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.

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.

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.

A population study of respiratory rehospitalisation in very preterm infants in the first 3 years of life.

AIM: Very premature infants consume healthcare resources following discharge from neonatal intensive care units (NICU). This study aimed to evaluate the burden of respiratory related rehospitalisation within the first 3 years post discharge in very premature infants in an Australian population. METHODS: Rehospitalisation of a 4-year cohort of NICU survivors, born less than 32 weeks gestation, was derived from data linkage of three state-wide databases including NSW Neonatal Intensive Care Units' Data Collection, Admitted Patient Data Collection and the Death Registry. Rehospitalisation diagnoses were determined by ICD-10 AM codes. RESULTS: Of the 2939 survivors, 525 (18%) had bronchopulmonary dysplasia (BPD) and 261 BPD infants (50%) were discharged on home oxygen. Almost two-third (1860, 63%) of the survivors are required rehospitalisation, respiratory causes, including 394 respiratory syncytial virus (RSV)-related, accounted for 2668 (48%) of the 5599 rehospitalisations. Significantly more home oxygen BPD survivors had respiratory (70%) and RSV-related (22%) rehospitalisations than the BPD infants not needing home oxygen (58% and 18%, respectively), and the survivors without BPD had the lowest rates (32% and 10%, P < 0.001). Most respiratory (61%) and RSV-related (74%) rehospitalisations occurred during the first 12 months post discharge. No RSV-related fatality occurred. Amongst the total 17 562 hospital days, respiratory and RSV-related admissions accounted for 10 905 (62%) and 3031 (17.2%) days. In multivariable logistic analyses, home oxygen and maternal indigenous status were independently associated with high (3 or more) respiratory and RSV rehospitalisation rates. CONCLUSIONS: Respiratory rehospitalisations are common in very premature survivors. Home oxygen and indigenous status are significant risk factors for respiratory and RSV-related rehospitalisations.

Population study of neurodevelopmental outcomes of extremely premature infants admitted after office hours.

AIM: The aim of the study was to compare neurodevelopmental outcomes of extremely preterm infants admitted during (OH) and after (AH) office hours. METHODS: A retrospective review of the New South Wales and Australian Capital Territory Neonatal Intensive Care Units' (NICUs) Data Collection of all infants <29 weeks gestation admitted to New South Wales and Australian Capital Territory NICUs between January 1998 and December 2004 was conducted. The primary outcome was moderate/severe functional disability (FD) at 2-3 years follow-up defined as developmental delay (Griffiths Mental Developmental Scales general quotient or Bayley Scales of Infant Development-II mental developmental index >2 standard deviations below the mean), cerebral palsy (unable to walk without aids), deafness (requiring bilateral hearing aids) or blindness (visual acuity <6/60 in the better eye). RESULTS: Mortality and age at follow-up were comparable between the AH and OH groups. Developmental outcome was evaluated in 972 (74.9%) infants admitted during AH and 501 (74.6%) admitted during OH. FD was not significantly different between the AH and OH groups (17.1% vs. 14.8%, adjusted odds ratio 1.131, 95% confidence interval 1.131 (0.839-1.523), P = 0.420). There were no significant differences between AH and OH infants with cerebral palsy (9.6% vs. 7.6%), developmental delay (5.4% vs. 5.0%) or any other component of FD. CONCLUSION: There is little circadian variation in mortality and adverse neurodevelopmental outcomes in an NICU network with the current model of after hours staffing and support, and sharing of NICU workload within a network.

Infant neurodevelopment following in utero exposure to antidepressant medication.

AIM: To examine the impact of pregnancy exposure to antidepressants on infant neurodevelopment. METHODS: A prospective, longitudinal study in which antidepressant-exposed (n = 35) and nonexposed (n = 23) infants were administered the Bayley Scales of Infant Development (BSID-III) at 18 months, which measures neurodevelopment across five domains. Data on obstetric and perinatal complications, maternal IQ, presence of mood disorder in pregnancy and up to and including 18 months, and psychosocial status were also collected. RESULTS: Almost 90% of infants were exposed throughout the second and third trimesters to therapeutic antidepressant doses. Bivariate analysis showed no difference between exposed and unexposed infants in any of the neurodevelopmental outcomes. Maternal depression around birth or up to time of developmental testing was not associated with neurodevelopmental outcomes. CONCLUSION: Our results suggest that pregnancy antidepressant exposure (mostly serotonin reuptake inhibitors) is not associated with poorer cognitive, motor or language development outcomes in infants at 18 months. This information supports earlier studies and adds into the available data used by clinicians and mothers making key decisions around the use of antidepressants in pregnancy. However, given the small sample size, and some degree of heterogeneity in terms of antidepressant exposure, these results need to be treated with caution.

Profile of infants born to drug-using mothers: a state-wide audit.

AIMS: To ascertain the characteristics and short-term outcomes of infants born to illicit drug-using mothers in public hospitals in the state of New South Wales and the Australian Capital Territory during 2004. METHODS: Patients were identified retrospectively by hospital records searches using ICD-10 morbidity codes and records of local Drug and Alcohol Services. Records were reviewed on site. All public hospitals (n= 101) with obstetric services were included. RESULTS: A total of 879 (1.4%, 95% confidence interval: 1.3-1.5%) drug-using mothers were identified from 62,682 confinements. Opiates (46.8%), amphetamines (23.0%) and polydrug (16.4%) exposure were most common. There were eight stillbirths. Among these 871 infants, prematurity (23.6%) and low birthweight (27.1%) were common and 51.1% were admitted to nurseries for further care. Two infants died. Major congenital anomalies were detected in 15 infants. Pharmacological treatment for withdrawal was required for 202 (23.2%), and 143 (70.8%) infants were discharged home on medication. Infants who completed inpatient pharmacological treatment were hospitalised longer (median 26.0 vs. 12.0 days) and were more likely to be premature (37.3 vs. 14.0%). Child-at-risk notifications affected 40.6% of the infants, and 7.6% were fostered prior to discharge. A total of 333 (38.2%) infants were breastfed at discharge. CONCLUSIONS: Our regional study highlights a substantial prevalence of drug use in pregnancy with considerable adverse perinatal and hospital outcomes in infants born to these mothers. Coordinated health care and resources are needed to support these mother-infant pairs because of their social, medical and mental-health issues.

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.

Respiratory disease and early serum S100A12 changes in very premature infants.

AIM: The role of granulocyte-specific S100A12, a marker for inflammatory disorders, in newborn lung disease is unknown. We compared postnatal blood S100A12 concentrations against respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD). METHODS: Blood samples from 92 newborns were collected on admission, 12 h, day 1, day 3-4 and day 7, and analysed for S100A12. IL-8 and IL-6 were assayed in 52 infants. RESULTS: Infants with RDS were significantly more premature (median 27 vs. 34 weeks), more likely to receive antenatal corticosteroids (84% vs. 26%) and have lower neutrophil counts (median 2.4 vs. 3.8 × 10(9) /L) at admission. S100A12 levels peaked during the first day and were significantly lower in preterm infants with RDS compared to those without (median 250 vs. 616 ng/mL at 12 h, 281 vs. 828 ng/mL day 1, respectively). S100A12 levels were low among the 35 very preterm infants (24-29 week gestation) regardless of the presence of BPD (285 vs. 288 ng/mL on day 1). In comparison, IL-8 and IL-6 levels were not different between groups. CONCLUSION: Plasma S100A12 is low in infants with RDS, possibly because of gestationally related differences in neutrophil response or to the effects of antenatal corticosteroids. It is therefore not a useful marker of BPD development.

The temporal influence of a heroin shortage on pregnant drug users and their newborn infants in Sydney, Australia.

BACKGROUND: Heroin availability and purity decreased precipitously in Australian markets between 2000 and 2001. This led to increased use of non-opiate drugs in the general community but whether pregnant drug users and their newborn infants were affected remains unknown. AIM: To determine if perinatal drug exposure and outcomes are affected by changes in street drug availability. METHODS: Retrospective review was carried out of known drug-exposed mothers delivering live-born infants at the Royal Hospital for Women, Randwick, Australia (n = 316). Study periods were divided into preshortage (A = 1998-2000, n = 79), shortage (B = 2001-2002, n = 92) and post-shortage (C = 2003-2006, n = 122) periods. Cannabis-only users were excluded (n = 23). RESULTS: The percentage of confined women who admitted to using heroin decreased significantly (65%(A) vs 34%(B), P < 0.01) as did women on methadone programmes (90%(A), 80%(B), 75%(C), P = 0.024). The use of cocaine (7% (A) vs 33% (B), P = 0.031) and amphetamines (4% (A) vs 22% (C), P = 0.01), tripled. Most infants were born full-term and healthy but the duration of infant hospitalisation increased significantly from (median [interquartile range]) 8 [10, 38](A) to 13 [7, 23](C) days (P < 0.01). Approximately 50% of infants required withdrawal treatment but more needed phenobarbitone as an adjunct to morphine during the shortage (4/80 (0.5%) vs 15/93 (16%), P = 0.026), probably because of increased exposure to non-opiate drugs. CONCLUSIONS: The types of drugs used by pregnant drug users follow street trends and may affect infant hospitalisation and withdrawal treatment. Of concern is the rise in amphetamine-use and there needs to be increased vigilance for similar trends, especially in previously unidentified drug users.

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.

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.

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.