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OBJECTIVE: To determine the causal relationship between exposure to early hyperoxemia and death or major disability in infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We analyzed data from the Infant Cooling Evaluation (ICE) trial that enrolled newborns ≥35 weeks' gestation with moderate-severe HIE, randomly allocated to hypothermia or normothermia. The primary outcome was death or major sensorineural disability at 2 years. We included infants with arterial pO2 measured within 2 hours of birth. Using a directed acyclic graph, we established that markers of severity of perinatal hypoxia-ischemia and pCO2 were a minimally sufficient set of variables for adjustment in a regression model to estimate the causal relationship between arterial pO2 and death/disability. RESULTS: Among 221 infants, 116 (56%) had arterial pO2 and primary outcome data. The unadjusted analysis revealed a U-shaped relationship between arterial pO2 and death or major disability. Among hyperoxemic infants (pO2 100-500 mmHg) the proportion with death or major disability was 40/58 (0.69), while the proportion in normoxemic infants (pO2 40-99 mmHg) was 20/48 (0.42). In the adjusted model, hyperoxemia increased the risk of death or major disability (adjusted risk ratio 1.61, 95% CI 1.07-2.00, P = .03) in relation to normoxemia. CONCLUSION: Early hyperoxemia increased the risk of death or major disability among infants who had an early arterial pO2 in the ICE trial. Limitations include the possibility of residual confounding and other causal biases. Further work is warranted to confirm this relationship in the era of routine therapeutic hypothermia.

INTRODUCTION: Recent reports have raised concerns of cardiorespiratory deterioration in some infants receiving respiratory support at birth. We aimed to independently determine whether respiratory support with a facemask is associated with a decrease in heart rate (HR) in some late-preterm and term infants. METHODS: Secondary analysis of data from infants born at ≥32+0 weeks of gestation at 2 perinatal centres in Melbourne, Australia. Change in HR up to 120 s after facemask placement, measured using 3-lead electrocardiography, was assessed every 3 s until 60 s and every 5 s thereafter from video recordings. RESULTS: In the 15 s after facemask placement, 10/68 (15%) infants had a decrease in mean HR by >10 beats per minute (bpm) compared with their individual baseline mean HR in the 15 s before facemask placement. In 4 (6%) infants, HR decreased to <100 bpm. Nine out of 68 (13%) infants had an increase in mean HR by >10 bpm; 7 of these infants had a baseline HR <120 bpm. In univariable comparisons, the following characteristics were found not to be risk factors for a decrease in HR by >10 bpm: prematurity; type of respiratory support; hypoxaemia; early cord clamping; mode of birth; HR <120 bpm before mask placement. Six out of 63 infants (10%) who had HR ≥120 bpm after facemask placement had a late decrease in HR to <100 bpm between 30 and 120 s after facemask placement. CONCLUSION: Facemask respiratory support at birth is temporally associated with a decrease in HR in a subset of late-preterm and term infants.

'Apnoeic oxygenation' describes the diffusion of oxygen across the alveolar-capillary interface in the absence of tidal respiration. Apnoeic oxygenation requires a patent airway, the diffusion of oxygen to the alveoli, and cardiopulmonary circulation. Apnoeic oxygenation has varied applications in adult medicine including facilitating tubeless anaesthesia or improving oxygenation when a difficult airway is known or anticipated. In the paediatric population, apnoeic oxygenation prolongs the time to oxygen desaturation, facilitating intubation. This application has gained attention in neonatal intensive care where intubation remains a challenging procedure. Difficulties are related to the infant's size and decreased respiratory reserve. In addition, policy changes have led to limited opportunities for operators to gain proficiency. Until recently, evidence of benefit of apnoeic oxygenation in the neonatal population came from a small number of infants recruited to paediatric studies. Evidence specific to neonates is emerging and suggests apnoeic oxygenation may increase intubation success and limit physiological instability during the procedure. The best way to deliver oxygen to facilitate apnoeic oxygenation remains an important question.

BACKGROUND: Extremely preterm infants often require invasive mechanical ventilation, and clinicians aim to extubate these infants as soon as possible. However, extubation failure occurs in up to 60% of extremely preterm infants and is associated with increased mortality and morbidity. Nasal continuous positive airway pressure (nCPAP) is the most common post-extubation respiratory support, but there is no consensus on the optimal nCPAP level to safely avoid extubation failure in extremely preterm infants. We aimed to determine if higher nCPAP levels compared with standard nCPAP levels would decrease rates of extubation failure in extremely preterm infants within 7 days of their first extubation. METHODS: In this multicentre, randomised, open-label controlled trial done at three tertiary perinatal centres in Australia, we assigned extremely preterm infants to extubation to either higher nCPAP (10 cmH2O) or standard nCPAP (7 cmH2O). Infants were eligible if they were born at less than 28 weeks' gestation, were receiving mechanical ventilation via an endotracheal tube, and were being extubated for the first time to nCPAP. Eligible infants must have received previous treatment with exogenous surfactant and caffeine. Infants were ineligible if they were planned to be extubated to a mode of respiratory support other than nCPAP, if they had a known major congenital anomaly that might affect breathing, or if ongoing intensive care was not being provided. Parents or guardians provided prospective, written, informed consent. Infants were maintained within an assigned nCPAP range for a minimum of 24 h after extubation (higher nCPAP group 9-11 cmH2O and standard nCPAP group 6-8 cmH2O). Randomisation was stratified by both gestation (22-25 completed weeks or 26-27 completed weeks) and recruiting centre. The primary outcome was extubation failure within 7 days and analysis was by intention to treat. This trial was prospectively registered with the Australian New Zealand Clinical T

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: Lung ultrasound (LUS) may not detect small, dynamic changes in lung volume. Mean greyscale measurement using computer-assisted image analysis (Q-LUSMGV) may improve the precision of these measurements. METHODS: Preterm lambs (n = 40) underwent LUS of the dependent or non-dependent lung during static pressure-volume curve mapping. Total and regional lung volumes were determined using the super-syringe technique and electrical impedance tomography. Q-LUSMGV and gold standard measurements of lung volume were compared in 520 images. RESULTS: Dependent Q-LUSMGV moderately correlated with total lung volume (rho = 0.60, 95% CI 0.51-0.67) and fairly with right whole (rho = 0.39, 0.27-0.49), central (rho = 0.38, 0.27-0.48), ventral (rho = 0.41, 0.31-0.51) and dorsal regional lung volumes (rho = 0.32, 0.21-0.43). Non-dependent Q-LUSMGV moderately correlated with total lung volume (rho = 0.57, 0.48-0.65) and fairly with right whole (rho = 0.43, 0.32-0.52), central (rho = 0.46, 0.35-0.55), ventral (rho = 0.36, 0.25-0.47) and dorsal lung volumes (rho = 0.36, 0.25-0.47). All correlation coefficients were statistically significant. Distinct inflation and deflation limbs, and sonographic pulmonary hysteresis occurred in 95% of lambs. The greatest changes in Q-LUSMGV occurred at the opening and closing pressures. CONCLUSION: Q-LUSMGV detected changes in total and regional lung volume and offers objective quantification of LUS images, and may improve bedside discrimination of real-time changes in lung volume. IMPACT: Lung ultrasound (LUS) offers continuous, radiation-free imaging that may play a role in assessing lung recruitment but may not detect small changes in lung volume. Mean greyscale image analysis using computer-assisted quantitative LUS (Q-LUSMGV) moderately correlated with changes in total and regional lung volume. Q-LUSMGV identified opening and closing pressure and pulmonary hysteresis in 95% of lambs. Computer-assisted image analysis may enhance LUS estimat

BACKGROUND: Effective lung protective ventilation requires reliable, real-time estimation of lung volume at the bedside. Neonatal clinicians lack a readily available imaging tool for this purpose. OBJECTIVE: To determine the ability of lung ultrasound (LUS) of the dependent region to detect real-time changes in lung volume, identify opening and closing pressures of the lung, and detect pulmonary hysteresis. METHODS: LUS was performed on preterm lambs (n=20) during in vivo mapping of the pressure-volume relationship of the respiratory system using the super-syringe method. Electrical impedance tomography was used to derive regional lung volumes. Images were blindly graded using an expanded scoring system. The scores were compared with total and regional lung volumes, and differences in LUS scores between pressure increments were calculated. RESULTS: Changes in LUS scores correlated moderately with changes in total lung volume (r=0.56, 95% CI 0.47-0.64, p<0.0001) and fairly with right whole (r=0.41, CI 0.30-0.51, p<0.0001), ventral (r=0.39, CI 0.28-0.49, p<0.0001), central (r=0.41, CI 0.31-0.52, p<0.0001) and dorsal (r=0.38, CI 0.27-0.49, p<0.0001) regional lung volumes. The pressure-volume relationship of the lung exhibited hysteresis in all lambs. LUS was able to detect hysteresis in 17 (85%) lambs. The greatest changes in LUS scores occurred at the opening and closing pressures. CONCLUSION: LUS was able to detect large changes in total and regional lung volume in real time and correctly identified opening and closing pressures but lacked the precision to detect small changes in lung volume. Further work is needed to improve precision prior to translation to clinical practice.

UNLABELLED: To identify characteristics associated with delivery room clinical instability in at-risk infants. Prospective cohort study. Two perinatal centres in Melbourne, Australia. Infants born at ≥ 35+0 weeks' gestation with a first-line paediatric doctor requested to attend. Clinical instability defined as any one of heart rate < 100 beats per minute for ≥ 20 s in the first 10 min after birth, maximum fraction of inspired oxygen of ≥ 0.70 in the first 10 min after birth, 5-min Apgar score of < 7, intubated in the delivery room or admitted to the neonatal unit for respiratory support. Four hundred and seventy-three infants were included. The median (IQR) gestational age at birth was 39+4 (38+4-40+4) weeks. Eighty (17%) infants met the criteria for clinical instability. Independent risk factors for clinical instability were labour without oxytocin administration, presence of a medical pregnancy complication, difficult extraction at birth and unplanned caesarean section in labour. Decision tree analysis determined that infants at highest risk were those whose mothers did not receive oxytocin during labour (25% risk). Infants at lowest risk were those whose mothers received oxytocin during labour and did not have a medical pregnancy complication (7% risk). CONCLUSIONS: We identified characteristics associated with clinical instability that may be useful in alerting less experienced clinicians to call for senior assistance early. The decision trees provide intuitive visual aids but require prospective validation. WHAT IS KNOWN: • First-line clinicians attending at-risk births may need to call senior colleagues for assistance depending on the infant's condition. • Delays in effectively supporting a compromised infant at birth is an important cause of neonatal morbidity and infant-mother separation. WHAT IS NEW: • This study identifies risk factors for delivery room clinical instability in at-risk infants born at ≥ 35+0 weeks' gestation. • The decision trees presented

BACKGROUND AND OBJECTIVE: The association between birth weight, particularly relative to gestational age, and adult lung function is uncertain. We investigated the associations between birth weight relative to gestational age and measures of lung function in middle age, and mediation of these associations by adult height. METHODS: Participants in the Tasmanian Longitudinal Health Study who had both known birth weight and lung function assessment at age 45 years were included (n = 849). Linear regression models were fitted to investigate the association between small for gestational age and birth weight with post-bronchodilator lung function measures (forced expiratory volume in 1 second [FEV1 ], forced vital capacity [FVC], FEV1 /FVC, diffusing capacity for carbon monoxide [DL co], residual volume [RV] and total lung capacity [TLC]), adjusting for potential confounders. The contribution of adult height as a mediator of these associations was investigated. RESULTS: Compared with infants born with normal weight for gestational age, those born small for gestational age had reduced FEV1 (coefficient: -191 ml [95%CI: -296, -87]), FVC (-205 ml [-330, -81]), TLC (-292 ml [-492, -92]), RV (-126 ml [-253, 0]) and DL co (-0.42 mmol/min/kPa [-0.79, -0.041]) at age 45 years. However, they had comparable FEV1 /FVC. For every 1 kg increase in birth weight, lung function indices increased by an average of 117 ml (95%CI: 40, 196) for FEV1 , 124 ml (30, 218) for FVC, 215 ml (66, 365) for TLC and 0.36 mmol/min/kPa (0.11, 0.62) for DL co, independent of gestational age, but again not for FEV1 /FVC. These associations were significantly mediated by adult height (56%-90%). CONCLUSION: Small for gestational age was associated with reduced lung function that is likely due to smaller lungs with little evidence of any specific parenchymal impairment.

BACKGROUND: The Taste And Smell To Enhance nutrition (TASTE) trial investigated the effects of smell and taste of milk with tube feeding compared to routine care on the growth of preterm infants. There was no difference between groups in growth (weight, head circumference, length) z-scores at discharge from the hospital. Infants in the intervention group had higher head circumference and length z-scores at 36 weeks postmenstrual age, both secondary outcomes. The objective of this follow-up study is to assess 2-year neurodevelopmental and growth outcomes after exposure of preterm infants to the smell and taste of milk with tube feeding compared to routine care. METHODS: This is a neurodevelopmental follow-up study of a two-center, placebo-controlled randomized trial. Infants born before 29 weeks postmenstrual age and/or with a birth weight of less than 1250 g were randomized to smell and taste of milk with each tube feed or routine care. The current follow-up assessed the 2-year neurodevelopmental and growth outcomes of participants of the TASTE trial discharged from the hospital (n = 334). The primary outcome is survival free of any major neurodevelopmental impairment comprising any moderate/severe cerebral palsy (Gross Motor Function Classification System score II-V), Bayley Scales of Infant and Toddler Development, Third/Fourth Edition (Bayley-III/Bayley-4) motor, cognitive, or language scores < -2SD, blindness, or deafness at 2 years of age. Other outcomes include death, breastfeeding within the first year, and respiratory support, oral feeding, and anthropometric parameters at 2 years of age. The Human Research Ethics Committees of Mater Misericordiae Limited and the Royal Women's Hospital approved the TASTE trial including the neurodevelopmental follow-up described in this protocol. DISCUSSION: For patients and their families, the neurodevelopmental outcomes of preterm infants are of utmost importance. Consequently, they should be investigated following any int

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

OBJECTIVE: Mechanisms of non-invasive high-frequency oscillatory ventilation (nHFOV) in preterm infants are unclear. We aimed to compare lung volume changes during apnoeas in preterm infants on nHFOV and nasal continuous positive airway pressure (nCPAP). METHODS: Analysis of electrical impedance tomography (EIT) data from a randomised crossover trial comparing nHFOV with nCPAP in preterm infants at 26-34 weeks postmenstrual age. EIT data were screened by two reviewers to identify apnoeas ≥10 s. End-expiratory lung impedance (EELI) and tidal volumes (VT) were calculated before and after apnoeas. Oxygen saturation (SpO2) and heart rate (HR) were extracted for 60 s after apnoeas. RESULTS: In 30 preterm infants, 213 apnoeas were identified. During apnoeas, oscillatory volumes were detectable during nHFOV. EELI decreased significantly during apnoeas (∆EELI nCPAP: -8.0 (-11.9 to -4.1) AU/kg, p<0.001; ∆EELI nHFOV: -3.4 (-6.5 to -0.3), p=0.03) but recovered over the first five breaths after apnoeas. Compared with before apnoeas, VT was increased for the first breath after apnoeas during nCPAP (∆VT: 7.5 (3.1 to 11.2) AU/kg, p=0.001). Falls in SpO2 and HR after apnoeas were greater during nCPAP than nHFOV (mean difference (95% CI): SpO2: 3.6% (2.7 to 4.6), p<0.001; HR: 15.9 bpm (13.4 to 18.5), p<0.001). CONCLUSION: Apnoeas were characterised by a significant decrease in EELI which was regained over the first breaths after apnoeas, partly mediated by a larger VT. Apnoeas were followed by a considerable drop in SpO2 and HR, particularly during nCPAP, leading to longer episodes of hypoxemia during nCPAP. Transmitted oscillations during nHFOV may explain these benefits. TRIAL REGISTRATION NUMBER: ACTRN12616001516471.

AIM: Systemic postnatal corticosteroids are used to treat or prevent bronchopulmonary dysplasia (BPD) in extremely preterm (EP) or extremely low birth weight (ELBW) infants but are associated with long-term harm. We aimed to assess the relationship between cumulative postnatal corticosteroid dose and neurodevelopmental outcomes. METHODS: Longitudinal cohort study of all EP/ELBW livebirths in Victoria, Australia 2016-2017. Perinatal data were collected prospectively. Neurodevelopmental assessment was performed at 2 years' corrected age. Linear and logistic regression were used to determine relationships between cumulative corticosteroid dose and neurodevelopment, adjusted for gestational age, birth weight, sex and major intraventricular haemorrhage. RESULTS: Seventy-six EP/ELBW infants received postnatal corticosteroids to treat or prevent BPD, 62/65 survivors were seen at 2 years. Median (IQR) cumulative postnatal corticosteroid dose was 1.36 (0.92-3.45) mg/kg dexamethasone equivalent. Higher cumulative corticosteroid dose was associated with increased odds of cerebral palsy, adjusted OR (95% CI) 1.47 (1.04, 2.07). Higher cumulative corticosteroid dose was also associated with lower cognitive and motor developmental scores, however, this weakened after adjustment for confounding variables: cognitive composite score adjusted coefficient (95% CI) -1.3 (-2.7, 0.1) and motor composite score adjusted coefficient (95% CI) -1.3 (-2.8, 0.2). CONCLUSION: Higher cumulative postnatal corticosteroid dose in EP/ELBW infants is associated with increased odds of cerebral palsy at 2 years' corrected age. Adequately powered studies are needed to assess the independent effects of cumulative steroid dose on neurodevelopmental outcomes.

Background Preterm infants are susceptible to the damaging effects of hyperoxia which may lead to bronchopulmonary dysplasia (BPD) and intestinal damage. Hyperoxia also affects intestinal microbiota. The optimal initial FiO2 for the resuscitation of premature infants is unknown. Objective To determine the effect of different initial oxygen concentrations on BPD, oxidative stress markers, damage to the gastrointestinal mucosa, and the intestinal microbiome. Methods We conducted an unblinded, randomized controlled clinical trial in premature infants requiring supplemental oxygen in the first minutes of life. Infants started at an FiO2 of either 30% (low) or 50% (moderate), which was adjusted to achieve target oxygen saturations (SpO2) of 88-92% by 10 minutes of life using pulse oximetry. The primary outcome was incidence of BPD. Secondary outcomes included markers of oxidative stress [oxidized glutathione (GSH)/reduced glutathione (GSSG) ratio and malondialdehyde (MDA)], intestinal integrity indicated by fecal alpha-1 antitrypsin (AAT), and intestinal microbiota on fecal examination. Results Eighty-four infants were recruited. There was no significant difference in rates of BPD between the 30% FiO2 and 50% FiO2 groups (42.8% vs. 40.5%, respectively). Nor were there significant differences in GSH/GSSG ratios, MDA concentrations, fecal AAT levels, or changes in facultative anaerobic and anaerobic microbiota between groups. Conclusion In premature infants resuscitated using low vs. moderate initial FiO2 levels, we find no significant differences in BPD incidence, markers of oxidative stress, intestinal mucosa integrity, or intestinal microbiota.

BACKGROUND: Prematurity has been linked to reduced lung function up to age 33 years, but its long-term effects on lung function and chronic obstructive pulmonary disease (COPD) are unknown. To address this question, we investigated associations between prematurity, lung function, and COPD in the sixth decade of life using data from the Tasmanian Longitudinal Health Study (TAHS). METHODS: Data were analysed from 1445 participants in the TAHS. Lung function was measured at 53 years of age. Gestational ages were very preterm (28 weeks to <32 weeks), moderate preterm (32 weeks to <34 weeks), late preterm (34 weeks to <37 weeks) and term (≥37 weeks). Linear and logistic regression models were fitted to investigate associations of prematurity with lung function measures (FEV1, forced vital capacity [FVC], FEV1/FVC ratio, forced expiratory flow at 25-75% of FVC [FEF25-75%], diffusing capacity for carbon monoxide [DLCO]) and COPD (post-bronchodilator FEV1/FVC less than the lower limit of normal), adjusting for sex, age, height, parental smoking during pregnancy, number of older siblings, maternal age at birth, and childhood socioeconomic status. Interactions with smoking and asthma were also investigated. RESULTS: Of 3565 individuals with available data on gestational age from the TAHS cohort, 1445 (41%) participants were included in this study, 740 (51%) of whom were female. Compared with term birth, very to moderate preterm birth was significantly associated with an increased risk of COPD at age 53 years (odds ratio 2·9 [95% CI 1·1-7·7]). Very-to-moderate preterm birth was also associated with lower post-bronchodilator FEV1/FVC ratio (beta-coefficient -2·9% [95% CI -4·9 to -0·81]), FEV1 (-190 mL [-339 to -40]), DLCO (-0·55 mmol/min/kPa [-0·97 to -0·13]), and FEF25-75% (-339 mL/s [-664 to -14]). The association between very-to-moderate preterm birth and FEV1/FVC ratio was only significant among smokers (pinteraction=0·0082). Similar findings were observed for moderate pret

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 cmH2O and positive end-expiratory airway pressure of 5 cmH2O. Expired tidal volumes (Vt) were measured with a respiratory function monitor. Target range for Vt 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 Vt of 4.6 (3.3 - 6.2) ml/kg. Median Vt 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).

Randomised trials in emergency settings must quickly confirm eligibility and allocate participants to an intervention group without delaying treatment. We report rapid randomisation during two neonatal resuscitation trials using the non-commercial REDCap platform accessed via smartphone. This simple, reliable method has wide applicability for trials in emergency settings. What is Known: • Randomised trials in emergency settings need to rapidly allocate participants to an intervention group. • This process should not delay treatment. What is New: • This non-commercial, smartphone-accessible application enabled rapid, accurate randomisation at the bedside. • This has broad applicability for emergency setting trials.

BACKGROUND: Lung ultrasound (LUS) is a safe and non-invasive tool that can potentially assess regional lung aeration in newborn infants and reduce the need for X-ray imaging. LUS produces images with characteristic artifacts caused by the presence of air in the lung, but it is unknown if LUS can accurately detect changes in lung air volumes after birth. This study compared LUS images with lung volume measurements from high-resolution computed tomography (CT) scans to determine if LUS can accurately provide relative measures of lung aeration. METHODS: Deceased near-term newborn lambs (139 days gestation, term ∼148 days) were intubated and the chest imaged using LUS (bilaterally) and phase contrast x-ray CT scans at increasing static airway pressures (0-50 cmH2O). CT scans were analyzed to calculate regional air volumes and correlated with measures from LUS images. These measures included (i) LUS grade; (ii) brightness (mean and coefficient of variation); and (iii) area under the Fourier power spectra within defined frequency ranges. RESULTS: All LUS image analysis techniques correlated strongly with air volumes measured by CT (p < 0.01). When imaging statistics were combined in a multivariate linear regression model, LUS predicted the proportion of air in the underlying lung with moderate accuracy (95% prediction interval ± 22.15%, r 2 = 0.71). CONCLUSION: LUS can provide relative measures of lung aeration after birth in neonatal lambs. Future studies are needed to determine if LUS can also provide a simple means to assess air volumes and individualize aeration strategies for critically ill newborns in real time.

INTRODUCTION: 3%-8% of newborns need positive pressure ventilation (PPV) after birth. Heart rate (HR) is considered the most sensitive indicator of the newborns' condition and response to resuscitative interventions. According to guidelines, HR should be assessed and PPV initiated within 60 s after birth in non-breathing newborns. Dry electrode ECG can provide accurate feedback on HR immediately after birth and continuously during resuscitation. The impact of early and continuous HR feedback is unknown. METHOD AND ANALYSIS: This single-centre randomised controlled trial seeks to determine if HR feedback by dry electrode ECG immediately after birth and continuously during newborn resuscitation results in more timely initiation of PPV, improved ventilation and short-term outcomes compared with standard HR assessment.In all newborns≥34 gestational weeks, the dry electrode ECG sensor is placed on the upper abdomen immediately after birth as an additional modality of HR assessment. The device records and stores HR signals. In intervention subjects, the HR display is visible to guide decision-making and further management, in control subjects the display is masked. Standard HR assessment is by stethoscope, gel-electrode ECG and/or pulse oximetry (PO).Time of birth is registered in the Liveborn app. Time of initiation and duration of PPV is calculated from video recordings. Ventilation parameters are retrieved from the ventilation monitor, oxygen saturation and HR from the PO and gel-electrode ECG monitors.The primary endpoint is proportion of resuscitated newborns who receive PPV within 60 s after birth. To detect a 50% increase with power of 90% using an overall significance level of 0.05 and 1 interim analysis, 169 newborns are needed in each group. ETHICS AND DISSEMINATION: Approval by the Norwegian National Research Ethics Committee West (2018/338). Parental consent is sought at routine screening early in pregnancy. The results will be published in peer-reviewed journ

AIM: To examine the association between Apgar score at 5 min and childhood developmental and educational outcome. METHODS: A population-based data linkage study of births ≥37 weeks' gestation linked to developmental outcomes at preparatory school and educational outcomes at school grades 3, 5 and 7 in Victoria, Australia. Multivariable logistic regressions and generalised estimating equations were used. RESULTS: There were 167,126 singleton infants with developmental results and 392,933 singleton infants with at least one educational result. There was an inverse relationship between Apgar score at 5 min and poor developmental and educational outcomes, with the worst outcomes among Apgar scores of 0-3. Apgar scores of 7, 8 and 9 were all associated with poorer developmental outcomes (aOR = 1.31, 95% CI: 1.12-1.54; aOR = 1.17, 95% CI: 1.05-1.29; aOR = 1.08, 95% CI: 1.02-1.13 respectively), while Apgar scores of 7 and 8 were associated with poorer educational outcomes at grades 3, 5, and 7. With progression through grades 3, 5, and 7, the extent of the difference in educational outcomes diminished (e.g. for Apgar scores of 0-3: aOR = 3.33, 95% CI: 1.85-6.00 in grade 3 and aOR = 1.49, 95% CI: 0.75-2.96 in grade 7). CONCLUSION: Apgar scores below 10 at 5 min are associated with poorer developmental and educational outcomes in school.

BACKGROUND: Moral distress is prevalent within the neonatal intensive care unit (NICU) and can negatively affect clinicians. Studies have evaluated the causes of moral distress and interventions to mitigate its harmful effects. However, the effects of participating in moral distress studies have not been evaluated. OBJECTIVE: To evaluate the impact of participation in a longitudinal, non-intervention research project on moral distress in the NICU. DESIGN: Clinicians who previously participated in an 18-month longitudinal research study on moral distress at two NICUs were invited to complete a questionnaire on the impact of participation. The original study required regular completion of surveys that sought predictions of death, disability and the intensity/nature of moral distress experienced by clinicians caring for extremely preterm babies. Individual and unit-wide effects were explored. Free-text responses to open-ended questions were analyzed using inductive content analysis. RESULTS: A total of 249/463 (53%) eligible clinicians participated. Participation in the original 18-month study was perceived as having a positive impact by 58% of respondents. Clinicians found articulating their views therapeutic (76%) and useful in clarifying personal opinions about the babies (85%). Free-text responses revealed the research stimulated increased reflection, validated feelings and increased dialogue amongst clinicians. Respondents generally did not find participation distressing (70%). However, a small number of physicians felt the focus of discussion shifted from the baby to the clinicians. Intensity and prevalence of moral distress did not significantly change over the 18-month period. CONCLUSIONS: Participating in moral distress research prompted regular reflection regarding attitudes toward fragile patients, improving ethical awareness. This is useful in clarifying personal views that may influence patient care. Participation also enhanced communication around difficu

INTRODUCTION: Non-invasive high-frequency oscillatory ventilation (nHFOV) is an extension of nasal continuous positive airway pressure (nCPAP) support in neonates. We aimed to compare global and regional distribution of lung volumes during nHFOV versus nCPAP. METHODS: In 30 preterm infants enrolled in a randomised crossover trial comparing nHFOV with nCPAP, electrical impedance tomography data were recorded in prone position. For each mode of respiratory support, four episodes of artefact-free tidal ventilation, each comprising 30 consecutive breaths, were extracted. Tidal volumes (VT) in 36 horizontal slices, indicators of ventilation homogeneity and end-expiratory lung impedance (EELI) for the whole lung and for four horizontal regions of interest (non-gravity-dependent to gravity-dependent; EELINGD, EELImidNGD, EELImidGD, EELIGD) were compared between nHFOV and nCPAP. Aeration homogeneity ratio (AHR) was determined by dividing aeration in non-gravity-dependent parts of the lung through gravity-dependent regions. MAIN RESULTS: Overall, 228 recordings were analysed. Relative VT was greater in all but the six most gravity-dependent lung slices during nCPAP (all p<0.05). Indicators of ventilation homogeneity were similar between nHFOV and nCPAP (all p>0.05). Aeration was increased during nHFOV (mean difference (95% CI)=0.4 (0.2 to 0.6) arbitrary units per kilogram (AU/kg), p=0.013), mainly due to an increase in non-gravity-dependent regions of the lung (∆EELINGD=6.9 (0.0 to 13.8) AU/kg, p=0.028; ∆EELImidNGD=6.8 (1.2 to 12.4) AU/kg, p=0.009). Aeration was more homogeneous during nHFOV compared with nCPAP (mean difference (95% CI) in AHR=0.01 (0.00 to 0.02), p=0.0014). CONCLUSION: Although regional ventilation was similar between nHFOV and nCPAP, end-expiratory lung volume was higher and aeration homogeneity was slightly improved during nHFOV. The aeration difference was greatest in non-gravity dependent regions, possibly due to the oscillatory pressure waveform. The c

Positive end-expiratory pressure (PEEP) is critical to the preterm lung at birth, but the optimal PEEP level remains uncertain. The objective of this study was to determine the effect of maximum PEEP levels at birth on the physiological and injury response in preterm lambs. Steroid-exposed preterm lambs (124-127 days gestation; n = 65) were randomly assigned from birth to either 1) positive pressure ventilation (PPV) at 8 cmH2O PEEP or 3-min dynamic stepwise PEEP strategy (DynPEEP), with either 2) 20 cmH2O maximum PEEP (10 PEEP second steps) or 3) 14 cmH2O maximum PEEP (20-s steps), all followed by standardized PPV for 90 min. Lung mechanics, gas exchange, regional ventilation and aeration (electrical impedance tomography), and histological and molecular measures of lung injury were compared between groups. Dynamic compliance was greatest using a maximum 20 cmH2O (DynPEEP). There were no differences in gas exchange, end-expiratory volume, and ventilator requirements. Regional ventilation became more uniform with time following all PEEP strategies. For all groups, gene expression of markers of early lung injury was greater in the gravity nondependent lung, and inversely related to the magnitude of PEEP, being lowest in the 20 cmH2O DynPEEP group overall. PEEP levels had no impact on lung injury in the dependent lung. Transient high maximum PEEP levels using dynamic PEEP strategies may confer more lung protection at birth.

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

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).

The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation task force science experts. Topics covered by systematic reviews in this summary include resuscitation topics of video-based dispatch systems; head-up cardiopulmonary resuscitation; early coronary angiography after return of spontaneous circulation; cardiopulmonary resuscitation in the prone patient; cord management at birth for preterm and term infants; devices for administering positive-pressure ventilation at birth; family presence during neonatal resuscitation; self-directed, digitally based basic life support education and training in adults and children; coronavirus disease 2019 infection risk to rescuers from patients in cardiac arrest; and first aid topics, including cooling with water for thermal burns, oral rehydration for exertional dehydration, pediatric tourniquet use, and methods of tick removal. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations or good practice statements. Insights into the deliberations of the task forces are provided in Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces listed priority knowledge gaps for further research.

Rationale: There is increasing evidence for a clinical benefit of noninvasive high-frequency oscillatory ventilation (nHFOV) in preterm infants. However, it is still unknown whether the generated oscillations are effectively transmitted to the alveoli.Objectives: To assess magnitude and regional distribution of oscillatory volumes (VOsc) at the lung level.Methods: In 30 prone preterm infants enrolled in a randomized crossover trial comparing nHFOV with nasal continuous positive airway pressure, electrical impedance tomography recordings were performed. During nHFOV, the smallest amplitude to achieve visible chest wall vibration was used, and the frequency was set at 8 hertz.Measurements and Main Results: Thirty consecutive breaths during artifact-free tidal ventilation were extracted for each of the 228 electrical impedance tomography recordings. After application of corresponding frequency filters, Vt and VOsc were calculated. There was a signal at 8 and 16 Hz during nHFOV, which was not detectable during nasal continuous positive airway pressure, corresponding to the set oscillatory frequency and its second harmonic. During nHFOV, the mean (SD) VOsc/Vt ratio was 0.20 (0.13). Oscillations were more likely to be transmitted to the non-gravity-dependent (mean difference [95% confidence interval], 0.041 [0.025-0.058]; P < 0.001) and right-sided lung (mean difference [95% confidence interval], 0.040 [0.019-0.061]; P < 0.001) when compared with spontaneous Vt.Conclusions: In preterm infants, VOsc during nHFOV are transmitted to the lung. Compared with the regional distribution of tidal breaths, oscillations preferentially reach the right and non-gravity-dependent lung. These data increase our understanding of the physiological processes underpinning nHFOV and may lead to further refinement of this novel technique.

Nasal or noninvaisve intermittent positive pressure ventilation (NIPPV) refers to well-established noninvasive respiratory support strategies combining a continuous distending pressure with intermittent pressure increases. Uncertainty remains regarding the benefits provided by the various devices and techniques used to generate NIPPV. Our included meta-analyses of trials comparing NIPPV with continuous positive airway pressure (CPAP) in preterm infants demonstrate that both primary and postextubation NIPPV are superior to CPAP to prevent respiratory failure leading to additional ventilatory support. This short-term benefit is associated with a reduction in bronchopulmonary dysplasia, but not with mortality. Benefits are greatest when ventilator-generated, synchronized NIPPV is used.

AIM: To determine whether the use of a respiratory function monitor (RFM) during PPV of extremely preterm infants at birth, compared with no RFM, leads to an increase in percentage of inflations with an expiratory tidal volume (Vte) within a predefined target range. METHODS: Unmasked, randomised clinical trial conducted October 2013 - May 2019 in 7 neonatal intensive care units in 6 countries. Very preterm infants (24-27 weeks of gestation) receiving PPV at birth were randomised to have a RFM screen visible or not. The primary outcome was the median proportion of inflations during manual PPV (face mask or intubated) within the target range (Vte 4-8 mL/kg). There were 42 other prespecified monitor measurements and clinical outcomes. RESULTS: Among 288 infants randomised (median (IQR) gestational age 26+2 (25+3-27+1) weeks), a total number of 51,352 inflations were analysed. The median (IQR) percentage of inflations within the target range in the RFM visible group was 30.0 (18.0-42.2)% vs 30.2 (14.8-43.1)% in the RFM non-visible group (p = 0.721). There were no differences in other respiratory function measurements, oxygen saturation, heart rate or FiO2. There were no differences in clinical outcomes, except for the incidence of intraventricular haemorrhage (all grades) and/or cystic periventricular leukomalacia (visible RFM: 26.7% vs non-visible RFM: 39.0%; RR 0.71 (0.68-0.97); p = 0.028). CONCLUSION: In very preterm infants receiving PPV at birth, the use of a RFM, compared to no RFM as guidance for tidal volume delivery, did not increase the percentage of inflations in a predefined target range. TRIAL REGISTRATION: Dutch Trial Register NTR4104, clinicaltrials.gov NCT03256578.

Rationale: The transition to air breathing at birth is a seminal respiratory event common to all humans, but the intrathoracic processes remain poorly understood. Objectives: The objectives of this prospective, observational study were to describe the spatiotemporal gas flow, aeration, and ventilation patterns within the lung in term neonates undergoing successful respiratory transition. Methods: Electrical impedance tomography was used to image intrathoracic volume patterns for every breath until 6 minutes from birth in neonates born by elective cesearean section and not needing resuscitation. Breaths were classified by video data, and measures of lung aeration, tidal flow conditions, and intrathoracic volume distribution calculated for each inflation. Measurements and Main Results: A total of 1,401 breaths from 17 neonates met all eligibility and data analysis criteria. Stable FRC was obtained by median (interquartile range) 43 (21-77) breaths. Breathing patterns changed from predominantly crying (80.9% first min) to tidal breathing (65.3% sixth min). From birth, tidal ventilation was not uniform within the lung, favoring the right and nondependent regions; P < 0.001 versus left and dependent regions (mixed-effects model). Initial crying created a unique volumetric pattern with delayed midexpiratory gas flow associated with intrathoracic volume redistribution (pendelluft flow) within the lung. This preserved FRC, especially within the dorsal and right regions. Conclusions: The commencement of air breathing at birth generates unique flow and volume states associated with marked spatiotemporal ventilation inhomogeneity not seen elsewhere in respiratory physiology. At birth, neonates innately brake expiratory flow to defend FRC gains and redistribute gas to less aerated regions.

INTRODUCTION: Docosahexaenoic acid (DHA) is an omega-3 (n-3) fatty acid that accumulates into neural tissue during the last trimester of pregnancy, as the fetal brain is undergoing a growth spurt. Infants born <29 weeks' gestation are deprived the normal in utero supply of DHA during this period of rapid brain development. Insufficient dietary DHA postnatally may contribute to the cognitive impairments common among this population. This follow-up of the N-3 fatty acids for improvement in respiratory outcomes (N3RO) randomised controlled trial aims to determine if enteral DHA supplementation in infants born <29 weeks' gestation during the first months of life improves cognitive development at 5 years of age corrected for prematurity. METHODS AND ANALYSIS: N3RO was a randomised controlled trial of enteral DHA supplementation (60 mg/kg/day) or a control emulsion (without DHA) in 1273 infants born <29 weeks' gestation to determine the effect on bronchopulmonary dysplasia (BPD). We showed that DHA supplementation did not reduce the risk of BPD and may have increased the risk.In this follow-up at 5 years' corrected age, a predefined subset (n=655) of children from five Australian sites will be invited to attend a cognitive assessment with a psychologist. Children will be administered the Wechsler Preschool and Primary Scale of Intelligence (fourth edition) and a measure of inhibitory control (fruit stroop), while height, weight and head circumference will be measured.The primary outcome is full-scale IQ. To ensure 90% power, a minimum of 592 children are needed to detect a four-point difference in IQ between the groups.Research personnel and families remain blinded to group assignment. ETHICS AND DISSEMINATION: The Women's and Children Health Network Human Research Ethics Committee reviewed and approved the study (HREC/17/WCHN/187). Caregivers will give informed consent prior to taking part in this follow-up study. Findings of this study will be disseminated through peer

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.

AIM: To determine predictors and outcomes of extubation failure in extremely preterm (EP) infants born <28 weeks' gestational age (GA). METHODS: Retrospective clinical audit across two tertiary-level neonatal intensive care units in Melbourne, Australia. Two-hundred and four EP infants who survived to their first extubation from mechanical ventilation. Extubation failure (re-intubation) within 7 days after the first extubation. RESULTS: Lower GA (odds ratio [OR] 0.71, 95% confidence interval (CI), 0.61-0.89, P < 0.001) and higher pre-extubation measured mean airway pressure (MAP) on the mechanical ventilator (OR 1.9 [95% CI 1.41-2.51], P < 0.001) predicted extubation failure. The area under a receiver operating characteristic curve for GA and MAP was 0.77 (95% CI 0.70-0.82). After adjustment for GA, infants who experienced extubation failure had higher rates of bronchopulmonary dysplasia (P < 0.001), post-natal systemic corticosteroid treatment (P < 0.001), airway trauma (P < 0.003), longer durations of treatment with mechanical ventilation (P < 0.001), non-invasive respiratory support (P < 0.001), supplemental oxygen therapy (P = 0.05) and longer hospitalisation (P = 0.025). CONCLUSIONS: Lower GA and higher pre-extubation measured MAP were predictive of extubation failure within 7 days in extremely preterm infants. Extubation failure was associated with increased morbidity and extended periods of respiratory support and hospitalisation.

OBJECTIVE: To identify risk factors associated with delivery room respiratory support in at-risk infants who are initially vigorous and received delayed cord clamping (DCC). DESIGN: Prospective cohort study. SETTING: Two perinatal centres in Melbourne, Australia. PATIENTS: At-risk infants born at ≥35+0 weeks gestation with a paediatric doctor in attendance who were initially vigorous and received DCC for >60 s. MAIN OUTCOME MEASURES: Delivery room respiratory support defined as facemask positive pressure ventilation, continuous positive airway pressure and/or supplemental oxygen within 10 min of birth. RESULTS: Two hundred and ninety-eight infants born at a median (IQR) gestational age of 39+3 (38+2-40+2) weeks were included. Cord clamping occurred at a median (IQR) of 128 (123-145) s. Forty-four (15%) infants received respiratory support at a median of 214 (IQR 156-326) s after birth. Neonatal unit admission for respiratory distress occurred in 32% of infants receiving delivery room respiratory support vs 1% of infants who did not receive delivery room respiratory support (p<0.001). Risk factors independently associated with delivery room respiratory support were average heart rate (HR) at 90-120 s after birth (determined using three-lead ECG), mode of birth and time to establish regular cries. Decision tree analysis identified that infants at highest risk had an average HR of <165 beats per minute at 90-120 s after birth following caesarean section (risk of 39%). Infants with an average HR of ≥165 beats per minute at 90-120 s after birth were at low risk (5%). CONCLUSIONS: We present a clinical decision pathway for at-risk infants who may benefit from close observation following DCC. Our findings provide a novel perspective of HR beyond the traditional threshold of 100 beats per minute.

OBJECTIVE: To determine heart rate centiles during the first 5 min after birth in healthy term newborns delivered vaginally with delayed cord clamping. DESIGN: Single-centre prospective observational study. SETTING: Stavanger University Hospital, Norway, March-August 2019. PATIENTS: Term newborns delivered vaginally were eligible for inclusion. Newborns delivered by vacuum or forceps or who received any medical intervention were excluded. INTERVENTIONS: A novel dry electrode electrocardiography monitor (NeoBeat) was applied to the newborn's chest immediately after birth. The newborns were placed on their mother's chest or abdomen, dried and stimulated, and cord clamping was delayed for at least 1 min. MAIN OUTCOME MEASURES: Heart rate was recorded at 1 s intervals, and the 3rd, 10th, 25th, 50th, 75th, 90th and 97th centiles were calculated from 5 s to 5 min after birth. RESULTS: 898 newborns with a mean (SD) birth weight 3594 (478) g and gestational age 40 (1) weeks were included. The heart rate increased rapidly from median (IQR) 122 (98-146) to 168 (146-185) beats per minute (bpm) during the first 30 s after birth, peaking at 175 (157-189) bpm at 61 s after birth, and thereafter slowly decreasing. The third centile reached 100 bpm at 34 s, suggesting that heart rates <100 bpm during the first minutes after birth are uncommon in healthy newborns after delayed cord clamping. CONCLUSION: This report presents normal heart rate centiles from 5 s to 5 min after birth in healthy term newborns delivered vaginally with delayed cord clamping.

INTRODUCTION: During the last trimester of pregnancy, the fetal brain undergoes a rapid growth spurt and accumulates essential nutrients including docosahexaenoic acid (DHA). This takes place ex-utero for infants born <29 weeks' gestation, without the in-utero provisions of DHA. Infants born <29 weeks' are more likely to experience behavioural and emotional difficulties than their term-born counterparts. It has been hypothesised that supplementing preterm infants with dietary DHA may alleviate insufficiency and subsequently prevent or minimise behavioural problems. This protocol describes a follow-up of infants born <29 weeks gestation who were enrolled in a randomised controlled trial (RCT) of DHA supplementation. We aim to determine whether DHA supplementation improves the behaviour, and general health of these infants. METHODS AND ANALYSIS: Infants born <29 weeks' gestation were enrolled in a multicentre blinded RCT of enteral DHA supplementation. Infants were randomised to receive an enteral emulsion that provided 60 mg/kg/day of DHA or a control emulsion commenced within the first 3 days of enteral feeding, until 36 weeks' postmenstrual age or discharge home, whichever occurred first. Families of surviving children (excluding those who withdrew from the study) from the Australian sites (up to 955) will be invited to complete a survey. The survey will include questions regarding child behavioural and emotional functioning, executive functioning, respiratory health and general health. We hypothesise that the DHA intervention will have a benefit on the primary outcome, parent-rated behaviour and emotional status as measured using the Total Difficulties score of the Strengths and Difficulties Questionnaire. Detecting a 2-point difference between groups (small effect size of 0.25 SD) with 90% power will require follow-up of 676 participants. ETHICS AND DISSEMINATION: The Women's and Children Health Network Human Research Ethics Committee reviewed and approved the st

INTRODUCTION: Respiratory distress syndrome is a complication of prematurity and extremely preterm infants born before 28 weeks' gestation often require endotracheal intubation and mechanical ventilation. In this high-risk population, mechanical ventilation is associated with lung injury and contributes to bronchopulmonary dysplasia. Therefore, clinicians attempt to extubate infants as quickly and use non-invasive respiratory support such as nasal continuous positive airway pressure (CPAP) to facilitate the transition. However, approximately 60% of extremely preterm infants experience 'extubation failure' and require reintubation. While CPAP pressures of 5-8 cm H2O are commonly used, the optimal CPAP pressure is unknown, and higher pressures may be beneficial in avoiding extubation failure. Our trial is the Extubation CPAP Level Assessment Trial (ÉCLAT). The aim of this trial is to compare higher CPAP pressures 9-11 cm H2O with a current standard pressures of 6-8 cmH2O on extubation failure in extremely preterm infants. METHODS AND ANALYSIS: 200 extremely preterm infants will be recruited prior to their first extubation from mechanical ventilation to CPAP. This is a parallel group randomised controlled trial. Infants will be randomised to one of two set CPAP pressures: CPAP 10 cmH2O (intervention) or CPAP 7 cmH2O (control). The primary outcome will be extubation failure (reintubation) within 7 days. Statistical analysis will follow standard methods for randomised trials on an intention to treat basis. For the primary outcome, this will be by intention to treat, adjusted for the prerandomisation strata (GA and centre). We will use the appropriate parametric and non-parametric statistical tests. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Monash Health Human Research Ethics Committees. Amendments to the trial protocol will be submitted for approval. The findings of this study will be written into a clinical trial report manuscript and disseminate

AIM: Timely delivery of fetal growth restriction (FGR) is a balance between avoiding stillbirth and minimising prematurity. We sought to assess the neonatal outcomes for babies suspected of FGR, both true and false positives. METHODS: This population cohort study examined all singleton births in Victoria, Australia from 2000 to 2017 (n = 1 231 415). Neonatal morbidities associated with neonatal intensive care unit (NICU) admission were assessed for babies born ≥32 weeks' with severe FGR (<3rd centile) and babies with birthweight ≥10th centile who were iatrogenically delivered for suspected FGR. RESULTS: Babies with severe FGR iatrogenically delivered for suspected FGR were more likely to require NICU admission than babies with severe FGR who were not detected (3.0% vs. 1.1%, P < 0.001). After adjusting for potential confounders, the odds of NICU admission were increased (adjusted odds ratio (aOR) = 3.00, 95% confidence interval = 2.45-3.67; P < 0.001). Rates of NICU admission were also higher in ≥10th centile babies iatrogenically delivered for suspected FGR than for ≥10th centile babies who entered labour spontaneously (1.8% vs. 0.5%, P < 0.001). After adjustments, the odds of NICU admission were increased (aOR = 3.91, 95% confidence interval = 3.40-4.49; P < 0.001). NICU admissions were associated with morbidities related to iatrogenic prematurity. CONCLUSIONS: Detection and planned delivery of FGR reduces stillbirth but may be associated with increased neonatal morbidity related to iatrogenic prematurity.

BACKGROUND: Fetal scalp blood sampling for lactate measurement (FBSLM) is sometimes used to assist in identification of the need for expedited birth in the presence of an abnormal cardiotocograph (CTG). However, there is no randomised controlled trial evidence to support this. AIM: To determine whether adding FBSLM reduces the risk of birth by emergency caesarean section in labours complicated by an abnormal CTG, compared with CTG without FBS. MATERIAL AND METHODS: Labouring women at a tertiary maternity hospital in Melbourne, Australia with a singleton, cephalic presentation, at ≥37 weeks gestation with an abnormal CTG pattern were randomised to the intervention (n = 61), with intermittent FBSLM in addition to CTG monitoring, or control (CTG without FBS, n = 62). The primary outcome was rate of birth by caesarean section. Secondary outcomes included overall operative birth and fetal and neonatal safety endpoints. TRIAL REGISTRATION: ACTRN12611000172909. RESULTS: The smaller than anticipated sample was unable to demonstrate an effect from adding FBSLM to CTG monitoring on birth by caesarean section vs monitoring by CTG without FBS (25/61 and 28/62 respectively, P = 0.64, risk ratio 0.91, 95% confidence intervals 0.60-1.36). One newborn infant in the CTG group met the criteria for the composite neonatal outcome of death or serious outcome, neonatal encephalopathy, five-minute Apgar score < 4, neonatal resuscitation, admission to neonatal intensive care unit for 96 h or more. CONCLUSION: We were unable to provide robust evidence of the effectiveness of FBSLM to improve the specificity of the CTG in the assessment of fetal wellbeing.

BACKGROUND: Neonatal endotracheal intubation is often associated with physiological instability. The Neonatal Resuscitation Program recommends a time-based limit (30 s) for intubation attempts in the delivery room, but there are limited physiological data to support recommendations in the neonatal intensive care unit (NICU). We aimed to determine the time to desaturation after ceasing spontaneous or assisted breathing in preterm infants undergoing elective endotracheal intubation in the NICU. METHODS: Observational study at The Royal Women's Hospital, Melbourne. A secondary analysis was performed of video recordings of neonates ≤32 weeks' postmenstrual age undergoing elective intubation. Infants received premedication including atropine, a sedative and muscle relaxant. Apnoeic oxygenation time (AOT) was defined as the time from the last positive pressure or spontaneous breath until desaturation (SpO2 <90%). RESULTS: Seventy-eight infants were included. The median (IQR) gestational age at birth was 27 (26-29) weeks and birth weight 946 (773-1216) g. All but five neonates desaturated to SpO2 <90% (73/78, 94%). The median (IQR) AOT was 22 (14-32) s. The median (IQR) time from ceasing positive pressure ventilation to desaturation <80% was 35 (24-44) s and to desaturation <60% was 56 (42-68) s. No episodes of bradycardia were seen. CONCLUSIONS: This is the first study to report AOT in preterm infants. During intubation of preterm infants in the NICU, desaturation occurs quickly after cessation of positive pressure ventilation. These data are important for the development of clinical guidelines for neonatal intubation. TRIAL REGISTRATION NUMBER: ACTRN12614000709640.