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Background: Clinicians favour low oxygen concentrations when resuscitating preterm infants immediately after birth despite inconclusive evidence to support this practice. Prospective meta-analysis (PMA) is a novel approach where studies are identified as eligible for inclusion in the meta-analysis before their results are known., Aims: To explore whether high (60%) or low (30%) oxygen is associated with greater efficacy and safety for the initial resuscitation (immediately after birth) of preterm infants born at <29 weeks' gestation., Methods: We will conduct a prospective meta-analysis (PMA) with individual participant data (IPD). We will perform a systematic search to identify ongoing RCTs including infants <29 weeks' gestation randomised to high (60%) or low (30%) oxygen for initial resuscitation after birth. IPD will be sought for all infants randomised for the purpose of meta-analysis. We will employ a one-stage random-effects approach to IPD meta-analysis. Potential heterogeneity and the differential effect of high or low oxygen will be explored through subgroup and interaction analyses. The primary outcome of this study is all-cause mortality prior to hospital discharge. There will be a follow-up analysis of neurodevelopmental outcomes once available., Results/conclusion: The results of neonatal outcomes at hospital discharge are expected by 2025, and neurodevelopmental outcomes by 2027., (© 2022 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Background: Globally, are skincare practices and skin injuries in extremely preterm infants comparable? This study describes skin injuries, variation in skincare practices and investigates any association between them., Methods: A web-based survey was conducted between February 2019 and August 2021. Quantifying skin injuries and describing skincare practices in extremely preterm infants were the main outcomes. The association between skin injuries and skincare practices was established using binary multivariable logistic regression adjusted for regions., Results: Responses from 848 neonatal intensive care units, representing all geographic regions and income status groups were received. Diaper dermatitis (331/840, 39%) and medical adhesive-related skin injuries (319/838, 38%) were the most common injuries. Following a local skincare guideline reduced skin injuries [medical adhesive-related injuries: adjusted odds ratios (aOR) = 0.63, 95% confidence interval (CI) = 0.45-0.88; perineal injuries: aOR = 0.66, 95% CI = 0.45-0.96; local skin infections: OR = 0.41, 95% CI = 0.26-0.65; chemical burns: OR = 0.46, 95% CI = 0.26-0.83; thermal burns: OR = 0.51, 95% CI = 0.27-0.96]. Performing skin assessments at least every four hours reduced skin injuries (abrasion: aOR = 0.48, 95% CI = 0.33-0.67; pressure: aOR = 0.51, 95% CI = 0.34-0.78; diaper dermatitis: aOR = 0.71, 95% CI = 0.51-0.99; perineal: aOR = 0.52, 95% CI = 0.36-0.75). Regional and resource settings-based variations in skin injuries and skincare practices were observed., Conclusions: Skin injuries were common in extremely preterm infants. Consistency in practice and improved surveillance appears to reduce the occurrence of these injuries. Better evidence regarding optimal practices is needed to reduce skin injuries and minimize practice variations., (© 2022. The Author(s).)

Introduction: Reports on the influence of postnatal cytomegalovirus (pCMV) infection in neonatal outcomes of preterm babies vary while guidance on management including screening is lacking. We aim to determine the association between symptomatic pCMV infection and chronic lung disease (CLD) and mortality in preterm infants born less than 32 weeks gestation., Methods: We used data from the Neonatal Intensive Care Units' (NICUS) population-based prospective data registry of infants in 10 neonatal units in New South Wales and the Australian Capital Territory, Australia. De-identified perinatal and neonatal outcome data for 40,933 infants were examined. We identified 172 infants &lt;32 weeks gestation with symptomatic pCMV infection. Each was matched with one control infant., Results: Infants with symptomatic pCMV infection were 2.7 times more likely to develop CLD (OR 2.7, 95% CI: 1.7-4.5) and spend 25.2 days more in hospital (95% CI: 15.2-35.2). Seventy-five percent (129/172) of infants with symptomatic pCMV were extremely preterm (&lt;28 weeks). The mean age of symptomatic pCMV diagnosis was 62.5 ± 20.5 days or 34.7 ± 3.6 weeks-corrected gestational age. Ganciclovir treatment did not decrease CLD and death. CLD was 5.5 times predictive of death in patients with symptomatic pCMV infection. Symptomatic pCMV infection did not influence mortality nor increase neurologic impairment., Conclusion: Symptomatic pCMV is a modifiable factor affecting extreme preterm infants with significant impact on CLD. Prospective study on screening and treatment will help unveil potential benefits in our already at-risk preterm infants., (© 2023 S. Karger AG, Basel.)

Emergency research studies are high-stakes studies that are usually performed on the sickest patients, where many patients or guardians have no opportunity to provide full informed consent prior to participation. Many emergency studies self-select healthier patients who can be informed ahead of time about the study process. Unfortunately, results from such participants may not be informative for the future care of sicker patients. This inevitably creates waste and perpetuates uninformed care and continued harm to future patients. The waiver or deferred consent process is an alternative model that may be used to enroll sick patients who are unable to give prospective consent to participate in a study. However, this process generates vastly different stakeholder views which have the potential to create irreversible impediments to research and knowledge. In studies involving newborn infants, consent must be sought from a parent or guardian, and this adds another layer of complexity to already fraught situations if the infant is very sick. In this manuscript, we discuss reasons why consent waiver or deferred consent processes are vital for some types of neonatal research, especially those occurring at and around the time of birth. We provide a framework for conducting neonatal emergency research under consent waiver that will ensure the patient's best interests without compromising ethical, beneficial, and informative knowledge acquisition to improve the future care of sick newborn infants., (© 2023 S. Karger AG, Basel.)

Objective: To conduct a meta-analysis to determine the association between prenatal drug exposure and risk of sudden infant death syndrome (SIDS)., Design: Studies were searched using PubMed, Medline and Embase and restricted to English, with no publication date limit. Selected studies included published cohort, population or case studies comparing the incidence of SIDS among drug-exposed with drug-free controls. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Data were pooled using a random-effects model to evaluate risk ratios (RR)., Setting: High-income countries., Patients: Children with a history of prenatal drug exposure., Interventions: None., Main Outcome Measures: RR of SIDS between drug-exposed and control infants., Results: Sixteen studies (36 730 infants with any prenatal drug exposure, 21 661 exposed to opioids, 21 571 exposed to cocaine, 5031 exposed to methadone compared with 4 201 955 with no exposure). Any prenatal drug exposure was associated with an increased crude risk of SIDS (RR 7.84, 95% CI 5.21 to 11.81). Prenatal opioid exposure had the highest associative crude risk of SIDS (RR 9.76, 95% CI 5.28 to 18.05), followed by methadone (RR 9.52, 95% CI 4.60 to 19.70) and cocaine (RR 4.40, 95% CI 2.52 to 7.67). Increased crude risk persisted after adjusting for socioeconomic factors (RR 4.24, 95% CI 1.39 to 12.88). The incidence of SIDS for this cohort decreased between 1972 and 2020 but remained significantly higher than controls., Conclusion: Exposure to any drug of dependency during pregnancy is associated with an increased risk of SIDS after controlling for socioeconomic factors. Further study to evaluate mechanisms and contribution of other confounders (eg, smoking) is warranted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Achieving "normal oxygenation" in sick newborn infants requiring resuscitation is one of the most difficult and incompletely informed practices in neonatal care. Suboptimal oxygenation, whether too little or too much, has profound repercussions, including death. In the last two decades, clinicians have lost equipoise for the use of higher oxygen strategies due to concerns of hyperoxia but emerging evidence suggests that lower oxygen strategies may also be as detrimental, especially in infants with pulmonary pathologies such as those born at the cusp of viability. Practice at the coalface using rapidly evolving recommendations has also uncovered continuing complexities in the quest to achieve optimum oxygenation during the first critical minutes of life. There are adjustable factors, such as the practical impediments to acquiring knowledge, equipment and expertise as well as unadjustable factors, such as inherent infant pathology, that necessitates agile clinical manipulation to "first do no harm". This review will address the deficiencies in knowledge that currently impede our quest to determine the best and safest means to deliver oxygen to sick infants during the first critical minutes of life and suggest practical solutions for current practice while awaiting definitive evidence from large scale, well defined, randomized controlled studies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To determine the effects of lower (≤0.3) versus higher (≥0.6) initial fractional inspired oxygen (FiO 2 ) for resuscitation on death and/or neurodevelopmental impairment (NDI) in infants <32 weeks' gestation., Design: Meta-analysis of individual patient data from three randomised controlled trials., Setting: Neonatal intensive care units., Patients: 543 children <32 weeks' gestation., Intervention: Randomisation at birth to resuscitation with lower (≤0.3) or higher (≥0.6) initial FiO 2 ., Outcome Measures: Primary: death and/or NDI at 2 years of age.Secondary: post-hoc non-randomised observational analysis of death/NDI according to 5-minute oxygen saturation (SpO 2 ) below or at/above 80%., Results: By 2 years of age, 46 of 543 (10%) children had died. Of the 497 survivors, 84 (17%) were lost to follow-up. Bayley Scale of Infant Development (third edition) assessments were conducted on 377 children. Initial FiO 2 was not associated with difference in death and/or disability (difference (95% CI) -0.2%, -7% to 7%, p=0.96) or with cognitive scores <85 (2%, -5% to 9%, p=0.5). Five-minute SpO 2 >80% was associated with decreased disability/death (14%, 7% to 21%) and cognitive scores >85 (10%, 3% to 18%, p=0.01). Multinomial regression analysis noted decreased death with 5-minute SpO 2 ≥80% (odds (95% CI) 09.62, 0.98 to 0.96) and gestation (0.52, 0.41 to 0.65), relative to children without death or NDI., Conclusion: Initial FiO 2 was not associated with difference in risk of disability/death at 2 years in infants <32 weeks' gestation but CIs were wide. Substantial benefit or harm cannot be excluded. Larger randomised studies accounting for patient differences, for example, gestation and gender are urgently needed., Competing Interests: Competing interests: YR has patents for technology to guide oxygen titration during newborn resuscitation. He did not contribute to any aspects of the manuscript related to the targeting of oxygen saturation., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Objective: This study aimed to systematically review the current literature on the economic costs of micro preemie as well as evidence on the cost-effectiveness of interventions to improve outcomes for micro preemie babies with a birth weight of ≤500 g., Method: We searched MEDLINE, CINAHL, Scopus, ECONLIT, Business Source Premier and Cochrane Library for studies reporting costs of micro preemie from January 2000. Costs were inflated to 2019 United States dollars (US$). All full-text articles were assessed for eligibility and a quality assessment of included articles was conducted using the Drummond and the Larg and Moss checklists., Results: The search identified three studies that met the inclusion criteria; two cost-of-illness studies and one cost-effectiveness study. Across studies, the mean healthcare spending per micro preemie survivor (in 2019 US$) ranged from US$61,310 (birth admission) to US$263,958 (inpatient and outpatient for the first six months of life). One modelling study reported exclusive human milk diet for micro preemies at birth was more cost-effective compared to the standard approach with cow milk diet from the third-party payer and societal perspectives., Conclusion: Despite significant advances in perinatal care and expanded access to life-saving equipment to improve survival outcomes of micro preemie, there remains a paucity of research on economic costs associated with these babies. No study has utilised quality-adjusted life-years as an outcome measure. Given the chronic conditions and long-term neurologic disability associated with micro preemie survivors, an estimate of the lifetime cost to the individual, healthcare providers and society would provide a benchmark of the potential cost-savings that could accrue from cost-effective interventions to improve the survival rate of micro preemies., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The use of tobacco during pregnancy is the leading preventable cause of pregnancy complications and adverse birth outcomes. In high-income countries, around one in 10 pregnant women smokes tobacco, while smokeless tobacco is the primary form of tobacco used in many low- and middle-income countries. Although the risk of tobacco-related harms can be reduced substantially if mothers cease smoking in the first trimester of pregnancy, the proportion of women who successfully quit smoking during pregnancy remains modest. Psychosocial interventions are first-line treatment, with some high-quality evidence showing that counselling is effective in promoting smoking cessation among pregnant women. There is insufficient evidence regarding the efficacy and safety of smoking cessation pharmacotherapies when used during pregnancy, although in some countries nicotine replacement therapy is recommended for pregnant women who have been unable to quit without pharmacological assistance. E-cigarettes are increasingly being used as a smoking cessation aid in the general population of smokers, but more research is needed to determine if e-cigarettes are a safe and effective treatment option for pregnant women., (© 2021 Society for the Study of Addiction.)

There are no standardized procedures for the resuscitation of micropreemies but respiratory and circulatory stabilization immediately after birth should be prioritized. Without aggressive support by positive pressure ventilation, establishing effective respiration among micropreemies is not possible. The first step in postnatal stabilization is initiated by positive airway pressure with a bag and mask. Once the heart rate increases above 100 beats/m, intratracheal intubation should be achieved because it is unusual for a micropreemie to breathe spontaneously or by non-invasive respiratory support for a protracted duration. Until further information is available, initial FiO 2 should be between 0.3 and 0.6, and titrated to achieve SpO 2 obtained from healthy term infants for the first 10 min of life. Temperature control of infants is also critical for successful resuscitation and heat-loss minimizing procedures should be used e.g. with insulating bags. After securing the intratracheal tube, the infants should be transferred to the NICU for further procedures, including pulmonary surfactant installation and umbilical cord catheterization. Procedures in a delivery room under a radiant warmer should be limited to the initial resuscitation. In NICUs, the infants should be placed into a closed incubator to maintain high environmental temperature and humidity as well as decrease exposure to intervention and noise. Increased number of staff will also be needed to stabilize the infants further in the NICU. Finally, appropriate equipment (e.g. appropriate sized laryngoscopes) should be made readily available, along with regular practical training and education, whether in person or through SIM courses which are essential for all staff to achieve competence in successful resuscitation of the newborn micropreemie., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Internationally recognized guidelines recommend the judicious use of low oxygen (21-30%), titrated to peripheral oxygen saturation targets, for the initiation of resuscitation of very and extremely preterm infants (<32 weeks' gestation). However, despite more than 10 randomized controlled trials on this question, the ideal initial oxygen concentration for this group of vulnerable infants remains uncertain., Aims: This study aims to assess the effect of various initial oxygen concentrations on (1) all-cause mortality, chronic lung disease, intraventricular hemorrhage, and retinopathy of prematurity; and (2) reaching the prescribed oxygen saturation targets by 5 min after birth, in preterm infants requiring resuscitation., Methods: We will conduct a systematic review and network meta-analysis using individual participant data. Studies of preterm infants <32 weeks' gestation, randomized to initial oxygen concentration, will be included. We will systematically search medical databases and trial registries for eligible studies (published or unpublished). Records will be screened by two independent reviewers, with conflicts resolved by the inclusion of a third reviewer. Identified initial oxygen concentrations will be grouped into the following nodes: low (≤30%), intermediate (60%), and high (≥90%) oxygen. A two-step random-effects contrast-based network meta-regression will be calculated to compare and rank different oxygen concentrations. Analyses will be intention-to-treat, with the primary outcome of all-cause mortality., Discussion: This is the first individual participant data network meta-analysis of initial oxygen concentrations for the resuscitation of preterm infants. This novel approach may address long-standing uncertainty regarding optimal oxygen supplementation practice for the resuscitation of preterm infants <32 weeks' gestation., (© 2022 S. Karger AG, Basel.)

Introduction: We aimed to determine global professional opinion and practice for the use of therapeutic hypothermia (TH) for treating infants with mild hypoxic-ischaemic encephalopathy (HIE)., Methods: A web-based survey (REDCap) was distributed via emails, social networking sites, and professional groups from October 2020 to February 2021 to neonatal clinicians in 35 countries., Results: A total of 484 responses were obtained from 35 countries and categorized into low/middle-income (43%, LMIC) or high-income (57%, HIC) countries. Of the 484 respondents, 53% would provide TH in mild HIE on case-to-case basis and only 25% would never cool. Clinicians from LMIC were more likely to routinely offer TH in mild HIE (25% v HIC 16%, p < 0.05), have a unit protocol for providing TH (50% v HIC 26%, p < 0.05), use adjunctive tools, e.g., aEEG (49% v HIC 32%, p < 0.001), conduct an MRI post TH (48% v HIC 40%, p < 0.05) and less likely to use neurological examinations as a HIE severity grading tool (80% v HIC 95%, p < 0.001). The majority of respondents (91%) would support a randomized controlled trial that was sufficiently large to examine neurodevelopmental outcomes in mild HIE after TH., Conclusions: This is the first survey of global opinion for TH in mild HIE. The overwhelming majority of professionals would consider "cooling" an infant with mild HIE, but LMIC respondents were more likely to routinely cool infants with mild HIE and use adjunctive tools for diagnosis and follow-up. There is wide practice heterogeneity and a sufficiently large RCT designed to examine neurodevelopmental outcomes, is urgently needed and widely supported., (© 2022 S. Karger AG, Basel.)

Methamphetamine (MA) is the second most commonly used illicit drug in the world, after cannabis. There are limited data on the outcomes of pregnant MA users but there is rapidly emerging evidence to suggest that they are more vulnerable, marginalized and impoverished compared with other drug-using mothers. MA use during pregnancy is associated with worse pregnancy outcomes and significantly higher rates of co-existing health and psychosocial problems. Newborn infants exposed to MA are at increased risk of perinatal complications, present differently at birth to infants exposed to other drugs of dependency such as opioids and have poorer neurological adaptation and feeding difficulties. Sparse literature from neuroimaging and cohort studies suggests that the neurocognitive deficits in MA exposed children persist, even into adulthood. Current clinical practice guidelines for the care of substance exposed pregnant women are opioid-centric with little attention paid to the consequences of prenatal MA exposure., (© 2021 Society for the Study of Addiction.)

Aim: The aim of this study was to determine clinician opinion regarding oxygen management in moderate-late preterm resuscitation., Methods: An anonymous online questionnaire was distributed through email/social messaging platforms to neonatologists in 21 countries (October 2020-March 2021) via REDCap., Results: Of the 695 respondents, 69% had access to oxygen blenders and 90% had pulse oximeters. Respondents from high-income countries were more likely to have oxygen blenders than those from middle-income countries (72% vs. 66%). Most initiated respiratory support with FiO 2 0.21 (43%) or 0.3 (36%) but only 45% titrated FiO 2 to target SpO 2 . Most (89%) considered heart rate as a more important indicator of response than SpO 2 . Almost all (96%) supported the need for well-designed trials to examine oxygenation in moderate-late preterm resuscitation., Conclusion: Most clinicians resuscitated moderate-late preterm infants with lower initial FiO 2 but some cannot/will not target SpO 2 or titrate FiO 2 . Most consider heart rate as a more important indicator of infant response than SpO 2 .Large and robust clinical trials examining oxygen use for moderate-late preterm resuscitation, including long-term neurodevelopmental outcomes, are supported amongst clinicians., (©2021 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

This study assessed the economic evidence on the pharmacological and non-pharmacological management of infants with neonatal opioid withdrawal syndrome (NOWS). Six databases were searched up to October 2020 for peer-reviewed studies. After titles and abstracts were screened, 79 studies remained for full-text review, and finally, 8 studies were eligible for inclusion in the review. The methodological quality of included studies was assessed using the Drummond checklist. The review showed significant limitations in these studies, with one study being rated as good and the remaining seven studies as of poor quality. There are methodological issues that require addressing, including a lack of detail on cost categories, a robust investigation of uncertainty, and extending the time horizon to consider longer-term outcomes beyond the initial birth hospitalization. Despite these limitations, existing evidence suggests non-pharmacological strategies such as rooming-in were associated with a shorter hospital stay and a decreased need for pharmacological treatment, thereby lowering hospitalization costs. The review highlights the paucity of high-quality studies assessing the cost-effectiveness of intervention strategies for NOWS. There is also a lack of evidence on long-term outcomes associated with NOWS and the treatment of NOWS. The inclusion of economic analyses in future studies will provide evidence to inform policymakers on resource allocation decisions for this patient population.

For more than 200 years, pure oxygen was given ad libitum to newborn infants requiring resuscitation. Due to oxidative stress and injury concerns, a paradigm shift towards using "less" oxygen, including air (21% oxygen) instead of pure (100%) oxygen, occurred about twenty years ago. A decade later, clinicians were advised to adjust fractional inspired oxygen (FiO 2 ) to target oxygen saturations (SpO 2 ) that were derived from spontaneously breathing, healthy, mature infants. Whether these recommendations are achievable, beneficial, harmful or redundant is uncertain. The underlying pathology leading to resuscitation varies between infants and may considerably alter an infant's response to supplemental oxygen. In this review, we summarize available evidence for the use of SpO 2 monitoring at delivery for newborn infants, elucidate existing knowledge and service gaps, and suggest future research recommendations that will lead to the safest clinical strategies for this standard and important practice., (Copyright © 2021. Published by Elsevier Ltd.)

Even a few minutes of exposure to oxygen in the delivery room in very preterm and immature infants may have detrimental effects. The initial oxygenation in the delivery room should therefore be optimized, but knowledge gaps, including initial fraction of oxygen (FiO2) and how FiO2 should be changed to reach an optimal oxygen saturation measured by pulse oximetry (SpO2) target within the first 5-10 min of life, remain. In order to answer this question, we therefore reviewed relevant literature. For newly born infants with gestational age (GA) <32 weeks in need of positive pressure ventilation (PPV) immediately after birth, we identified 2 fundamental issues: (1) the optimal initial FiO2 and (2) the target SpO2 within the first 5-10 min of life. For newly born infants between 29 and 31 weeks of GA, an initial FiO2 of 0.3 hit the target defined by the International Liaison Committee on Resuscitation (ILCOR) best. Newborn infants with GA <29 weeks in need of PPV and supplementary oxygen, we suggest starting with FiO2 0.3 and adjusting the FiO2 to reach SpO2 of 80% within 5 min of life for best outcomes. Prolonged bradycardia (heart rate <100 bpm for >2 min) is associated with increased risk of adverse outcomes, including death. The combination of strict control of development of SpO2 in the first 10 min of life and a heart rate >100 bpm represents the best tool today to achieve the most optimal outcome in the delivery room of very preterm and immature newborn infants., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Background: Eye exam for Retinopathy of prematurity (ROP) is a painful procedure and pharmacological analgesia might be ineffective. We hypothesized that magnetic auricular acupuncture (MAA) compared to placebo will decrease pain during ROP exam in preterm infants. Methods: Multicentre randomized controlled trial conducted in three hospitals (Australia, Canada, and Malaysia). Eligibility: >32 weeks, ROP exam, not sedated, and parental consent. A total of 100 infants were randomized (1:1) to MAA ( n = 50) or placebo ( n = 50). MAA stickers or placebo were placed on both ears by an unblinded investigator. Pain was assessed using the Premature Infant Pain Profile. Primary analyses were by intention-to-treat. ClinicalTrials.gov:NCT03650621. Findings: The mean (standard deviation, SD) gestation, birthweight, and postnatal age were (MAA 28(3) vs. placebo 28(2) weeks; MAA 1,057(455) vs. placebo 952(273) g; MAA 7(3) vs. placebo 7(3) weeks. Placebo infants had significantly higher PIPP scores during [mean difference 1.6 points (95%CI 0.1-3.1)] and 1 h mean difference 1.5 points (95%CI 0.7-2.2) after the procedure ( p < 0.03). Heart rate was lower (173(22) vs. 184(18)/min) and oxygen saturations were higher (93.8(6.2) vs. 91.7(6.1)%, p = 0.05) in MAA infants. No adverse effects. Interpretation: MAA may reduce physiological pain responses during and after ROP exam in preterm infants. Assessment of long-term effects are warranted. Clinical trial registration : www.ClinicalTrials.gov, identifier: NCT03650621., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Gan, Oei, Quah-Smith, Kamar, Lordudass, Liem, Lindrea, Daly, Gaunker, Mangat, Yaskina and Schmölzer.)

Aim: To determine characteristics of death in children with neonatal abstinence syndrome (NAS)., Methods: A population-based linkage study of children from birth to 13 years of age in New South Wales (NSW), Australia, born 1 July 2000 to 31 December 2011. Infants with an International Statistical Classification of Diseases and Related Problems, Australian modification coding of NAS (P96.1, n = 3842) were compared to infants (n = 1 018 421) without NAS by birth, hospitalisation and death records linkage., Results: Forty-five (1.2%) children with NAS died, compared to 3665 (0.4%) other children. Most deaths (n = 30, 66%) in NAS children occurred between 1 month and 1 year. Risk of death was independently increased in full-term children (hazard ratio 2.34, 95% confidence interval 1.63-3.35; P < 0.001) from lower socio-economic groups (1.23, 1.12-1.35; P < 0.001), most commonly from ill-defined or external causes, including assault and accidents (P < 0.001)., Conclusions: Children with NAS, especially those of term gestation and from lower socio-economic groups, are more likely to die, especially from external causes., (© 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

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., (©2020 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aims: To review the impact of prenatal alcohol exposure on the outcomes of the mother and child., Design: Narrative review., Setting: Review of literature., Participants: Mothers and infants affected by prenatal alcohol use., Measurements: Outcomes of mothers and children., Findings: Prenatal alcohol exposure is one of the most important causes of preventable cognitive impairment in the world. The developing neurological system is exquisitely sensitive to harm from alcohol and there is now also substantial evidence that alcohol-related harm can extend beyond the individual person, leading to epigenetic changes and intergenerational vulnerability and disadvantage. There is no known safe level or timing of drinking for pregnant or lactating women and binge drinking (> four drinks within 2 hours for women) is the most harmful. Alcohol-exposure increases the risk of congenital problems, including Fetal Alcohol Spectrum Disorder (FASD) and its most severe form, Fetal Alcohol Syndrome (FAS)., Conclusion: The impact of FASD and FAS is enduring and life-long with no current treatment or cure. Emerging therapeutic options may mitigate the worst impact of alcohol exposure but significant knowledge gaps remain. This review discusses the history, epidemiology and clinical presentations of prenatal alcohol exposure, focusing on FASD and FAS, and the impact of evidence on future research, practice and policy directions., (© 2020 Society for the Study of Addiction.)

Oxygen has been used for newborn infant resuscitation for more than two centuries. In the last two decades, concerns about oxidative stress and injury have changed this practice. Air (FiO 2 0.21) is now preferred as the starting point for respiratory support of infants 34 weeks gestation and above. These recommendations are derived from studies that were conducted on asphyxiated, term infants, recruited more than 10 years ago using strategies that are not commonly used today. The applicability of these recommendations to current practice, is uncertain. In addition, whether initiating respiratory support with air for infants with pulmonary disorders provides sufficient oxygenation is also unclear. This review will address these concerns and provide suggestions for future steps to address knowledge and practice gaps., Competing Interests: Declaration of competing interest Neither of the authors have any financial and personal relationships with other people or organizations that could inappropriately influence (bias) the content of this article., (© 2019 Elsevier Ltd. All rights reserved.)

Premature infants undergo a complex postnatal adaptation at birth. For last two centuries, oxygen has been integral to respiratory support of preterm infants at birth. Excess oxygen can cause oxidative stress and tissue injury. Preterm infants due to lung immaturity may need oxygen for successful transition at birth. Although, considerable progress has been made in the last 3 decades, optimum oxygen therapy for preterm delivery room resuscitation remains unknown. In this review, we discuss the history and physiology behind oxygen therapy in the delivery room, evaluate current literature, provide practice points and point out knowledge gaps of oxygen therapy in preterm infant at birth., (© 2020 Published by Elsevier Ltd.)

Background: Diaphragm-triggered non-invasive respiratory support, commonly referred to as NIV-NAVA (non-invasive neurally adjusted ventilatory assist), uses the electrical activity of the crural diaphragm to trigger the start and end of a breath. It provides variable inspiratory pressure that is proportional to an infant's changing inspiratory effort. NIV-NAVA has the potential to provide effective, non-invasive, synchronised, multilevel support and may reduce the need for invasive ventilation; however, its effects on short- and long-term outcomes, especially in the preterm infant, are unclear., Objectives: To assess the effectiveness and safety of diaphragm-triggered non-invasive respiratory support in preterm infants (< 37 weeks' gestation) when compared to other non-invasive modes of respiratory support (nasal intermittent positive pressure ventilation (NIPPV); nasal continuous positive airway pressure (nCPAP); high-flow nasal cannulae (HFNC)), and to assess preterm infants with birth weight less than 1000 grams or less than 28 weeks' corrected gestation at the time of intervention as a sub-group., Search Methods: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 5), MEDLINE via PubMed (1946 to 10 May 2019), Embase (1947 to 10 May 2019), and CINAHL (1982 to 10 May 2019). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials., Selection Criteria: Randomised and quasi-randomised controlled trials that compared diaphragm-triggered non-invasive versus other non-invasive respiratory support in preterm infants., Data Collection and Analysis: Two review authors independently selected trials, assessed trial quality and extracted data from included studies. We performed fixed-effect analyses and expressed treatment effects as mean difference (MD), risk ratio (RR), and risk difference (RD) with 95% confidence intervals (CIs). We used the generic inverse variance method to analyse specific outcomes for cross-over trials. We used the GRADE approach to assess the certainty of evidence., Main Results: There were two small randomised controlled trials including a total of 23 infants eligible for inclusion in the review. Only one trial involving 16 infants included in the analysis reported on either of the primary outcomes of the review. This found no difference in failure of modality between NIV-NAVA and NIPPV (RR 0.33, 95% CI 0.02 to 7.14; RD -0.13, 95% CI -0.41 to 0.16; 1 study, 16 infants; heterogeneity not applicable). Both trials reported on secondary outcomes of the review, specific for cross-over trials (total 22 infants; 1 excluded due to failure of initial modality). One study involving seven infants reported a significant reduction in maximum FiO₂ with NIV-NAVA compared to NIPPV (MD -4.29, 95% CI -5.47 to -3.11; heterogeneity not applicable). There was no difference in maximum electric activity of the diaphragm (Edi) signal between modalities (MD -1.75, 95% CI -3.75 to 0.26; I² = 0%) and a significant increase in respiratory rate with NIV-NAVA compared to NIPPV (MD 7.22, 95% CI 0.21 to 14.22; I² = 72%) on a meta-analysis of two studies involving a total of 22 infants. The included studies did not report on other outcomes of interest., Authors' Conclusions: Due to limited data and very low certainty evidence, we were unable to determine if diaphragm-triggered non-invasive respiratory support is effective or safe in preventing respiratory failure in preterm infants. Large, adequately powered randomised controlled trials are needed to determine if diaphragm-triggered non-invasive respiratory support in preterm infants is effective or safe., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Depression frequently first emerges during adolescence, and one in five young people will experience an episode of depression by the age of 18 years. Despite advances in treatment, there has been limited progress in addressing the burden at a population level. Accordingly, there has been growing interest in prevention approaches as an additional pathway to address depression. Depression can be prevented using evidence-based psychological programmes. However, barriers to implementing and accessing these programmes remain, typically reflecting a requirement for delivery by clinical experts and high associated delivery costs. Digital technologies, specifically smartphones, are now considered a key strategy to overcome the barriers inhibiting access to mental health programmes. The Future Proofing Study is a large-scale school-based trial investigating whether cognitive behaviour therapies (CBT) delivered by smartphone application can prevent depression., Methods: A randomised controlled trial targeting up to 10,000 Year 8 Australian secondary school students will be conducted. In Stage I, schools will be randomised at the cluster level either to receive the CBT intervention app (SPARX) or to a non-active control group comparator. The primary outcome will be symptoms of depression, and secondary outcomes include psychological distress, anxiety and insomnia. At the 12-month follow-up, participants in the intervention arm with elevated depressive symptoms will participate in an individual-level randomised controlled trial (Stage II) and be randomised to receive a second CBT app which targets sleep difficulties (Sleep Ninja) or a control condition. Assessments will occur post intervention (both trial stages) and at 6, 12, 24, 36, 48 and 60 months post baseline. Primary analyses will use an intention-to-treat approach and compare changes in symptoms from baseline to follow-up relative to the control group using mixed-effect models., Discussion: This is the first trial testing the effectiveness of smartphone apps delivered to school students to prevent depression at scale. Results from this trial will provide much-needed insight into the feasibility of this approach. They stand to inform policy and commission decisions concerning if and how such programmes should be deployed in school-based settings in Australia and beyond., Trial Registration: Australian and New Zealand Clinical Trial Registry, ACTRN12619000855123. Registered on 31 May 2019. Clinical Trial Notification Scheme (CTN), CT-2019-CTN-02110-1-v1. Registered on 30 June 2019.

Aim: To validate the diagnostic discharge coding of neonatal abstinence syndrome (NAS) (International Classification of Diseases [ICD]-10-AM, P96.1)., Methods: Retrospective record review of infants diagnosed with NAS (P96.1) in a non-tertiary Australian hospital between 2000 and 2016. NAS criteria were predetermined to include the following: (i) maternal opioid use; (ii) infant requiring NAS medication and (iii) at least one score of ≥8 on the Finnegan Neonatal Abstinence Scoring Tool (FNAST)., Results: Of the 253 infants coded with P96.1, 82/146 (56%) opioid-exposed infants and 9/107(18%) infants exposed to non-opioid drugs only received withdrawal medication: sensitivity 56.2 (95% confidence interval: 47.7-64.3), specificity 91.6 (84.2-95.8%), positive predictive value (PPV) 90.1 (81.6-95.1%) and negative predictive value (NPV) 60.5 (52.5-68.0%) for all three criteria. Using the criterion of ≥1 FNAST score ≥8 resulted in 58.0 (51.3-64.4%) sensitivity, 63.6 (40.8-82.0%) specificity, 94.4 (88.8-97.4%) PPV and 12.6 (7.3-20.6%) NPV for identifying need for NAS medications., Conclusion: A diagnosis of P96.1 is highly specific and predictive but poorly sensitive for identifying opioid-exposed infants requiring medications for withdrawal., (©2019 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objective: In a population-based cohort study, we determined the association between the age at first severe respiratory syncytial virus (RSV) disease and subsequent asthma., Methods: Incidence rates and rate ratios of the first asthma-associated hospitalization after 2 years of age in children hospitalized for RSV disease at <3 months, 3 to <6 months, 6 to <12 months, and 12-24 months of age were calculated., Results: The incidence of asthma-associated hospitalization per 1000 child-years among children hospitalized for RSV disease at <3 months of age was 0.5 (95% confidence interval [CI], .2-.7); at 3 to <6 months of age, 0.9 (95% CI,.5-1.3); at 6 to <12 months of age, 2.0 (95% CI, 1.4-2.7); and at 12-24 months of age, 1.7 (95% CI, 1.0-2.5). The rate ratio of hospitalization for asthma was 2-7-fold greater among children hospitalized for RSV disease at ages ≥6 months than that among those hospitalized for RSV disease at ages 0 to <6 months., Conclusions: Although the burden of RSV disease is highest in children aged <6 months, the burden of subsequent asthma is higher in children who develop RSV disease at ages ≥6 months., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Importance: Prenatal opioid exposure (POE) is one of the fastest-growing global health problems, but its association with long-term neurologic and physical development remains unknown., Objective: To assess the association between POE and cognitive and motor development in children from age 6 months to 18 years., Data Sources: Key search terms included prenatal opioid exposure, neonatal abstinence syndrome, and neurocognitive development. Studies were searched using PubMed and Embase, with no publication date restriction, through August 20, 2018., Study Selection: Only published cohort studies comparing the results of age-appropriate standardized cognitive and/or motor tests between children with any POE (aged 0-18 years) with drug-free controls were included. Data that were not convertible to means and SDs were excluded., Data Extraction and Synthesis: This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Data were pooled using a random-effects model., Main Outcomes and Measures: Standardized mean difference of cognitive and motor tests between POE and nonexposed children., Results: Twenty-six peer-reviewed cohort studies were included. Cognitive outcomes were compared for a total of 1455 children with POE and 2982 nonexposed children across 3 age groups (mean [SE] age at cognitive testing was 13 [1.58] months for the toddler group; 4.5 [0.38] years for the preschool group; and 13 [2.36] years for the school-aged group). Motor outcomes were compared for 688 children with POE and 1500 nonexposed children up to age 6 years (mean [SD] age at motor testing, 2 [0.45] years). Standardized mean difference was lower in cognitive tests for children with POE at 0 to 2 years (d = -0.52; 95% CI, -0.74 to -0.31; P < .001) and 3 to 6 years (d = -0.38; 95% CI, -0.69 to -0.07; P < .001); the difference was not significant for those aged 7 to 18 years (d = -0.44; 95% CI, -1.16 to 0.28; P = .23). Motor scores were lower in children with POE (d = 0.49; 95% CI, 0.23-0.74; P < .001)., Conclusions and Relevance: Prenatal opioid exposure appeared to be negatively associated with neurocognitive and physical development from age 6 months, and this association persisted until adolescence. The cause and association of this with POE or other factors (eg, withdrawal treatment) are uncertain but suggest that POE necessitates long-term support and intervention.

Aim: To determine the relationship between clinical practice and publication of an Australian consensus statement for management of extremely preterm infants in 2006., Methods: A population-based study using linked data from New South Wales, Australia for births between 22 + 0 and 26 + 6 weeks of gestation between 2000 and 2011., Results: There were 4746 births of whom 2870 were liveborn and 1876 were stillborn. Of the live births, 2041 (71%) were resuscitated, 1914 (67%) were admitted into a neonatal intensive care unit (NICU) and 1310 (46%) survived to hospital discharge. Thirty-nine (2%) stillbirths were resuscitated but none survived. No 22-week infant survived to hospital discharge. Fewer 23-week gestation infants were resuscitated between 2004 (52%) and 2005 (20%) but resuscitation rates increased by 2008 (44%). There was no difference at other gestations. Adjusted odds ratio (OR) for resuscitation was increased by birthweight (OR: 1.01), tertiary hospital birth (OR: 3.4) and Caesarean delivery (OR: 11.3) and decreased by rural residence (OR: 0.4) and male gender (OR: 0.7)., Conclusion: Expert recommendations may be shaped by clinical practice rather than the converse, especially for 23-week gestation infants. Recommendations should be revised regularly to include clinical practice changes., (©2019 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Data on burden of severe influenza in children with a range of chronic lung diseases (CLDs) remain limited., Method: We performed a cohort study to estimate burden of influenza-associated hospitalization in children with CLDs using population-based linked data. The cohort comprised all children in New South Wales, Australia, born between 2001 and 2010 and was divided into five groups, children with: (a) severe asthma; (b) bronchopulmonary dysplasia (BPD); (c) cystic fibrosis (CF); (d) other congenital/chronic lung conditions; and (e) children without CLDs. Incidence rates and rate ratios for influenza-associated hospitalization were calculated for 2001-2011. Average cost/episode of hospitalization was estimated using public hospital cost weights., Results: Our cohort comprised 888 157 children; 11 058 (1.2%) had one of the CLDs. The adjusted incidence/1000 child-years of influenza-associated hospitalization in children with CLDs was 3.9 (95% CI: 2.6-5.2) and 0.7 (95% CI: 0.5-0.9) for children without. The rate ratio was 5.4 in children with CLDs compared to children without. The adjusted incidence/1000 child-years (95% CI) in children with severe asthma was 1.1 (0.6-1.6), with BPD was 6.0 (3.7-8.3), with CF was 7.4 (2.6-12.1), and with other congenital/chronic lung conditions was 6.9 (4.9-8.9). The cost/episode (95% CI) of influenza-associated hospitalization was AUD 19 704 (95% CI: 11 715-27 693) for children with CLDs compared to 4557 (95% CI: 4129-4984) for children without., Discussion: This large population-based study suggests a significant healthcare burden associated with influenza in children with a range of CLDs., (© 2019 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Mothers have used opioids for thousands of years but neonatal abstinence syndrome (NAS) or rather, survivors of NAS, is a modern phenomenon. Unrecognized and/or untreated opioid withdrawal was almost always fatal but with greater awareness and standardization of treatment, NAS is now an uncommon direct cause of infant death. However, opioids are now increasingly accessible and potent and the outcomes of children after the neonatal period are of great concern, especially when coupled with multiple other social and health risks. Complex individual, environmental and genetic factors need to be considered when assessing outcomes or future research for babies with NAS. Any intervention or research efforts must address these multifactorial complexities. This review will discuss pertinent post neonatal outcomes, including mortality, physical and mental health and social functioning of children with a history of NAS., (Crown Copyright © 2019 Published by Elsevier Ltd. All rights reserved.)

Objective: To describe the risk of death and hospitalisation until adolescence of children after group B streptococcus (GBS) infection during infancy., Design: Population-based cohort study., Setting: New South Wales, Australia., Patients: All registered live births from 2000 to 2011., Interventions: Comparison of long-term outcomes in children with the International Statistical Classification of Diseases and Related Health Problems-10th Revision discharge codes corresponding to GBS infections and those without., Main Outcome Measures: Death and hospitalisation., Results: A total of 1206 (0.1%) children (936 (77.6%)≥37 weeks' gestation) were diagnosed with GBS infection. Over the study period, infection rates decreased from 2.1 (95% CI 1.8 to 2.4) to 0.7 (95% CI 0.5 to 0.9) per 1000 live births. Infants with GBS infection were born at lower gestation (mean 37.6 vs 39.0 weeks), were more likely very low birth weight (<1500 g, OR 9.1(95% CI 7.4 to 11.3)), born premature (OR 3.9(95% CI 3.4 to 4.5)) and have 5 min Apgar scores ≤5 (OR 6.7(95% CI 5.1 to 8.8)). Children with GBS had three times the adjusted odds of death (adjusted OR (AOR) 3.0(95% CI 2.1 to 4.3)) or rehospitalisations (AOR 3.1(95% CI 2.7 to 3.5)). Thirty-six (3.0%) with GBS died, with >50% of deaths occurring <28 days. Children with GBS were hospitalised more frequently (median 2 vs 1), for longer duration (mean 3.7 vs 2.2 days) and were at higher risk for problems with genitourinary (OR 3.1(95% CI 2.8 to 3.5)) and nervous (OR 2.0 (95% CI1.7 to 2.3)) systems., Conclusions: Despite decreasing GBS rates, the risk of poor health outcomes for GBS-infected children remains elevated, especially during the first 5 years. Survivors continue to be at increased risk of death and chronic conditions requiring hospitalisations, such as cerebral palsy and epilepsy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is currently no reliable non-invasive method of measuring cardiac output in neonatal intensive care. Spatiotemporal image correlation (STIC) is a novel four-dimensional (4D) ultrasound technique that was developed to assess the foetal heart, and it may be a useful way to assess neonatal haemodynamics., Objective: This study aimed to evaluate the feasibility and reproducibility of determining neonatal cardiac output using STIC ultrasound in newborn infants., Design: Infants were recruited opportunistically from a neonatal intensive care unit and then examined by 2 independent observers. STIC was used to obtain images of the heart. End-diastolic and end-systolic ventricular volumes were measured using virtual organ computer-aided analysis (VOCAL) and used to calculate cardiac output. Reproducibility was assessed with intraclass correlation coefficients (ICC) and agreement with Bland-Altman analysis., Results: Twenty-four clinically stable infants of 34-43 weeks corrected gestational age were assessed. Both observers successfully acquired 4D STIC volumes in all infants. Left ventricular output showed good reproducibility, with an intra-observer ICC of 0.86 (0.69-0.94) and inter-observer ICC of 0.87 (0.70-0.95). Right ventricular output also showed good reproducibility, with an intra-observer ICC of 0.88 (0.70-95) and inter-observer ICC of 0.84 (0.63-0.93)., Conclusions: Determining cardiac output using 4D STIC ultrasound is feasible and reproducible in well newborn infants. With further evaluation, this technique may provide valuable information about haemodynamic status in newborn infants requiring intensive care., (© 2019 S. Karger AG, Basel.)

Oxygen is one of the most critical components of life. Nature has taken billions of years to develop optimal atmospheric oxygen concentrations for human life, evolving from very low, peaking at 30% before reaching 20.95%. There is now increased understanding of the potential toxicity of both too much and too little oxygen, especially for preterm and asphyxiated infants and of the potential and lifelong impact of oxygen exposure, even for a few minutes after birth. In this review, we discuss the contribution of knowledge gleaned from basic science studies and their implication in the care and outcomes of the human infant within the first few minutes of life and afterwards. We emphasize current knowledge gaps and research that is needed to answer a problem that has taken Nature a considerably longer time to resolve.

Competing Interests: Competing interests: None declared.

Aim: The attitudes of neonatologists towards the active management of extremely premature infants in a developing country like China are uncertain., Methods: A web-based survey was sent to neonatologists from 16 provinces representing 59.6% (824.2 million) of the total population of China on October 2015 and December 2017., Results: A total of 117 and 219 responses were received in 2015 and 2017, respectively. Compared to 2015, respondents in 2017 were more likely to resuscitate infants <25 weeks of gestation (86% vs. 72%; p < 0.05), but few would resuscitate infants ≤23 weeks of gestation in either epoch (10% vs. 6%). In both epochs, parents were responsible for >50% of the costs of intensive care, but in 2017, significantly fewer clinicians would cease intensive care (75% vs. 88%; p < 0.05) and more would request for economic aid (40% vs. 20%; p < 0.05) if parents could not afford to pay. Resource availability (e.g. ventilators) was not an important factor in either initiation or continuation of intensive care (~60% in both epochs)., Conclusion: Cost is an important factor in the initiation and continuation of neonatal intensive care in a developing country like China. Such factors need to be taken into consideration when interpreting outcome data from these regions., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: This study aimed to determine whether neonatal intensive care therapies increase the risk of carcinogenesis in childhood., Methods: This study used population-based data on 1 072 957 infants born in New South Wales, Australia, between 2000 and 2011 and multivariate logistic regression to examine any associations between therapies used in the neonatal intensive care unit and diagnoses of cancer until mid 2012., Results: A total of 1126 of 1 072 957 (0.1%) children were diagnosed with cancer. Cancer risk was significantly increased by preterm birth (gestation <37 weeks; adjusted odds ratio (aOR) 1.3 (95% confidence interval: 1.0-1.6), birth weight ≥4 kg (aOR 1.4, 1.2-1.6) and caesarean delivery (aOR 1.2, 1.1-1.4). Extremely preterm (<28 weeks of gestation) infants were more likely to develop hepatic tumours (aOR 12.7, 3.3-48.3) than term infants. The only therapy used in the neonatal intensive care that was independently associated with an increased risk of cancer was nitric oxide (aOR 8.6, 4.3-17.4). Eight of the 790 (1%) infants treated with nitric oxide developed cancer (gestation range 30-41 weeks, age of cancer diagnosis: four months-five years)., Conclusion: Treatment with nitric oxide was associated with a higher risk of childhood cancer. These findings require further research., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Oxygen has been used to stabilize newborn infants for more than a century. Over the last two decades, a paradigm shift towards using less oxygen has occurred but without firm evidence of benefit. Using lower levels of oxygen has also added new conundrums to clinical care. Can oxygen delivery to sick newborn babies meet the Goldilocks principle, of being "just right"? This review discusses the history of oxygen use in the delivery room and the impetus to change from the long-established practice of using pure oxygen to using lower oxygen concentrations. The review also highlights knowledge gaps, particularly for oxygen exposure and monitoring, as well as the sequelae of oxygen administration, including short- and long-term outcomes., (© 2018 Elsevier Ltd. All rights reserved.)

Aim: The diagnosis of tongue-tie (or ankyloglossia) has increased more than 10-fold in some countries. Whether this is a global phenomenon or related to cultural and professional differences is uncertain., Methods: An online survey in English, Japanese, Chinese and Spanish was disseminated between May and November 2016 via 27 international professional bodies to >30 clinical professions chosen a priori to represent occupations involved in the management of neonatal ankyloglossia., Results: A total of 1721 responses came from nursing (51%), medical (40%), dental (6%) and allied health (4%) clinicians. Nurses (40%) and allied health (34%) professionals were more likely than doctors (8%) to consider ankyloglossia as important for lactation problems, as were western (83%) compared to Asian (52%) clinicians. Referrals to clinicians for ankyloglossia management originated mainly from parents (38%). Interprofessional referrals were not clearly defined. Frenectomies were most likely to be performed by surgeons (65%) and dentists (35%), who were also less likely to be involved in lactation support. Clinicians performing frenectomies were more likely to consider analgesia as important compared to those not performing frenectomies., Conclusion: The diagnosis and treatment of ankyloglossia vary considerably around the world and between professions. Efforts to standardise management are required., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)