Effect of maternal prebiotic supplementation on human milk immunological composition: Insights from the SYMBA study.

BACKGROUND: Immunomodulatory proteins in human milk (HM) can shape infant immune development. However, strategies to modulate their levels are currently unknown. This study investigated whether maternal prebiotic supplementation alters the levels of immunomodulatory proteins in HM. METHODS: The study was nested within the SYMBA double-blind randomized controlled trial (ACTRN12615001075572), which investigated the effects of maternal prebiotic (short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides) supplementation from <21 weeks gestation during pregnancy until 6 months postnatal during lactation on child allergic disease risk. Mother-child dyads receiving prebiotics (n = 46) or placebo (n = 54) were included in this study. We measured the levels of 24 immunomodulatory proteins in HM collected at 2, 4, and 6 months. RESULTS: Cluster analysis showed that the overall immunomodulatory protein composition of milk samples from both groups was similar. At 2 months, HM of prebiotic-supplemented women had decreased levels of TGF-ß1 and TSLP (95% CI: -17.4 [-29.68, -2.28] and -57.32 [-94.22, -4.7] respectively) and increased levels of sCD14 (95% CI: 1.81 [0.17, 3.71]), when compared to the placebo group. At 4 months, IgG1 was lower in the prebiotic group (95% CI: -1.55 [-3.55, -0.12]) compared to placebo group. CONCLUSION: This exploratory study shows that prebiotic consumption by lactating mothers selectively alters specific immunomodulatory proteins in HM. This finding is crucial for understanding how prebiotic dietary recommendations for pregnant and lactating women can modify the immune properties of HM and potentially influence infant health outcomes through immune support from breastfeeding.

Psychomotor Vigilance Testing on Neonatal Transport: A Western Australian Experience.

OBJECTIVE: This study aimed to assess whether undertaking retrieval was associated with fatigue independent of sleep and circadian disruption. It also aimed to assess the feasibility of routinely measuring the psychomotor vigilance test (PVT) on neonatal transport. Fatigue is associated with impaired clinician performance and safety. The association between shift work, sleep deprivation, and circadian disruption is well established. No studies have specifically assessed the independent effect of the retrieval environment on fatigue. METHODS: Medical and nursing staff of the neonatal retrieval team were prospectively recruited over a 12-month period. Simple reaction times (RTs) were recorded at the start and end of a day shift using a validated 3-minute PVT. RESULTS: The end-of-shift RT increased (not significant) by 6.38 milliseconds (95% confidence interval [CI], -2.17 to 14.92 milliseconds; P = .149) when retrieval was undertaken. A 1-millisecond increase in RT increased the odds of being in a subjective sleepy category by 0.57% (95% CI, 0.0036-0.0078; P < .001). Consuming caffeine during the shift increased the mean RT by 16.26 milliseconds (95% CI, 4.43-28.1 milliseconds; P < .01). CONCLUSION: The RT of participants exposed to the retrieval environment was not significantly increased. Further studies are needed to consolidate these results as well as to further assess longer-range air medical retrievals.

Health service utilisation for acute respiratory infections in infants graduating from the neonatal intensive care unit: a population-based cohort study.

BACKGROUND: Despite advances in neonatal intensive care, babies admitted to Neonatal Intensive Care Units (NICU) suffer from adverse outcomes. We aim to describe the longer-term respiratory infectious morbidity of infants discharged from NICU using state-wide population-based linked data in Western Australia. STUDY DESIGN: We used probabilistically linked population-based administrative data to analyse respiratory infection morbidity in a cohort of 23,784 infants admitted to the sole tertiary NICU, born 2002-2013 with follow up to 2015. We analysed incidence rates of secondary care episodes (emergency department presentations and hospitalisations) by acute respiratory infection (ARI) diagnosis, age, gestational age and presence of chronic lung disease (CLD). Poisson regression was used to investigate the differences in rates of ARI hospital admission between gestational age groups and those with CLD, after adjusting for age at hospital admission. RESULTS: From 177,367 child-years at risk (i.e., time that a child could experience an ARI outcome), the overall ARI hospitalisation rate for infants and children aged 0-8 years was 71.4/1000 (95% confidence interval, CI: 70.1, 72.6), with the highest rates in infants aged 0-5 months (242.9/1000). For ARI presentations to emergency departments, equivalent rates were 114/1000 (95% CI: 112.4, 115.5) and 337.6/1000, respectively. Bronchiolitis was the most common diagnosis among both types of secondary care, followed by upper respiratory tract infections. Extremely preterm infants (< 28 weeks gestation at birth) were 6.5 (95% CI: 6.0, 7.0) times more likely and those with CLD were 5.0 (95% CI: 4.7, 5.4) times more likely to be subsequently admitted for ARI than those in NICU who were not preterm or had CLD after adjusting for age at hospital admission. CONCLUSIONS: There is an ongoing burden of ARI in children who graduate from the NICU, especially those born extremely preterm, that persists into early childhood. Early life interventions to prevent respiratory infections in these children and understanding the lifelong impact of early ARI on later lung health are urgent priorities.

Implementation of a strategy to facilitate effective medical follow-up for Australian First Nations children hospitalised with lower respiratory tract infections: study protocol.

BACKGROUND: First Nations children hospitalised with acute lower respiratory infections (ALRIs) are at increased risk of future bronchiectasis (up to 15-19%) within 24-months post-hospitalisation. An identified predictive factor is persistent wet cough a month after hospitalisation and this is likely related to protracted bacterial bronchitis which can progress to bronchiectasis, if untreated. Thus, screening for, and optimally managing, persistent wet cough one-month post-hospitalisation potentially prevents bronchiectasis in First Nations' children. Our study aims to improve the post-hospitalisation medical follow-up for First Nations children hospitalised with ALRIs and thus lead to improved respiratory health. We hypothesize that implementation of a strategy, conducted in a culturally secure manner, that is informed by barriers and facilitators identified by both parents and health care providers, will improve medical follow-up and management of First Nations children hospitalized with ALRIs. METHODS: Our trial is a multi-centre, pseudo-randomized stepped wedge design where the implementation of the strategy is tailored for each study site through a combined Participatory Action Research and implementation science approach informed by the Consolidated Framework of Implementation Research. Outcome measures will consist of three categories related to (i) health, (ii) economics and (iii) implementation. The primary outcome measure will be Cough-specific Quality of Life (PC-QoL). Outcomes will be measures at each study site/cluster in three different stages i.e., (i) nil-intervention control group, (ii) health information only control group and (iii) post-intervention group. DISCUSSION: If our hypothesis is correct, our study findings will translate to improved health outcomes (cough related quality of life) in children who have persistent wet cough a month after hospitalization for an ALRI. Trial registration ACTRN12622000224729, prospectively registered 8 February 2022, URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382886&isReview=true .

Maternal immune-related conditions during pregnancy may be a risk factor for neuropsychiatric problems in offspring throughout childhood and adolescence.

BACKGROUND: Emerging research suggests that maternal immune activation (MIA) may be associated with an increased risk of adverse neurodevelopmental and mental health outcomes in offspring. Using data from the Raine Study, we investigated whether MIA during pregnancy was associated with increased behavioral and emotional problems in offspring longitudinally across development. METHODS: Mothers (Generation 1; N = 1905) were classified into the following categories: AAAE (Asthma/Allergy/Atopy/Eczema; N = 1267); infection (during pregnancy; N = 1082); no AAAE or infection (N = 301). The Child Behavior Checklist (CBCL) was administered for offspring at ages 5, 8, 10, 14, and 17. Generalized estimating equations were used to investigate the effect of maternal immune status on CBCL scores. RESULTS: AAAE conditions were associated with significant increases in CBCL Total (ß 2.49; CI 1.98-3.00), Externalizing (ß 1.54; CI 1.05-2.03), and Internalizing (ß 2.28; CI 1.80-2.76) scores. Infection conditions were also associated with increased Total (ß 1.27; CI 0.77-1.78), Externalizing (ß 1.18; CI 0.70-1.66), and Internalizing (ß 0.76; CI 0.28-1.24) scores. Exposure to more than one AAAE and/or infection condition was associated with a greater elevation in CBCL scores than single exposures in males and females. Females showed greater increases on the Internalizing scale from MIA, while males showed similar increases on both Internalizing and Externalizing scales. CONCLUSIONS: MIA was associated with increased behavioral and emotional problems in offspring throughout childhood and adolescence. This highlights the need to understand the relationship between MIA, fetal development, and long-term outcomes, with the potential to advance early identification and intervention strategies.

Investigating associations between birth order and autism diagnostic phenotypes.

BACKGROUND: Birth order effects have been linked to variability in intelligence, educational attainment and sexual orientation. First- and later-born children have been linked to an increased likelihood of an Autism Spectrum Disorder (ASD) diagnosis, with a smaller body of evidence implicating decreases in cognitive functioning with increased birth order. The present study investigated the potential association between birth order and ASD diagnostic phenotypes in a large and representative population sample. METHODS: Data were obtained from an ongoing prospective diagnostic registry, collected between 1999 and 2017, including children (1-18 years of age, n = 5,404) diagnosed with ASD in the state of Western Australia. Children with ASD were ranked relative to sibling's birth to establish birth order within families at time of ASD diagnosis. Information reported to the registry by health professionals at the time of diagnostic evaluation included demographic and family characteristics, functional abilities and intellectual capacity. RESULTS: Adaptive functioning and intelligence scores decreased with increasing birth order, with later-born children more likely to have an intellectual disability. Compared to first-born children with siblings, first-born children without siblings at the time of diagnosis also exhibited decreased cognitive functioning. CONCLUSIONS: These findings demonstrate for the first time an association between increasing birth order and variability in ASD clinical phenotypes at diagnosis, with potential evidence of reproductive curtailment in children without siblings. Taken together, these findings have significant implications for advancing understanding about the potential mechanisms that contribute to heterogeneity in ASD clinical presentations as a function of birth order and family size.

Deconstructing the repetitive behaviour phenotype in autism spectrum disorder through a large population-based analysis.

OBJECTIVE: Restricted and repetitive pattern of behaviours and interests (RRB) are a cardinal feature of autism spectrum disorder (ASD), but there remains uncertainty about how these diverse behaviours vary according to individual characteristics. This study provided the largest exploration to date of the relationship between Repetitive Motor Behaviours, Rigidity/Insistence on Sameness and Circumscribed Interests with other individual characteristics in newly diagnosed individuals with ASD. METHOD: Participants (N = 3,647; 17.7% females; Mage = 6.6 years [SD = 4.7]) were part of the Western Australian (WA) Register for ASD, an independent, prospective collection of demographic and diagnostic data of newly diagnosed cases of ASD in WA. Diagnosticians rated each of the DSM-IV-TR criteria on a 4-point Likert severity scale, and here we focused on the Repetitive Motor Behaviours, Insistence on Sameness and Circumscribed Interests symptoms. RESULTS: The associations between RRB domains, indexed by Kendall's Tau, were weak, ranging from non-significant for both Circumscribed Interests and Repetitive Motor Behaviours to significant (.20) for Insistence on Sameness and Repetitive Motor Behaviours. Older age at diagnosis was significantly associated with lower Circumscribed Interests and significantly associated with higher Insistence on Sameness and Repetitive Motor Behaviours. Male sex was significantly associated with higher Repetitive Motor Behaviours but not Insistence on Sameness or Circumscribed Interests. CONCLUSIONS: The pattern of associations identified in this study provides suggestive evidence for the distinctiveness of Repetitive Motor Behaviours, Insistence on Sameness and Circumscribed Interests, highlighting the potential utility of RRB domains for stratifying the larger ASD population into smaller, more phenotypically homogeneous subgroups that can help to facilitate efforts to understand diverse ASD aetiology and inform design of future interventions.

Consumption of energy drinks is associated with depression, anxiety, and stress in young adult males: Evidence from a longitudinal cohort study.

BACKGROUND: Energy drinks (EDs) claim to boost mental performance, however, few studies have examined the prospective effects of EDs on mental health. This study examined longitudinal associations between ED use and mental health symptoms in young adults aged 20 years over a 2-year period. METHODS: Data were drawn from Gen2 (Generation 2) of the Raine Study, a prospective population-based study in Western Australia. Self-report questionnaires assessed ED consumption and mental health symptoms (Depression Anxiety Stress Scale [DASS]-21) when Gen2 participants were 20 and 22 years old. Changes in ED use and DASS-21 scores over time were analyzed and results presented for the whole sample and by sex. RESULTS: For the whole sample (n = 429), participants who changed from being a non-ED user to an ED user had an average increase in stress scores of 2.30 (95% confidence interval [CI] = 0.04, 4.55) across the 2-year follow-up. Males, but not females who changed from being a non-ED user to an ED user had an average increase in depression, anxiety, and stress scores of 6.09 (95% CI = 3.36, 8.81), 3.76 (95% CI = 1.82, 5.70), and 3.22 (95% CI = 0.47, 5.97), respectively. CONCLUSION: ED consumption may be a possible marker for mental health symptoms in young male adults. Practicing clinicians could consider screening for ED use in routine assessments of mental health, particularly for young males presenting with depression, anxiety, and stress symptoms.

Racial discrimination and allostatic load among First Nations Australians: a nationally representative cross-sectional study.

BACKGROUND: Increased allostatic load is linked with racial discrimination exposure, providing a mechanism for the biological embedding of racism as a psychosocial stressor. We undertook an examination of how racial discrimination interacts with socioecological, environmental, and health conditions to affect multisystem dysregulation in a First Nations population. METHODS: We conducted latent class analysis (LCA) using indicators of life stress, socioeconomic background, and physical and mental health from a nationally representative sample of Australian Aboriginal adults (N = 2056). We used LCA with distal outcomes to estimate the effect of the latent class variable on our derived allostatic load index and conducted a stratified analysis to test whether allostatic load varied based on exposure to racial discrimination across latent classes. RESULTS: Our psychosocial, environmental, and health measures informed a four-class structure; 'Low risk', 'Challenged but healthy', 'Mental health risk' and 'Multiple challenges'. Mean allostatic load was highest in 'Multiple challenges' compared to all other classes, both in those exposed (4.5; 95% CI: 3.9, 5.0) and not exposed (3.9; 95% CI: 3.7, 4.2) to racial discrimination. Allostatic load was significantly higher for those with exposure to racial discrimination in the 'Multiple challenges' class (t = 1.74, p = .04) and significantly lower in the 'Mental health risk' class (t = - 1.67, p = .05). CONCLUSIONS: Racial discrimination may not always modify physiological vulnerability to disease. Social and economic contexts must be considered when addressing the impact of racism, with a focus on individuals and sub-populations experiencing co-occurring life challenges.

Caregiver-perceived racial discrimination is associated with diverse mental health outcomes in Aboriginal and Torres Strait Islander children aged 7-12 years.

BACKGROUND: Racial discrimination is acknowledged as a central social determinant of Australian Aboriginal and Torres Strait Islander (hereafter referred to as Aboriginal) health, although quantitative empirical literature on the impacts of racism on Aboriginal children remains sparse. We use a novel, longitudinal dataset to explore the relationship between caregiver-perceived racism exposure and a range of mental health and related behavioural and physiological outcomes in childhood. METHOD: The study cohort comprised 1759 Aboriginal children aged 4-12 years from waves 2-8 (2009-2015) of the Footprints in Time: The Longitudinal Study of Indigenous Children (LSIC) dataset. We examined exposure to caregiver-perceived racism between 4 and 11 years as a predictor for mental health and related outcomes at ages 7-12 and substance use at 10-12 years. Unadjusted models and models adjusted for remoteness, community-level and family-level socio-economic status, child age and gender were used in analysis. Multilevel logistic regression was used in all analysis. RESULTS: In fully adjusted models, perceived exposure to racism at ages 4-11 was associated with twice the risk of negative mental health (95% CI: 1.3-3.0), sleep difficulties (95% CI: 1.4-3.0), and behaviour issues at school (95% CI: 1.2-2.9), 1.7 times the risk of obesity (95% CI: 1.1-2.5), and nearly 7 times the risk of trying cigarettes (95% CI: 1.1-43.9). Increased risks were also found for being underweight and trying alcohol though estimates did not reach statistical significance. There was no evidence that racism was associated with poorer general health. CONCLUSION: Exposure to racial discrimination in Aboriginal children increased the risk for a spectrum of interrelated psychological, behavioural and physiological factors linked to negative mental health. Our results further affirm the importance of interventions aimed at reducing the prevalence of racial discrimination for the benefits of population health and health inequalities. The services and institutions which aim to support the mental health and wellbeing of Aboriginal children should also support interventions to reduce racism and implement accountable policies which prioritise this goal.

Real-world outcomes of insulin pump compared to injection therapy in a population-based sample of children with type 1 diabetes.

BACKGROUND: Long-term glycemic outcomes in people with type 1 diabetes (T1D) on insulin pump therapy (continuous subcutaneous insulin infusion [CSII]) with appropriate control data are limited. Randomized controlled studies of technology in diabetes care are generally limited in duration and likely to have a selection bias. Hence, evaluation of population-based data provides a robust alternative evaluation of the benefits of insulin pump therapy. AIM: To investigate the outcomes of insulin pump therapy, as compared to injection therapy, in children with T1D attending a state-wide diabetes service in Western Australia. METHODS: Patients using insulin pump therapy between January 1999 and July 2016 were matched to patients on injection therapy on the basis of age, date of diagnosis, and hemoglobin A1C (HbA1c) at the start of pump therapy. RESULTS: A total of 513 pump-injection matches were identified. The pump cohort had a significantly lower mean HbA1c for the first 6 years of follow-up. The difference in HbA1c between the cohorts was observed by 6 months (3 mmol/mol [0.3%], standard error of the mean (SEM) 0.05, N = 463 matched pairs, P < 0.001) and was sustained with the greatest difference in HbA1c at 6 years (4 mmol/mol [0.4%], SEM 0.21, N = 112 matched pairs, P = 0.04). Beyond 6 years of follow-up, the HbA1c was not significantly lower in the pump cohort (N < 70 matched pairs). CONCLUSIONS: Patients using insulin pump therapy had a better long-term glycemic control relative to the matched injection therapy cohort. Large population-based cohort studies using real-world data provide a valuable perspective on evaluation of new technologies in children with T1D.

A randomised controlled trial of an iPad-based application to complement early behavioural intervention in Autism Spectrum Disorder.

BACKGROUND: Technology-based interventions for Autism Spectrum Disorder (ASD) have proliferated, but few have been evaluated within the context of a randomised controlled trial (RCT). This RCT evaluated the efficacy of one technology-based early intervention programme (Therapy Outcomes By You; TOBY) in young children with ASD. METHODS: TOBY is an app-based learning curriculum designed for children and parents as a complement to early behavioural intervention. Eighty children (16 female) were recruited to this RCT within 12 months of receiving a diagnosis of ASD (M age = 3.38; SD = 0.69) and randomised to receive either treatment-as-usual (community-based intervention, n = 39) or the TOBY therapy (at least 20 min/day) plus treatment-as-usual (n = 41) for a period of 6 months. Outcomes were assessed at 3 and 6 months postbaseline. (Australian New Zealand Clinical Trials Registry: ACTRN12614000738628; www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365463). RESULTS: Children in the TOBY intervention group averaged 19 min/day engaging with the app in the first 3 months, but only 2 min/day during the second 3 months. There was no group difference in scores on the primary outcome, the Autism Treatment Evaluation Checklist, at either the 3- or 6-month follow-up. However, significant improvements at the 6-month follow-up were observed in the TOBY intervention group relative to the treatment-as-usual group on three secondary outcomes: the Fine Motor and Visual Reception subscales of the Mullen Scale of Early Learning and the Total Words Understood scale of the MacArthur-Bates Communicative Development Index. Statistical trends towards improvement in the TOBY intervention group were observed on measures of adaptive function, although these decreased in magnitude from the 3- to 6-month follow-up. CONCLUSIONS: This study provides evidence that technology-based interventions may provide a relatively low-cost addition to existing therapist-delivered interventions for children with ASD. However, sustained use of the app over the full 6-month period was a challenge for most families.

The impact of racial discrimination on the health of Australian Indigenous children aged 5-10 years: analysis of national longitudinal data.

BACKGROUND: A growing body of literature highlights that racial discrimination has negative impacts on child health, although most studies have been limited to an examination of direct forms of racism using cross-sectional data. We aim to provide further insights on the impact of early exposure to racism on child health using longitudinal data among Indigenous children in Australia and multiple indicators of racial discrimination. METHODS: We used data on 1239 Indigenous children aged 5-10 years from Waves 1-6 (2008-2013) of Footprints in Time, a longitudinal study of Indigenous children across Australia. We examined associations between three dimensions of carer-reported racial discrimination (measuring the direct experiences of children and vicarious exposure by their primary carer and family) and a range of physical and mental health outcomes. Analysis was conducted using multivariate logistic regression within a multilevel framework. RESULTS: Two-fifths (40%) of primary carers, 45% of families and 14% of Indigenous children aged 5-10 years were reported to have experienced racial discrimination at some point in time, with 28-40% of these experiencing it persistently (reported at multiple time points). Primary carer and child experiences of racial discrimination were each associated with poor child mental health status (high risk of clinically significant emotional or behavioural difficulties), sleep difficulties, obesity and asthma, but not with child general health or injury. Children exposed to persistent vicarious racial discrimination were more likely to have sleep difficulties and asthma in multivariate models than those with a time-limited exposure. CONCLUSIONS: The findings indicate that direct and persistent vicarious racial discrimination are detrimental to the physical and mental health of Indigenous children in Australia, and suggest that prolonged and more frequent exposure to racial discrimination that starts in the early lifecourse can impact on multiple domains of health in later life. Tackling and reducing racism should be an integral part of policy and intervention aimed at improving the health of Australian Indigenous children and thereby reducing health disparities between Indigenous and non-Indigenous children.

School performance in children with type 1 diabetes: a contemporary population-based study.

AIMS: Our aim was to examine the school performance of children with type 1 diabetes in comparison to their peers, exploring changes over time, and the impact of clinical factors on school performance. METHODS: The study included data on 666 children with type 1 diabetes from the Western Australia Children's Diabetes Database. (WACDD), a population-based registry, and 3260 school and school year matched non-diabetic children. Records from the National Assessment Program - Literacy and Numeracy (NAPLAN) (2008-2011), which examines four educational outcome domains and is administered annually to all years 3, 5, 7, and 9 children in Australia, were sourced for both groups. Clinical data were obtained for the children with diabetes from the WACDD. RESULTS: No significant difference was observed between those with type 1 diabetes and their peers, across any of the tested domains and school years analysed. No decline over time was observed, and no decline following diagnosis was observed. Type 1 diabetes was associated with decreased school attendance, 3% fewer days attended per year. Poorer glycaemic control [higher haemoglobin A1c (HbA1c)] was associated with a lower test score [0.2-0.3 SD per 1% (10.9 mmol/mol) increase in HbA1c], and with poorer attendance [1.8% decrease per 1% (10.9 mmol/mol) increase in HbA1c]. No association was observed with history of severe hypoglycaemia, diabetic ketoacidosis or age of onset and school test scores. CONCLUSION: These results suggest that type 1 diabetes is not associated with a significant decrement in school performance, as assessed by NAPLAN. The association of poorer glycaemic control with poorer school performance serves as further evidence for clinicians to focus on improving glycaemic control.

Maternal smoking during pregnancy and the risk of childhood type 1 diabetes in Western Australia.

AIMS/HYPOTHESIS: The aim of this study was to investigate the association between maternal smoking during pregnancy and type 1 diabetes in the offspring, using complete population data sources available in Western Australia. METHODS: A prospective cohort study was undertaken with cases defined as children born in Western Australia between 1998 and 2008 who were diagnosed with type 1 diabetes at <15 years of age up to 31 December 2010. Eligible cases were identified from the prospective, population-based Western Australian Children's Diabetes Database. Record linkage was performed to identify perinatal records of cases from the Western Australian Midwives' Notification System, which contains data on >99% of all births in Western Australia. Cox regression was used to analyse the data and adjust for recognised risk factors such as birthweight, gestational age, maternal age and socioeconomic status. RESULTS: The unadjusted HR for babies born to mothers who smoked during pregnancy being diagnosed with childhood type 1 diabetes was 0.70 (95% CI: 0.50, 0.97). After adjustment, the confidence interval widened but the point estimate remained relatively unchanged at 0.76 (95% CI: 0.54, 1.08). CONCLUSIONS/INTERPRETATION: Analyses of data from this population-based study indicate that maternal smoking during pregnancy may be associated with a reduced risk of childhood type 1 diabetes. Further investigation in larger populations with more detailed smoking data could lead to novel hypotheses regarding mechanisms that influence the immunopathogenesis of type 1 diabetes in early life.

Metagenomic Characterisation of the Gut Microbiome and Effect of Complementary Feeding on Bifidobacterium spp. in Australian Infants.

Complementary feeding induces dramatic ecological shifts in the infant gut microbiota toward more diverse compositions and functional metabolic capacities, with potential implications for immune and metabolic health. The aim of this study was to examine whether the age at which solid foods are introduced differentially affects the microbiota in predominantly breastfed infants compared with predominantly formula-fed infants. We performed whole-genome shotgun metagenomic sequencing of infant stool samples from a cohort of six-month-old Australian infants enrolled in a nested study within the ORIGINS Project longitudinal birth cohort. Infants born preterm or those who had been administered antibiotics since birth were excluded. The taxonomic composition was highly variable among individuals at this age. Predominantly formula-fed infants exhibited a higher microbiome diversity than predominantly breastfed infants. Among the predominantly breastfed infants, the introduction of solid foods prior to five months of age was associated with higher alpha diversity than solid food introduction after six months of age, primarily due to the loss of Bifidobacterium infantis. In contrast, the age at which solid food was introduced was not associated with the overall change in diversity among predominantly formula-fed infants but was associated with compositional changes in Escherichia abundance. Examining the functional capacity of the microbiota in relation to these changes, we found that the introduction of solid foods after six months of age was associated with elevated one-carbon compound metabolic pathways in both breastfed and formula-fed infants, although the specific metabolic sub-pathways differed, likely reflecting different taxonomic compositions. Our findings suggest that the age of commencement of solid foods influences the gut microbiota composition differently in predominantly breastfed infants than in predominantly formula-fed infants.

Tonsils at Telethon: developing a standardised collection of tonsil photographs for group A streptococcal (GAS) research.

Introduction: Group A streptococcus (GAS) infections, such as pharyngitis and impetigo, can lead to rheumatic fever and rheumatic heart disease (RHD). Australian Aboriginal and Torres Strait Islander populations experience high rates of RHD and GAS skin infection, yet rates of GAS pharyngitis are unclear. Anecdotally, clinical presentations of pharyngitis, including tonsillar hypertrophy and sore throat, are uncommon. This study aimed to develop a standardised set of tonsil photographs and determine tonsil size distribution from an urban paediatric population. Methods: A prospective cohort of children aged 3-15 years were recruited at the public events "Discover Day" and "Telethon Weekend" (October 2017) in Perth, Western Australia, Australia. Tonsil photographs, symptomatology, and GAS rapid antigen detection tests (RADT) were collected. Tonsil size was graded from the photographs using the Brodsky Grading Scale of tonsillar hypertrophy (Brodsky) by two independent clinicians, and inter-rater reliability calculated. Pharyngitis symptoms and GAS RADT were correlated, and immediate results provided. Results: Four hundred and twenty-six healthy children participated in the study over three days. The median age was seven years [interquartile range (IQR) 5.9-9.7 years]. Tonsil photographs were collected for 92% of participants, of which 62% were rated as good-quality photographs and 79% were deemed of adequate quality for assessment by both clinicians. When scored by two independent clinicians, 57% received the same grade. Average Brodsky grades (between clinicians) were 11%, 35%, 28%, 22% and 5% of grades 0,1,2,3 and 4, respectively. There was moderate agreement in grading using photographs, and minimal to weak agreement for signs of infection. Of 394 participants, 8% reported a sore throat. Of 334 GAS RADT performed, <1% were positive. Discussion: We report the first standardised use of paediatric tonsil photographs to assess tonsil size in urban-living Australian children. This provides a proof of concept from an urban-living cohort that could be compared with children in other settings with high risk of GAS pharyngitis or rheumatic fever such as remote-living Australian Indigenous populations.

Study Protocol for a Stepped-Wedge Cluster (Nested) Randomized Controlled Trial of Antenatal Colostrum Expression (ACE) Instruction in First-Time Mothers: The ACE Study.

BACKGROUND: Although many mothers initiate breastfeeding, supplementation with human-milk substitutes (formula) during the birth hospitalization is common and has been associated with early breastfeeding cessation. Colostrum hand expressed in the last few weeks before birth, known as antenatal colostrum expression (ACE), can be used instead of human-milk substitutes. However, evidence is lacking on the efficacy of ACE on breastfeeding outcomes and in non-diabetic mothers. METHODS AND PLANNED ANALYSIS: This multicenter stepped-wedge cluster (nested) randomized controlled trial aims to recruit 945 nulliparous pregnant individuals. The trial is conducted in two phases. During Phase 1, control group participants are under standard care. During Phase 2, participants are randomized to ACE instruction via a pre-recorded online video or a one-on-one session with a midwife. Adjusted logistic regression analysis will be used to examine the relationship between ACE instruction and breastfeeding outcomes. RESEARCH AIMS AND QUESTIONS: Primary aim: (1) Does advising pregnant individuals to practice ACE and providing instruction improve exclusive breastfeeding rates at 4 months postpartum? Secondary research questions: (2) Do individuals who practice ACE have higher rates of exclusive breastfeeding during the initial hospital stay after birth? (3) Is teaching ACE via an online video non-inferior to one-on-one instruction from a midwife? (4) Does expressing colostrum in pregnancy influence time to secretory activation, or (5) result in any differences in the composition of postnatal colostrum? DISCUSSION: Trial findings have important implications for maternity practice, with the online video providing an easily accessible opportunity for ACE education as part of standard antenatal care.

Long-term outcome of insulin pump therapy in children with type 1 diabetes assessed in a large population-based case-control study.

AIMS/HYPOTHESIS: We determined the impact of insulin pump therapy on long-term glycaemic control, BMI, rate of severe hypoglycaemia and diabetic ketoacidosis (DKA) in children. METHODS: Patients on pump therapy at a single paediatric tertiary hospital were matched to patients treated by injections on the basis of age, duration of diabetes and HbA1c at the time of pump start. HbA1c, anthropometric data, episodes of severe hypoglycaemia and rates of hospitalisation for DKA were collected prospectively. RESULTS: A total of 345 patients on pump therapy were matched to controls on injections. The mean age, duration of diabetes at pump start and length of follow-up were 11.4 (± 3.5), 4.1 (± 3.0) and 3.5 (± 2.5) years, respectively. The mean HbA1c reduction in the pump cohort was 0.6% (6.6 mmol/mol). This improved HbA1c remained significant throughout the 7 years of follow-up. Pump therapy reduced severe hypoglycaemia from 14.7 to 7.2 events per 100 patient-years (p < 0.001). In contrast, severe hypoglycaemia increased in the non-pump cohort over the same period from 6.8 to 10.2 events per 100 patient-years. The rate of hospitalisation for DKA was lower in the pump cohort (2.3 vs 4.7 per 100 patient-years, p = 0.003) over the 1,160 patient-years of follow-up. CONCLUSIONS/INTERPRETATION: This is the longest and largest study of insulin pump use in children and demonstrates that pump therapy provides a sustained improvement in glycaemic control, and reductions of severe hypoglycaemia and hospitalisation for DKA compared with a matched cohort using injections.

A population-based study of risk factors for severe hypoglycaemia in a contemporary cohort of childhood-onset type 1 diabetes.

AIMS/HYPOTHESIS: Severe hypoglycaemia is a major barrier to optimising glycaemic control. Recent changes in therapy, however, may have altered the epidemiology of severe hypoglycaemia and its associated risk factors. The aim of this study was to examine the incidence rates and risk factors associated with severe hypoglycaemia in a contemporary cohort of children and adolescents with type 1 diabetes. METHODS: Subjects were identified from a population-based register containing data on >99% of patients (<16 years of age) who were being treated for type 1 diabetes in Western Australia. Patients attend the clinic approximately every 3 months, where data pertaining to diabetes management, demographics and complications including hypoglycaemia are prospectively recorded. A severe hypoglycaemic event was defined as an episode of coma or convulsion associated with hypoglycaemia. Risk factors assessed included age, duration of diabetes, glycaemic control, sex, insulin therapy, socioeconomic status and calendar year. RESULTS: Clinical visit data from 1,770 patients, providing 8,214 patient-years of data between 2000 and 2011 were analysed. During follow-up, 841 episodes of severe hypoglycaemia were observed. No difference in risk of severe hypoglycaemia was observed between age groups. Good glycaemic control (HbA1c <7% [53 mmol/mol]) compared with the cohort average (HbA1c 8-9% [64-75 mmol/mol]) was not associated with an increased risk of severe hypoglycaemia. When compared with patients on injection regimens, subjects aged 12-18 years on pump therapy were at reduced risk of severe hypoglycaemia (incidence risk ratio 0.6; 95% CI 0.4, 0.9). CONCLUSIONS/INTERPRETATION: In this population-based sample of children and adolescents with type 1 diabetes, contemporary therapy is associated with a changed pattern and incidence of severe hypoglycaemia.