Nasal High-Flow Therapy during Neonatal Endotracheal Intubation.

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.).

Human papillomavirus prevalence among Australian men aged 18-35 years in 2015-2018 according to vaccination status and sexual preference.

BACKGROUND: Australia introduced a national HPV vaccination program for girls in 2007 and boys in 2013, achieving high coverage in both populations. We assessed HPV prevalence among men who have sex with women (MSW) and men who have sex with men (MSM) aged 18-35 years and examined program effects by vaccination status. METHODS: Men recruited between 2015-2018 self-collected a penile or intra-anal swab for HPV genotyping. HPV vaccination status was confirmed with the National Register. HPV prevalence was examined by age groups and vaccination status. RESULTS: Of 1,625 men included (median age 27 years; IQR [23-30]), 231 (14.2%) were vaccinated, and 1,370 (84.3%) were unvaccinated. Among 984 MSW, the prevalence of quadrivalent vaccine-targeted HPV types (6,11,16,18) was 10.6% (95%CI: 8.7-12.8) in unvaccinated and 10.7% (5.7-19.3%) in vaccinated men (p=0.96). Prevalence was lowest in the youngest age groups regardless of vaccination status. Among MSM, quadrivalent HPV type prevalence was 40.3% (36.0-44.8%) in unvaccinated and 29.9% (23.1-37.8%) in vaccinated men (p=0.02). In unvaccinated MSM, prevalence was high regardless of age, whereas among vaccinated MSM, prevalence was lowest in the youngest age-group (p=0.001). Among those with confirmed doses, quadrivalent HPV types were detected in 0% (0-7.7%; n=46) of men who had their first dose at 13-19 years and 37.2% (27.5-47.8%; n=94) of those who received their first dose at 20 years or older. CONCLUSION: Our data demonstrates the importance of universal adolescent HPV vaccination to ensure MSM receive the same benefits as MSW.

Practical approaches for supporting informed consent in neonatal clinical trials.

The survival and health of preterm and critically ill infants have markedly improved over the past 50 years, supported by well-conducted neonatal research. However, newborn research is difficult to undertake for many reasons, and obtaining informed consent for research in this population presents several unique ethical and logistical challenges. In this article, we explore methods to facilitate the consent process, including the role of checklists to support meaningful informed consent for neonatal clinical trials. CONCLUSION: The authors provide practical guidance on the design and implementation of an effective consent checklist tailored for use in neonatal clinical research.

Chlamydia retesting remains low among young women in Australia: an observational study using sentinel surveillance data, 2018-2022.

BACKGROUND: Chlamydia remains the most notified bacterial sexually transmissible infection in Australia with guidelines recommending testing for re-infection at 3months post treatment. This paper aimed to determine chlamydia retesting and repeat positivity rates within 2-4months among young women in Australia, and to evaluate what factors increase or decrease the likelihood of retesting. METHODS: Chlamydia retesting rates among 16-29-year-old women were analysed from Australian Collaboration for Coordinated Enhanced Sentinel Surveillance of sexually transmissible infection and bloodborne virus (ACCESS) sentinel surveillance data (n =62 sites). Among women with at least one positive test between 1 January 2018 and 31 August 2022, retesting counts and proportions within 2-4months were calculated. Logistic regression was performed to assess factors associated with retesting within 2-4months. RESULTS: Among 8758 women who were positive before 31 August 2022 to allow time for follow up, 1423 (16.2%) were retested within 2-4months, of whom 179 (12.6%) tested positive. The odds of retesting within 2-4months were 25% lower if tested in a coronavirus disease 2019 (COVID-9) pandemic year (2020-2022) (aOR=0.75; 95% CI 0.59-0.95). Among 9140 women with a positive test before 30 November 2022, 397 (4.3%) were retested too early (within 7days to 1month) and 81 (20.4%) of those were positive. CONCLUSIONS: Chlamydia retesting rates remain low with around a sixth of women retested within 2-4months in line with guidelines. Re-infection is common with around one in eight retesting positive. An increase in retesting is required to reduce the risk of reproductive complications and onward transmission.

Evaluation of a person-centred, nurse-led model of care delivering hepatitis C testing and treatment in priority settings: a mixed-methods evaluation of the Tasmanian Eliminate Hepatitis C Australia Outreach Project, 2020-2022.

INTRODUCTION: Australia has experienced sustained reductions in hepatitis C testing and treatment and may miss its 2030 elimination targets. Addressing gaps in community-based hepatitis C prescribing in priority settings that did not have, or did not prioritise, hepatitis C testing and treatment care pathways is critical. METHODS: The Tasmanian Eliminate Hepatitis C Australia Outreach Project delivered a nurse-led outreach model of care servicing hepatitis C priority populations in the community through the Tasmanian Statewide Sexual Health Service, supported by the Eliminating Hepatitis C Australia partnership. Settings included alcohol and other drug services, needle and syringe programs and mental health services. The project provided clients with clinical care across the hepatitis C cascade of care, including testing, treatment, and post-treatment support and hepatitis C education for staff. RESULTS: Between July 2020 and July 2022, a total of 43 sites were visited by one Clinical Nurse Consultant. There was a total of 695 interactions with clients across 219 days of service delivery by the Clinical Nurse Consultant. A total of 383 clients were tested for hepatitis C (antibody, RNA, or both). A total of 75 clients were diagnosed with hepatitis C RNA, of which 95% (71/75) commenced treatment, 83% (62/75) completed treatment and 52% (39/75) received a negative hepatitis C RNA test at least 12 weeks after treatment completion. CONCLUSIONS: Providing outreach hepatitis C services in community-based services was effective in engaging people living with and at-risk of hepatitis C, in education, testing, and care. Nurse-led, person-centred care was critical to the success of the project. Our evaluation underscores the importance of employing a partnership approach when delivering hepatitis C models of care in community settings, and incorporating workforce education and capacity-building activities when working with non-specialist healthcare professionals.

Young People's Experiences of Returning to Physical Leisure Activities after a Severe Acquired Brain Injury.

AIMS: To understand the experiences of young people returning to physical leisure activities following a severe acquired brain injury (ABI). METHODS: Seven young people (5 male; 14-19 years) participated. Semi-structured interviews were conducted with young people who sustained a severe ABI 1-3 years prior to the study. Data thematically analyzed using Braun and Clarke's six-phase approach. RESULTS: Three main themes were created: My changing sense of identity around physical activity after my brain injury (how important physical activity was to them, how participation changed following their ABI); Why I take part in physical leisure activities (fun, friendships, help with recovery and physical and emotional health); and I can't do it alone (need for trusted adults to practically and emotionally support them to try and activities and continue to participate). DISCUSSION: Returning to physical leisure activities after ABI was important to young people, especially if they were active prior to their injury. However, participating with changed abilities was practically and emotionally challenging. Services need a multidisciplinary approach to ensure young people are supported with psychological processes of loss, adjustment, identity and resilience in addition to the practical help necessary to enable meaningful participation in activities they consider fun.

Nasal High-Flow Therapy for Newborn Infants in Special Care Nurseries.

BACKGROUND: Nasal high-flow therapy is an alternative to nasal continuous positive airway pressure (CPAP) as a means of respiratory support for newborn infants. The efficacy of high-flow therapy in nontertiary special care nurseries is unknown. METHODS: We performed a multicenter, randomized, noninferiority trial involving newborn infants (<24 hours of age; gestational age, ≥31 weeks) in special care nurseries in Australia. Newborn infants with respiratory distress and a birth weight of at least 1200 g were assigned to treatment with either high-flow therapy or CPAP. The primary outcome was treatment failure within 72 hours after randomization. Infants in whom high-flow therapy failed could receive CPAP. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome, with a noninferiority margin of 10 percentage points. RESULTS: A total of 754 infants (mean gestational age, 36.9 weeks, and mean birth weight, 2909 g) were included in the primary intention-to-treat analysis. Treatment failure occurred in 78 of 381 infants (20.5%) in the high-flow group and in 38 of 373 infants (10.2%) in the CPAP group (risk difference, 10.3 percentage points; 95% confidence interval [CI], 5.2 to 15.4). In a secondary per-protocol analysis, treatment failure occurred in 49 of 339 infants (14.5%) in the high-flow group and in 27 of 338 infants (8.0%) in the CPAP group (risk difference, 6.5 percentage points; 95% CI, 1.7 to 11.2). The incidences of mechanical ventilation, transfer to a tertiary neonatal intensive care unit, and adverse events did not differ significantly between the groups. CONCLUSIONS: Nasal high-flow therapy was not shown to be noninferior to CPAP and resulted in a significantly higher incidence of treatment failure than CPAP when used in nontertiary special care nurseries as early respiratory support for newborn infants with respiratory distress. (Funded by the Australian National Health and Medical Research Council and Monash University; HUNTER Australian and New Zealand Clinical Trials Registry number, ACTRN12614001203640.).

Neonatal Golden Hour: A survey of Australian and New Zealand Neonatal Network units' early stabilisation practices for very preterm infants.

AIM: To identify current 'Golden Hour' practices for initial stabilisation of very preterm infants <32 weeks' gestational age (GA) within tertiary neonatal intensive care units (NICUs) in the Australian and New Zealand Neonatal Network (ANZNN). METHODS: A 76-question survey regarding delivery room (DR) and NICU stabilisation practices was distributed electronically to directors of tertiary perinatal NICUs in the ANZNN in January 2019. Responses were categorised into GA subgroups: 23-24, 25-27 and 28-31 weeks' GA. RESULTS: The response rate was 100% (24/24 units). Delayed cord clamping (DCC) was practised 'always' or 'often' by 21 units (88%). All units used oximetry to target oxygen saturations, and 23/24 (96%) commenced resuscitation in <40% oxygen. Ten units (42%) routinely used DR electrocardiography monitoring. CPAP was preferred as primary respiratory support in one-third of units for infants born 23-24 weeks' GA, compared with 19 units (79%) at 25-27 weeks' GA and 23 units (96%) at 28-31 weeks' GA. DR skin-to-skin care was uncommon, particularly at lower GAs. Five units (21%) used minimally invasive surfactant therapy for non-intubated infants at 23-24 weeks' GA, 13 units (54%) at 25-27 weeks' GA and 16 units (67%) at 28-31 weeks' GA. CONCLUSIONS: Most Golden Hour stabilisation practices align with international guidelines. Consistency exists with respect to DCC, oxygen saturation targeting and primary CPAP use for infants 25 weeks' GA and above. Where evidence is less certain, practices vary across ANZNN NICUs. Time targets for stabilisation measures may help standardise practice for this population.

Predictors and Outcomes of Early Intubation in Infants Born at 28-36 Weeks of Gestation Receiving Noninvasive Respiratory Support.

OBJECTIVE: To identify predictors and outcomes of early intubation in preterm infants with respiratory distress, and predictors of need for brief respiratory support (≤1 day). STUDY DESIGN: Secondary analysis of data from a randomized trial comparing nasal high-flow with continuous positive airway pressure as primary respiratory support in preterm infants born at 28-36 weeks of gestation. Intubation was assessed within 72 hours of randomization. RESULTS: There were 564 included infants with a mean (SD) gestational age of 32.0 (2.2) weeks and birth weight 1744 (589) g; 76 infants (13.5%) received early intubation. On multivariable analysis, lower gestational age and higher pre-randomization fraction of inspired oxygen (FiO2) predicted intubation. A test based on gestational age of <30 weeks and an FiO2 of ≥0.30 produced a likelihood ratio of 9.1. Intubation was associated with prolonged duration of respiratory support and supplemental oxygen, with pneumothorax and nasal trauma, and in infants born at <32 weeks of gestational, with bronchopulmonary dysplasia and patent ductus arteriosus requiring treatment. Greater gestational age and lower FiO2 predicted the need for ≤1 day of respiratory support. A test based on a gestational age of ≥34 weeks and an FiO2 of 0.21 produced a likelihood ratio of 4.7. CONCLUSIONS: In preterm infants 28-36 week of gestation receiving primary noninvasive respiratory support, lower gestational age, and higher FiO2 predicted need for intubation within 72 hours. Intubation was associated with adverse respiratory outcomes. Greater gestational age and lower FiO2 predicted need for ≤1 day of respiratory support. It may be reasonable to defer the use of respiratory support in more mature infants with low FiO2 requirements. TRIAL REGISTRATION AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12613000303741.

Predicting Nasal High-Flow Treatment Success in Newborn Infants with Respiratory Distress Cared for in Nontertiary Hospitals.

OBJECTIVE: To evaluate demographic and clinical variables as predictors of nasal high-flow treatment success in newborn infants with respiratory distress cared for in Australian nontertiary special care nurseries. STUDY DESIGN: A secondary analysis of the HUNTER trial, a multicenter, randomized controlled trial evaluating nasal high-flow as primary respiratory support for newborn infants with respiratory distress who were born ≥31 weeks of gestation and with birth weight ≥1200 g, and cared for in Australian nontertiary special care nurseries. Treatment success within 72 hours after randomization to nasal high-flow was determined using objective criteria. Univariable screening and multivariable analysis was used to determine predictors of nasal high-flow treatment success. RESULTS: Infants (n = 363) randomized to nasal high-flow in HUNTER were included in the analysis; the mean gestational age was 36.9 ± 2.7 weeks and birth weight 2928 ± 782 g. Of these infants, 290 (80%) experienced nasal high-flow treatment success. On multivariable analysis, nasal high-flow treatment success was predicted by higher gestational age and lower fraction of inspired oxygen immediately before randomization, but not strongly. The final model was found to have an area under the curve of 0.65, which after adjustment for optimism was found to be 0.63 (95% CI, 0.57-0.70). CONCLUSIONS: Gestational age and supplemental oxygen requirement may be used to guide decisions regarding the most appropriate initial respiratory support for newborn infants in nontertiary special care nurseries. Further prospective research is required to better identify which infants are most likely to be successfully treated with nasal high-flow. TRIAL REGISTRATION: ACTRN12614001203640.

Review of guidelines and recommendations from 17 countries highlights the challenges that clinicians face caring for neonates born to mothers with COVID-19.

AIM: This review examined how applicable national and regional clinical practice guidelines and recommendations for managing neonates born to mothers with COVID-19 mothers were to the evolving pandemic. METHODS: A systematic search and review identified 20 guidelines and recommendations that had been published by May 25, 2020. We analysed documents from 17 countries: Australia, Brazil, Canada, China, France, India, Italy, Japan, Saudi Arabia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, the UK and the United States. RESULTS: The documents were based on expert consensus with limited evidence and were of variable, low methodological rigour. Most did not provide recommendations for delivery methods or managing symptomatic infants. None provided recommendations for post-discharge assimilation of potentially infected infants into the community. The majority encouraged keeping mothers and infants together, subject to infection control measures, but one-third recommended separation. Although breastfeeding or using breastmilk was widely encouraged, two countries specifically prohibited this. CONCLUSION: The guidelines and recommendations for managing infants affected by COVID-19 were of low, variable quality and may be unsustainable. It is important that transmission risks are not increased when new information is incorporated into clinical recommendations. Practice guidelines should emphasise the extent of uncertainty and clearly define gaps in the evidence.

Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants.

BACKGROUND: Treatment with nasal high-flow therapy has efficacy similar to that of nasal continuous positive airway pressure (CPAP) when used as postextubation support in neonates. The efficacy of high-flow therapy as the primary means of respiratory support for preterm infants with respiratory distress has not been proved. METHODS: In this international, multicenter, randomized, noninferiority trial, we assigned 564 preterm infants (gestational age, ≥28 weeks 0 days) with early respiratory distress who had not received surfactant replacement to treatment with either nasal high-flow therapy or nasal CPAP. The primary outcome was treatment failure within 72 hours after randomization. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome; the chosen margin of noninferiority was 10 percentage points. Infants in whom high-flow therapy failed could receive rescue CPAP; infants in whom CPAP failed were intubated and mechanically ventilated. RESULTS: Trial recruitment stopped early at the recommendation of the independent data and safety monitoring committee because of a significant difference in the primary outcome between treatment groups. Treatment failure occurred in 71 of 278 infants (25.5%) in the high-flow group and in 38 of 286 infants (13.3%) in the CPAP group (risk difference, 12.3 percentage points; 95% confidence interval [CI], 5.8 to 18.7; P<0.001). The rate of intubation within 72 hours did not differ significantly between the high-flow and CPAP groups (15.5% and 11.5%, respectively; risk difference, 3.9 percentage points; 95% CI, -1.7 to 9.6; P=0.17), nor did the rate of adverse events. CONCLUSIONS: When used as primary support for preterm infants with respiratory distress, high-flow therapy resulted in a significantly higher rate of treatment failure than did CPAP. (Funded by the National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12613000303741 .).

Nasal high flow therapy for neonates: Current evidence and future directions.

Nasal high flow (nHF) therapy is a commonly used method of providing non-invasive respiratory support for neonates. It has several potential mechanisms of action: continuous distending pressure, nasopharyngeal dead space washout, provision of heated and humidified gases and reduction of work of breathing. nHF is used in a number of clinical scenarios for preterm and term infants, including primary respiratory and post-extubation support. In recent years, large trials have generated evidence pertinent to these indications. Novel applications for nHF in neonates warrant further research: during endotracheal intubation, for initial delivery room stabilisation of preterm infants and in conjunction with minimally invasive surfactant therapy.

A national study of the clinical management of HIV-positive women in Australia: what are the successes and where are the gaps?

Background Women comprise ~10% of people living with HIV in Australia, so are often underrepresented in research. METHODS: This study invited clinicians providing care to women living with HIV to complete an anonymous survey containing questions related to four key areas: HIV (including diagnosis, treatment and virological outcomes), reproductive health (including sexual activity, contraception, pregnancy and outcomes) and linkage and retention in care. RESULTS: In total, 484 surveys were received, with responses from all states and territories. Most women living with HIV in Australia are on treatment (>90%) and virologically suppressed (>90% have a viral load <50 copies mL-1). Almost 75% of women have had at least one switch in treatment (with toxicity almost as common as simplification as the indication). Treatment interruption is also relatively common, but is more likely the longer a woman has been diagnosed, if she is on benefits (P = 0.007) and is the primary carer of children without a partner (P = 0.001). In Australia, women living with HIV are a diverse heterogeneous group, with over 70 different countries of birth and almost half speaking a language other than English at home. Mental health diagnosis was the most common co-morbid condition identified. A total of 21% of women were post-menopausal, with 42% reporting symptoms to their healthcare provider, but only 17% were receiving treatment for symptoms attributed to menopause. CONCLUSIONS: As well as strategies to support women vulnerable to treatment interruption, important areas for future investment in research and clinical care include co-morbid mental health and menopause symptoms and treatment.

Effect of Sustained Inflations vs Intermittent Positive Pressure Ventilation on Bronchopulmonary Dysplasia or Death Among Extremely Preterm Infants: The SAIL Randomized Clinical Trial.

Importance: Preterm infants must establish regular respirations at delivery. Sustained inflations may establish lung volume faster than short inflations. Objective: To determine whether a ventilation strategy including sustained inflations, compared with standard intermittent positive pressure ventilation, reduces bronchopulmonary dysplasia (BPD) or death at 36 weeks' postmenstrual age without harm in extremely preterm infants. Design, Setting, and Participants: Unmasked, randomized clinical trial (August 2014 to September 2017, with follow-up to February 15, 2018) conducted in 18 neonatal intensive care units in 9 countries. Preterm infants 23 to 26 weeks' gestational age requiring resuscitation with inadequate respiratory effort or bradycardia were enrolled. Planned enrollment was 600 infants. The trial was stopped after enrolling 426 infants, following a prespecified review of adverse outcomes. Interventions: The experimental intervention was up to 2 sustained inflations at maximal peak pressure of 25 cm H2O for 15 seconds using a T-piece and mask (n = 215); standard resuscitation was intermittent positive pressure ventilation (n = 211). Main Outcome and Measures: The primary outcome was the rate of BPD or death at 36 weeks' postmenstrual age. There were 27 prespecified secondary efficacy outcomes and 7 safety outcomes, including death at less than 48 hours. Results: Among 460 infants randomized (mean [SD] gestational age, 25.30 [0.97] weeks; 50.2% female), 426 infants (92.6%) completed the trial. In the sustained inflation group, 137 infants (63.7%) died or survived with BPD vs 125 infants (59.2%) in the standard resuscitation group (adjusted risk difference [aRD], 4.7% [95% CI, -3.8% to 13.1%]; P = .29). Death at less than 48 hours of age occurred in 16 infants (7.4%) in the sustained inflation group vs 3 infants (1.4%) in the standard resuscitation group (aRD, 5.6% [95% CI, 2.1% to 9.1%]; P = .002). Blinded adjudication detected an imbalance of rates of early death possibly attributable to resuscitation (sustained inflation: 11/16; standard resuscitation: 1/3). Of 27 secondary efficacy outcomes assessed by 36 weeks' postmenstrual age, 26 showed no significant difference between groups. Conclusions and Relevance: Among extremely preterm infants requiring resuscitation at birth, a ventilation strategy involving 2 sustained inflations, compared with standard intermittent positive pressure ventilation, did not reduce the risk of BPD or death at 36 weeks' postmenstrual age. These findings do not support the use of ventilation with sustained inflations among extremely preterm infants, although early termination of the trial limits definitive conclusions. Trial Registration: clinicaltrials.gov Identifier: NCT02139800.

The evolution of modern respiratory care for preterm infants.

Preterm birth rates are rising, and many preterm infants have breathing difficulty after birth. Treatments for infants with prolonged breathing difficulty include oxygen therapy, exogenous surfactant, various modes of respiratory support, and postnatal corticosteroids. In this Series paper, we review the history of neonatal respiratory care and its effect on long-term outcomes, and we outline the future direction of the research field. The delivery and monitoring of oxygen therapy remains controversial, despite being in use for more than 50 years. Exogenous surfactant replacement has been used for 25 years and has dramatically reduced mortality and morbidity, but more research on when and how it is administered is needed. Methods and techniques of neonatal respiratory support are evolving. Clinicians are moving away from routine intubation and ventilation, and new modes of non-invasive support are being investigated. Postnatal corticosteroids have a limited role in infants with evolving bronchopulmonary dysplasia, but more research is needed to identify the best timing, type, dose, and method of administration. Despite advances in neonatal care in the past 50 years, bronchopulmonary dysplasia, with all its adverse short-term and long-term consequences, is still a serious problem in neonatal care. The challenge remains to support breathing in preterm infants, with special attention to risk factors in the subpopulation of infants that are at highest risk of bronchopulmonary dysplasia, without damaging their lungs or adversely affecting their long-term health.

Towards evidence-based resuscitation of the newborn infant.

Effective resuscitation of the newborn infant has the potential to save many lives around the world and reduce disabilities in children who survive peripartum asphyxia. In this Series paper, we highlight some of the important advances in the understanding of how best to resuscitate newborn infants, which includes monitoring techniques to guide resuscitative efforts, increasing awareness of the adverse effects of hyperoxia, delayed umbilical cord clamping, the avoidance of routine endotracheal intubation for extremely preterm infants, and therapeutic hypothermia for hypoxic-ischaemic encephalopathy. Despite the challenges of performing high-quality clinical research in the delivery room, researchers continue to refine and advance our knowledge of effective resuscitation of newborn infants through scientific experiments and clinical trials.

Refining the Use of Nasal High-Flow Therapy as Primary Respiratory Support for Preterm Infants.

OBJECTIVE: To identify clinical and demographic variables that predict nasal high-flow (nHF) treatment failure when used as a primary respiratory support for preterm infants. STUDY DESIGN: This secondary analysis used data from a multicenter, randomized, controlled trial comparing nHF with continuous positive airway pressure as primary respiratory support in preterm infants 28-36 completed weeks of gestation. Treatment success or failure with nHF was determined using treatment failure criteria within the first 72 hours after randomization. Infants in whom nHF treatment failed received continuous positive airway pressure, and were then intubated if failure criteria were again met. RESULTS: There were 278 preterm infants included, with a mean gestational age (GA) of 32.0 ± 2.1 weeks and a birth weight of 1737 ± 580 g; of these, nHF treatment failed in 71 infants (25.5%). Treatment failure was moderately predicted by a lower GA and higher prerandomization fraction of inspired oxygen (FiO2): area under a receiver operating characteristic curve of 0.76 (95% CI, 0.70-0.83). Nasal HF treatment success was more likely in infants born at ≥30 weeks GA and with prerandomization FiO2 <0.30. CONCLUSIONS: In preterm infants ≥28 weeks' GA enrolled in a randomized, controlled trial, lower GA and higher FiO2 before randomization predicted early nHF treatment failure. Infants were more likely to be successfully treated with nHF from soon after birth if they were born at ≥30 weeks GA and had a prerandomization FiO2 <0.30. However, even in this select population, continuous positive airway pressure remains superior to nHF as early respiratory support in preventing treatment failure. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12613000303741.

Cost-Effectiveness Analysis of Nasal Continuous Positive Airway Pressure Versus Nasal High Flow Therapy as Primary Support for Infants Born Preterm.

OBJECTIVE: To compare the cost-effectiveness of 2 common "noninvasive" modes of respiratory support for infants born preterm. STUDY DESIGN: An economic evaluation was conducted as a component of a multicenter, randomized control trial from 2013 to 2015 enrolling infants born preterm at ≥28 weeks of gestation with respiratory distress, <24 hours old, who had not previously received endotracheal intubation and mechanical ventilation or surfactant. The economic evaluation was conducted from a healthcare sector perspective and the time horizon was from birth until death or first discharge. The cost-effectiveness of continuous positive airway pressure (CPAP) vs high-flow with "rescue" CPAP backup and high-flow without rescue CPAP backup (as sole primary support) were analyzed by using the hospital cost of inpatient stay in a tertiary center and the rates of endotracheal intubation and mechanical ventilation during admission. RESULTS: Hospital inpatient cost records for 435 infants enrolled in all Australian centers were obtained. With "rescue" CPAP backup, an incremental cost-effectiveness ratio was estimated of A$179 000 (US$123 000) per ventilation avoided if CPAP was used compared with high flow. Without rescue CPAP backup, cost per ventilation avoided was A$7000 (US$4800) if CPAP was used compared with high flow. CONCLUSIONS: As sole primary support, CPAP is highly likely to be cost-effective compared with high flow. Neonatal units choosing to use only one device should apply CPAP as primary respiratory support. Compared with high-flow with rescue CPAP backup, CPAP is unlikely to be cost-effective if willingness to pay per ventilation avoided is less than A$179 000 (US$123 000).