ORCID Profile
0000-0002-6580-0346
Current Organisations
Barwon Health
,
Deakin University
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Publisher: Elsevier BV
Date: 02-2020
Publisher: Springer Science and Business Media LLC
Date: 14-03-2017
DOI: 10.1038/SREP44423
Abstract: Human parechovirus types 1–16 (HPeV1–16) are positive strand RNA viruses in the family Picornaviridae . We investigated a 2015 outbreak of HPeV3 causing illness in infants in Victoria, Australia. Virus genome was extracted from clinical material and isolates and sequenced using a combination of next generation and Sanger sequencing. The HPeV3 outbreak genome was 98.7% similar to the HPeV3 Yamagata 2011 lineage for the region encoding the structural proteins up to nucleotide position 3115, but downstream of that the genome varied from known HPeV sequences with a similarity of 85% or less. Analysis indicated that recombination had occurred, may have involved multiple types of HPeV and that the recombination event/s occurred between March 2012 and November 2013. However the origin of the genome downstream of the recombination site is unknown. Overall, the capsid of this virus is highly conserved, but recombination provided a different non-structural protein coding region that may convey an evolutionary advantage. The indication that the capsid encoding region is highly conserved at the amino acid level may be helpful in directing energy towards the development of a preventive vaccine for expecting mothers or antibody treatment of young infants with severe disease.
Publisher: Wiley
Date: 29-04-2019
DOI: 10.1111/JPC.14436
Abstract: The burden of wheezing illnesses in Australian infants has not been documented since the success of initiatives to reduce maternal cigarette smoking. We aimed to determine the incidence of wheeze and related health-care utilisation during the first year of life among a contemporary Australian birth cohort. A birth cohort of 1074 infants was assembled between 2010 and 2013. Parents completed questionnaires periodically. Several non-exclusive infant respiratory disease phenotypes were defined, including any wheeze, wheeze with shortness of breath and recurrent wheeze. Skin prick testing was performed to determine atopic wheeze. Health-care utilisation for respiratory disease was determined from questionnaires and hospital medical records. Retention to 1 year was 840/1074 (83%). The incidence of any wheeze was 51.8% (95% confidence interval (CI) 48.3-55.2%), wheeze with shortness of breath 20.6% (95% CI 17.9-23.5), recurrent wheeze 19.4% (95% CI 16.8-22.2) and atopic wheeze 6% (95% CI 4.6-7.8). Respiratory illness resulted in primary health-care utilisation in 82.2% (95% CI 79.3-84.8) of participants and hospital presentation in 8.8% (95% CI 7.2-10.6). Maternal smoking during pregnancy was uncommon (15.7%) and was not associated with wheeze or health resource utilisation. Male gender, familial atopy and asthma and smaller household size were associated with a higher incidence of wheeze. The incidence of wheezing illness among Australian infants remains high despite relatively low rates of maternal smoking during pregnancy. The majority of the health-care burden is borne by primary health-care services. Further research is required to inform novel prevention strategies.
Publisher: eLife Sciences Publications, Ltd
Date: 10-05-2022
DOI: 10.7554/ELIFE.75170
Abstract: The risk of adult onset cardiovascular and metabolic (cardiometabolic) disease accrues from early life. Infection is ubiquitous in infancy and induces inflammation, a key cardiometabolic risk factor, but the relationship between infection, inflammation, and metabolic profiles in early childhood remains unexplored. We investigated relationships between infection and plasma metabolomic and lipidomic profiles at age 6 and 12 months, and mediation of these associations by inflammation. Matched infection, metabolomics, and lipidomics data were generated from 555 infants in a pre-birth longitudinal cohort. Infection data from birth to 12 months were parent-reported (total infections at age 1, 3, 6, 9, and 12 months), inflammation markers (high-sensitivity C-reactive protein [hsCRP] glycoprotein acetyls [GlycA]) were quantified at 12 months. Metabolic profiles were 12-month plasma nuclear magnetic resonance metabolomics (228 metabolites) and liquid chromatography/mass spectrometry lipidomics (776 lipids). Associations were evaluated with multivariable linear regression models. In secondary analyses, corresponding inflammation and metabolic data from birth (serum) and 6-month (plasma) time points were used. At 12 months, more frequent infant infections were associated with adverse metabolomic (elevated inflammation markers, triglycerides and phenylalanine, and lower high-density lipoprotein [HDL] cholesterol and apolipoprotein A1) and lipidomic profiles (elevated phosphatidylethanolamines and lower trihexosylceramides, dehydrocholesteryl esters, and plasmalogens). Similar, more marked, profiles were observed with higher GlycA, but not hsCRP. GlycA mediated a substantial proportion of the relationship between infection and metabolome/lipidome, with hsCRP generally mediating a lower proportion. Analogous relationships were observed between infection and 6-month inflammation, HDL cholesterol, and apolipoprotein A1. Infants with a greater infection burden in the first year of life had proinflammatory and proatherogenic plasma metabolomic/lipidomic profiles at 12 months of age that in adults are indicative of heightened risk of cardiovascular disease, obesity, and type 2 diabetes. These findings suggest potentially modifiable pathways linking early life infection and inflammation with subsequent cardiometabolic risk. The establishment work and infrastructure for the BIS was provided by the Murdoch Children’s Research Institute (MCRI), Deakin University, and Barwon Health. Subsequent funding was secured from National Health and Medical Research Council of Australia (NHMRC), The Shepherd Foundation, The Jack Brockhoff Foundation, the Scobie & Claire McKinnon Trust, the Shane O’Brien Memorial Asthma Foundation, the Our Women’s Our Children’s Fund Raising Committee Barwon Health, the Rotary Club of Geelong, the Minderoo Foundation, the Ilhan Food Allergy Foundation, GMHBA, Vanguard Investments Australia Ltd, and the Percy Baxter Charitable Trust, Perpetual Trustees. In-kind support was provided by the Cotton On Foundation and CreativeForce. The study sponsors were not involved in the collection, analysis, and interpretation of data writing of the report or the decision to submit the report for publication. Research at MCRI is supported by the Victorian Government’s Operational Infrastructure Support Program. This work was also supported by NHMRC Senior Research Fellowships to ALP (1008396) DB (1064629) and RS (1045161) , NHMRC Investigator Grants to ALP (1110200) and DB (1175744), NHMRC-A*STAR project grant (1149047). TM is supported by an MCRI ECR Fellowship. SB is supported by the Dutch Research Council (452173113).
Publisher: Springer Science and Business Media LLC
Date: 24-03-2020
DOI: 10.1038/S41467-020-14552-1
Abstract: In mice, the maternal microbiome influences fetal immune development and postnatal allergic outcomes. Westernized populations have high rates of allergic disease and low rates of gastrointestinal carriage of Prevotella , a commensal bacterial genus that produces short chain fatty acids and endotoxins, each of which may promote the development of fetal immune tolerance. In this study, we use a prebirth cohort ( n = 1064 mothers) to conduct a nested case-cohort study comparing 58 mothers of babies with clinically proven food IgE mediated food allergy with 258 randomly selected mothers. Analysis of the V4 region of the 16S rRNA gene in fecal s les shows maternal carriage of Prevotella copri during pregnancy strongly predicts the absence of food allergy in the offspring. This association was confirmed using targeted qPCR and was independent of infant carriage of P. copri . Larger household size, which is a well-established protective factor for allergic disease, strongly predicts maternal carriage of P. copri .
Publisher: Wiley
Date: 29-09-2022
DOI: 10.1111/IJPO.12853
Abstract: The association between physical activity and adiposity in preschool‐aged children is unclear. To assess the cross‐sectional association between objectively measured physical activity and body fat in preschool‐aged children. In the preschool review in an Australian birth cohort study ( n = 1074), mean duration and time accumulated in ≥1‐min bouts of physical activity at light‐intensity (LPA), moderate‐ to vigorous‐intensity (MVPA) and light‐ to vigorous‐intensity (LMVPA) were computed from accelerometer (ActiGraph GT3X+) data. Percent body fat was assessed by bioelectrical impedance. Associations between physical activity and percent body fat were examined by multiple regression, adjusted for accelerometer wear time, MVPA (in analyses of LPA), maternal body mass index (BMI) and maternal education. A total of 450 participants ( n = 450) had valid data. There was evidence of associations between physical activity and adiposity: each additional hour of LVPA was associated with 0.6% (CI 95 –0.2%, 1.3%) higher body fat ≥1‐min bouts of LPA was associated with 1.0% (CI 95 0.1%, 1.9%) higher body fat each additional hour of MVPA was associated with −0.8% (CI 95 −1.6%, −0.1%) less body fat and ≥1‐min bouts of MVPA was associated with −1.3% (CI 95 −2.5%, −0.1%) body fat. Among a cohort of preschool‐aged children, there was evidence that more intensive physical activity assessed by an accelerometer is associated with reduced body fat.
Publisher: Wiley
Date: 06-2022
DOI: 10.1111/PAI.13810
Abstract: Children born to larger households have less allergic disease. T regulatory cell (Treg) development may be a relevant mechanism, but this has not been studied longitudinally. We aim to (i) describe how prenatal and postnatal environmental factors are associated with Treg development and (ii) investigate whether serial Treg measures predict allergic outcomes at 1 year of age. A birth cohort ( n = 1074) with information on prenatal and postnatal early life factors. Both naïve Treg (nTreg) and activated Treg (aTreg) cell populations (as a proportion of CD4 + T cells) were available in 463 infants at birth (cord blood), 600 at 6 months, and 675 at 12 months. 191 infants had serial measures. Measures of allergic status at 12 months were polysensitization (sensitization to 2 or more allergens), clinically proven food allergy, atopic eczema, and atopic wheeze. Infants born to larger households (3 or more residents) had higher longitudinal nTreg proportions over the first postnatal year with a mean difference (MD) of 0.67 (95% CI 0.30–1.04)%. Higher nTreg proportions at birth were associated with a reduced risk of infant allergic outcomes. Childcare attendance and breastfeeding were associated with higher longitudinal nTreg proportions (MD 0.48 (95% CI 0.08–0.80)%. Multiple prenatal and postnatal microbial factors are associated with nTreg and aTreg development. Larger household size was associated with higher nTreg at birth which in turn was associated with reduced allergic sensitization and disease at 12 months of age.
Publisher: MDPI AG
Date: 27-07-2015
DOI: 10.3390/NU7085271
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.CLINBIOCHEM.2015.04.014
Abstract: In widely used protocols for the collection and isolation of cord blood mononuclear cells, investigators are left with substantial volumes of diluted plasma which could be used for other measurements. The aim of this study was to ascertain the validity of umbilical cord blood (UCB) diluted plasma s les for vitamin D, A and E analysis compared to UCB serum s les. Twenty UCB matched s les of diluted plasma and serum were collected. The s les were analysed by two liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods on two separate occasions. The results of 25(OH)D3 obtained by the two laboratories demonstrated close agreement with a mean difference of 0.14nmol/L [95% confidence interval (95% CI), -6.8 to 7.1]. Both methods demonstrate close agreement for 25(OH)D3 in UCB serum versus diluted UCB plasma mean difference 2.2nmol/L [95% CI, -9.5 to 13.9] and 4.1nmol/L [95% CI, -14.5 to 6.1] for the results from Lab A and Lab B, respectively. Vitamin A was quantified by Lab A in UCB serum and diluted UCB plasma mean difference 0.07μmol/L [95% CI, -0.41 to 0.28]. Results of 25(OH)D3 epimer and vitamin E in the diluted UCB plasma were below the limit of quantification, and could not be compared with UCB serum. Diluted UCB plasma can be used for the quantification of retinol and 25(OH)D3 by LC-MS/MS. By contrast, quantification of 25(OH)D3 epimer and vitamin E in diluted UCB plasma is not supported by this study due to limitations in analytical sensitivity.
Publisher: Elsevier BV
Date: 08-2008
DOI: 10.1016/J.MEHY.2008.01.033
Abstract: Osteoporotic fractures, falls and obesity are major health problems in developed nations. Evidence suggests that there are antenatal factors predisposing to these conditions. Data are emerging from Australia and elsewhere to suggest that maternal vitamin D status in pregnancy affects intrauterine skeletal mineralisation and skeletal growth together with muscle development and adiposity. Given that low levels of vitamin D have been documented in many urbanised populations, including those in countries with abundant sunlight, an important issue for public health is whether maternal vitamin D insufficiency during pregnancy has adverse effects on offspring health. The developing fetus may be exposed to low levels of vitamin D during critical phases of development as a result of maternal hypovitaminosis D. We hypothesise that this may have adverse effects on offspring musculoskeletal health and other aspects of body composition. Further research focused on the implications of poor gestational vitamin D nutrition is warranted as these developmental effects are likely to have a sustained influence on health during childhood and in adult life. We suggest that there is a clear rationale for randomised clinical trials to assess the potential benefits and harmful effects of vitamin D supplementation during pregnancy.
Publisher: Elsevier BV
Date: 10-2013
Publisher: Elsevier BV
Date: 12-2020
Publisher: Springer Science and Business Media LLC
Date: 29-03-2016
DOI: 10.1038/TP.2016.32
Abstract: Compelling evidence suggests that maternal mental health in pregnancy can influence fetal development. The imprinted genes, insulin-like growth factor 2 ( IGF2 ) and H19, are involved in fetal growth and each is regulated by DNA methylation. This study aimed to determine the association between maternal mental well-being during pregnancy and differentially methylated regions (DMRs) of IGF2 (DMR0) and the IGF2/H19 imprinting control region (ICR) in newborn offspring. Maternal depression, anxiety and perceived stress were assessed at 28 weeks of pregnancy in the Barwon Infant Study ( n =576). DNA methylation was measured in purified cord blood mononuclear cells using the Sequenom MassArray Platform. Maternal anxiety was associated with a decrease in average ICR methylation (Δ=−2.23% 95% CI=−3.68 to −0.77%), and across all six of the in idual CpG units in anxious compared with non-anxious groups. Birth weight and sex modified the association between prenatal anxiety and infant methylation. When stratified into lower (⩽3530 g) and higher ( g) birth weight groups using the median birth weight, there was a stronger association between anxiety and ICR methylation in the lower birth weight group (Δ=−3.89% 95% CI=−6.06 to −1.72%), with no association in the higher birth weight group. When stratified by infant sex, there was a stronger association in female infants (Δ=−3.70% 95% CI=−5.90 to −1.51%) and no association in males. All the linear regression models were adjusted for maternal age, smoking and folate intake. These findings show that maternal anxiety in pregnancy is associated with decreased IGF2 / H19 ICR DNA methylation in progeny at birth, particularly in female, low birth weight neonates. ICR methylation may help link poor maternal mental health and adverse birth outcomes, but further investigation is needed.
Publisher: S. Karger AG
Date: 2018
DOI: 10.1159/000487506
Abstract: b i Background: /i /b Lipid metabolism is vital to fetal development and cardiometabolic health and the final weeks of gestation are known to be a time of intense metabolic activity. New techniques such as lipidomics allow investigation of a complex lipidomic profile in infants. b i Objectives: /i /b This research aimed to (1) describe variations in lipidomic profile in late preterm and term infants and (2) compare variations to an adult lipidomic profile with known clinical implications. b i Methods: /i /b The Barwon Infant Study ( i n /i = 1,074) is a population-derived pre-birth cohort study. The lipidomic profile of cord blood was measured by liquid chromatography-mass spectrometry in 225 participants and the association between gestational age and lipidomic profile was investigated using multiple linear regression adjusting for birth weight, exposure to labour, and infant sex. Patterns of association with gestational age across the lipidomic profile were compared with associations between body mass index (BMI) and lipidomic profile observed among adults in the San Antonia Family Heart Study ( i n /i = 994). b i Results: /i /b Gestational age was independently associated with the abundances of 39% of lipid species. Variations in the lipidomic profile with increasing gestational age were comparable to some variations observed in association with increasing BMI among adults. b i Conclusion: /i /b There is a strong relationship between gestational age and the cord blood lipid profile at birth, providing further evidence for the importance of metabolic changes of late gestation. A number of the variations in the lipid profile with increasing gestational age are analogous to differences observed in the adult lipid profile with an increasing BMI.
Publisher: Informa UK Limited
Date: 24-06-2022
Publisher: Wiley
Date: 07-06-2016
DOI: 10.1111/JPC.13232
Abstract: Data regarding temporal trends in per capita paediatric hospital presentations and admissions are required to inform health system and workforce planning. Emergency Department (ED) presentations and admissions to the University Hospital Geelong among patients aged 0 to 16 years over a 12-month period (2012-2013) were determined by review of hospital records and then compared with similar data collected during 1996/1997. Since 1996/1997, per capita paediatric presentations to the ED increased from 643 to 1837 per 10 000 (186% 95% confidence interval 181% to 191%). Moreover, the proportion of paediatric ED presentations resulting in hospital admission increased from 12.3% to 18.3% (49% 95% confidence interval 39% to 59%). There has been a substantial absolute and per capita increase in paediatric ED presentations and hospital admissions since the 1990s. These trends place an increasing burden on the public hospital system, and strategies are required to promote paediatric acute care in the ambulatory setting.
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.CLINBIOCHEM.2014.01.033
Abstract: Food allergy has a dramatic impact on a child's (and their family's) quality of life and places a major financial burden on the community. It has been hypothesized that the increase in food allergy may relate to the concordant rise in prevalence of vitamin D insufficiency. More recently a second hypothesis has implicated vitamin A sufficiency in the development of immune tolerance. Together, these hypotheses have prompted investigation into the circulating levels of vitamins A and D in relation to food allergy prevalence. This review aims to examine the relationship between vitamins A and D and food allergy. The first part of this review presents the available epidemiological data which proposes a dramatic increase of food allergy and related anaphylaxis during the last two decades. There is some indirect evidence that variation in food allergy prevalence within countries might be linked with ambient ultra violet radiation exposure and thus potentially with vitamin D levels. Only a few studies to date have directly examined the relationship between measured serum vitamin D levels and either food sensitization or allergy. The significance of vitamin A in food allergy prevalence is only provided through a hypothetical association due to its role in the immune system. The second part of this review discusses the relevant aspects of the analytical methods to assess vitamin A and D levels in children. The primary methods utilized relate to measuring the main circulating forms of vitamins A and D in blood i.e. retinol and 25-hydroxy-vitamin-D3 respectively. Chromatographic separation coupled with mass spectrometric detection is considered the gold standard method for both vitamins. These analytical methods should be fully validated for the use in pediatric populations to ensure they are fit for their clinical purpose.
Publisher: Springer Science and Business Media LLC
Date: 11-01-2013
DOI: 10.1038/PR.2013.6
Abstract: Cardiovascular disease (CVD) is the leading cause of death worldwide and originates in early life. The exact mechanisms of this early-life origin are unclear, but a likely mediator at the molecular level is epigenetic dysregulation of gene expression. Epigenetic factors have thus been posited as the likely drivers of early-life programming of adult-onset diseases. This review summarizes recent advances in epidemiology and epigenetic research of CVD risk in children, with a particular focus on twin studies. Classic twin studies enable partitioning of phenotypic variance within a population into additive genetic, shared, and nonshared environmental variances, and are invaluable in research in this area. Longitudinal cohort twin studies, in particular, may provide important insights into the role of epigenetics in the pathogenesis of CVD. We describe candidate gene and epigenome-wide association studies (EWASs) and transgenerational epigenetic inheritance of CVD, and discuss the potential for evidence-based interventions. Identifying epigenetic changes associated with CVD-risk biomarkers in children will provide new opportunities to unravel the underlying biological mechanism of the origins of CVD and enable identification of those at risk for early-life interventions to alter the risk trajectory and potentially reduce CVD incidence later in life.
Publisher: Frontiers Media SA
Date: 08-02-2022
DOI: 10.3389/FIMMU.2021.830049
Abstract: Early childhood is characterised by repeated infectious exposures that result in inflammatory responses by the innate immune system. In addition, this inflammatory response to infection is thought to contribute to the epidemiological evidence linking childhood infection and adult non-communicable diseases. Consequently, the relationship between innate immune responses and inflammation during early life may inform prevention of NCDs later in life. In adults, non-genetic host factors such as age, sex, and obesity, strongly impact cytokine production and circulating mediators, but data in children are lacking. Here, we assessed cytokine responses and inflammatory markers in a population of healthy preschool children (mean age 4.2 years). We studied associations between cytokines, plasma inflammatory markers and non-genetic host factors, such as sex, age, adiposity, season, and immune cell composition. Similar to adults, boys had a higher inflammatory response than girls, with IL-12p70 and IL-10 upregulated following TLR stimulation. Adiposity and winter season were associated with increased circulating inflammatory markers but not cytokine production. The inflammatory markers GlycA and hsCRP were positively associated with production of a number of cytokines and may therefore reflect innate immune function and inflammatory potential. This dataset will be informative for future prospective studies relating immune parameters to preclinical childhood NCD phenotypes.
Publisher: Springer Science and Business Media LLC
Date: 25-07-2022
DOI: 10.1186/S12916-022-02432-Y
Abstract: Lipids play a vital role in health and disease, but changes to their circulating levels and the link with obesity remain poorly characterized in expecting mothers and their offspring in early childhood. LC-MS/MS-based quantitation of 480 lipid species was performed on 2491 plasma s les collected at 4 time points in the mother-offspring Asian cohort GUSTO (Growing Up in Singapore Towards healthy Outcomes). These 4 time points constituted s les collected from mothers at 26–28 weeks of gestation ( n =752) and 4–5 years postpartum ( n =650), and their offspring at birth ( n =751) and 6 years of age ( n =338). Linear regression models were used to identify the pregnancy and developmental age-specific variations in the plasma lipidomic profiles, and their association with obesity risk. An independent birth cohort ( n =1935), the Barwon Infant Study (BIS), comprising mother-offspring dyads of Caucasian origin was used for validation. Levels of 36% of the profiled lipids were significantly higher (absolute fold change 1.5 and P adj 0.05) in antenatal maternal circulation as compared to the postnatal phase, with phosphatidylethanolamine levels changing the most. Compared to antenatal maternal lipids, cord blood showed lower concentrations of most lipid species (79%) except lysophospholipids and acylcarnitines. Changes in lipid concentrations from birth to 6 years of age were much higher in magnitude (log 2 FC=−2.10 to 6.25) than the changes observed between a 6-year-old child and an adult (postnatal mother) (log 2 FC=−0.68 to 1.18). Associations of cord blood lipidomic profiles with birth weight displayed distinct trends compared to the lipidomic profiles associated with child BMI at 6 years. Comparison of the results between the child and adult BMI identified similarities in association with consistent trends ( R 2 =0.75). However, large number of lipids were associated with BMI in adults (67%) compared to the children (29%). Pre-pregnancy BMI was specifically associated with decrease in the levels of phospholipids, sphingomyelin, and several triacylglycerol species in pregnancy. In summary, our study provides a detailed landscape of the in utero lipid environment provided by the gestating mother to the growing fetus, and the magnitude of changes in plasma lipidomic profiles from birth to early childhood. We identified the effects of adiposity on the circulating lipid levels in pregnant and non-pregnant women as well as offspring at birth and at 6 years of age. Additionally, the pediatric vs maternal overlap of the circulating lipid phenotype of obesity risk provides intergenerational insights and early opportunities to track and intervene the onset of metabolic adversities. This birth cohort is a prospective observational study, which was registered on 1 July 2010 under the identifier NCT01174875 .
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.JAIP.2017.12.011
Abstract: Despite the rising rates of anaphylaxis in older children and adolescents, risk factors for food allergy among this age group are understudied. The objective of this study was to investigate the risk factors for current adolescent food allergy using a population-based s le. The SchoolNuts study was a questionnaire survey among 10- to 14-year-old adolescents and their parents, followed by clinic evaluation including oral food challenge when food allergy was suspected from questionnaire response. We investigated the association between food allergy and demographic and environmental factors among a total of 4,991 adolescents using multiple logistic regression. Males and those with early-onset eczema had a higher risk of current food allergy in adolescence (adjusted odds ratio [aOR], 1.55 95% confidence interval [CI], 1.12-2.15 and aOR, 14.08 95% CI, 10.25-19.33). Those with Asian parents had increased risk compared with those with Caucasian parents (aOR, 2.82 95% CI, 1.91-4.16), whereas being born in Asia compared with being born in Australia had decreased risk (aOR, 0.16 95% CI, 0.04-0.67). Family history risk was higher for those with multiple members versus only 1 member (aOR, 4.62 95% CI, 2.75-7.74 and aOR, 2.32 95% CI, 1.36-3.97, respectively). Dog exposure during the first 5 years of life was associated with a decreased risk (aOR, 0.58 95% CI, 0.38-0.91). Early-onset eczema, Asian background, and family history of allergic disease were associated with an increased risk of food allergy, whereas dog exposure in early life reduced the risk in 10- to14-year-old adolescents. Factors predicting food allergy risk in an adolescent population-based cohort appear remarkably similar to those predicting early-onset food allergy in infancy.
Publisher: Hindawi Limited
Date: 07-01-2020
DOI: 10.1111/PEDI.12952
Abstract: Microbial exposures in utero and early life shape the infant microbiome, which can profoundly impact on health. Compared to the bacterial microbiome, very little is known about the virome. We set out to characterize longitudinal changes in the gut virome of healthy infants born to mothers with or without type 1 diabetes using comprehensive virome capture sequencing. Healthy infants were selected from Environmental Determinants of Islet Autoimmunity (ENDIA), a prospective cohort of Australian children with a first-degree relative with type 1 diabetes, followed from pregnancy. Fecal specimens were collected three-monthly in the first year of life. Among 25 infants (44% born to mothers with type 1 diabetes) at least one virus was detected in 65% (65/100) of s les and 96% (24/25) of infants during the first year of life. In total, 26 genera of viruses were identified and >150 viruses were differentially abundant between the gut of infants with a mother with type 1 diabetes vs without. Positivity for any virus was associated with maternal type 1 diabetes and older infant age. Enterovirus was associated with older infant age and maternal smoking. We demonstrate a distinct gut virome profile in infants of mothers with type 1 diabetes, which may influence health outcomes later in life. Higher prevalence and greater number of viruses observed compared to previous studies suggests significant underrepresentation in existing virome datasets, arising most likely from less sensitive techniques used in data acquisition.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.JAIP.2018.06.025
Abstract: Adolescence is well recognized as a period of increased risk for severe and fatal food-induced anaphylaxis. Current Australian adrenaline autoinjector (AAI) prescription guidelines therefore suggest that consideration be given to AAI prescription in all adolescents with a food allergy. To date, however, few studies have assessed the AAI carriage behavior of adolescents prescribed AAI devices. To determine the carriage behavior of prescribed AAI devices in a population-based s le of young Australian adolescents. Students aged 10 to 14 years (and their parents) from randomly selected schools in metropolitan Melbourne completed self-administered questionnaires regarding the history and management of food allergy, including prescription and carriage of AAI device in different domains of school and social life. A total of 9816 students completed the questionnaire (46% response): 620 students were assessed to have likely IgE-mediated food allergy and 234 (38%) of these had been prescribed an AAI. Most students (93% 95% CI, 89%-96%) who were prescribed AAIs reported that they provided their AAI and anaphylaxis action plan to their school. Adherence to AAI carriage in other domains of social life was poor, with 49% (95% CI, 42%-56%) never carrying their AAI in 1 or more locations. Carriage of the AAI device was particularly poor when students were independent of parental supervision: 32% (95% CI, 25%-39%) never carried it when they were by themselves, 28% (95% CI, 22%-36%) never carried it while out with friends, and 36% (95% CI, 30%-43%) never carried their AAI to sporting activities. Carriage of AAI devices is suboptimal in young adolescents prescribed AAIs, particularly when young adolescents are independent of parental supervision.
Publisher: Informa UK Limited
Date: 22-06-2016
DOI: 10.1080/17549507.2016.1193898
Abstract: Many children are requiring tube weaning intervention as a result of increased survival rates of high risk infants and the temporary use of feeding tubes. This study aimed to describe service delivery models and treatment approaches in a variety of paediatric feeding/tube weaning programs. A questionnaire on tube weaning was formulated based on a literature review. Purposive maximum variation s ling was used to include feeding/ weaning programs operating in a variety of settings and countries. Eight feeding teams in Australia, Europe and the USA agreed to participate and completed the questionnaire. All teams employed sensori-motor interventions, with the majority also offering psychological interventions. Six of eight teams utilised hunger induction during the initiation of tube weaning, and in many cases this preceded eating skill development or controlled sensory modulation. A multi-model tube weaning approach is commonly adopted by many centres worldwide. In many cases, psychological theory and theoretical orientation is fundamental to tube weaning practice. Further investigation regarding the efficacy and effectiveness of weaning interventions is recommended to ensure clinical practice is based on sound evidence. This may present as a challenge given many interventions occur concomitantly and the psychotherapeutic experience is difficult to evaluate.
Publisher: Wiley
Date: 16-12-2014
DOI: 10.1111/APA.12457
Abstract: Atherosclerosis is a chronic inflammatory process that begins in early life. Improved identification of markers of early atherosclerosis via neonatal aortic intima-media thickness (aIMT) measurement may allow the development of interventions to prevent or reduce later cardiovascular disease. Using aIMT, studies have shown that antenatal factors such as intra-uterine growth retardation, prematurity, maternal factors and inflammation are associated with early cardiovascular changes.
Publisher: Springer Science and Business Media LLC
Date: 10-07-2019
DOI: 10.1038/S41467-019-10703-1
Abstract: Maternal immune dysregulation seems to affect fetal or postnatal immune development. Preecl sia is a pregnancy-associated disorder with an immune basis and is linked to atopic disorders in offspring. Here we show reduction of fetal thymic size, altered thymic architecture and reduced fetal thymic regulatory T (Treg) cell output in preecl tic pregnancies, which persists up to 4 years of age in human offspring. In germ-free mice, fetal thymic CD4 + T cell and Treg cell development are compromised, but rescued by maternal supplementation with the intestinal bacterial metabolite short chain fatty acid (SCFA) acetate, which induces upregulation of the autoimmune regulator (AIRE), known to contribute to Treg cell generation. In our human cohorts, low maternal serum acetate is associated with subsequent preecl sia, and correlates with serum acetate in the fetus. These findings suggest a potential role of acetate in the pathogenesis of preecl sia and immune development in offspring.
Publisher: Wiley
Date: 28-04-2009
DOI: 10.1111/J.1440-1754.2009.01489.X
Abstract: Interventions are required to expedite the identification and treatment of seriously ill children in the emergency department (ED). The aim of this study was to test the hypothesis that the implementation of a features of serious illness in children checklist (FSIC) for ED nursing staff would be associated with a reduction in the presentation-to-treatment time (PTTT) among children who required hospital admission and active treatment. An observational study was conducted 8 weeks before and 8 weeks after the implementation of the FSIC. The study was conducted in a busy combined adult and paediatric ED. Participants were children admitted to the hospital via the ED with a potentially life-threatening illness. A total of 3640 patients age less than 18 years attended the ED during the observation period. Of these, 214 patients met the eligibility criteria: 111 pre-FSIC and 103 post-FSIC. The overall ED workload and case-mix were similar during the two observation periods. The PTTT was on average 16% (95% confidence interval, 17-33% P = 0.302) longer following the implementation of the FSIC. The implementation of a checklist to assist ED nursing staff in the identification of seriously ill children was not effective in reducing the delay between presentation and the initiation of treatment among children who were admitted to the hospital. Larger studies are required to determine whether similar strategies are effective among a more critically ill subgroup. Consideration should also be given to alternative strategies to expedite the identification and treatment of seriously ill children in the ED.
Publisher: Wiley
Date: 23-02-2017
DOI: 10.1111/ALL.13122
Abstract: Ecological evidence suggests vitamin D insufficiency (VDI) due to lower ambient ultraviolet radiation (UVR) exposure may be a risk factor for IgE-mediated food allergy. However, there are no studies relating directly measured VDI during early infancy to subsequent challenge-proven food allergy. To prospectively investigate the association between VDI during infancy and challenge-proven food allergy at 1 year. In a birth cohort (n = 1074), we used a case-cohort design to compare 25-hydroxyvitamin D Within the random subcohort, VDI was present in 45% (105/233) of newborns and 24% (55/227) of infants at 6 months. Food allergy prevalence at 1 year was 7.7% (61/786), and 6.5% (53/808) were egg-allergic. There was no evidence of an association between VDI at either birth (aRR 1.25, 95% CI 0.70-2.22) or 6 months (aRR 0.93, 95% CI 0.41-2.14) and food allergy at 1 year. There was no evidence that VDI during the first 6 months of infancy is a risk factor for food allergy at 1 year of age. These findings primarily relate to egg allergy, and larger studies are required.
Publisher: Massachusetts Medical Society
Date: 03-03-2011
DOI: 10.1056/NEJMC1100063
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.JAIP.2019.05.057
Abstract: Cashew is a common cause of tree nut allergy in children. To date there have been few studies of diagnostic tests for cashew allergy, and positive predictive values (PPVs) for cashew as well as other tree nuts are largely extrapolated from studies of peanut allergy. How relevant these cutoffs are for cashew has not been formally explored. We aimed to establish skin prick test (SPT) wheal sizes that correlated to 95% PPV for a positive food challenge for cashew. We included all cashew oral food challenges (OFCs) conducted as part of the HealthNuts (n = 108 age, 4-6 years) and SchoolNuts (n = 37 age, 10-14 years) studies, both recruited from the community (population cohort). A second cohort of all cashew OFCs conducted at the Royal Children's Hospital (RCH) allergy center (n = 343) (2011-2016) and a private allergy clinic based at RCH (n = 43) was included via electronic medical record review (clinic cohort). The 95% PPV for cashew SPT was calculated for both cohorts. Among the population cohort (n = 145), 62% of cashew OFCs were positive compared with 20% of the clinic cohort (n = 386). The SPT cutoff for 95% PPV derived from the population cohort was 10 mm (95% confidence interval [CI], 7.5-12.0). For the clinic cohort, the 95% PPV was 14 mm (95% CI, 9.5-unknown). An SPT wheal size of 8 mm had a PPV of 89% (95% CI, 79-95) in the population cohort and 62% (95% CI, 45-78) in the clinic cohort. A higher SPT wheal size may be more appropriate than the commonly used 8 mm cutoff to guide clinical decisions around when to perform OFC for cashew.
Publisher: Wiley
Date: 26-03-2018
DOI: 10.1002/SIM.7650
Abstract: Paediatric respiratory researchers have widely adopted the multiple-breath washout (MBW) test because it allows assessment of lung function in unsedated infants and is well suited to longitudinal studies of lung development and disease. However, a substantial proportion of MBW tests in infants fail current acceptability criteria. We hypothesised that a model-based approach to analysing the data, in place of traditional simple empirical summaries, would enable more efficient use of these tests. We therefore developed a novel statistical model for infant MBW data and applied it to 1197 tests from 432 in iduals from a large birth cohort study. We focus on Bayesian estimation of the lung clearance index, the most commonly used summary of lung function from MBW tests. Our results show that the model provides an excellent fit to the data and shed further light on statistical properties of the standard empirical approach. Furthermore, the modelling approach enables the lung clearance index to be estimated by using tests with different degrees of completeness, something not possible with the standard approach. Our model therefore allows previously unused data to be used rather than discarded, as well as routine use of shorter tests without significant loss of precision. Beyond our specific application, our work illustrates a number of important aspects of Bayesian modelling in practice, such as the importance of hierarchical specifications to account for repeated measurements and the value of model checking via posterior predictive distributions.
Publisher: Wiley
Date: 29-11-2019
DOI: 10.1111/JPC.14695
Abstract: To investigate the relationship between factors which influence external microbial exposures (FEMEs), previously identified to be protective or to increase the risk of the development of allergic disease, and cognition and behaviour in infants 2 years of age in an Australian population. The Barwon Infant Study is a birth cohort (n = 1074) in Victoria, Australia. Comprehensive questionnaire, clinical and biological measures were collected at multiple time oints. Multiple linear regression was used to evaluate the associations between 56 FEMEs and 3 outcomes cognition (Bayley Scales of Infant and Toddler Development (BAYLEY-III)) (n = 667, mean (standard deviation) age = 2.45 (0.14) years), internalising and externalising behaviour (Child Behavior Checklist) (n = 666, mean (standard deviation) age = 2.45 (0.14) years). Overall, there were no consistent patterns or dose response found within an outcome nor across all three outcomes, although there was some evidence for in idual associations. Breastfeeding and child care were associated with higher cognitive scores (adjusted mean difference (95% confidence interval) = 3.20 (0.23-6.17) and 0.68 (0.12-1.24), respectively), and increasing sibling number was associated with lower internalising behaviour (adjusted mean difference (95% confidence interval) = -4.13 (-6.34, -1.91)). In contrast to allergic disease, there was an absence of epidemiological evidence to support the association between these FEMEs and cognition and behaviour. Direct investigations into the relationship between exposures which influence gut-microbial composition and cognition and behaviour are now needed.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1016/J.ENVPOL.2022.120332
Abstract: Prenatal exposure to plastic chemicals has been associated with alterations to early-life immune function in children. However, previous studies have generally been small and focused on limited repertoires of immune indices. In a large population-based pre-birth cohort (n = 1074), third-trimester measurements of eight phthalate metabolites and three analogues of bisphenols were used to estimate prenatal exposure to phthalate and bisphenol compounds. In cord blood, immune cell populations were measured by flow cytometry and an extensive panel of cytokines and chemokines were measured by multiplex immunoassay. We used these cord blood analytes to estimate "early life" immune profiles. The full study s le comprises data from 774 infants with prenatal plastic metabolite measurements and any cord blood immune data. Multiple linear regression analysis was used to evaluate whether prenatal phthalate and bisphenol exposure was prospectively associated with cord blood immune cell populations and cytokine and chemokine levels. Generally, inverse associations were observed between prenatal phthalate exposure and cord blood immune indices. Higher exposure to di-n-butyl phthalate was associated with lower cord blood levels of platelet-derived growth factor (PDGF) and interferon gamma-induced protein 10 (IP-10) higher exposure to the sum of dibutyl phthalates was associated with lower cord blood levels of IP-10 and higher exposure to benzyl butyl phthalate was associated with lower cord blood levels of interleukin 1 beta (IL-1β). There was less evidence of associations between bisphenols and cord blood immune indices. These results extend previous work examining prenatal plastic chemical exposure and early-life immune development and highlight the importance of further examination of potential associations with health-related outcomes.
Publisher: Informa UK Limited
Date: 27-06-2020
Publisher: Wiley
Date: 07-01-2019
DOI: 10.1002/CCR3.1928
Publisher: Wiley
Date: 06-2016
DOI: 10.1111/JPC.13201
Publisher: Frontiers Media SA
Date: 25-04-2018
Publisher: Springer Science and Business Media LLC
Date: 06-08-2021
DOI: 10.1186/S40168-021-01104-Y
Abstract: The gut microbiome changes in response to a range of environmental conditions, life events and disease states. Pregnancy is a natural life event that involves major physiological adaptation yet studies of the microbiome in pregnancy are limited and their findings inconsistent. Pregnancy with type 1 diabetes (T1D) is associated with increased maternal and fetal risks but the gut microbiome in this context has not been characterized. By whole metagenome sequencing (WMS), we defined the taxonomic composition and function of the gut bacterial microbiome across 70 pregnancies, 36 in women with T1D. Women with and without T1D exhibited compositional and functional changes in the gut microbiome across pregnancy. Profiles in women with T1D were distinct, with an increase in bacteria that produce lipopolysaccharides and a decrease in those that produce short-chain fatty acids, especially in the third trimester. In addition, women with T1D had elevated concentrations of fecal calprotectin, a marker of intestinal inflammation, and serum intestinal fatty acid-binding protein (I-FABP), a marker of intestinal epithelial damage. Women with T1D exhibit a shift towards a more pro-inflammatory gut microbiome during pregnancy, associated with evidence of intestinal inflammation. These changes could contribute to the increased risk of pregnancy complications in women with T1D and are potentially modifiable by dietary means.
Publisher: Cold Spring Harbor Laboratory
Date: 05-07-2021
DOI: 10.1101/2021.07.04.21259873
Abstract: Chronic respiratory diseases are often difficult to cure and are likely to originate early in life. Therefore, early identification of such diseases is of interest for early prevention. We explored the potential to predict these almost from birth using data at 1 month of age, we attempted to predict disease occurrence 4 years later in life. Our data came from the Barwon Infant Study after cleaning and processing, we had measurements on 41 variables from 401 participants. We considered three respiratory diseases: asthma, wheeze and hay fever. As predictors, we used a variety of information that would be available in a clinical setting. Of particular interest to our investigation was whether lung function measurements (newly available at such an early age) would helpfully improve predictive accuracy. We also investigated whether maternal smoking (previously associated with respiratory illnesses) is a helpful predictor. Our methods included logistic regression as the main model, multiple imputation to deal with missing values, stepwise selection and LASSO to select variables, and cross-validation to assess performance. We measured predictive performance using AUC (area under the receiver operating characteristic curve), sensitivity and specificity. Broadly, we found that the best models had only modest predictive power for each disease. For ex le, for asthma we achieved an AUC of 0.67, a sensitivity of 68% and a corresponding specificity of 63%. Performance for the other two diseases was similar. We also found that our lung function measurements did not improve predictive performance some-what surprisingly, this was also true for maternal smoking. The most useful predictors included, among others, family history of these diseases and variables relating to the size of the infants. Given the modest performance of these models, our findings suggest that very early prediction of respiratory illnesses is still a challenging task.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Cold Spring Harbor Laboratory
Date: 02-12-2021
DOI: 10.1101/2021.12.02.21267173
Abstract: The risk of adult onset cardiovascular and metabolic (cardiometabolic) disease accrues from early life. Infection is ubiquitous in infancy and induces inflammation, a key cardiometabolic risk factor, but the relationship between infection, inflammation, and metabolic profiles in early childhood remains unexplored. We investigated relationships between infection and plasma metabolomic and lipidomic profiles at age 12 months, and mediation of these associations by inflammation. Matched infection, metabolomics and lipidomics data were generated from 555 infants in a pre-birth longitudinal cohort. Infection data from birth to 12 months were parent-reported (total infections at age 1, 3, 6, 9, and 12 months), inflammation markers (high-sensitivity C-reactive protein, hsCRP) glycoprotein acetyls GlycA) were quantified at 12 months. Metabolic profiles were 12-month plasma nuclear magnetic resonance metabolomics (228 metabolites) and liquid-chromatography/mass-spectrometry lipidomics (776 lipids). Associations were evaluated with multivariable linear regression models. Frequent infant infections were associated with adverse metabolomic (elevated inflammation markers, triglycerides, phenylalanine, and lower HDL cholesterol, apolipoprotein A1, and omega-3 fatty acids) and lipidomic profiles (elevated phosphatidylethanolamines and lower hexosylceramides, trihexosylceramides, and cholesteryl esters). Similar, more marked, profiles were observed with higher GlycA, but not hsCRP. GlycA, but not hsCRP, mediated a substantial proportion of the relationship between infection and metabolome/lipidome. Infants with a greater infection burden from birth to 12 months had pro-inflammatory and pro-atherogenic plasma metabolomic/lipid profiles, indicative of heightened risk of cardiovascular disease, obesity, and type 2 diabetes in adults. These findings suggest potentially modifiable pathways linking early life infection and inflammation with subsequent cardiometabolic risk. The establishment work and infrastructure for the BIS was provided by the Murdoch Children’s Research Institute (MCRI), Deakin University and Barwon Health. Subsequent funding was secured from National Health and Medical Research Council of Australia (NHMRC), The Shepherd Foundation, The Jack Brockhoff Foundation, the Scobie & Claire McKinnon Trust, the Shane O’Brien Memorial Asthma Foundation, the Our Women’s Our Children’s Fund Raising Committee Barwon Health, the Rotary Club of Geelong, the Minderoo Foundation, the Ilhan Food Allergy Foundation, GMHBA, Vanguard Investments Australia Ltd, and the Percy Baxter Charitable Trust, Perpetual Trustees. In-kind support was provided by the Cotton on Foundation and CreativeForce. The study sponsors were not involved in the collection, analysis, and interpretation of data writing of the report or the decision to submit the report for publication. Research at MCRI is supported by the Victorian Government’s Operational Infrastructure Support Program. This work was also supported by NHMRC Senior Research Fellowships (1008396 to ALP 1064629 to DB 1045161 to RS), NHMRC Investigator Grants to ALP (1110200) and DB (1175744), NHMRC-A*STAR project grant (1149047). TM is supported by an MCRI ECR Fellowship. SB is supported by the Dutch Research Council (452173113).
Publisher: MDPI AG
Date: 16-12-2013
Publisher: Wiley
Date: 09-08-2021
DOI: 10.1111/ALL.15022
Abstract: Bacille Calmette‐Guérin (BCG) vaccine could play a role in counteracting the rising prevalence of atopic diseases, through its beneficial off‐target effects. We aimed to determine whether neonatal BCG vaccination reduces the incidence of eczema in infants. Randomized controlled trial with 1272 infants allocated to receive BCG‐Denmark or no BCG at birth. The primary outcome was the 12‐month incidence of eczema based on 3‐monthly questionnaires. Eczema was also assessed at a 12‐month clinic visit. ClinicalTrial.gov: NCT01906853. The 12‐month eczema incidence was 32.2% in the BCG group compared with 36.6% in the control group (adjusted risk difference (aRD) −4.3%, 95% CI −9.9% to 1.3%, multiple imputation model). In addition, comparing infants in the BCG group with the control group, 15.7% vs. 19.2% had eczema lesions at the 12‐month visit (aRD −3.5%, 95% CI −8.0% to 1.0%) 35.7% vs. 39.0% reported using topical steroids (aRD −3.3, 95% CI −9.2 to 2.7) and 7.3% vs. 10.2% had severe eczema scores (aRD −3.0%, 95% CI −8.8% to 2.7%). In 344 high‐risk infants (two atopic parents), the 12‐month eczema incidence was 35.3% in the BCG group compared with 46.8% in the control group (aRD −11.5%, 95% CI −21.9% to −1.2% number needed to treat 8.7, 95% CI 4.6 to 83.3). There is insufficient evidence to recommend neonatal BCG vaccination in all infants for the prevention of eczema in the first year of life however, a modest beneficial effect was observed among high‐risk infants. A single dose of BCG‐Denmark soon after birth could reduce the incidence of eczema in infants with two atopic parents.
Publisher: Elsevier BV
Date: 04-2013
Publisher: Cambridge University Press (CUP)
Date: 17-12-2019
DOI: 10.1017/S2040174419000849
Abstract: Gut bacteria from the genus Prevotella are found in high abundance in faeces of non-industrialised communities but low abundance in industrialised, Westernised communities. Prevotella copri is one of the principal Prevotella species within the human gut. As it has been associated with developmental health and disease states, we sought to (i) develop a real-time polymerase chain reaction (PCR) to rapidly determine P. copri abundance and (ii) investigate its abundance in a large group of Australian pregnant mothers. The Barwon Infant Study is a pre-birth cohort study ( n = 1074). Faecal s les were collected from mothers at 36 weeks gestation. Primers with a probe specific to the V3 region of P. copri 16S rRNA gene were designed and optimised for real-time PCR. Universal 16S rRNA gene primers lified pan-bacterial DNA in parallel. Relative abundance of P. copri was calculated using a 2 -Δ Ct method. Relative abundance of P. copri by PCR was observed in 165/605 (27.3%) women. The distribution was distinctly bimodal, defining women with substantial ( n = 115/165, 69.7%) versus very low P. copri expression ( n = 50/165, 30.3%). In addition, abundance of P. copri by PCR correlated with 16S rRNA gene MiSeq sequencing data ( r 2 = 0.67, P 0.0001, n = 61). We have developed a rapid and cost-effective technique for identifying the relative abundance of P. copri using real-time PCR. The expression of P. copri was evident in only a quarter of the mothers, and either at substantial or very low levels. PCR detection of P. copri may facilitate assessment of this species in large, longitudinal studies across multiple populations and in various clinical settings.
Publisher: Frontiers Media SA
Date: 21-09-2022
DOI: 10.3389/FIMMU.2022.986340
Abstract: Preclinical studies have shown that maternal gut microbiota during pregnancy play a key role in prenatal immune development but the relevance of these findings to humans is unknown. The aim of this prebirth cohort study was to investigate the association between the maternal gut microbiota in pregnancy and the composition of the infant’s cord and peripheral blood immune cells over the first year of life. The Barwon Infant Study cohort ( n =1074 infants) was recruited using an unselected s ling frame. Maternal fecal s les were collected at 36 weeks of pregnancy and flow cytometry was conducted on cord eripheral blood collected at birth, 6 and 12 months of age. Among a randomly selected sub-cohort with available s les ( n =293), maternal gut microbiota was characterized by sequencing the 16S rRNA V4 region. Operational taxonomic units (OTUs) were clustered based on their abundance. Associations between maternal fecal microbiota clusters and infant granulocyte, monocyte and lymphocyte subsets were explored using compositional data analysis. Partial least squares (PLS) and regression models were used to investigate the relationships/associations between environmental, maternal and infant factors, and OTU clusters. We identified six clusters of co-occurring OTUs. The first two components in the PLS regression explained 39% and 33% of the covariance between the maternal prenatal OTU clusters and immune cell populations in offspring at birth. A cluster in which Dialister, Escherichia , and Ruminococcus were predominant was associated with a lower proportion of granulocytes ( p =0.002), and higher proportions of both central naïve CD4 + T cells (CD4 + /CD45RA + /CD31 − ) ( p & .001) and naïve regulatory T cells (Treg) (CD4 + /CD45RA + /FoxP3 low ) ( p =0.02) in cord blood. The association with central naïve CD4 + T cells persisted to 12 months of age. This birth cohort study provides evidence consistent with past preclinical models that the maternal gut microbiota during pregnancy plays a role in shaping the composition of innate and adaptive elements of the infant’s immune system following birth.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 13-01-2016
DOI: 10.1126/SCITRANSLMED.AAD4322
Abstract: Infants who develop food allergy display hyperresponsive innate immunity at birth that promotes nonclassical T H 2 differentiation.
Publisher: Oxford University Press (OUP)
Date: 07-04-2017
DOI: 10.1093/IJE/DYW042
Abstract: The maternal and infant microbiome may influence infant cardiovascular risk through immune programming. The maternal vagino-enteric microbiome is often s led for group B streptococcus (GBS) colonization during pregnancy. Our aim was to investigate the association between maternal GBS colonization, intrapartum antibiotics, antenatal pet exposure and infant aortic intima-media thickness (aIMT), an intermediate vascular phenotype, and whether this association varied by mode of delivery. The Barwon Infant Study is a population-derived pre-birth cohort. Perinatal data were collected on participants. Women were tested for vagino-enteric group B streptococcus (GBS) colonization during third trimester. Six-week infant aIMT was measured by trans-abdominal ultrasound. Adjustment for confounders included maternal age, pre-pregnancy body mass index (BMI), smoking, socioeconomic status, gestational diabetes, length of gestation, infant sex, birthweight and aortic internal diameter. Data were available on 835 mother-infant pairs. Of these, 574 (69%) women delivered vaginally of those, 129 (22%) were GBS-colonized and of these women, 111 (86%) received prophylactic intrapartum antibiotics. An association between maternal GBS colonization and infant aIMT was observed among those delivered vaginally (β = 19.5 µm, 95% CI 9.5, 29.4 P < 0.0001) but not by Caesarean section ( P for interaction = 0.02). A similar pattern was seen for intrapartum antibiotics. There was a negative association between antenatal pet exposure and aIMT observed in those delivered vaginally. Maternal GBS colonization and intrapartum antibiotics were associated with increased infant aIMT in those delivered vaginally, whereas antenatal pet exposure was associated with decreased aIMT. These data suggest that differences in early life microbial experience may contribute to an increased cardiovascular risk.
Publisher: Mary Ann Liebert Inc
Date: 16-02-2022
Publisher: Springer Science and Business Media LLC
Date: 27-02-2020
Publisher: Springer Science and Business Media LLC
Date: 03-06-2014
Publisher: Elsevier BV
Date: 10-2019
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.CELREP.2016.05.047
Abstract: The incidence of food allergies in western countries has increased dramatically in recent decades. Tolerance to food antigens relies on mucosal CD103(+) dendritic cells (DCs), which promote differentiation of regulatory T (Treg) cells. We show that high-fiber feeding in mice improved oral tolerance and protected from food allergy. High-fiber feeding reshaped gut microbial ecology and increased the release of short-chain fatty acids (SCFAs), particularly acetate and butyrate. High-fiber feeding enhanced oral tolerance and protected against food allergy by enhancing retinal dehydrogenase activity in CD103(+) DC. This protection depended on vitamin A in the diet. This feeding regimen also boosted IgA production and enhanced T follicular helper and mucosal germinal center responses. Mice lacking GPR43 or GPR109A, receptors for SCFAs, showed exacerbated food allergy and fewer CD103(+) DCs. Dietary elements, including fiber and vitamin A, therefore regulate numerous protective pathways in the gastrointestinal tract, necessary for immune non-responsiveness to food antigens.
Publisher: Elsevier BV
Date: 08-2022
Publisher: Springer Science and Business Media LLC
Date: 16-10-2017
Publisher: Wiley
Date: 10-10-2019
DOI: 10.1111/APA.14932
Abstract: We investigated the effect of early-life factors, namely sex, delivery mode, feeding method and antibiotic exposure, on antibody responses to routine vaccinations administered during the first year of life. One and seven months after the primary course of routine vaccines and 1 month after routine vaccines at 12 months of age, antibodies against 26 vaccine antigens were measured in 398 healthy infants. The geometric mean concentration (GMC) of antibodies (adjusted for effect modifiers with multiple linear regression) and the seroprotection rate for each vaccine were compared for each early-life factor. Sex had an influence on GMCs. Antibody concentrations were significantly lower at 7 months of age in females for tetanus and filamentous haemagglutinin and at 13 months of age for pertactin. In contrast, at 13 months of age, antibody concentrations were significantly higher in females for polio type 3, pneumococcal serotype 6A and measles. Sex did not have an influence on seroprotection rates. Delivery mode, feeding method and antibiotic exposure did not exert a substantial influence on vaccine antibody concentrations. There is a difference between males and females in the humoral response to routine vaccinations in the first year of life.
Publisher: Wiley
Date: 28-05-2013
DOI: 10.1111/CEA.12048
Abstract: A variety of hypotheses have been proposed to explain the recently described increase in food allergy among children living in developed countries. In this study, we summarize the emerging risk factors for IgE-mediated food allergy in early life, and then review the evidence for and against an association between low vitamin status (VDS) and food allergy. We consider whether each of the epidemiological variables that have been associated with food allergy may also be associated with VDS and argue that future studies must adequately account for the potential relationships between risk factors for food allergy and VDS, and must also discriminate between vitamin D derived by sun exposure, diet and oral supplementation.
Publisher: Cambridge University Press (CUP)
Date: 22-05-2014
DOI: 10.1017/S2040174414000282
Abstract: Childhood cardiovascular risk factors affect vascular function long before overt cardiovascular disease. Twin studies provide a unique opportunity to examine the influence of shared genetic and environmental influences on childhood cardiovascular function. We examined the relationship between birth parameters, markers of adiposity, insulin resistance, lipid profile and blood pressure and carotid–femoral pulse wave velocity (PWV), a validated non-invasive measure of arterial stiffness in a healthy cohort of school-aged twin children. PWV was performed on a population-based birth cohort of 147 twin pairs aged 7–11 years. Fasting blood s les, blood pressure and adiposity measures were collected concurrently. Mixed linear regression models were used to account for twin clustering, within- and between-twin pair associations. There were positive associations between both markers of higher adiposity, insulin resistance, elevated triglycerides and PWV, which remained significant after accounting for twin birth-set clustering. There was a positive association between both diastolic and mean arterial blood pressure and PWV in within-pair analysis in dizygotic, but not monozygotic twins, indicating genetic differences evident in dizygotic not monozygotic twins may affect these associations. Increased blood pressure, triglycerides and other metabolic markers are associated with increased PWV in school-aged twins. These results support both the genetic and environmental contribution to higher PWV, as a marker of arterial stiffness, and reiterate the importance of preventing metabolic syndrome from childhood.
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.NEURO.2016.05.011
Abstract: Accumulating evidence, from animal models and human observational studies, implicates the in utero (and early postnatal) environment in the 'programming' of risk for a variety of adverse outcomes and health trajectories. The modern environment is replete with man-made compounds such as plastic product chemicals (PPC), including phenols and phthalates. Evidence from several human cohorts implicates exposure to these chemicals in adverse offspring neurodevelopment, though a direct causal relationship has not been firmly established. In this review we consider a potential causal pathway that encompasses epigenetic human variation, and how we might test this mechanistic hypothesis in human studies. In the first part of this report we outline how PPCs induce epigenetic change, focusing on the brain derived neurotrophic factor (BDNF) gene, a key regulator of neurodevelopment. Further, we discuss the role of the epigenetics of BDNF and other genes in neurodevelopment and the emerging human evidence of an association between phthalate exposure and adverse offspring neurodevelopment. We discuss aspects of epidemiological and molecular study design and analysis that could be employed to strengthen the level of human evidence to infer causality. We undertake this using an exemplar recent research ex le: maternal prenatal smoking, linked to methylation change at the aryl hydrocarbon receptor repressor (AHRR) gene at birth, now shown to mediate some of the effects of maternal smoking on birth weight. Characterizing the relationship between the modern environment and the human molecular pathways underpinning its impact on early development is paramount to understanding the public health significance of modern day chemical exposures.
Publisher: Wiley
Date: 27-07-2017
DOI: 10.1111/JPC.13616
Abstract: The aim of this study was to describe antibiotic exposure in Australian infants during the first year of life, focusing on antibiotic class, indication, risk factors associated with exposure and comparison with international counterparts. The Barwon Infant Study is a birth cohort study (n = 1074) with an unselected antenatal s ling frame from a large regional centre in Victoria, Australia. Longitudinal data on infection and medication were collected at 1, 3, 6, 9 and 12 months by parental questionnaire and from general practitioner and hospital records. Predictors of questionnaire non-completion were identified. A total of 660 infants with complete serial data were comprehensively examined. Antibiotic exposure was calculated as (i) antibiotic prescriptions and (ii) antibiotic days-exposed per person-year. Mean antibiotic prescription rate was 0.92 prescriptions (95% confidence interval (CI), 0.83-1.02) per person-year, with the highest rates in those aged <1 month (1.50 (95% CI, 1.09-1.91) per person-year). A total of 50.0% of infants were exposed to at least one antibiotic in their first year of life. Increasing number of siblings was associated with increased antibiotic exposure. Penicillin with extended spectrum (365 of 661 antibiotic prescriptions, 52.6%) and cephalosporins (12.0%) were the most frequently prescribed antibiotics. One fifth of antibiotics were prescribed for respiratory tract infections and bronchiolitis. Australian infants in this large population-based study are exposed to considerably more antibiotics than the majority of their international counterparts. Interventions aimed at addressing avoidable prescribing by medical practitioners and modifiable risk factors associated with antibiotic exposure may reduce antibiotic use.
Publisher: Bentham Science Publishers Ltd.
Date: 02-07-2015
DOI: 10.2174/1389557515666150519111328
Abstract: Studies from several countries have reported an association between latitudes further from the equator and proxy markers of food allergy prevalence. As latitudes further from the equator are associated with lower sun exposure and vitamin D status (VDS), it has been proposed that low VDS may be a risk factor for food allergy. A range of basic science evidence supports the biological plausibility of this hypothesis and recent work has identified a cross sectional association between low VDS and challenge proven food allergy in infants. Overall, however, the evidence regarding the relationship between VDS and food allergy remains controversial and the limited longitudinal data are discouraging. In this review we consider the evidence for and against low VDS as a risk factor for food allergy and discuss the possibility that other factors (including genetic variables) may contribute to the inconsistent nature of the available observational evidence. We then discuss whether genetic and/or environmental factors may modify the potential influence of VDS on food allergy risk. Finally, we argue that given the rising burden of food allergy, the balance of available evidence regarding the potential relevance of VDS to this phenomenon, and the inherent limitations of the existing observational data, there is a compelling case for conducting randomised clinical trials of vitamin D supplementation for the prevention of food allergy during early life.
Publisher: Wiley
Date: 19-07-2021
DOI: 10.1111/DME.14638
Publisher: Portland Press Ltd.
Date: 04-02-2016
DOI: 10.1042/CS20150685
Abstract: Infant body composition and postnatal weight gain have been implicated in the development of adult obesity and cardiovascular disease, but there are limited prospective data regarding the association between infant adiposity, postnatal growth and early cardiovascular parameters. Increased aortic intima-media thickness (aortic IMT) is an intermediate phenotype of early atherosclerosis. The aim of the present study was to investigate the relationship between weight and adiposity at birth, postnatal growth and aortic IMT. The Barwon Infant Study (n=1074 mother–infant pairs) is a population-derived birth cohort. Infant weight and other anthropometry were measured at birth and 6 weeks of age. Aortic IMT was measured by trans-abdominal ultrasound at 6 weeks of age (n=835). After adjustment for aortic size and other factors, markers of adiposity including increased birth weight (β=19.9 μm/kg, 95%CI 11.1, 28.6 P& .001) and birth skinfold thickness (β=6.9 μm/mm, 95%CI 3.3, 10.5 P& .001) were associated with aortic IMT at 6 weeks. The association between birth skinfold thickness and aortic IMT was independent of birth weight. In addition, greater postnatal weight gain was associated with increased aortic IMT, independent of birth weight and age at time of scan (β=11.3 μm/kg increase, 95%CI 2.2, 20.3 P=0.01). Increased infant weight and adiposity at birth, as well as increased early weight gain, were positively associated with aortic IMT. Excessive accumulation of adiposity during gestation and early infancy may have adverse effects on cardiovascular risk.
Publisher: Wiley
Date: 17-01-2019
DOI: 10.1111/ALL.14159
Abstract: A few studies have investigated the antecedents and outcomes of infants who demonstrate IgE sensitization to foods that they clinically tolerate. Improved understanding of this sensitized-tolerant phenotype may inform strategies for the prevention of food allergy. In an Australian birth cohort (n = 1074), assembled using an unselected antenatal s ling frame, participants were categorized as nonsensitized (NS), sensitizedtolerant (ST), or food allergic (FA) based on skin prick testing and food challenge at 12 months of age. Environmental exposures were recorded throughout. Cord blood regulatory T-cell populations were measured at birth. Subsequent childhood allergic disease was assessed by parent report, clinical examination, and repeat skin prick testing. The covariates of interest varied between NS (n = 698), ST (n = 27), and FA (n = 61) groups as follows, suggesting that across these measures, the ST group was more similar to the NS than the FA group: family history of eczema NS 44.6%, ST. 44.6%, FA 65.6% pet ownership at 12 months: NS 71.5%, ST 81.5%, FA 45.8% eczema during the first 12 months: NS 19%, ST 32%, FA 64% and aeroallergen sensitization at 4 years: NS 19.1%, ST 28.6%, FA 44.4%. At birth, a higher proportion of activated regulatory T cells was associated with ST (OR = 2.89, 95% CI 1.03-8.16, P = .045). Food-sensitized-tolerance in infancy appears to be associated with a similar pattern of exposures, immunity, and outcomes to nonsensitized infants. In addition, we found some evidence that an elevated proportion of activated regulatory T cells at birth was specific to the sensitized-tolerant infants, which may be relevant to suppression of clinical disease.
Publisher: Springer Science and Business Media LLC
Date: 21-10-2020
DOI: 10.1038/S41366-019-0472-3
Abstract: Leptin regulates satiety and energy homoeostasis, and plays a key role in placentation in pregnancy. Previous studies have demonstrated regulation of leptin gene (LEP) expression and/or methylation in placenta and cord blood in association with early life exposures, but most have been small and have not considered the influence of genetic variation. Here, we investigated the relationship between maternal factors in pregnancy, infant anthropometry and LEP genetic variation with LEP promoter methylation at birth and 12 months of age. LEP methylation was measured in cord (n = 877) and 12-month (n = 734) blood in the Barwon Infant Study, a population-based pre-birth cohort. Infant adiposity at birth and 12-months was measured as triceps and subscapular skinfold thickness. Cross-sectional regression tested associations of methylation with pregnancy and anthropometry measures, while longitudinal regression tested if birth anthropometry predicted 12-month LEP methylation levels. Male infants had lower LEP methylation in cord blood (-2.07% average methylation, 95% CI (-2.92, -1.22), p < 0.001). Genetic variation strongly influenced DNA methylation at a single CpG site, which was also negatively associated with birth weight (r = -0.10, p = 0.003). Pre-ecl sia was associated with lower cord blood methylation at another CpG site (-6.06%, 95% CI (-10.70, -1.42), p = 0.01). Gestational diabetes was more modestly associated with methylation at two other CpG units. Adiposity at birth was associated with 12-month LEP methylation, modified by rs41457646 genotype. There was no association of LEP methylation with 12-month anthropometric measures. Infant sex, weight, genetic variation, and exposure to pre-ecl sia and gestational diabetes, are associated with LEP methylation in cord blood. Infant adiposity at birth predicts 12-month blood LEP methylation in a genotype-dependent manner. These findings are consistent with genetics and anthropometry driving altered LEP epigenetic profile and expression in infancy. Further work is required to confirm this and to determine the long-term impact of altered LEP methylation on health.
Publisher: BMJ
Date: 03-06-2010
Abstract: There are a variety of reasons why there may be an association between asthma and anxiety in children. Research into the relation between asthma and anxiety has been limited by the sole use of parent-reported or self-reported asthma symptoms to define asthma status. The objective of this study was to determine if children with physician-defined asthma are more likely to suffer anxiety than children without asthma. A population-based, cross-sectional assessment, of self-reported anxiety symptoms. Children aged 5-13 years from Barwon region of Victoria, Australia. Asthma status was determined by review with a paediatrician. Controls were a s le of children without asthma symptoms (matched for age, gender and school). The Spence Children's Anxiety Scale (SCAS) written questionnaire. The authors compared the mean SCAS score, and the proportion of children with an SCAS score in the clinical range, between the groups. Questionnaires were issued to 205 children with asthma (158 returned, response rate 77%), and 410 controls (319 returned, response rate 78%). The SCAS scores were higher in asthmatics than controls (p<0.001) and were more likely to be in the clinical range (OR=2.5, 95% CI 1.1 to 5.8, p=0.036). There was no evidence that these associations could be explained by known confounding factors. Children with asthma are substantially more likely to suffer anxiety than children without asthma. Future studies are required to determine the sequence of events that leads to this comorbidity, and to test strategies to prevent and treat anxiety among children with asthma.
Publisher: Wiley
Date: 19-02-2014
DOI: 10.1111/JPC.12495
Abstract: We present the case of a 16-year-old male who presented reporting a 6-month history of lowered mood, fatigue, anhedonia, disturbed sleep and heightened anxiety. On further questioning he reported restricted eating and weightlifting for at least 1 h on a daily basis. Investigations revealed findings compatible with secondary hypogonadism. The potential causes of secondary hypogonadism including structural lesions, muscle dysmorphia and use of illicit anabolic steroids are discussed.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Cold Spring Harbor Laboratory
Date: 14-06-2022
DOI: 10.1101/2022.06.08.22275892
Abstract: Prenatal phthalate exposure has previously been linked to the development of autism spectrum disorder (ASD). However, the underlying biological mechanisms remain unclear. We investigated whether maternal and child central carbon metabolism is involved as part of the Barwon Infant Study, a population-based birth cohort of 1074 Australian children. We estimated phthalate daily intakes using third-trimester urinary phthalate metabolite concentrations and other relevant indices. The metabolome of maternal serum in the third trimester, cord blood at birth and child plasma at 1 year were measured by nuclear magnetic resonance. We used the Small Molecule Pathway Database and principal component analysis to construct composite metabolite scores reflecting metabolic pathways. ASD symptoms at 2 and 4 years were measured by subscales of the Child Behavior Checklist and the Strengths and Difficulties Questionnaire, respectively. Multivariable linear regression analyses demonstrated (i) associations between higher prenatal di(2-ethylhexyl) phthalate (DEHP) levels and increased activity in maternal non-oxidative energy metabolism pathways, specifically non-oxidative pyruvate metabolism and the Warburg Effect, and (ii) associations between increased activity in these pathways and increased offspring ASD symptomology at 2 and 4 years of age. Mediation analyses suggested that part of the mechanism by which higher prenatal DEHP exposure influences the development of ASD symptoms in early childhood is through a maternal metabolic shift in pregnancy towards non-oxidative energy pathways, which are inefficient compared to oxidative metabolism. Interventions targeting maternal metabolic activity in pregnancy may be beneficial in reducing the potential risk to the developing fetus.
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.JACI.2014.11.012
Abstract: Rapid environmental transition and modern lifestyles are likely driving changes in the bio ersity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity for multisystem effects. Changes in microbial composition are implicated in the increasing propensity for a broad range of inflammatory diseases, such as allergic disease, asthma, inflammatory bowel disease (IBD), obesity, and associated noncommunicable diseases (NCDs). There are also suggestive implications for neurodevelopment and mental health. These erse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For ex le, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti-inflammatory properties. Specific probiotics also have immunomodulatory and metabolic effects. However, when evaluated in clinical trials, the effects are variable, preliminary, or limited in magnitude. Fecal microbiota transplantation is another emerging therapy that regulates inflammation in experimental models. In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention.
Publisher: SAGE Publications
Date: 22-02-2022
DOI: 10.1177/19322968221079867
Abstract: The Environmental Determinants of Islet Autoimmunity (ENDIA) study is an Australia-wide pregnancy-birth cohort study following children who have a first-degree relative with type 1 diabetes (ACTRN1261300794707). A dedicated ENDIA Facebook page was established in 2013 with the aim of enhancing recruitment and supporting participant retention through dissemination of study information. To measure the impact of Facebook, we evaluated the sources of referral to the study, cohort demographics, and withdrawal rates. We also investigated whether engagement with Facebook content was associated with specific post themes. Characteristics of Facebook versus conventional recruits were compared using linear, logistic, and multinomial logistic regression models. Logistic regression was used to determine the risk of study withdrawal. Data pertaining to 794 Facebook posts over 7.5 years were included in the analysis. Facebook was the third largest source of referral (300/1511 19.9%). Facebook recruits were more frequently Australian-born ( P .001) enrolling postnatally ( P = .01) and withdrew from the study at a significantly lower rate compared with conventional recruits (4.7% vs 12.3% P .001) after a median of follow-up of 3.3 years. Facebook content featuring stories and images of participants received the highest engagement even though % of the 2337 Facebook followers were enrolled in the study. Facebook was a valuable recruitment tool for ENDIA. Compared with conventional recruits, Facebook recruits were three times less likely to withdraw during long-term follow-up and had different sociodemographic characteristics. Facebook content featuring participants was the most engaging. These findings inform social media strategies for future cohort and type 1 diabetes studies. Australia New Zealand Clinical Trials Registry: ACTRN1261300794707.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.JSAMS.2018.11.021
Abstract: Higher physical activity (PA) levels in adults are associated with lower cardiovascular disease risk, however it is unclear whether this association is evident in children younger than five years. Given that cardiovascular disease has early life origins, this study systematically reviews evidence of associations between PA and cardiovascular disease risk factors among children aged 3-5.5years. Systematic review. A systematic search of multiple data bases was conducted to identify published papers reporting associations between any measure of PA and cardiovascular disease risk factors. English language peer-reviewed original quantitative research mean age or majority of s le to be between 3.0-5.5years. Studies where the s le was characterised by a health condition (e.g. obese, hypertensive) were not eligible for inclusion. Twelve papers met the inclusion criteria. At least one study for each cardiovascular disease risk factor except inflammation was included. PA was not associated with insulin resistance, and inconsistently associated with the remaining cardiovascular disease risk factors. Studies were mostly cross-sectional and methodologically heterogeneous. Longitudinal and experimental study designs and objective measurement of PA may help provide a clearer indication of the interplay between PA and cardiovascular disease risk in the preschool population.
Publisher: Springer Science and Business Media LLC
Date: 12-03-2018
DOI: 10.1038/S41598-018-22491-7
Abstract: To optimise fecal s ling for reproducible analysis of the gut microbiome, we compared different methods of s le collection and sequencing of 16S rRNA genes at two centers. S les collected from six in iduals on three consecutive days were placed in commercial collection tubes (OMNIgeneGut OMR-200) or in sterile screw-top tubes in a home fridge or home freezer for 6–24 h, before transfer and storage at −80 °C. Replicate s les were shipped to centers in Australia and the USA for DNA extraction and sequencing by their respective PCR protocols, and analysed with the same bioinformatic pipeline. Variation in gut microbiome was dominated by differences between in iduals. Minor differences in the abundance of taxa were found between collection-processing methods and day of collection, and between the two centers. We conclude that collection with storage and transport at 4 °C within 24 h is adequate for 16S rRNA analysis of the gut microbiome. Other factors including differences in PCR and sequencing methods account for relatively minor variation compared to differences between in iduals.
Publisher: Frontiers Media SA
Date: 31-03-2017
Publisher: BMJ
Date: 12-2015
Publisher: Wiley
Date: 06-08-2007
DOI: 10.1111/J.1742-6723.2007.01001.X
Abstract: To test the hypothesis that urinary tract infections (UTI) in young infants are rarely associated with meningitis. We undertook a review of the laboratory results from 322 infants, 90 days of age or younger, with an admission or discharge diagnosis of UTI or meningitis. The study was conducted in a tertiary paediatric hospital. The primary outcome measure was the incidence of coexisting urinary tract and cerebrospinal fluid sepsis. In total, 161 of the 322 (50%) infants with an admission or discharge diagnosis of UTI or meningitis were subsequently shown to have a culture-proven UTI. Of the children with a culture-proven UTI, 75 (47%) had cerebrospinal fluid obtained. We detected one case of probable bacterial meningitis in association with UTI. UTI is rarely associated with meningitis in infants 90 days of age or younger.
Publisher: AMPCo
Date: 08-2007
DOI: 10.5694/J.1326-5377.2007.TB01203.X
Abstract: To determine (i) the relationship between asthma management and socioeconomic status (ii) whether recent estimates from the International Study of Asthma and Allergies in Childhood (ISAAC) conducted in Melbourne apply to a broader cross-section of Victorian children and (iii) age-related trends in asthma prevalence. A questionnaire survey, based on the ISAAC protocol. Subjects were children aged 4-13 years from a random s le of primary schools in the Barwon region of Victoria. The survey was conducted between March and September 2005. Parent-reported wheeze and wheeze-related use of health resources during the preceding 12 months. Questionnaires were returned by 7813/9258 students (84%). Lower socioeconomic status was associated with increased frequency of regular asthma reviews (P or = 12 episodes of wheeze (P = 0.01) but an age-related decrease in emergency department visits (P = 0.02). Disadvantaged children have good access to regular asthma reviews and are no more likely to attend an emergency department with an episode of acute wheeze. Asthma prevalence in 6- and 7-year-old children in the Barwon region is similar to that in Melbourne. The prevalence of children with very frequent wheeze increases with age, but their use of health resources decreases.
Publisher: Wiley
Date: 19-07-2006
Publisher: Elsevier BV
Date: 10-2020
Publisher: MDPI AG
Date: 21-04-2022
DOI: 10.3390/IJMS23094601
Abstract: Environmental factors can accelerate telomere length (TL) attrition. Shortened TL is linked to attention deficit/hyperactivity disorder (ADHD) symptoms in school-aged children. The onset of ADHD occurs as early as preschool-age, but the TL-ADHD association in younger children is unknown. We investigated associations between infant TL and ADHD symptoms in children and assessed environmental factors as potential confounders and/or mediators of this association. Relative TL was measured by quantitative polymerase chain reaction in cord and 12-month blood in the birth cohort study, the Barwon Infant Study. Early life environmental factors collected antenatally to two years were used to measure confounding. ADHD symptoms at age two years were evaluated by the Child Behavior Checklist Attention Problems (AP) and the Attention Deficit/Hyperactivity Problems (ADHP). Associations between early life environmental factors on TL or ADHD symptoms were assessed using multivariable regression models adjusted for relevant factors. Telomere length at 12 months (TL12), but not at birth, was inversely associated with AP (β = −0.56 95% CI (−1.13, 0.006) p = 0.05) and ADHP (β = −0.66 95% CI (−1.11, −0.21) p = 0.004). Infant secondhand smoke exposure at one month was independently associated with shorter TL12 and also higher ADHD symptoms. Further work is needed to elucidate the mechanisms that influence TL attrition and early neurodevelopment.
Publisher: eLife Sciences Publications, Ltd
Date: 02-03-2022
DOI: 10.7554/ELIFE.72779
Abstract: There is mounting evidence that in utero and early life exposures may predispose an in idual to metabolic disorders in later life and dysregulation of lipid metabolism is critical in such outcomes. However, there is limited knowledge about lipid metabolism and factors causing lipid dysregulation in early life that could result in adverse health outcomes in later life. We studied the effect of antenatal factors such as gestational age, birth weight, and mode of birth on lipid metabolism at birth changes in the circulating lipidome in the first 4 years of life and the effect of breastfeeding in the first year of life. From this study, we aim to generate a framework for deeper understanding into factors effecting lipid metabolism in early life, to provide early interventions for those at risk of developing metabolic disorders including cardiovascular diseases. We performed comprehensive lipid profiling of 1074 mother-child dyads in the Barwon Infant Study (BIS), a population-based pre-birth cohort and measured 776 distinct lipid features across 39 lipid classes using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). We measured lipids in 1032 maternal serum s les at 28 weeks’ gestation, 893 cord serum s les at birth, 793, 735, and 511 plasma s les at 6, 12 months, and 4 years, respectively. Cord serum was enriched with long chain poly-unsaturated fatty acids (LC-PUFAs), and corresponding cholesteryl esters relative to the maternal serum. We performed regression analyses to investigate the associations of cord serum lipid species with antenatal factors: gestational age, birth weight, mode of birth and duration of labour. The lipidome differed between mother and newborn and changed markedly with increasing child’s age. Alkenylphosphatidylethanolamine species containing LC-PUFAs increased with child’s age, whereas the corresponding lysophospholipids and triglycerides decreased. Majority of the cord serum lipids were strongly associated with gestational age and birth weight, with most lipids showing opposing associations. Each mode of birth showed an independent association with cord serum lipids. Breastfeeding had a significant impact on the plasma lipidome in the first year of life, with up to 17-fold increases in a few species of alkyldiaclylglycerols at 6 months of age. This study sheds light on lipid metabolism in infancy and early childhood and provide a framework to define the relationship between lipid metabolism and health outcomes in early childhood. This work was supported by the A*STAR-NHMRC joint call funding (1711624031).
Publisher: SAGE Publications
Date: 11-01-2022
DOI: 10.1177/13623613211068223
Abstract: Mounting evidence finds that early life environmental factors increased the probability of autism spectrum disorder. We estimated prospective associations between early life environmental factors and autism spectrum disorder symptoms in children at the age of 2 years in a population-derived birth cohort, the Barwon Infant Study. Autism spectrum disorder symptoms at the age of 2 years strongly predicted autism spectrum disorder diagnosis by the age of 4 years (area under curve = 0.93 95% CI (0.82, 1.00)). After adjusting for child’s sex and age at the time of behavioural assessment, markers of socioeconomic disadvantage, such as lower household income and lone parental status maternal health factors, including younger maternal age, maternal pre-pregnancy body mass index, higher gestational weight gain and prenatal maternal stress prenatal alcohol environmental air pollutant exposures, including particulate matter 2.5 µm at birth, child secondhand tobacco smoke exposure at 12 months, d ness/mould and home heating with oil, kerosene or diesel heaters at 2 years postnatal. Lower socioeconomic indexes for area, later birth order, higher maternal prenatal depression, and maternal smoking frequency had a dose-response relationship with autism spectrum disorder symptoms. Future studies on environmental factors and autism spectrum disorder should consider the reasons for the socioeconomic disparity and the combined impact of multiple environmental factors through common mechanistic pathways. Mounting evidence indicates the contribution of early life environmental factors in autism spectrum disorder. We aim to report the prospective associations between early life environmental factors and autism spectrum disorder symptoms in children at the age of 2 years in a population-derived birth cohort, the Barwon Infant Study. Autism spectrum disorder symptoms at the age of 2 years strongly predicted autism spectrum disorder diagnosis by the age of 4 years (area under curve = 0.93 95% CI (0.82, 1.00)). After adjusting for child’s sex and age at the time of behavioural assessment, markers of socioeconomic disadvantage, such as lower household income and lone parental status maternal health factors, including younger maternal age, maternal pre-pregnancy body mass index, higher gestational weight gain and prenatal maternal stress maternal lifestyle factors, such as prenatal alcohol and environmental air pollutant exposures, including particulate matter 2.5 μm at birth, child secondhand tobacco smoke at 12 months, d ness/mould and home heating with oil, kerosene or diesel heaters at 2 years postnatal. Lower socioeconomic indexes for area, later birth order, higher maternal prenatal depression and maternal smoking frequency had a dose-response relationship with autism spectrum disorder symptoms. Future studies on environmental factors and autism spectrum disorder should consider the reasons for the socioeconomic disparity and the combined impact of multiple environmental factors through common mechanistic pathways.
Publisher: BMJ
Date: 03-2010
DOI: 10.1136/BMJ.C843
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.JACI.2015.05.051
Abstract: There is evolving evidence that vitamin D insufficiency may contribute to food allergy, but findings vary between populations. Lower vitamin D-binding protein (DBP) levels increase the biological availability of serum vitamin D. Genetic polymorphisms explain almost 80% of the variation in binding protein levels. We sought to investigate whether polymorphisms that lower the DBP could compensate for adverse effects of low serum vitamin D on food allergy risk. From a population-based cohort study (n = 5276) we investigated the association between serum 25-hydroxyvitamin D3 (25[OH]D3) levels and food allergy at age 1 year (338 challenge-proven food-allergic and 269 control participants) and age 2 years (55 participants with persistent and 50 participants with resolved food allergy). 25(OH)D3 levels were measured using liquid chromatography-tandem mass spectrometry and adjusted for season of blood draw. Analyses were stratified by genotype at rs7041 as a proxy marker of DBP levels (low, the GT/TT genotype high, the GG genotype). Low serum 25(OH)D3 level (≤50 nM/L) at age 1 years was associated with food allergy, particularly among infants with the GG genotype (odds ratio [OR], 6.0 95% CI, 0.9-38.9) but not in those with GT/TT genotypes (OR, 0.7 95% CI, 0.2-2.0 P interaction = .014). Maternal antenatal vitamin D supplementation was associated with less food allergy, particularly in infants with the GT/TT genotype (OR, 0.10 95% CI, 0.03-0.41). Persistent vitamin D insufficiency increased the likelihood of persistent food allergy (OR, 12.6 95% CI, 1.5-106.6), particularly in those with the GG genotype. Polymorphisms associated with lower DBP level attenuated the association between low serum 25(OH)D3 level and food allergy, consistent with greater vitamin D bioavailability in those with a lower DBP level. This increases the biological plausibility of a role for vitamin D in the development of food allergy.
Publisher: Wiley
Date: 23-05-2007
DOI: 10.1111/J.1440-1754.2007.01108.X
Abstract: To determine (i) the proportion of doctors who recommend parent-initiated oral corticosteroids (PIOCS) for acute asthma and (ii) the proportion of parents who have received this advice. (i) An internet-based survey of doctors involved in the care of children with asthma and (ii) a questionnaire-based survey of parents of children aged 4-13 years who were identified from a random s le of primary schools within the Barwon region of Victoria. Eight-five per cent (95% confidence interval 80.0-89.1%) of responding doctors reported recommending PIOCS to parents of children with asthma. However, only 16.5% (95% confidence interval 14.2-18.7%) of parents of children with recent asthma symptoms report that they have received such advice. The majority of responding doctors involved in the care of children with asthma report recommending PIOCS to parents. By contrast, a minority of parents of children with asthma report that they have received such advice.
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/565160
Abstract: The incidence of gestational diabetes is increasing worldwide, exposing large numbers of infants to hyperglycaemia whilst in utero . This exposure may have a long-term negative impact on the cardiovascular health of the offspring. Novel methods to assess cardiovascular status in the neonatal period are now available—including measuring arterial intima-media thickness and retinal photography. These measures will allow researchers to assess the relative impact of intrauterine exposures, distinguishing these from genetic or postnatal environmental factors. Understanding the long-term impact of the intrauterine environment should allow the development of more effective health policy and interventions to decrease the future burden of cardiovascular disease. Initiating disease prevention aimed at the developing fetus during the antenatal period may optimise community health outcomes.
Publisher: Wiley
Date: 04-2015
DOI: 10.14814/PHY2.12347
Publisher: Wiley
Date: 23-09-2020
DOI: 10.1111/JPC.15174
Publisher: Elsevier BV
Date: 06-2021
Publisher: The American Association of Immunologists
Date: 15-02-2021
Abstract: Vitamin D has shown immune-modulatory effects but mostly in in vitro and animal studies. Regulatory T cells (Treg) are important for a balanced immune system. The relationship between vitamin D on the number of circulating neonatal Treg is unclear. We sought to investigate the association between maternal and neonatal vitamin D metabolites and cord blood (CB) Treg subsets. In a cohort of Australian infants (n = 1074), recruited using an unselected antenatal s ling frame, 158 mother–infant pairs had data on the following: 1) 25-hydroxyvitamin D3 (25(OH)D3) measures in both maternal peripheral blood (28- to 32-wk gestation) and infant CB 2) proportions (percentage of CD4+ T cells) of CB Treg subsets (CD4+CD45RA+ FOXP3low naive Treg, and CD4+CD45RA− FOXP3high activated Treg [aTreg]) and 3) possible confounders, including maternal personal UV radiation. Multiple regression analyses were used. The median 25(OH)D3 was 85.4 and 50.7 nmol/l for maternal and CB s les, respectively. Higher maternal 25(OH)D3 levels were associated with increased CB naive Treg (relative adjusted mean difference [AMD] per 25 nmol/l increase: 5% 95% confidence interval [CI]: 1–9%), and aTreg (AMD per 25 nmol/l increase: 17% 95% CI: 6–28%). Furthermore, a positive association between CB 25(OH)D3 levels and CB aTreg (AMD per 25 nmol/l increase: 29% 95% CI: 13–48%) was also evident. These results persisted after adjustment for other factors such as maternal personal UV radiation and season of birth. 25(OH)D3, may play a role in the adaptive neonatal immune system via induction of FOXP3+ Tregs. Further studies of immune priming actions of antenatal 25(OH)D3 are warranted.
Publisher: MDPI AG
Date: 29-03-2022
Abstract: The developing brain is highly sensitive to environmental disturbances, and adverse exposures can act through oxidative stress. Given that oxidative stress susceptibility is determined partly by genetics, multiple studies have employed genetic scores to explore the role of oxidative stress in human disease. However, traditional approaches to genetic score construction face a range of challenges, including a lack of interpretability, bias towards the disease outcome, and often overfitting to the study they were derived on. Here, we develop an alternative strategy by first generating a genetic pathway function score for oxidative stress (gPFSox) based on the transcriptional activity levels of the oxidative stress response pathway in brain and other tissue types. Then, in the Barwon Infant Study (BIS), a population-based birth cohort (n = 1074), we show that a high gPFSox, indicating reduced ability to counter oxidative stress, is linked to higher autism spectrum disorder risk and higher parent-reported autistic traits at age 4 years, with AOR values (per 2 additional pro-oxidant alleles) of 2.10 (95% CI (1.12, 4.11) p = 0.024) and 1.42 (95% CI (1.02, 2.01) p = 0.041), respectively. Past work in BIS has reported higher prenatal phthalate exposure at 36 weeks of gestation associated with offspring autism spectrum disorder. In this study, we examine combined effects and show a consistent pattern of increased neurodevelopmental problems for in iduals with both a high gPFSox and high prenatal phthalate exposure across a range of outcomes, including high gPFSox and high DEHP levels against autism spectrum disorder (attributable proportion due to interaction 0.89 95% CI (0.62, 1.16) p 0.0001). The results highlight the utility of this novel functional genetic score and add to the growing evidence implicating gestational phthalate exposure in adverse neurodevelopment.
Publisher: Wiley
Date: 05-2010
Publisher: Wiley
Date: 21-05-2017
DOI: 10.1111/CEA.12942
Abstract: Food allergies pose a considerable world-wide public health burden with incidence as high as one in ten in 12-month-old infants. Few food allergy genetic risk variants have yet been identified. The Th2 immune gene IL13 is a highly plausible genetic candidate as it is central to the initiation of IgE class switching in B cells. Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge-proven IgE-mediated food allergy. We genotyped nine IL13 "tag" single nucleotide polymorphisms (tag SNPs) in 367 challenge-proven food allergic cases, 199 food-sensitized tolerant cases and 156 non-food allergic controls from the HealthNuts study. 12-month-old infants were phenotyped using open oral food challenges. SNPs were tested using Cochran-Mantel-Haenszel test adjusted for ancestry strata. A replication study was conducted in an independent, co-located s le of four paediatric cohorts consisting of 203 food allergic cases and 330 non-food allergic controls. Replication s le phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed. IL13 rs1295686 was associated with challenge-proven food allergy in the discovery s le (P=.003 OR=1.75 CI=1.20-2.53). This association was also detected in the replication s le (P=.03, OR=1.37, CI=1.03-1.82) and further supported by a meta-analysis (P=.0006, OR=1.50). However, we cannot rule out an association with food sensitization. Carriage of the rs1295686 variant A allele was also associated with elevated total plasma IgE. We show for the first time, in two independent cohorts, that IL13 polymorphism rs1295686 (in complete linkage disequilibrium with functional variant rs20541) is associated with challenge-proven food allergy.
Publisher: American Diabetes Association
Date: 02-02-2022
DOI: 10.2337/DC21-2335
Abstract: Pregnancy and type 1 diabetes are each associated with increased anxiety and depression, but the combined impact on well-being is unresolved. We compared the mental health of women with and without type 1 diabetes during pregnancy and postpartum and examined the relationship between mental health and glycemic control. Participants were women enrolled from 2016 to 2020 in the Environmental Determinants of Islet Autoimmunity (ENDIA) study, a pregnancy to birth prospective cohort following children with a first-degree relative with type 1 diabetes. Edinburgh Postnatal Depression Scale (EPDS) and Perceived Stress Scale (PSS) were completed during the third trimester (T3) (median [interquartile range] 34 [32, 36] weeks) and postpartum (14 [13, 16] weeks) by 737 women (800 pregnancies) with (n = 518) and without (n = 282) type 1 diabetes. EPDS and PSS scores did not differ between women with and without type 1 diabetes during T3 and postpartum. EPDS scores were marginally higher in T3: predicted mean (95% CI) 5.7 (5.4, 6.1) than postpartum: 5.3 (5.0, 5.6), independent of type 1 diabetes status (P = 0.01). HbA1c levels in type 1 diabetes were 6.3% [5.8, 6.9%] in T3 and did not correlate with EPDS or PSS scores. Reported use of psychotropic medications was similar in women with (n = 44 of 518 [8%]) and without type 1 diabetes (n = 17 of 282 [6%]), as was their amount of physical activity. Overall, mental health in late pregnancy and postpartum did not differ between women with and without type 1 diabetes, and mental health scores were not correlated with glycemic control.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.BBI.2021.12.002
Abstract: Poor cognitive outcomes in early childhood predict poor educational outcomes and diminished health over the life course. We sought to investigate (i) whether maternal metabolites predict child cognition, and (ii) if maternal metabolomic profile mediates the relationship between environmental exposures and child cognition. Metabolites were measured using nuclear magnetic resonance-based metabolomics in pregnant women from a population-derived birth cohort. Child cognition was measured at age 2 years. In 662 mother-child pairs, elevated inflammatory markers (β = -2.62 95% CI -4.10, -1.15 P = 0.0005) and lower omega-3 fatty acid-related metabolites (β = 0.49 95% CI 0.09, 0.88 P = 0.02) in the mother were associated with lower child cognition and partially mediated the association between lower child cognition and multiple risk factors common to socioeconomic disadvantage. Modifying maternal prenatal metabolic pathways related to inflammation and omega-3 fatty acids may offset the adverse associations between prenatal risk factors related to socioeconomic disadvantage and low child cognition.
Publisher: Informa UK Limited
Date: 16-09-2021
Publisher: Hogrefe Publishing Group
Date: 06-2017
DOI: 10.1024/0301-1526/A000630
Abstract: Abstract. Background: Carotid intima-media thickness (CIMT), an ultrasonographic marker of cardiovascular risk, is increasingly used in adults and children. The choice of specific images used to quantify CIMT from a cine sequence is often based on image quality rather than on a consistent point in the cardiac cycle. This methodological study quantified the imprecision that may be introduced by variation of CIMT during the cardiac cycle. Probands and methods: Data from four-year-olds, 11 to 12-year-olds, and adults (n=30 each age group) were selected retrospectively from two population-derived studies. Far wall CIMT of the right common carotid artery was measured at end-diastole and peak systole using standardized protocols. All images were analysed using semi-automated edge-detection software. Results: In all age groups CIMT varied significantly during the cardiac cycle and was largest at end-diastole. The mean difference in CIMT between end-diastole and peak systole was greater in four-year-olds (38 μm 95 % confidence interval (CI) 33 to 43 μm) and 11 to 12-year-olds (31 μm CI 26 to 36 μm) than in adults (18 μm CI 16 to 22 μm). Carotid IMT increased by 8.8 % (CI 7.7 to 9.8 %), 6.9 % (CI 5.8 to 8.1 %), and 3.8 % (CI 3.1 to 4.5 %) between minimum and maximum arterial diameter in four-year-olds, 11 to 12-year-olds, and adults, respectively. The greatest variation in CIMT during the cardiac cycle was observed in children (up to 14 %). Conclusions: Inconsistent timing of CIMT measurement during the cardiac cycle is an avoidable source of imprecision, especially in children, in whom inter-in idual differences are smallest. As CIMT is largest at end-diastole, this is the most appropriate time point for consistent and comparable measurements to be made.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.DIABRES.2022.109189
Abstract: Studies of the gut microbiome have focused on its bacterial composition. We aimed to characterize the gut fungal microbiome (mycobiome) across pregnancy in women with and without type 1 diabetes. Faecal s les (n = 162) were collected from 70 pregnant women (45 with and 25 without type 1 diabetes) across all trimesters. Fungi were analysed by internal transcribed spacer 1 licon sequencing. Markers of intestinal inflammation (faecal calprotectin) and intestinal epithelial integrity (serum intestinal fatty acid binding protein I-FABP), and serum antibodies to Saccharomyces cerevisiae (ASCA) were measured. Women with type 1 diabetes had decreased fungal alpha ersity by the third trimester, associated with an increased abundance of Saccharomyces cerevisiae that was inversely related to the abundance of the anti-inflammatory butyrate-producing bacterium Faecalibacterium prausnitzii. Women with type 1 diabetes had higher concentrations of calprotectin, I-FABP and ASCA. Women with type 1 diabetes exhibit a shift in the gut mycobiome across pregnancy associated with evidence of gut inflammation and impaired intestinal barrier function. The relevance of these findings to the higher rate of pregnancy complications in type 1 diabetes warrants further study.
Publisher: Springer Science and Business Media LLC
Date: 17-08-2018
DOI: 10.1038/S41467-018-05608-4
Abstract: Food allergy poses a significant clinical and public health burden affecting 2–10% of infants. Using integrated DNA methylation and transcriptomic profiling, we found that polyclonal activation of naive CD4+ T cells through the T cell receptor results in poorer lymphoproliferative responses in children with immunoglobulin E (IgE)-mediated food allergy. Reduced expression of cell cycle-related targets of the E2F and MYC transcription factor networks, and remodeling of DNA methylation at metabolic ( RPTOR , PIK3D , MAPK1 , FOXO1 ) and inflammatory genes ( IL1R , IL18RAP , CD82 ) underpins this suboptimal response. Infants who fail to resolve food allergy in later childhood exhibit cumulative increases in epigenetic disruption at T cell activation genes and poorer lymphoproliferative responses compared to children who resolved food allergy. Our data indicate epigenetic dysregulation in the early stages of signal transduction through the T cell receptor complex, and likely reflects pathways modified by gene–environment interactions in food allergy.
Publisher: Wiley
Date: 05-05-2022
DOI: 10.1111/IJPO.12928
Abstract: Rapid weight gain (RWG) in infancy is strongly associated with subsequent obesity risk, but little is known about the factors driving RWG. This study explored the child and maternal factors associated with infant RWG. Data from seven Australian and New Zealand cohorts were used (n = 4542). Infant RWG was defined as a change in weight z‐score ≥0.67 from birth to age 1 year. Univariable and multivariable logistic regression assessed the association between child and maternal factors and infant RWG in each cohort. Meta‐analysis was conducted to obtain pooled effect sizes. Multivariable analyses revealed boys were more likely to experience RWG (OR 1.42 95% CI 1.22, 1.66) than girls. Higher birth weight in kg (OR 0.09, 95% CI 0.04, 0.20) and gestational age in weeks (OR 0.69, 95% CI 0.48, 0.98) were associated with lower RWG risk. Children who were breastfed for ≥6 months showed lower RWG risk (OR 0.45, 95% CI 0.38, 0.53). Children of native‐born versus overseas‐born women appeared to have higher RWG risk (OR 1.37, 95% CI 0.99, 1.90). Maternal smoking during pregnancy increased RWG risk (OR 1.60, 95% CI 1.28, 2.01), whereas children who started solids ≥6 months (OR 0.77, 95% CI 0.63, 0.93) and children with siblings (OR 0.68, 95% CI 0.57, 0.81) showed lower RWG risk in univariable analysis, but these associations were attenuated in multivariable analysis. No association was found for maternal age, education, marital status and pre‐pregnancy BMI. Maternal country of birth, smoking status, child sex, birth weight, gestational age, infant feeding and parity were potential determinants of infant RWG.
Publisher: Hindawi Limited
Date: 09-06-2020
DOI: 10.1111/PEDI.13056
Publisher: Oxford University Press (OUP)
Date: 16-01-2019
DOI: 10.1093/OFID/OFZ025
Abstract: The importance of gut bacteria in human physiology, immune regulation, and disease pathogenesis is well established. In contrast, the composition and dynamics of the gut virome are largely unknown particularly lacking are studies in pregnancy. We used comprehensive virome capture sequencing to characterize the gut virome of pregnant women with and without type 1 diabetes (T1D), longitudinally followed in the Environmental Determinants of Islet Autoimmunity study. In total, 61 pregnant women (35 with T1D and 26 without) from Australia were examined. Nucleic acid was extracted from serial fecal specimens obtained at prenatal visits, and viral genomes were sequenced by virome capture enrichment. The frequency, richness, and abundance of viruses were compared between women with and without T1D. Two viruses were more prevalent in pregnant women with T1D: picobirnaviruses (odds ratio [OR], 4.2 95% confidence interval [CI], 1.0–17.1 P = .046) and tobamoviruses (OR, 3.2 95% CI, 1.1–9.3 P = .037). The abundance of 77 viruses significantly differed between the 2 maternal groups (≥2-fold difference P & .02), including 8 Enterovirus B types present at a higher abundance in women with T1D. These findings provide novel insight into the composition of the gut virome during pregnancy and demonstrate a distinct profile of viruses in women with T1D.
Publisher: Oxford University Press (OUP)
Date: 30-03-2015
DOI: 10.1093/IJE/DYV026
Abstract: The modern environment is associated with an increasing burden of non-communicable diseases (NCDs). Mounting evidence implicates environmental exposures, experienced early in life (including in utero), in the aetiology of many NCDs, though the cellular/molecular mechanism(s) underlying this elevated risk across the life course remain unclear. Epigenetic variation has emerged as a candidate mediator of such effects. The Barwon Infant Study (BIS) is a population-derived birth cohort study (n = 1074 infants) with antenatal recruitment, conducted in the south-east of Australia (Victoria). BIS has been designed to facilitate a detailed mechanistic investigation of development within an epidemiological framework. The broad objectives are to investigate the role of specific environmental factors, gut microbiota and epigenetic variation in early-life development, and subsequent immune, allergic, cardiovascular, respiratory and neurodevelopmental outcomes. Participants have been reviewed at birth and at 1, 6, 9 and 12 months, with 2- and 4-year reviews under way. Biological s les and measures include: maternal blood, faeces and urine during pregnancy infant urine, faeces and blood at regular intervals during the first 4 years lung function at 1 month and 4 years cardiovascular assessment at 1 month and 4 years skin-prick allergy testing and food challenge at 1 year and neurodevelopmental assessment at 9 months, 2 and 4 years. Data access enquiries can be made at [www.barwoninfantstudy.org.au] or via [peter.vuillermin@deakin.edu.au].
Publisher: Springer Science and Business Media LLC
Date: 15-09-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2011
Publisher: Hindawi Limited
Date: 15-08-2016
DOI: 10.1111/PEDI.12425
Abstract: The incidence of type 1 diabetes globally has increased dramatically over the last 50 years. Proposed environmental reasons for this increase mirror the modern lifestyle. Type 1 diabetes can be viewed as part of the non- communicable disease epidemic in our modern society. Meanwhile rapidly evolving new technologies are advancing our understanding of how human microbial communities interface with the immune system and metabolism, and how the modern pro-inflammatory environment is changing these communities and contributing to the rapid rise of non-communicable disease. The majority of children who present with clinical type 1 diabetes are of school age however 80% of children who develop type 1 diabetes by 18 years of age will have detectable islet autoantibodies by 3 years of age. The evolving concept that type 1 diabetes in many children has developmental origins has directed research questions in search of prevention back to pregnancy and early life. To this end the world's first pregnancy to early childhood cohort study in at-risk children has commenced.
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.JACI.2016.03.012
Abstract: A biomarker is an accurately and reproducibly quantifiable biological characteristic that provides an objective measure of health status or disease. Benefits of biomarkers include identification of therapeutic targets, monitoring of clinical interventions, and development of personalized (or precision) medicine. Challenges to the use of biomarkers include optimizing s le collection, processing and storage, validation, and often the need for sophisticated laboratory and bioinformatics approaches. Biomarkers offer better understanding of disease processes and should benefit the early detection, treatment, and management of multiple noncommunicable diseases (NCDs). This review will consider the utility of biomarkers in patients with allergic and other immune-mediated diseases in childhood. Typically, biomarkers are used currently to provide mechanistic insight or an objective measure of disease severity, with their future role in risk stratification/disease prediction speculative at best. There are many lessons to be learned from the biomarker strategies used for cancer in which biomarkers are in routine clinical use and industry-wide standardized approaches have been developed. Biomarker discovery and validation in children with disease lag behind those in adults given the early onset and therefore potential lifelong effect of many NCDs, there should be more studies incorporating cohorts of children. Many pediatric biomarkers are at the discovery stage, with a long path to evaluation and clinical implementation. The ultimate challenge will be optimization of prevention strategies that can be implemented in children identified as being at risk of an NCD through the use of biomarkers.
Publisher: AMPCo
Date: 12-2011
DOI: 10.5694/MJA11.10493
Publisher: Wiley
Date: 24-11-2020
DOI: 10.5694/MJA2.50427
Abstract: To investigate blood lead levels in an Australian birth cohort of children to identify factors associated with higher lead levels. Cross-sectional study within the Barwon Infant Study, a population birth cohort study in the Barwon region of Victoria (1074 infants, recruited June 2010 - June 2013). Data were adjusted for non-participation and attrition by propensity weighting. Blood lead was measured in 523 of 708 children appraised in the Barwon Infant Study pre-school review (mean age, 4.2 years SD, 0.3 years). Blood lead concentration in whole blood (μg/dL). The median blood lead level was 0.8 μg/dL (range, 0.2-3.7 μg/dL) the geometric mean blood lead level after propensity weighting was 0.97 μg/dL (95% CI, 0.92-1.02 μg/dL). Children in houses 50 or more years old had higher blood lead levels (adjusted mean difference [AMD], 0.13 natural log units 95% CI, 0.02-0.24 natural log units P = 0.020), as did children of families with lower household income (per $10 000, AMD, -0.035 natural log units 95% CI, -0.056 to -0.013 natural log units P = 0.002) and those living closer to Point Henry (inverse square distance relationship P = 0.002). Associations between hygiene factors and lead levels were evident only for children living in older homes. Blood lead levels in our pre-school children were lower than in previous Australian surveys and recent surveys in areas at risk of higher exposure, and no children had levels above 5 μg/dL. Our findings support advice to manage risks related to exposure to historical lead, especially in older houses.
Publisher: Wiley
Date: 23-05-2007
DOI: 10.1111/J.1440-1754.2007.01107.X
Abstract: Intermittent wheezing illnesses, which include viral-associated wheeze and asthma, are among the most common reasons for children to present urgently to a doctor. The objectives of this systematic review were to assess the benefits and harmful effects of parent-initiated oral corticosteroids (PIOCS) in the management of intermittent wheezing illness in children. The Cochrane Airways Group Specialised Register, The Cochrane Controlled Trials Register (CENTRAL), MEDLINE, EMBASE, LILACS, Web of Science and Dissertation Abstracts were searched. Only randomised clinical trials studying patients aged between 1 and 18 years, with an intermittent wheezing illness were included. From 572 original citations, a total of two randomised clinical trials (303 randomised participants) were included. The quality of the included trials was high however, marked clinical heterogeneity precluded a meta-analysis. The two trials did not find evidence that PIOCS are associated with a benefit in terms of hospital admissions, unscheduled medical reviews, symptoms scores, or bronchodilator use. Limited current evidence is available and it is inconclusive regarding the benefit from PIOCS therapy in the treatment of intermittent wheezing illnesses in children. Oral corticosteroids have a clearly defined role in the management of acute asthma in the hospital setting. Therefore, it is reasonable for clinicians to recommend PIOCS when (i) the child has a history of severe acute asthma and (ii) the parents are able to assess asthma status. However, widespread use of PIOCS cannot be recommended until the benefits and harms can be clarified further.
Publisher: Cold Spring Harbor Laboratory
Date: 22-09-2021
DOI: 10.1101/2021.09.15.21263636
Abstract: There is mounting evidence that in utero and early life exposures may predispose an in idual to metabolic disorders in later life and dysregulation of lipid metabolism is critical in such outcomes. However, there is limited knowledge about lipid metabolism and factors causing lipid dysregulation in early life that could result in adverse health outcomes in later life. In this study, we aim to understand the lipid metabolism in pregnancy, and from birth to four years. We performed comprehensive lipid profiling of 1074 mother-child dyads in the Barwon Infant Study (BIS), a population based pre-birth cohort and measured 776 distinct lipid species across 42 lipid classes using ultra high-performance liquid chromatography (UHPLC). We measured lipids in 1032 maternal serum s les at 28 weeks’ gestation, 893 cord serum s les at birth, 793, 735, and 511 plasma s les at six, twelve months, and four years, respectively. The lipidome differed between mother and newborn and changed markedly with increasing postnatal age. Cord serum was enriched with long chain poly-unsaturated fatty acids (LC-PUFAs), and corresponding cholesteryl esters relative to the maternal serum. Alkenyl-phosphatidylethanolamine species containing LC-PUFAs increased with postnatal age, whereas the corresponding lysophospholipids and triglycerides decreased. We performed regression analyses to investigate the associations of cord serum lipid species with birth factors: gestational age, birth weight, mode of birth and duration of labor. Majority of the cord serum lipids were strongly associated with gestational age and birth weight, with most lipids showing opposing associations. Each mode of birth showed an independent association with cord serum lipids. There were marked changes in the plasma lipidome over the first four years of life. This study sheds light on lipid metabolism in infancy and early childhood and provide a framework to define the relationship between lipid metabolism and health outcomes in early childhood. This work was supported by the A*STAR-NHMRC joint call funding (1711624031).
Publisher: Elsevier BV
Date: 2023
Publisher: Wiley
Date: 23-02-2009
DOI: 10.1111/J.1398-9995.2009.01970.X
Abstract: The period of immune programming during early life presents a critical window of opportunity for the prevention of allergic diseases. There is mounting evidence that inappropriate immune programming may involve disruption of specific epigenetic modifications (switches) at immune-related genes. This novel area of research has great potential, as epigenetic changes are known to be sensitive to environmental factors and may therefore provide a mechanistic link for the observed association between specific environmental cues, faulty immune development, and the risk of allergic disease. In addition, the dynamic and potentially reversible nature of epigenetic modifications offers potentially novel targets for therapeutic and/or preventative interventions. We review the evidence that (1) failure to up-regulate the interferon gamma (IFNgamma) response during infancy is an important determinant of the risk of allergic disease, (2) expression of the IFNgamma gene in naïve T-cells is regulated by epigenetic mechanisms, and (3) failure to up-regulate IFNgamma gene expression of naïve T-cells associated with low early life microbial exposure. Taken together, these lines of evidence suggest that low microbial exposure during early life increases the risk of allergic disease by reducing demethylation (activation) of the IFNgamma gene of naive T-cells.
Publisher: Springer Science and Business Media LLC
Date: 26-01-2019
Publisher: Cambridge University Press (CUP)
Date: 04-04-2016
DOI: 10.1017/S0954579416000183
Abstract: Maternal mental health during pregnancy has been linked to health outcomes in progeny. Mounting evidence implicates fetal “programming” in this process, possibly via epigenetic disruption. Maternal mental health has been associated with glucocorticoid receptor methylation (nuclear receptor subfamily 3, group C, member 1 [ NR3C1 ]) in the neonate however, most studies have been small ( n 100) and have failed to control for multiple testing in the statistical analysis. The Barwon Infant Study is a population-derived birth cohort with antenatal recruitment. Maternal depression and anxiety were assessed using the Edinburgh Postnatal Depression Scale and psychological distress using the Perceived Stress Scale. NR3C1 cord blood methylation levels were determined using Sequenom MassArray for 481 participants. Maternal psychological distress and anxiety were associated with a small increase in neonate NR3C1 methylation at specific CpG sites, thus replicating some previous findings. However, associations were only nominally significant and did not remain after correction for the number of CpG sites and exposures investigated. As the largest study to explore the relationship between maternal well-being and offspring NR3C1 cord blood methylation, our results highlight the need for caution when interpreting previous findings in this area. Future studies must ensure they are adequately powered to detect the likely small effect sizes while controlling for multiple testing.
Publisher: JMIR Publications Inc.
Date: 04-10-2021
Abstract: ecruitment and retention of research participants is challenging. Social media, particularly Facebook, has emerged as a tool for connecting with participants due to its high uptake in the community. The Environmental Determinants of Islet Autoimmunity (ENDIA) study is an Australia-wide prospective pregnancy-birth cohort following children who have a first-degree relative with type 1 diabetes (ACTRN1261300794707). A dedicated Facebook page was established for the ENDIA study in 2013 with the aim to enhance recruitment and support participant retention. he purpose of this investigation was to evaluate the long-term impact of Facebook as a recruitment and retention tool. The hypotheses were that (1) Facebook was an important source of referral to the ENDIA study, (2) the sociodemographic characteristics of participants recruited by Facebook would be different from those of participants recruited by other means (i.e., ‘conventional recruits’), and (3) recruitment by Facebook would be associated with long-term retention. We also evaluated the most effective types of Facebook content based on post engagement. ecruitment of 1511 ENDIA participants was completed in December 2019. Characteristics of participants recruited through Facebook were compared to conventional recruits using linear, logistic, and multinomial logistic regression models. A logistic regression model was used to determine the risk of study withdrawal. Data pertaining to 794 Facebook posts over 7.5 years from June 2013 until December 2020 were extracted using the Facebook ‘Insights’ function for thematic analysis. acebook was the third largest source of referral to the ENDIA study (300/1511 19.9%) behind in-person clinics (500/1511, 33.1%) and healthcare professional referrals (347/1511, 23.0%). The ENDIA Facebook page had 2337 followers at the close of recruitment. Approximately 20% of these could be identified as participating parents. Facebook recruits were more frequently Australian-born (P .001) enrolling postnatally (P=.01) and withdrew from the study at a significantly lower rate compared to conventional recruits (4.7% vs 12.3% P .001) after a median of follow-up of 3.3 years. acebook was a valuable recruitment tool for the ENDIA study and participants recruited through Facebook were three times less likely to withdraw during long-term follow-up. The sociodemographic characteristics of Facebook recruits were different to conventional recruits, but perhaps in unintended ways. Facebook content featuring stories and images of participants received the highest engagement despite the fact that most Facebook followers were not enrolled in the study. These findings should inform social media strategies for future cohort studies involving pregnant women and young families, and for type 1 diabetes risk studies. ustralia New Zealand Clinical Trials Registry: ACTRN1261300794707 R2-0.1186/1471-2431-13-124
Publisher: Wiley
Date: 03-04-2018
DOI: 10.1111/JPC.13895
Abstract: World-wide, approximately 14% of children have prevalent asthma. As most bone accrual occurs in childhood, and data suggest a detrimental role in bone from asthma and/or medications, we investigated whether asthma was associated with radiologically confirmed fractures in a large cohort of children. Data from the Barwon Asthma Study (2005), a population-based, cross-sectional survey of all children attending 91 primary schools in the Barwon Statistical Division, were linked to the Geelong Osteoporosis Study Fracture Grid (2006-2007), a fracture register encompassing the Barwon Statistical Division (n = 16 438 50.5% boys aged 3.5-13.6 years). Asthma, ascertained from parent-reported symptoms using the International Study of Asthma and Allergies in Childhood questionnaire, was categorised as: (i) recent wheeze and number of (ii) recent wheezy episodes (iii) doctor visits for wheeze symptoms and (iv) doctor visits for asthma check-ups. Using logistic regression analyses, stratified by sex and adjusted for age and medication use, we determined whether asthma was associated with radiologically confirmed fractures. In total, 961 fractures were observed among 823 Barwon Asthma Study participants (5.9% of total s le 61.1% boys). Recent wheeze and 1-3 recent wheezy episodes were associated with increased odds of fracture in boys (odds ratio (OR) 1.26, 95% confidence interval (CI) 1.03-1.55 OR 1.40, 95% CI 1.12-1.77, respectively), but not girls (OR 1.03, 95% CI 0.78-1.37 OR 0.67, 95% CI 0.38-1.19). Results were independent of age, and sustained after adjustment for medication. Independent of age, asthma was associated with fracture for boys, but not girls. There is an imperative for strategies to promote bone health among children with asthma.
Publisher: Wiley
Date: 09-10-2018
DOI: 10.1111/JPC.14224
Abstract: There are minimal data to guide the continuing medical education (CME) of general paediatricians working in non-tertiary hospitals. The aim of this study was to determine the procedural and resuscitation skills required by non-tertiary paediatricians and the frequency with which these skills are utilised. Over a 12-month period (December 2012 to December 2013), each of the 11 paediatricians involved in acute inpatient care at University Hospital Geelong (UHG) completed a weekly online survey regarding their inpatient clinical experience. This included procedures performed or directly supervised as well as their resuscitation involvement. Each of the 11 paediatricians who managed inpatients on a regular or semi-regular basis during the study period agreed to participate, and each completed all of the weekly surveys. There were seven UHG paediatricians with an inpatient appointment (each with a 0.27 full-time equivalent (FTE) paediatrician workload) and four paediatricians providing inpatient cover on a locum basis. Over the course of 12 months, each 0.27 FTE paediatrician was, on average, involved in 11.3 neonatal, 1.7 infant and 2.4 child resuscitations and performed 0.9 intubations. Paediatricians working at non-tertiary hospitals are required to perform and supervise critical procedural and resuscitation skills but have limited opportunities to maintain proficiency in such skills. General paediatric training and consultant paediatrician CME programmes should ensure the acquisition and maintenance of the procedural and resuscitation skills required for the management of seriously ill children in non-tertiary acute care settings.
Publisher: MDPI AG
Date: 03-10-2019
DOI: 10.3390/V11100913
Abstract: Human parechovirus (HPeV), particularly type 3 (HPeV3), is an important cause of sepsis-/meningitis-like illness in young infants. Laboratory records identified a total of ten HPeV-positive cases in Southeastern Australia between January and July 2019. The HPeV present in these cases were typed by Sanger sequencing of the partial viral capsid protein 1 (VP1) region and selected cases were further characterised by additional Sanger or Ion Torrent near-full length virus sequencing. In seven of the ten cases, an HPeV type 5 (HPeV5) was identified, and in the remaining three cases, an HPeV type 1 was identified. The HPeV5-positive cases were infants under the age of 3 months admitted to hospital with fever, rash, lethargy and/or sepsis-like clinical signs. Near full-length virus sequencing revealed that the HPeV5 was most likely a recombinant virus, with structural genes most similar to an HPeV5 from Belarus in 2018, and a polymerase gene most similar to an HPeV3 from Australia in 2013/14. While HPeV5 is not typically associated with severe clinical signs, the HPeV5 identified here may have been able to cause more severe disease in young infants through the acquisition of genes from a more virulent HPeV.
Publisher: Wiley
Date: 09-06-2014
DOI: 10.1111/JPC.12608
Abstract: The aim of this study was to describe paediatric feeding-tube weaning practice in Australian children's hospitals and to compare this with practice in tube weaning programmes internationally. A literature review regarding tube weaning practices was conducted to inform questionnaire design. Six Australian children's hospitals and six international paediatric service providers completed a written questionnaire. Four of six Australian children's hospitals surveyed reported that they have adopted informal paediatric tube weaning practices four of six lacked clinical practice guidelines (CPGs), and five of six lacked a clearly defined case leadership. Practice varied substantially within and between these Australian feeding teams. By comparison, all six international feeding teams reported having developed formal CPGs. Five of six reported clearly defined case leadership with no more than three lead professionals overseeing cases and concordantly reported a high level of practice consistency within and between teams. The majority of Australian children's hospitals lack a formal CPG and clearly defined case leadership to guide tube weaning practices, and accordingly, there is considerable practice variation. This is in contrast to the situation in a select group of international centres. There is a need for further research to define best practice models and for Australian CPGs.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Wiley
Date: 24-10-2020
DOI: 10.1111/PAI.13128
Abstract: High folate status in pregnancy has been implicated in the increased prevalence of allergic disease, but there are no published data relating directly measured folate status in pregnancy to challenge-proven food allergy among offspring. The study aim was to examine the association between red blood cell (RBC) folate status in trimester three of pregnancy and allergic disease among offspring. Red blood cell folate levels were measured at 28-32 weeks' gestation in a prospective birth cohort (n = 1074). Food allergy outcomes were assessed in 1-year-old infants by skin prick testing and subsequent food challenge. Eczema was assessed by questionnaire and clinical review. High trimester three RBC folate was defined as greater than (>) 1360 nmol/L. Binomial regression was used to examine associations between trimester three RBC folate and allergic outcomes, adjusting for potential confounders. Red blood cell folate levels were measured in 88% (894/1064) of pregnant women. The mean concentration was 1695.6 nmol/L (standard deviation 415.4) with 82% (731/894) >1360 nmol/L. There was no evidence of either linear or non-linear relationships between trimester three RBC folate and allergic outcomes, nor evidence of associations between high RBC folate and food allergy (adjusted risk ratio (aRR) 2.89, 95% CI 0.90-9.35), food sensitization (aRR 1.72, 95% CI 0.85-3.49), or eczema (aRR 0.97, 95% CI 0.67-1.38). The majority of pregnant women in this study had high RBC folate levels. There was no evidence of associations between trimester three RBC folate and food allergy, food sensitization, or eczema among the offspring, although larger studies are required.
Publisher: Wiley
Date: 09-10-2016
DOI: 10.1111/IJPO.12187
Abstract: Excess adiposity and adiposity-related inflammation are known risk factors for cardiovascular disease in adults however, little is known regarding the determinants of adiposity-related inflammation at birth. The aim of this study was to investigate the association between maternal pre-pregnancy BMI and newborn adiposity and inflammation. Paired maternal (28-week gestation) and infant (umbilical cord) blood s les were collected from a population-derived birth cohort (Barwon Infant Study, n = 1074). Data on maternal comorbidities and infant birth anthropomorphic measures were compiled, and infant aortic intima-media thickness was measured by trans-abdominal ultrasound. In a selected subgroup of term infants (n = 161), matched maternal and cord lipids, high-sensitivity C-reactive protein (hsCRP) and maternal soluble CD14 were measured. Analysis was completed by using pairwise correlation and linear regression. Because of their non-normal distribution, pathology blood measures were log transformed prior to analysis. Maternal pre-pregnancy BMI was positively associated with increased birth weight (mean difference 17.8 g per kg m Higher maternal pre-pregnancy BMI is associated with increased newborn adiposity and inflammation. These associations may be partially mediated by maternal inflammation during pregnancy.
Publisher: Oxford University Press (OUP)
Date: 23-12-2019
DOI: 10.1093/HMG/DDZ287
Abstract: Despite the many advances made in the diagnosis and management of preecl sia, this syndrome remains a leading cause of maternal mortality and life-long morbidity, as well as adverse fetal outcomes. Successful prediction and therapeutic intervention require an improved understanding of the molecular mechanisms, which underlie preecl sia pathophysiology. We have used an integrated approach to discover placental genetic and epigenetic markers of preecl sia and validated our findings in an independent cohort of women. We observed the microRNA, MIR138, to be upregulated in singleton preecl tic placentas however, this appears to be a female infant sex-specific effect. We did not identify any significant differentially methylated positions (DMPs) in singleton pregnancies, indicating that DNA methylation changes in mild forms of the disease are likely limited. However, we identified infant sex-specific preecl sia-associated differentially methylated regions among singletons. Disease-associated DMPs were more obvious in a limited s ling of twin pregnancies. Interestingly, 2 out of the 10 most significant changes in methylation over larger regions overlap between singletons and twins and correspond to NAPRT1 and ZNF417.
Publisher: Wiley
Date: 17-06-2020
DOI: 10.1111/DME.13987
Abstract: To measure pancreatic area and exocrine function in young children with recent-onset Type 1 diabetes to determine whether the exocrine pancreas is also affected in the pathophysiology of early childhood diabetes. Thirty-two children (14 boys) aged 5.5 (4.5, 7.3) median (IQR) years presenting with recent-onset Type 1 diabetes and 90 controls (44 boys) of similar age had ultrasound imaging of the pancreas. Children with Type 1 diabetes were receiving insulin and were without ketosis. Transverse and longitudinal areas of the pancreas were measured by digitalized outline. Pancreatic faecal elastase-1 was analysed using an enzyme-linked immunosorbent assay kit in recent-onset Type 1 diabetes and 38 first-degree relative control children. Pancreatic area and exocrine function were reduced in Type 1 diabetes. Mean transverse area (SD) in Type 1 diabetes was 6.82 cm Pancreatic area and accompanying subclinical exocrine function were reduced in very young children with recent-onset Type 1 diabetes. This supports changes in the exocrine pancreas in the pathophysiology of Type 1 diabetes presenting in early life.
Publisher: Wiley
Date: 04-04-2017
DOI: 10.1111/ALL.13143
Abstract: A defective skin barrier is hypothesized to be an important route of sensitization to dietary antigens and may lead to food allergy in some children. Missense mutations in the serine peptidase inhibitor Kazal type 5 (SPINK5) skin barrier gene have previously been associated with allergic conditions. To determine whether genetic variants in and around SPINK5 are associated with IgE-mediated food allergy. We genotyped 71 "tag" single nucleotide polymorphisms (tag-SNPs) within a region spanning ~263 kb including SPINK5 (~61 kb) in n=722 (n=367 food-allergic, n=199 food-sensitized-tolerant and n=156 non-food-allergic controls) 12-month-old infants (discovery s le) phenotyped for food allergy with the gold standard oral food challenge. Transepidermal water loss (TEWL) measures were collected at 12 months from a subset (n=150) of these in iduals. SNPs were tested for association with food allergy using the Cochran-Mantel-Haenszel test adjusting for ancestry strata. Association analyses were replicated in an independent s le group derived from four paediatric cohorts, total n=533 (n=203 food-allergic, n=330 non-food-allergic), mean age 2.5 years, with food allergy defined by either clinical history of reactivity, 95% positive predictive value (PPV) or challenge, corrected for ancestry by principal components. SPINK5 variant rs9325071 (A⟶G) was associated with challenge-proven food allergy in the discovery s le (P=.001, OR=2.95, CI=1.49-5.83). This association was further supported by replication (P=.007, OR=1.58, CI=1.13-2.20) and by meta-analysis (P=.0004, OR=1.65). Variant rs9325071 is associated with decreased SPINK5 gene expression in the skin in publicly available genotype-tissue expression data, and we generated preliminary evidence for association of this SNP with elevated TEWL also. We report, for the first time, association between SPINK5 variant rs9325071 and challenge-proven IgE-mediated food allergy.
Publisher: Springer Science and Business Media LLC
Date: 17-01-2020
DOI: 10.1038/S41390-020-0762-4
Abstract: Nuclear magnetic resonance (NMR) metabolic profiling quantifies a large number of metabolites. From adolescence, specific metabolites are influenced by age, sex and body mass index data on early-life metabolic profiles are limited. We investigated associations between sex, birth weight, weight and adiposity with NMR metabolic profile at age 12 months. The plasma NMR metabolic profile was quantified in infants (n = 485) from the Barwon Infant Study. Associations between 74 metabolites and sex, birth weight z-score and 12-month measures (weight z-score, skinfold thickness, weight-for-length z-score) were examined using linear regression models. Several cholesterol and fatty acid measures were higher (0.2-0.3 SD) in girls than in boys we observed modest sex-specific associations of birth weight z-scores and 12-month sum of skinfold thicknesses with metabolites. The pattern of associations between weight z-score and weight-for-length z-score with metabolites at 12 months was more pronounced in girls, particularly for fatty acid ratios. We identified sex differences in the infant metabolic profile. Sex-specific patterns observed differ from those reported in older children and adults. We also identified modest cross-sectional associations between anthropometric and adiposity measures and metabolites, some of which were sex specific.
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.JACI.2017.05.041
Abstract: Rising rates of food-induced anaphylaxis have recently been shown in the adolescent age group, following earlier descriptions of a rise in children younger than 5 years. However, few population-based studies have examined the prevalence of food allergy in adolescence using objective measures such as oral food challenge (OFC). We sought to determine the prevalence of food allergy among a population-based s le of 10- to 14-year-old adolescents using clinical evaluation including OFC to confirm the diagnosis. Schools were randomly selected from greater metropolitan Melbourne, Australia. Students aged 10 to 14 years, and their parents, were asked to complete a questionnaire regarding the adolescent's food allergy or food-related reactions. Clinic evaluation, which consisted of skin prick tests and OFC where eligible, was undertaken if students were suspected to have current food allergy from parent response. Among 9816 students assessed, 5016 had complete parent response and clinic evaluation when eligible. An additional 4800 students had student questionnaires only. The prevalence of clinic-defined current food allergy based on history, sensitization data, and OFC results was 4.5% (95% CI, 3.9-5.1), with the most common food triggers being peanut, 2.7% (95% CI, 2.3-3.2), and tree nut, 2.3% (95% CI, 1.9-2.8). Among the additional group of 4800 adolescents who had only self-reported food allergy status available, the prevalence of self-reported current food allergy was 5.5% (95% CI, 4.9-6.2), with peanut, 2.8% (95% CI, 2.3-3.3), and tree nut, 2.3% (95% CI, 1.9-2.8), the most common. Approximately 1 in 20 10- to 14-year-old school students in Melbourne has current food allergy. This high prevalence suggests that the previously reported rise in food-induced anaphylaxis in this age group may reflect an increasing prevalence of food allergy rather than simply increased reporting of anaphylaxis.
Publisher: Springer Science and Business Media LLC
Date: 07-2019
Publisher: BMJ
Date: 03-2021
DOI: 10.1136/BMJOPEN-2020-041984
Abstract: Larger sibships are associated with poorer cognitive and language outcomes but have different impacts on child emotional development. Previous studies have not taken into account sibling age, nor have impacts across multiple neurodevelopmental domains been considered in the same participant group. This study investigated the influence of family size indicators on early childhood cognitive, language and emotional-behavioural development. The effect of sibling age was considered by evaluating these relationships separately for different sibling age categories. Prospective birth cohort study. Participants in the Barwon Infant Study were recruited from two major hospitals in the Barwon region of Victoria, Australia, between 2010 and 2013 (n=1074 children). The 755 children with any neurodevelopmental data at age 2–3 years excluding twins and those with an acquired neurodisability. Cognitive and language development was assessed using the Bayley Scales of Infant and Toddler Development, Third Edition, and emotional-behavioural development was measured with the Child Behaviour Checklist for Ages 1½−5. Greater household size was associated with a reduced cognitive development score (adjusted mean difference (AMD) −0.66 per extra household member 95% CI −0.96 to –0.37 p .001) without age-specific differences. However, poorer expressive language was only observed for exposure to siblings between 2–6 and 6–10 years older. Having siblings 2–6 years older was associated with less internalising behaviour (AMD −2.1 per sibling 95% CI −3.1 to –1.0 p .001). These associations persisted after multiple comparison adjustment. The influence of siblings on early childhood development varies substantially by sibling age and the neurodevelopmental outcome under study. Although family size alone appears important for cognitive development, age-specific findings emphasise the importance of sibling interaction in early childhood expressive language development and emotional behaviour.
Publisher: Wiley
Date: 02-06-2019
DOI: 10.1111/ALL.13822
Abstract: In previous studies, deficits in regulatory T-cell (Treg) number and function at birth have been linked with subsequent allergic disease. However, longitudinal studies that account for relevant perinatal factors are required. The aim of this study was to investigate the relationship between perinatal factors, naïve Treg (nTreg) over the first postnatal year and development of food allergy. In a birth cohort (n = 1074), the proportion of nTreg in the CD4 A higher proportion of nTreg at birth, larger birth size and male sex was each associated with higher nTreg in infancy. Exposure to labour, as compared to delivery by prelabour Caesarean section, was associated with a transient decrease nTreg. Infants that developed food allergy had decreased nTreg at birth, and the labour-associated decrease in nTreg at birth was more evident among infants with subsequent food allergy. Mode of birth was not associated with risk of food allergy, and there was no evidence that nTreg at either 6 or 12 months were related to food allergy. The proportion of nTreg at birth is a major determinant of the proportion present throughout infancy, highlighting the importance of prenatal immune development. Exposure to the inflammatory stimulus of labour appears to reveal differences in immune function among infants at risk of food allergy.
Publisher: Springer Science and Business Media LLC
Date: 29-10-2022
Publisher: Wiley
Date: 2013
DOI: 10.1111/JPC.12050
Publisher: BMJ
Date: 06-10-2008
Publisher: BMJ
Date: 16-02-2012
DOI: 10.1136/EMERMED-2011-200200
Abstract: Ovarian torsion (OT) is an important cause of abdominal pain in girls. Prompt recognition of OT may lead to higher rates of ovarian salvage. To identify clinical and laboratory findings that may indicate OT among girls with abdominal pain. Retrospective review of two cohorts of girls aged 5-17 years admitted to a children's hospital. Cohort 1: Girls admitted with abdominal pain from the emergency department (2008). Cohort 2: Girls with a discharge diagnosis of OT (2003-9). Cohort 1: 325 girls were admitted from the emergency department with abdominal pain during 2008. Of these, 9 (3%) were diagnosed with OT. Cohort 2: 37 girls were diagnosed with OT during 2003-9. Clinical or laboratory features differentiating OT from all abdominal pain could not be identified. A comparison of girls admitted with confirmed appendicitis showed that OT was more likely to be associated with a mass (RR=4.2, 95% CI 1.1 to 17), and less likely to be associated with anorexia (RR=0.46, 95% CI 0.23 to 0.93), guarding (RR=0.53, 95% CI 0.34 to 0.85), an elevated C reactive protein (RR=0.32, 95% CI 0.14 to 0.83), or leucocytosis (RR=0.4, 95% CI 0.21 to 0.78). Findings were similar in girls with an admission diagnosis of 'possible appendicitis'. Clinical or laboratory features that would identify cases of OT among girls admitted with abdominal pain could not be identified. Some findings help to differentiate OT from appendicitis, but there is a large degree of overlap. OT is an uncommon condition, but has important management implications, and should be considered in all girls presenting with abdominal pain.
Publisher: BMJ
Date: 08-2020
DOI: 10.1136/BMJOPEN-2019-036003
Abstract: The Vitamin D in Pregnancy Study is a long-term ongoing cohort study. It was conceived to explore relationships between maternal vitamin D status in pregnancy and offspring growth and development, and has since ersified to include a wide range of physical and mental health exposures and outcomes. Recruitment was from the University Hospital Geelong (Barwon Health) antenatal clinic, Geelong, Victoria, Australia, between 2002 and 2004. 475 women were initially recruited, which resulted in 400 eligible mother–child pairs at birth. The cohort has been followed up twice in pregnancy, at birth, and 1 year, 6 years and 11 years post birth. The study has reported an association between vitamin D in pregnancy and musculoskeletal health and body composition in the children. Subject to funding, there will be a prospective young adult follow-up. This profile aims to foster both cross-national and international collaborations with both existing and future data collection.
Start Date: 2019
End Date: 2016
Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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End Date: 2016
Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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