OBJECTIVE:To quantify systemic exposure to budesonide following intratracheal administration; evaluate the impact of intratracheal budesonide on blood glucocorticoid activity (cortisol plus betamethasone as cortisol equivalents); and relate the latter to outcomes. STUDY DESIGN:Sub-study of the PLUSS randomized trial(ACTRN12617000322336) of intratracheal budesonide with surfactant versus surfactant alone. RESULT:Among 63 infants enrolled at Kidz First Neonatal Care, Auckland, systemic exposure to intratracheal budesonide was low, and cortisol equivalents were similar between intervention groups at 36-48 h (adjusted-ratio-geometric-means = 1.16, 95% CI 0.52-2.57). Antenatal betamethasone <24 h before birth contributed to neonatal blood glucocorticoid activity for up to 24-48 h. Infants above the upper tertile for cortisol equivalents at <60 h, compared with those below the lower tertile, had increased likelihood of severe intraventricular hemorrhage and possibly death. CONCLUSION:Systemic exposure to intratracheal budesonide has little to no effect on cortisol equivalents at 36-48 h. High glucocorticoid activity after birth may be associated with poorer neonatal outcomes.

The biological mediators that initiate lung injury in extremely preterm infants during early postnatal life remain largely unidentified, limiting opportunities for early treatment and diagnosis. In this exploratory study, we used sequential window acquisition of all theoretical mass spectra mass spectrometry to identify bronchopulmonary dysplasia (BPD)-specific changes in protein abundance in plasma samples obtained in the first 72 hours of life from extremely preterm infants and bioinformatic analysis to identify BPD-related biological categories and pathways. Last, binary logistic regression analysis was used to test the BPD predictive potential of a base model alone (gestational age, birth weight, sex) and with the protein biomarker added, with bootstrap resampling used to internally validate protein predictors and adjust for overoptimism. We observed disturbance of key processes, including coagulation, complement activation, development, and extracellular matrix organization, in the first days of life in extremely preterm infants who later received diagnoses of BPD. In the BPD prediction analysis, 49 plasma proteins were identified; when each singularly was combined with birth characteristics the optimism-adjusted C index was 0.65-0.84, suggesting predictive potential for BPD outcomes. Taken together, the results of this study demonstrate that alterations in plasma proteins can be detected from 4 hours of age in extremely preterm infants who later develop BPD and that protein biomarkers, when combined with three birth characteristics, have the potential to predict BPD development within the first 72 hours of life.

ObjectiveNeonatal endotracheal intubation is a lifesaving but technically difficult procedure, particularly for inexperienced operators. This secondary analysis in a subgroup of inexperienced operators of the Stabilization with nasal High flow during Intubation of NEonates randomised trial aimed to identify the factors associated with successful intubation on the first attempt without physiological stability of the infant.MethodsIn this secondary analysis, demographic factors were compared between infants intubated by inexperienced operators and those intubated by experienced operators. Following this, for inexperienced operators only, predictors of successful intubation without physiological instability were analysed.ResultsA total of 251 intubations in 202 infants were included in the primary intention-to-treat analysis of the main trial. Inexperienced operators were more likely to perform intubations in larger and more mature infants in the neonatal intensive care unit where premedications were used. When intubations were performed by inexperienced operators, the use of nasal high flow therapy (nHF) and a higher starting fraction of inspired oxygen were associated with a higher rate of safe, successful intubation on the first attempt. There was a weaker association between premedication use and first attempt success.ConclusionsIn inexperienced operators, this secondary, non-randomised analysis suggests that the use of nHF and premedications, and matching the operator to the infant and setting, may be important to optimise neonatal intubation success.Trial registration numberACTRN12618001498280.

Importance Bronchopulmonary dysplasia (BPD) is a common adverse outcome in extremely preterm infants born at less than 28 weeks' gestation. Systemic corticosteroids are effective against BPD but may be associated with adverse outcomes. Corticosteroids given directly into the lungs may be effective and safer. Objective To investigate the effectiveness of early intratracheal corticosteroid administration on survival free of BPD in extremely preterm infants. Design, Setting, and Participants Double-blind randomized clinical trial conducted in 21 neonatal units in 4 countries (Australia, New Zealand, Canada, and Singapore), enrolling infants born at less than 28 weeks' gestation and less than 48 hours old who were mechanically ventilated (regardless of ventilator settings or oxygen requirements) or who were receiving noninvasive respiratory support and had a clinical decision to treat with surfactant. Recruitment occurred from January 2018 to March 2023. The last participant was discharged from the hospital in August 2023. Interventions Infants were randomly allocated (1:1) to receive budesonide, 0.25 mg/kg, mixed with surfactant (poractant alfa), administered via an endotracheal tube or thin catheter, or surfactant only. Main Outcomes and MeasuresThe primary outcome was survival free of BPD at 36 weeks' postmenstrual age. There were 15 secondary outcomes, including the 2 components of the primary outcome (survival at 36 weeks and BPD among survivors), and 9 predefined safety outcomes (adverse events). Results The primary analysis included 1059 infants, 524 in the budesonide and surfactant group and 535 in the surfactant-only group. Overall, infants had a mean gestational age of 25.6 weeks (SD, 1.3 weeks) and a mean birth weight of 775 g (SD, 197 g); 586 (55.3%) were male. Survival free of BPD occurred in 134 infants (25.6%) in the budesonide and surfactant group and 121 infants (22.6%) in the surfactant-only group (adjusted risk difference, 2.7% [95% CI, -2.1% to 7.4%]). At 36 weeks' postmenstrual age, 83.2% of infants were alive in the budesonide and surfactant group and 80.6% in the surfactant-only group. Of these, 69.3% and 71.9% were diagnosed with BPD, respectively. Conclusions and Relevance In extremely preterm infants receiving surfactant for respiratory distress syndrome, early intratracheal budesonide may have little to no effect on survival free of BPD.

Background: Blinding of treatment allocation from treating clinicians in neonatal randomised controlled trials can minimise performance bias, but its effectiveness is rarely assessed. Methods: To examine the effectiveness of blinding a procedural intervention from treating clinicians in a multicentre randomised controlled trial of minimally invasive surfactant therapy versus sham treatment in preterm infants of gestation 25–28 weeks with respiratory distress syndrome. The intervention (minimally invasive surfactant therapy or sham) was performed behind a screen within the first 6 h of life by a ‘study team’ uninvolved in clinical care including decision-making. Procedure duration and the study team’s words and actions during the sham treatment mimicked those of the minimally invasive surfactant therapy procedure. Post-intervention, three clinicians completed a questionnaire regarding perceived group allocation, with the responses matched against actual intervention and categorised as correct, incorrect, or unsure. Success of blinding was calculated using validated blinding indices applied to the data overall (James index, successful blinding defined as > 0.50), or to the two treatment allocation groups (Bang index, successful blinding: −0.30 to 0.30). Blinding success was measured within staff role, and the associations between blinding success and procedural duration and oxygenation improvement post-procedure were estimated. Results: From 1345 questionnaires in relation to a procedural intervention in 485 participants, responses were categorised as correct in 441 (33%), incorrect in 142 (11%), and unsure in 762 (57%), with similar proportions for each of the response categories in the two treatment arms. The James index indicated successful blinding overall 0.67 (95% confidence interval (CI) 0.65–0.70). The Bang index was 0.28 (95% CI 0.23–0.32) in the minimally invasive surfactant therapy group and 0.17 (95% CI 0.12–0.21) in the sham arm. Neonatologists more frequently guessed the correct intervention (47%) than bedside nurses (36%), neonatal trainees (31%), and other nurses (24%). For the minimally invasive surfactant therapy intervention, the Bang index was linearly related to procedural duration and oxygenation improvement post-procedure. No evidence of such relationships was seen in the sham arm. Conclusion: Blinding of a procedural intervention from clinicians is both achievable and measurable in neonatal randomised controlled trials.

Introduction: Nasal high flow (nHF) improves the likelihood of successful neonatal intubation on the first attempt without physiological instability. The effect of nHF on cerebral oxygenation is unknown. The aim of this study was to compare cerebral oxygenation during endotracheal intubation in neonates receiving nHF and those receiving standard care. Methods: A sub-study of a multicentre randomized trial of nHF during neonatal endotracheal intubation. A subset of infants had near-infrared spectroscopy (NIRS) monitoring. Eligible infants were randomly assigned to nHF or standard care during the first intubation attempt. NIRS sensors provided continuous regional cerebral oxygen saturation (rScO(2)) monitoring. The procedure was video recorded, and peripheral oxygen saturation and rScO(2) data were extracted at 2-second intervals. The primary outcome was the average difference in rScO(2) from baseline during the first intubation attempt. Secondary outcomes included average rScO(2) and rate of change of rScO(2). Results: Nineteen intubations were analyzed (11 nHF; 8 standard care). Median (interquartile range [IQR]) postmenstrual age was 27 (26.5-29) weeks, and weight was 828 (716-1,135) g. Median change in rScO(2) from baseline was -1.5% (-5.3 to 0.0) in the nHF group and -9.4% (-19.6 to -4.5) in the standard care group. rScO(2) fell more slowly in infants managed with nHF compared with standard care: median (IQR) rScO(2) change -0.08 (-0.13 to 0.00) % per second and -0.36 (-0.66 to -0.22) % per second, respectively. Conclusions: In this small sub-study, regional cerebral oxygen saturation was more stable in neonates who received nHF during intubation compared with standard care.

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 corticosteroids. Longer-term outcomes will be published separately, and include cost-effectiveness, early childhood health until 2 years of age, and neurodevelopmental outcomes at 2 years of age (corrected for prematurity). Statistical analysis plan A sample size of 1038 infants (519 in each group) is required to provide 90% power to detect a relative increase in survival free of BPD of 20% (an absolute increase of 10%), from the anticipated event rate of 50% in the control arm to 60% in the intervention (budesonide) arm, alpha error 0.05. To allow for up to 2% of study withdrawals or losses to follow-up, PLUSS aimed to enroll a total of 1060 infants (530 in each arm). The binary primary outcome will be reported as the number and percentage of infants who were alive without BPD at 36 weeks’ PMA for each randomization group. To estimate the difference in risk (with 95% CI), between the treatment and control arms, binary regression (a generalized linear multivariable model with an identity link function and binomial distribution) will be used. Along with the primary outcome, the individual components of the primary outcome (death, and physiological BPD at 36 weeks’ PMA), will be reported by randomization group and, again, binary regression will be used to estimate the risk difference between the two treatment groups for survival and physiological BPD at 36 weeks’ PMA.

Aim: To evaluate delivery room (DR) interventions to prevent hypothermia and improve outcomes in preterm newborn infants <34 weeks' gestation. Methods: Medline, Embase, CINAHL and CENTRAL were searched till 22nd July 2022. Randomized controlled trials (RCTs), non-RCTs and quality improvement studies were considered. A random effects meta-analysis was performed, and the certainty of evidence was evaluated using GRADE guidelines. Results: DR temperature of >= 23 degrees C compared to standard care improved temperature outcomes without an increased risk of hyperthermia (low certainty), whereas radiant warmer in servo mode compared to manual mode decreased mean body temperature (MBT) (moderate certainty). Use of a plastic bag or wrap (PBW) improved normothermia (low certainty), but with an increased risk of hyperthermia (moderate certainty). Plastic cap improved normothermia (moderate certainty) and when combined with PBW improved MBT (low certainty). Use of a cloth cap decreased moderate hypothermia (low certainty). Though thermal mattress (TM) improved MBT, it increased risk of hyperthermia (low certainty). Heated-humidified gases (HHG) for resuscitation decreased the risk of moderate hypothermia and severe intraventricular hemorrhage (very low to low certainty). None of the interventions was shown to improve survival, but sample sizes were insufficient. Conclusions: DR temperature of >= 23 degrees C, radiant warmer in manual mode, use of a PBW and a head covering is suggested for preterm newborn infants <34 weeks' gestation. HHG and TM could be considered in addition to PBW provided resources allow, in settings where hypothermia incidence is high. Careful monitoring to avoid hyperthermia is needed.

Importance:The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. Objective:To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. Design, Setting, and Participants:Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. Interventions:Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. Main Outcomes and Measures:The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. Results:Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). Conclusions and Relevance:In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. Trial Registration:anzctr.org.au Identifier: ACTRN12611000916943.

Video observations and recordings of respiratory signals from mannequin studies and delivery room (DR) resuscitations are described. This article discusses the uses of a respiratory function monitor (RFM) during training and resuscitations along with potential pitfalls and limitations. It adds objectivity to the clinical assessment. A respiratory function monitor provides real-time quantitative information including tidal volume and leak. It may be used to teach correct mask hold and positioning techniques during simulation-based mannequin. Examples demonstrating its potential usefulness during resuscitations are provided. However, further studies are needed to investigate whether it can help improve short-term and long-term outcomes.

Postnatal maturation of the immune system is poorly understood, as is its impact on illnesses afflicting term or preterm infants, such as bronchopulmonary dysplasia (BPD) and BPD-associated pulmonary hypertension. These are both cardiopulmonary inflammatory diseases that cause substantial mortality and morbidity with high treatment costs. Here, we characterized blood samples collected from 51 preterm infants longitudinally at five time points, 20 healthy term infants at birth and age 3 to 16 weeks, and 5 healthy adults. We observed strong associations between type 2 immune polarization in circulating CD3 + CD4 + T cells and cardiopulmonary illness, with odds ratios up to 24. Maternal magnesium sulfate therapy, delayed hepatitis B vaccination, and increasing fetal, but not maternal, chorioamnionitis severity were associated with attenuated type 2 polarization. Blocking type 2 mediators such as interleukin-4 (IL-4), IL-5, IL-13, or signal transducer and activator of transcription 6 (STAT6) in murine neonatal cardiopulmonary disease in vivo prevented changes in cell type composition, increases in IL-1β and IL-13, and losses of pulmonary capillaries, but not gains in larger vessels. Thereby, type 2 blockade ameliorated lung inflammation, protected alveolar and vascular integrity, and confirmed the pathological impact of type 2 cytokines and STAT6. In-depth flow cytometry and single-cell transcriptomics of mouse lungs further revealed complex associations between immune polarization and cardiopulmonary disease. Thus, this work advances knowledge on developmental immunology and its impact on early life disease and identifies multiple therapeutic approaches that may relieve inflammation-driven suffering in the youngest patients.

( N Engl J Med . 2022;386:1627–1637) Fetal intubation attempts frequently have low success rates and take longer versus international guidelines, especially when performed by inexperienced operators. This results in increased rates of intraventricular hemorrhage and airway injury in vulnerable neonatal patients. Transnasal humidified rapid insufflation ventilatory exchange, the use of nasal high-flow therapy (HFT) to aid respiratory support, is a proven useful aid in older children and adult intubation in a variety of circumstances. However, the relationship between neonates and nasal HFT during intubation was previously untested. This study examined the success rates of nasal HFT use during intubation against those not receiving HFTs. This study defined initial intubation attempt as the insertion length past the infant’s lips of the laryngoscope blade and successful intubation as the presence of carbon dioxide expiration after the placement of an endotracheal tube.

Background We sought to assess tidal volumes in (near) term infants during delivery room stabilization. Methods Secondary analysis of a prospective study comparing two facemasks used for positive pressure ventilation (PPV) in newborn infants ≥ 34 weeks gestation. PPV was provided with a T-piece device with a PIP of 30 cmH 2 O and positive end-expiratory airway pressure of 5 cmH 2 O. Expired tidal volumes (V t ) were measured with a respiratory function monitor. Target range for V t was defined to be 4 – 8 ml/kg. Results Twenty-three infants with a median (IQR) gestational age of 38.1 (36.4 – 39.0) weeks received 1828 inflations with a median V t of 4.6 (3.3 – 6.2) ml/kg. Median V t was in the target range in 12 infants (52%), lower in 9 (39%) and higher in 2 (9%). Thirty-six (25—27) % of the inflations were in the target rage over the duration of PPV while 42 (25 – 65) % and 10 (3 – 33) % were above and below target range. Conclusions Variability of expiratory tidal volume delivered to term and late preterm infants was wide. Reliance on standard pressures and clinical signs may be insufficient to provide safe and effective ventilation in the delivery room. Trial registration This is a secondary analysis of a prospectively registered randomized controlled trial (ACTRN12616000768493).

OBJECTIVES:To describe the prevalence of maladies and deaths among witches and wizards in the Harry Potter world, their causes, and associated therapies.DESIGN:Retrospective population-based observational study (report analysis) undertaken 10 February - 19 March 2022.SETTING:All locations described in the Harry Potter books, predominantly Hogwarts School of Witchcraft and Wizardry, but also selected locations, including Privet Drive No 4, Diagon Alley, the Ministry of Magic, and The Burrow.PARTICIPANTS:All witches and wizards mentioned at least once in any of the seven Harry Potter books.MAIN OUTCOME MEASURES:Overall numbers of maladies and deaths. Secondary outcomes were changes in morbidity and mortality over time, causes of morbidity and mortality, and treatments.RESULTS:A total of 603 wizards or witches named in the Potter books experienced 1541 maladies and injuries (1410 non-fatal) and 131 deaths. Overall morbidity incidence was 471 events per 1000 individuals, and mortality, after adjustment for Lord Voldemort's multi-mortality, was 20.6%. The most frequent causes of morbidity were traumatic injuries during duels or fights (553 cases, 39.2%), magical objects, potions, plants, or creatures (345, 24.5%), and non-combative trauma (221, 15.7%). Most deaths were related to wizarding duels (101 of 131, 77.1%). Treatments were rarely described; the most frequent were jinxes (274, 19.4%) and potions (136, 9.6%). Hospital stays were shorter than a week for almost all non-fatal maladies (1397 of 1410, 99.1%).CONCLUSIONS:Morbidity and, in particular, mortality were very high and predominantly caused by magical means. Further investigation into the safety at Hogwarts School of Witchcraft and Wizardry is warranted. The few treatments used had high success rates; rapid recovery was the rule, and hospital stays generally brief. Efforts should be undertaken to identify the magical therapies and interventions used and to introduce these novel remedies into Muggle medicine.

BACKGROUND:Globally, the majority of newborns requiring resuscitation at birth are full term or late-preterm infants. These infants typically have their umbilical cord clamped early (ECC) before moving to a resuscitation platform, losing the potential support of the placental circulation. Physiologically based cord clamping (PBCC) is clamping the umbilical cord after establishing lung aeration and holds promise as a readily available means of improving early newborn outcomes. In mechanically ventilated lambs, PBCC improved cardiovascular stability and reduced hypoxia. We hypothesised that PBCC compared to ECC would result in higher heart rate (HR) in infants needing resuscitation, without compromising safety.METHODS AND FINDINGS:Between 4 July 2018 and 18 May 2021, infants born at ≥32+0 weeks' gestation with a paediatrician called to attend were enrolled in a parallel-arm randomised trial at 2 Australian perinatal centres. Following initial stimulation, infants requiring further resuscitation were randomised within 60 seconds of birth using a smartphone-accessible web link. The intervention (PBCC) was to establish lung aeration, either via positive pressure ventilation (PPV) or effective spontaneous breathing, prior to cord clamping. The comparator was early cord clamping (ECC) prior to resuscitation. The primary outcome was mean HR between 60 to 120 seconds after birth, measured using 3-lead electrocardiogram, extracted from video recordings blinded to group allocation. Nonrandomised infants had deferred cord clamping (DCC) ≥120 seconds in the observational study arm. Among 508 at-risk infants enrolled, 123 were randomised (n = 63 to PBCC, n = 60 to ECC). Median (interquartile range, IQR) for gestational age was 39.9 (38.3 to 40.7) weeks in PBCC infants and 39.6 (38.4 to 40.4) weeks in ECC infants. Approximately 49% and 50% of the PBCC and ECC infants were female, respectively. Five infants (PBCC = 2, ECC = 3, 4% total) had missing primary outcome data. Cord clamping occurred at a median (IQR) of 136 (126 to 150) seconds in the PBCC arm and 37 (27 to 51) seconds in the ECC arm. Mean HR between 60 to 120 seconds after birth was 154 bpm (beats per minute) for PBCC versus 158 bpm for ECC (adjusted mean difference -6 bpm, 95% confidence interval (CI) -17 to 5 bpm, P = 0.39). Among 31 secondary outcomes, postpartum haemorrhage ≥500 ml occurred in 34% and 32% of mothers in the PBCC and ECC arms, respectively. Two hundred ninety-five nonrandomised infants (55% female) with median (IQR) gestational age of 39.6 (38.6 to 40.6) weeks received DCC. Data from these infants was used to create percentile charts of expected HR and oxygen saturation in vigorous infants receiving DCC. The trial was limited by the small number of infants requiring prolonged or advanced resuscitation. PBCC may provide other important benefits we did not measure, including improved maternal-infant bonding and higher iron stores.CONCLUSIONS:In this study, we observed that PBCC resulted in similar mean HR compared to infants receiving ECC. The findings suggest that for infants ≥32+0 weeks' gestation who receive brief, effective resuscitation at closely monitored births, PBCC does not provide additional benefit over ECC (performed after initial drying and stimulation) in terms of key physiological markers of transition. PBCC was feasible using a simple, low-cost strategy at both cesarean and vaginal births. The percentile charts of HR and oxygen saturation may guide clinicians monitoring the transition of at-risk infants who receive DCC.TRIAL REGISTRATION:Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618000621213.

BACKGROUND:Neonatal endotracheal intubation often involves more than one attempt, and oxygen desaturation is common. It is unclear whether nasal high-flow therapy, which extends the time to desaturation during elective intubation in children and adults receiving general anesthesia, can improve the likelihood of successful neonatal intubation on the first attempt.METHODS:We performed a randomized, controlled trial to compare nasal high-flow therapy with standard care (no nasal high-flow therapy or supplemental oxygen) in neonates undergoing oral endotracheal intubation at two Australian tertiary neonatal intensive care units. Randomization of intubations to the high-flow group or the standard-care group was stratified according to trial center, the use of premedication for intubation (yes or no), and postmenstrual age of the infant (≤28 or >28 weeks). The primary outcome was successful intubation on the first attempt without physiological instability (defined as an absolute decrease in the peripheral oxygen saturation of >20% from the preintubation baseline level or bradycardia with a heart rate of <100 beats per minute) in the infant.RESULTS:The primary intention-to-treat analysis included the outcomes of 251 intubations in 202 infants; 124 intubations were assigned to the high-flow group and 127 to the standard-care group. The infants had a median postmenstrual age of 27.9 weeks and a median weight of 920 g at the time of intubation. A successful intubation on the first attempt without physiological instability was achieved in 62 of 124 intubations (50.0%) in the high-flow group and in 40 of 127 intubations (31.5%) in the standard-care group (adjusted risk difference, 17.6 percentage points; 95% confidence interval [CI], 6.0 to 29.2), for a number needed to treat of 6 (95% CI, 4 to 17) for 1 infant to benefit. Successful intubation on the first attempt regardless of physiological stability was accomplished in 68.5% of the intubations in the high-flow group and in 54.3% of the intubations in the standard-care group (adjusted risk difference, 15.8 percentage points; 95% CI, 4.3 to 27.3).CONCLUSIONS:Among infants undergoing endotracheal intubation at two Australian tertiary neonatal intensive care units, nasal high-flow therapy during the procedure improved the likelihood of successful intubation on the first attempt without physiological instability in the infant. (Funded by the National Health and Medical Research Council; Australian New Zealand Clinical Trials Registry number, ACTRN12618001498280.).

Aim: Prevention of hypothermia after birth is a global problem in late preterm and term neonates. The aim of this systematic review and meta-analysis was to evaluate delivery room strategies to maintain normothermia and improve survival in late preterm and term neonates (>= 34 weeks' gestation). Methods: Medline, Embase, CINAHL, CENTRAL and international clinical trial registries were searched. Randomized controlled trials (RCTs), quasi-RCTs and observational studies were eligible for inclusion. Risk of bias for each study and GRADE certainty of evidence for each outcome were assessed. Results: 25 RCTs and 10 non-RCTs were included. Room temperature of 23 degrees C compared to 20 degrees C improved normothermia [Risk Ratio (RR), 95% Confidence Interval (CI): 1.26, 1.11-1.42)] and body temperature [Mean Difference (MD), 95% CI: 0.30 degrees C, 0.23-0.37 degrees C), and decreased moderate hypothermia (RR, 95% CI: 0.26, 0.16-0.42). Skin to skin care (SSC) compared to no SSC increased body temperature (MD, 95% CI: 0.32, 0.10-0.52), reduced hypoglycemia (RR, 95% CI: 0.16, 0.05-0.53) and hospital admission (RR, 95% CI: 0.34, 0.14-0.83). Though plastic bag or wrap (PBW) alone or when combined with SSC compared to SSC alone improved temperatures, the risk-benefit balance is uncertain. Clinical benefit or harm could not be excluded for the primary outcome of survival for any of the interventions. Certainty of evidence was low to very low for all outcomes. Conclusions: Room temperature of 23 degrees C and SSC soon after birth may prevent hypothermia in late preterm and term neonates. Though PBW may be an effective adjunct intervention, the risk-benefit balance needs further investigation.

Objective We sought to determine the effect of stimulation during positive pressure ventilation (PPV) on the number of spontaneous breaths, exhaled tidal volume (VTe), mask leak and obstruction. Design Secondary analysis of a prospective, randomised trial comparing two face masks. Setting Single-centre delivery room study. Patients Newborn infants ≥34 weeks’ gestation at birth. Methods Resuscitations were video recorded. Tactile stimulations during PPV were noted and the timing, duration and surface area of applied stimulus were recorded. Respiratory flow waveforms were evaluated to determine the number of spontaneous breaths, VTe, leak and obstruction. Variables were recorded throughout each tactile stimulation episode and compared with those recorded in the same time period immediately before stimulation. Results Twenty of 40 infants received tactile stimulation during PPV and we recorded 57 stimulations during PPV. During stimulation, the number of spontaneous breaths increased (median difference (IQR): 1 breath (0–3); padj<0.001) and VTe increased (0.5 mL/kg (−0.5 to 1.7), padj=0.028), whereas mask leak (0% (−20 to 1), padj=0.12) and percentage of obstructed inflations (0% (0–0), padj=0.14) did not change, compared with the period immediately prior to stimulation. Increased duration of stimulation (padj<0.001) and surface area of applied stimulus (padj=0.026) were associated with a larger increase in spontaneous breaths in response to tactile stimulation. Conclusions Tactile stimulation during PPV was associated with an increase in the number of spontaneous breaths compared with immediately before stimulation without a change in mask leak and obstruction. These data inform the discussion on continuing stimulation during PPV in term infants. Trial registration number Australian and New Zealand Clinical Trial Registry (ACTRN12616000768493). Secondary data analysis suggesting that neonates have more spontaneous breaths after birth following cutaneous stimulation.

INTRODUCTION:Early identification of infants requiring surfactant therapy improves outcomes. We evaluated the accuracy of delivery room lung ultrasound (LUS) to predict surfactant therapy in very- and extremely preterm infants. METHODS:Infants born at <320/7 weeks were prospectively enrolled at 2 centres. LUS videos of both sides of the chest were obtained 5-10 min, 11-20 min, and 1-3 h after birth. Clinicians were masked to the results of the LUS assessment and surfactant therapy was provided according to local guidelines. LUS videos were graded blinded to clinical data. Presence of unilateral type 1 ('whiteout') LUS or worse was considered test positive. Receiver Operating Characteristic (ROC) analysis compared the accuracy of LUS and an FiO2 threshold of 0.3 to predict subsequent surfactant therapy. RESULTS:Fifty-two infants with a median age of 276/7 weeks (IQR 260/7-286/7) were studied. Thirty infants (58%) received surfactant. Area under the ROC curve (AUC) for LUS at 5-10 min, 11-20 min and 1-3 h was 0.78 (95% CI, 0.66-0.90), 0.76 (95% CI, 0.65-0.88) and 0.86 (95% CI, 0.75-0.97) respectively, outperforming FiO2 at the 5-10 min timepoint (AUC 0.45, 95% CI 0.29-0.62, p = 0.001). At 11-20 min, LUS had a specificity of 95% (95% CI 77-100%) and sensitivity of 59% (95% CI, 39-77%) to predict surfactant therapy. All infants born at 23-276/7 weeks with LUS test positive received surfactant. Twenty-six infants (50%) had worsening of LUS grades on serial assessment. CONCLUSIONS:LUS in the delivery room and accurately predicts surfactant therapy in infants <320/7 weeks.

Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism. Chelation of excessive copper is recommended but data on the pharmacokinetics of trientine are limited. The aim of this study was to compare the pharmacokinetics of a new trientine tetrahydrochloride formulation (TETA 4HCl) with those of an established trientine dihydrochloride (TETA 2HCl) salt. A randomised single-centre crossover study to evaluate the pharmacokinetics, safety and tolerability of two different oral formulations of trientine (TETA 4HCl tablets vs TETA 2HCl capsules) in 23 healthy adult subjects receiving a single dose equivalent to 600 mg of trientine base was performed. Following oral administration, the median time to reach maximum plasma concentration (Tmax) was 2.00 h (TETA 4HCl) and 3.00 h (TETA 2HCl). The rate (maximum plasma concentration [Cmax]) and extent (area under the plasma concentration-time curve from time zero to infinity [AUC0–∞]) of absorption of the active moiety, trientine, were greater (by approximately 68% and 56%, respectively) for TETA 4HCl than for the TETA 2HCl formulation. The two formulations presented a similar terminal elimination rate (λz) and a similar terminal half-life (t½) for trientine. Differences between TETA 4HCl and TETA 2HCl in the levels of the two main mono- and diacetylated metabolites were less than seen for trientine. For both tested formulations, healthy male volunteers demonstrated higher trientine plasma levels but lower mono- and diacetylated metabolite levels compared with females, with no sex differences in terminal half-life (t½) observed. Single oral doses of both formulations were safe and well tolerated. Compared with an identical dose of a TETA 2HCl formulation, the TETA 4HCl formulation provided more rapid absorption of trientine and greater systemic exposure in healthy subjects. Clinical Trials Number EudraCT # 2015-002199-25.