Prophylaxis of Patent Ductus Arteriosus with Paracetamol in Extremely Low Gestational Age Newborns (ELGANs): A Single-Institution Observational Study in Vietnam.

INTRODUCTION: Prophylactic paracetamol for extremely low gestation age neonates (ELGAN, <27 weeks' gestation) with symptomatic patent ductus arteriosus (sPDA) in high-income countries (HIC) reduces medical and surgical interventions. Its effectiveness in low-to-middle-income countries (LMIC) remains uncertain. This study assesses prophylactic paracetamol's impact on sPDA interventions in ELGANs in an LMIC. METHODS: This is a retrospective cohort study that compared a historical cohort of ELGANs that were treated with oral ibuprofen or intravenous paracetamol after diagnosis of sPDA (n = 104) with infants (n = 76) treated with prophylactic paracetamol (20 mg/kg loading, 7.5 mg/kg qid for 4 days), in a tertiary neonatal intensive care unit (NICU) in Vietnam. Oral ibuprofen or intravenous therapeutic paracetamol were administered if prophylactic paracetamol failed to close sPDA. Surgical ligation was conducted if targeted medical intervention failed, or the infant deteriorated from conditions attributable to sPDA. RESULTS: In the historical cohort, 57 (55%) infants died within 7 days of life compared to 18 (24%) from the prophylactic cohort (p < 0.01). Of the survivors, 21 (45%) of the historical and 23 (39.7%) of the prophylactic cohort required surgical ligation (p = 0.6). Duration of hospitalization for survivors was lower in the prophylactic cohort (mean 74 vs. 97 days, p = 0.01). In the prophylactic cohort, 24 (41%) infants did not need further treatment while 34 (59%) required further treatment including ibuprofen and/or paracetamol 28 (48%) and surgical ligation 22 (38%). CONCLUSIONS: Prophylactic paracetamol for ELGAN in LMIC does not reduce the need for surgical ligation, sPDA rates, and other PDA-related morbidities in infants who survive beyond 7 days of age. It may reduce the risk of death and the duration of hospitalization but further study into the reasons behind this need to be determined with larger studies.

The Future Proofing Study: Design, methods and baseline characteristics of a prospective cohort study of the mental health of Australian adolescents.

OBJECTIVES: The Future Proofing Study (FPS) was established to examine factors associated with the onset and course of mental health conditions during adolescence. This paper describes the design, methods, and baseline characteristics of the FPS cohort. METHODS: The FPS is an Australian school-based prospective cohort study with an embedded cluster-randomized controlled trial examining the effects of digital prevention programs on mental health. Data sources include self-report questionnaires, cognitive functioning, linkage to health and education records, and smartphone sensor data. Participants are assessed annually for 5 years. RESULTS: The baseline cohort (N = 6388, M = 13.9 years) is broadly representative of the Australian adolescent population. The clinical profile of participants is comparable to other population estimates. Overall, 15.1% of the cohort met the clinical threshold for depression, 18.6% for anxiety, 31.6% for psychological distress, and 4.9% for suicidal ideation. These rates were significantly higher in adolescents who identified as female, gender diverse, sexuality diverse, or Aboriginal and/or Torres Strait Islander (all ps < 0.05). CONCLUSIONS: This paper provides current and comprehensive data about the status of adolescent mental health in Australia. The FPS cohort is expected to provide significant insights into the risk, protective, and mediating factors associated with development of mental health conditions during adolescence.

Neonatal Abstinence Syndrome: Prevention, Management and Outcomes: From Birth to Adulthood.

Neonatal abstinence syndrome (NAS), or-when specifically focused on opioids-neonatal opioid withdrawal syndrome (NOWS) is a withdrawal syndrome in neonates after birth causally related to the in utero exposure to drugs of dependence, and the subsequent acute interruption at delivery [...].

An economic analysis of the cost of survival of micro preemies: A systematic review.

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.

A trial protocol for the effectiveness of digital interventions for preventing depression in adolescents: The Future Proofing Study.

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.

Magnetic Non-invasive Auricular Acupuncture During Eye-Exam for Retinopathy of Prematurity in Preterm Infants: A Multicentre Randomized Controlled Trial.

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.

Impact of influenza on hospitalization rates in children with a range of chronic lung diseases.

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.

Long-term outcomes after group B streptococcus infection: a cohort study.

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.

Oxygen therapy of the newborn from molecular understanding to clinical practice.

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.

Association of Age at First Severe Respiratory Syncytial Virus Disease With Subsequent Risk of Severe Asthma: A Population-Based Cohort Study.

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.

A Review of Non-Pharmacological Treatments for Pain Management in Newborn Infants.

Pain is a major problem in sick newborn infants, especially for those needing intensive care. Pharmacological pain relief is the most commonly used, but might be ineffective and has side effects, including long-term neurodevelopmental sequelae. The effectiveness and safety of alternative analgesic methods are ambiguous. The objective was to review the effectiveness and safety of non-pharmacological methods of pain relief in newborn infants and to identify those that are the most effective. PubMed and Google Scholar were searched using the terms: "infant", "premature", "pain", "acupuncture", "skin-to-skin contact", "sucrose", "massage", "musical therapy" and 'breastfeeding'. We included 24 studies assessing different methods of non-pharmacological analgesic techniques. Most resulted in some degree of analgesia but many were ineffective and some were even detrimental. Sucrose, for example, was often ineffective but was more effective than music therapy, massage, breast milk (for extremely premature infants) or non-invasive electrical stimulation acupuncture. There were also conflicting results for acupuncture, skin-to-skin care and musical therapy. Most non-pharmacological methods of analgesia provide a modicum of relief for preterm infants, but none are completely effective and there is no clearly superior method. Study is also required to assess potential long-term consequences of any of these methods.

Oxygen and preterm infant resuscitation: what else do we need to know?

PURPOSE OF REVIEW: To evaluate current evidence for the use of lower or higher oxygen strategies for preterm infant resuscitation RECENT FINDINGS: The equipoise for using higher fraction of inspired oxygen (FiO2) (>0.4) to initiate preterm infant respiratory stabilization has been lost. Recent meta-analyses of randomized controlled trials assessing outcomes after using higher (FiO2 ≥ 0.6) vs. lower (FiO2 ≤ 0.3) oxygen strategies to initiate preterm resuscitation shows no difference in the rates of death or major morbidities. However, not achieving pulse oximetry saturations of at least 80% by 5 min of age, whether it was due to iatrogenic oxygen insufficiency or poor infant pulmonary function, was associated with lower heart rates (mean difference -8.37, 95% confidence interval: -15.73, -1.01) and major intraventricular hemorrhage. There remains scarce neurodevelopmental data in this area and information about the impact of oxygen targeting strategies in low resourced areas. These knowledge gaps are research priorities that must be addressed in large, well designed randomized controlled trials. SUMMARY: Most clinicians now use lower oxygen strategies to initiate respiratory support for all infants, including preterm infants with significant lung disease. However, the impact of such strategies, particularly for neurodevelopmental outcomes and for lower resourced areas, remains uncertain and must be urgently addressed.

Influence of early childhood burns on school performance: an Australian population study.

OBJECTIVES: To determine the influence of burn injuries on childhood performance in national standardised curriculum-based school tests. DESIGN: Birth and health records of 977 children who were hospitalised with a burn injury between 2000 and 2006 in the state of New South Wales, Australia, were linked to performance scores in the National Assessment Program: Literacy and Numeracy test, a compulsory nationwide curriculum-based test (CBT) and compared with children who were not hospitalised for burns and who were matched for birth year, gender, gestation and socioeconomic status. MAIN OUTCOME MEASURES: Test scores in years 3 (ages 8-9), 5 (ages 10-11) and 7 (ages 13-14) in numeracy, writing, reading, spelling, grammar and punctuation. RESULTS: Mean age at first burn injury was 28 months (median: 20, range: 0-140). Children with burns were significantly more likely to have younger mothers (28.5 vs 29.6 years) (P<0.001), be indigenous (OR 2.5 (95% CI 2.1 to 3.1)) (P<0.001) and have siblings (OR 1.2 (95% CI 1.1 to 1.4)) (P<0.001). They were also less likely to meet national minimum standards in most domains of testing until year 5, even after adjustment for parental education levels, parental smoking, maternal age and indigenous status. Each 10% increase in total body surface area burnt was associated with a decrease in year 5 scores by 37.0% in numeracy and 71.9% in writing. CONCLUSIONS: Most childhood burn injuries occur before the start of formal schooling. Children who are hospitalised for burns perform more poorly in CBT even after accounting for family and socioeconomic disadvantage. Rehabilitation of children with burn injuries must address school performance to decrease any long-term negative societal impact of burns.

Association between respiratory syncytial viral disease and the subsequent risk of the first episode of severe asthma in different subgroups of high-risk Australian children: a whole-of-population-based cohort study.

OBJECTIVE: To determine the contribution of respiratory syncytial virus (RSV) to the subsequent development of severe asthma in different subgroups of children at risk of severe RSV disease. SETTINGS: The study was conducted in New South Wales (NSW), Australia. PARTICIPANTS: The study comprised all children born in NSW between 2000 and 2010 with complete follow-up till 31 December 2011. The cohort was divided into three subgroups: (1) non-Indigenous high-risk children: non-Indigenous children born preterm or born with a low birth weight; (2) Indigenous children: children of mothers whose Indigenous status was recorded as Aboriginal and/or Torres Strait Islander and (3) non-Indigenous standard risk children: all other non-Indigenous term children. PRIMARY OUTCOME MEASURE: Risk of development of severe asthma in different subgroups of children who had RSV hospitalisation in the first 2 years of life compared with those who did not. DESIGN: We performed a retrospective cohort analysis using population-based linked administrative data. Extended Cox model was used to determine HR and 95% CI around the HR for first asthma hospitalisation in different subgroups of children. RESULTS: The cohort comprised 847 516 children born between 2000 and 2010. In the adjusted Cox model, the HR of first asthma hospitalisation was higher and comparable across all subgroups of children who had RSV hospitalisation compared with those who did not. The HR (95% CI) was highest in children aged 2-3 years; 4.3 (95% CI 3.8 to 4.9) for high-risk, 4.0 (95% CI 3.3 to 4.8) for Indigenous and 3.9 (95% CI 3.7 to 4.1) for non-Indigenous standard risk children. This risk persisted beyond 7 years of age. CONCLUSION: This large study confirms a comparable increased risk of first asthma hospitalisation following RSV disease in the first 2 years of life across different subgroups children at risk.