow source is limited.

BACKGROUND: Parent counselling and decision-making regarding the management of preterm labour and birth are influenced by information provided by healthcare professionals regarding potential infant outcomes. AIM: The aim of this study was to determine whether perinatal healthcare providers had accurate perceptions of survival and major neurosensory disability rates of very preterm infants born in non-tertiary hospitals ('outborn') and tertiary perinatal centres ('inborn'). MATERIALS AND METHODS: A web-based survey was distributed to midwives, nurses, obstetricians and neonatologists working in non-tertiary and tertiary maternity hospitals, and the perinatal/neonatal emergency transport services in Victoria, Australia. MAIN OUTCOME MEASURES: Estimates of survival rates at 24 and 28-weeks' gestation were compared with actual survival rates of a population-based cohort of 24 and 28-weeks' gestation infants, born free of lethal anomalies in Victoria in 2001-2009. Estimates of major neurosensory disability rates in 24 and 28-week survivors were compared with actual disability rates in 24 and 28-week children born in Victoria averaged over three eras: 1991-1992, 1997 and 2005. RESULTS: Response rates varied as follows: 83% of non-tertiary midwives, 4% of obstetricians, 55% of tertiary centre staff and 68% of transport team staff responded (total of 30%). Overall, respondents underestimated survival and overestimated major neurosensory disability rates in both outborn and inborn 24 and 28-week infants. Outborn infants were perceived to have much worse prospects for survival and for survival with major disability compared with inborn peers. CONCLUSION: Many clinicians overestimated rates of adverse outcomes. These clinicians may be misinforming parents about their child's potential for a favourable outcome.

BACKGROUND: As measurement of arterial oxygen saturation (SpO2) is common in the delivery room, target SpO2 ranges allow clinicians to titrate oxygen therapy for preterm infants in order to achieve saturation levels similar to those seen in normal term infants in the first minutes of life. However, the influence of the onset of ventilation and the timing of cord clamping on systemic and cerebral oxygenation is not known. AIM: We investigated whether the initiation of ventilation, prior to, or after umbilical cord clamping, altered systemic and cerebral oxygenation in preterm lambs. METHODS: Systemic and cerebral blood-flows, pressures and peripheral SpO2 and regional cerebral tissue oxygenation (SctO2) were measured continuously in apnoeic preterm lambs (126±1 day gestation). Positive pressure ventilation was initiated either 1) prior to umbilical cord clamping, or 2) after umbilical cord clamping. Lambs were monitored intensively prior to intervention, and for 10 minutes following umbilical cord clamping. RESULTS: Clamping the umbilical cord prior to ventilation resulted in a rapid decrease in SpO2 and SctO2, and an increase in arterial pressure, cerebral blood flow and cerebral oxygen extraction. Ventilation restored oxygenation and haemodynamics by 5-6 minutes. No such disturbances in peripheral or cerebral oxygenation and haemodynamics were observed when ventilation was initiated prior to cord clamping. CONCLUSION: The establishment of ventilation prior to umbilical cord clamping facilitated a smooth transition to systemic and cerebral oxygenation following birth. SpO2 nomograms may need to be re-evaluated to reflect physiological management of preterm infants in the delivery room.