Child Health Research Unit

Geelong, Australia

Child Health Research Unit

Geelong, Australia
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Ponsonby A.-L.,Murdoch Childrens Research Institute | Symeonides C.,Murdoch Childrens Research Institute | Vuillermin P.,Murdoch Childrens Research Institute | Vuillermin P.,Deakin University | And 4 more authors.
NeuroToxicology | Year: 2016

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 example: 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. © 2016 Elsevier B.V.

West C.E.,Umeå University | Renz H.,University of Marburg | Jenmalm M.C.,Linköping University | Kozyrskyj A.L.,University of Alberta | And 3 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015

Rapid environmental transition and modern lifestyles are likely driving changes in the biodiversity 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 diverse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For example, 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. © 2014 American Academy of Allergy, Asthma & Immunology.

Woodhill I.,Child Health Research Unit | Cooper C.,Child Health Research Unit | Zacharin M.,Royal Childrens Hospital | Cukier K.,Barwon Health | Vuillermin P.,Child Health Research Unit
Journal of Paediatrics and Child Health | Year: 2014

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. © 2014 The Authors. Journal of Paediatrics and Child Health.

Marco L.J.,Royal Womens Hospital | McCloskey K.,Murdoch Childrens Research Institute | McCloskey K.,Child Health Research Unit | Vuillermin P.J.,Murdoch Childrens Research Institute | And 8 more authors.
Experimental Diabetes Research | Year: 2012

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 availableincluding 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. © 2012 Laura J. Marco et al.

Zakariaeeabkoo R.,RMIT University | Allen K.J.,Murdoch Childrens Research Institute | Allen K.J.,University of Melbourne | Allen K.J.,Royal Childrens Hospital | And 6 more authors.
Clinical Biochemistry | Year: 2014

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. © 2014 The Canadian Society of Clinical Chemists.

Sun C.,Royal Melbourne Hospital | Burgner D.P.,Murdoch Childrens Research Institute | Burgner D.P.,University of Melbourne | Ponsonby A.-L.,Royal Melbourne Hospital | And 11 more authors.
Pediatric Research | Year: 2013

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. Copyright © 2013 International Pediatric Research Foundation, Inc.

McCloskey K.,Murdoch Childrens Research Institute | McCloskey K.,Child Health Research Unit | McCloskey K.,University of Melbourne | Vuillermin P.,Murdoch Childrens Research Institute | And 8 more authors.
Acta Paediatrica, International Journal of Paediatrics | Year: 2014

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. Conclusion 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. © 2013 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd.

Gardiner A.Y.,Barwon Health | Fuller D.G.,Barwon Health | Fuller D.G.,Child Health Research Unit | Vuillermin P.J.,Child Health Research Unit | And 2 more authors.
Journal of Paediatrics and Child Health | Year: 2014

Aim: 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. Methods: 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. Results: 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. Conclusions: 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. © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

PubMed | Murdoch Childrens Research Institute, University of Sydney and Child Health Research Unit
Type: | Journal: Pediatric obesity | Year: 2016

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 samples 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 17.8g per kgmHigher maternal pre-pregnancy BMI is associated with increased newborn adiposity and inflammation. These associations may be partially mediated by maternal inflammation during pregnancy.

PubMed | Child Health Research Unit
Type: Case Reports | Journal: Journal of paediatrics and child health | Year: 2014

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.

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