Inflammatory Origins
Understanding early life influences on infection and consequences for lifelong cardiovascular and metabolic disease risk
Inflammatory Origins tackles two related challenges for childhood and lifelong health.
The first is understanding why only a minority of children develop severe infection and inflammation, despite all children being exposed to life-threatening germs.
We also aim to understand the key roles that inflammation and infection play in the development of cardiovascular and metabolic disease (e.g. heart disease, stroke, type 2 diabetes and obesity) which are the leading causes of illness and death in Australia and worldwide.
These cardiometabolic diseases develop across the entire life course, offering an under-used opportunity for early and effective prevention. The Inflammatory Origins group also has clinical and research expertise in oral health and in Kawasaki disease.
We use a range of different study types, including total population data linkage, longitudinal population-based and high-risk cohort studies, mechanistic and omics data. We also (co)-lead several international cross-cohort and cross-disciplinary collaborations. Our multi-disciplinary approach is reflected in the diverse scientific and clinical expertise of our researchers. The Inflammatory Origins Group places considerable importance and resources on the career development of early and mid-career researchers.
The Inflammatory Origins group is particularly interested in how infection and inflammation may contribute to social inequalities in health across the life course and how psychosocial factors ‘get under the skin’ and impact health outcomes.
Through our collaborations on campus, nationally and internationally, we aim to reduce the burden of infection, inflammation and social inequalities in children and help prevent the development of cardiovascular and metabolic disease later in life.
Our projects
Total population studies of susceptibility and consequences of childhood infection
We leverage national and international population level data through our extensive collaborative network in several projects.
MODIFY (Maternal and Offspring Disease from InFancy to Youth)
MODIFY is an international data linkage study that investigates how exposures during pregnancy, birth and early childhood are associated with susceptibility to and severity of paediatric infection in children. We have shown that even small changes in birth weight and length, gestational age, as well as mode of birth (caesarean section versus vaginal delivery) and antibiotic exposure in pregnancy may be associated with increased risk of hospitalised infection through childhood. We are investigating how factors such as breastfeeding offset these risks. These epidemiological findings inform mechanistic and biomarker studies in longitudinal cohorts.
iPOP (international Perinatal Outcomes in the Pandemic)
iPOP is a collaborative global study, co-led by Inflammatory Origins, investigating the impact of COVID-19 pandemic lockdowns on the incidence of preterm birth and stillbirth and assess the underlying causative factors. The study, which has analysed data from 50 million births in 26 countries and involved 150 researchers, is by far the largest of its kind and the initial results were published in Nature Human Behaviour.
Heritable and environmental determinants of infection
This project uses twin and sibling epidemiological methods and Australian population-level linked data to explore the relative contribution of genetic and environmental determinants to hospitalisation with infection in childhood.
Methodological considerations in population data analyses of childhood infection
Many studies worldwide use population data to investigate childhood infection, but methodological approaches differ. We are analysing data from international cohorts to explore how varying definitions and methodologies may affect findings. We hope to develop consensus recommendations that will assist interpretation.
Childhood infection and cardiovascular and metabolic risk and disease
Building on our previous findings that hospitalisation with infection in childhood is associated with cardiovascular events and increased BMI in adulthood, we aim to replicate and extend these findings in other settings and undertake a meta-analysis.
Severity of childhood infections in those in larger bodies
We know that COVID-19 and influenza may be more severe in those with larger bodies, but it is largely unknown if the same is true for other infections. In collaboration with Danish researchers, we are investigating whether infections are more common and severe in those with higher BMI in early childhood. The findings will inform collaborative studies that investigate how immune and inflammatory responses vary with BMI and type 2 diabetes.
Patterns and consequences of antibiotic use in Victorian children
This is a Victorian statewide data linkage study to investigate sociodemographic and clinical factors associated with differential patterns of antibiotic use and how prior antibiotic use is related to hospital admission.
YoungLives Study
The YoungLives Study explores young people’s physical health and emotional wellbeing through the pandemic.
Population cohort studies
Inflammatory Origins is involved in cohort studies of participants drawn from the general population, investigating infection, inflammation, cardiometabolic risk and dental health. We have considerable experience performing cardiometabolic and inflammation assessments across the life course. We bring this expertise to a variety of population and disease-specific cohort studies locally, nationally and internationally.
Barwon Infant Study (BIS)
BIS is an NHMRC-supported population-derived pregnancy cohort study based in the Barwon region of Victoria. It is a collaborative project between Deakin University, Murdoch Children’s Research Institute and Barwon Health. Almost 1,100 pregnant women were recruited and their children are now 10 years old. Participants have had in-depth data and biosamples collected from pregnancy, infancy and throughout childhood. The biosamples have been run across several omics platforms and functional immunological assays have been performed. BIS participants have had preclinical cardiovascular measures performed repeatedly from birth onwards.
The Australian Temperament Study (ATP)
The ATP, which is led by researchers at Deakin University, is one of Australia’s longest running cohort studies with participants recruited from three generations over four decades. The study has a wealth of psychosocial data and we are now undertaking a detailed biomedical assessment, including cardiovascular and metabolic measures and collection of biosamples of participants at 10, 40 and 70 years of age.
Longitudinal Study of Australian Children’s (LSAC) Child Health CheckPoint
Checkpoint was a cross-sectional detailed biomedical assessment of about 1,500 children and 1,500 adults from the LSAC cohort. Inflammatory Origins is particularly involved in studies of infection, inflammation and cardiovascular and metabolic risk.
International cohorts: CHILD study Canada, Drakenstein Child Health Study, Tanzanian Child Cohorts (PONA I or STOPPAM studies)
Inflammatory Origins is involved in studies of infection, inflammation and cardiovascular and metabolic risk in international cohorts in a variety of high, low and middle-income settings.
LIQUID: LIfecourse QUantification of Inflammation and carDiometabolic health
Inflammatory Origins leads this major global collaboration of almost 750,000 participants from many international cohorts from infancy to old age. We are investigating how inflammation develops across the life course, the relationship to cardiovascular and metabolic disease risk and events as well as the socioeconomic patterning of these relationships.
High risk and disease specific studies
We lead studies that investigate cardiovascular and metabolic risk, innate immune responses and inflammation in children with inflammatory conditions and infections.
VASCFIND (VAScular Changes Following Infectious Disease)
Cardiovascular disease (heart attack and stroke) affects adults, but the ‘hardening of the arteries’ (atherosclerosis) begins in childhood. Atherosclerosis arises partly because inflammation over decades damages the wall of the artery. Conditions that increase inflammation, such as common infections, have been suggested to worsen atherosclerosis and possibly increase the risk of cardiovascular disease. Most infections occur in childhood and our group is interested in how infection and inflammation might affect the arteries and the later risk of cardiovascular disease. The overall aim of the VASCFIND study is to investigate the effects of acute infection on arteries and vascular health in school-age children. We are examining for the first time how arterial structure and function change in children following infection and whether there are alterations in the blood, such as differences in cholesterol or blood markers that vary with inflammation. The findings will provide important new information relating to the childhood origins of cardiovascular disease and offer possibilities for earlier prevention.
We’re recruiting eager PhD students to work on VASFIND. Express your interest today.
Cardiovascular risk phenotypes in children with chronic inflammatory conditions (CUPID)
Inflammation underpins the development of atherosclerosis and cardiovascular disease. Inflammatory Origins is investigating the relationship between children with chronic inflammatory conditions (inflammatory bowel disease, juvenile idiopathic arthritis and skin inflammatory conditions) and cardiovascular risk.
COBRA (Childhood Overweight BioRepository of Australia)
Inflammatory Origins works with a unique cohort of children and adolescents living with obesity. Ongoing studies include the investigation of cardiovascular and metabolic risk, immunity and inflammation, and the effects of changes in BMI.
iGrowWell
iGrowWell is an innovative project that will address key knowledge gaps in understanding how modifiable, non-traditional risk factors (including psychological factors), increase cardiovascular disease (CVD) risk among youth affected by obesity. This knowledge will provide evidence for the Youth Researcher-led co-design of an effective electronic-based intervention. The project introduces a fundamental change, focusing on health, with inflammation as the outcome, rather than weight alone. This project aims to centre the perspectives of youth and will consider cultural and social factors in the co-design of an intervention for youth affected by obesity.
World Scabies Program
The World Scabies Program is dedicated to reducing the impact of scabies and its complications on children and families using public health approaches that target whole populations. The program equips low and middle-income countries around the world with the tools and resources to detect, monitor and eliminate scabies in affected communities.
Oral health studies
The use of intraoral 3D scanning to measure and quantify dental caries and enamel hypomineralisation
Three-dimensional scanning promises the considerable potential for recording and monitoring oral health. Rapid developments in 3D technologies will expand its application to a much broader range of clinical and research settings, including caries detection and automatised diagnostics. Based at Murdoch Children's Research Institute and The Royal Children's Hospital and in collaboration with industry partners 3Shape Trios, this project will evaluate the validity of an intra-oral scanner to measure the presence and severity of dental caries and developmental defects in children of different ages in both primary and secondary dentition.
The first 2,000 days: Implications for dental health, disease risk and intervention
The first 2,000 days of life, from conception to school commencement, are recognised as a key period for the determination of future susceptibility to a broad range of illnesses. Early life is a time of intense development, marked by a never again repeated phase of rapid adaptability in the developing foetus/child. Environmental cues, from nutrition to attachment with caregivers, help guide this development. However, adverse events and exposures early in life, such as malnutrition, chemical toxins and psychological and physiological stress, can influence the future response to stress and lead to ‘biological embedding’ or programming of future disease. Leveraging the extensive early life data from our LifeCourse platform, including BCG for Allergy and Infection Reduction (MIS BAIR) and the Barwon Infant Study, this project seeks to understand the mechanistic process that drives the influences of early life events and exposures on oral health.
Early Childhood Caries: From Phenotype to Prevention
The Barwon Health Wide Smiles program is a unique community oral health promotion initiative extending beyond the Geelong and Colac region into rural areas including Mortlake, Apollo Bay, Cobden, and Terang. The overall aim of this project is to leverage extensive clinical data collected through Wide Smiles, a Barwon Health oral health promotion program, to understand and classify patterns of dental caries in children and in response to preventive interventions. In addition, this project will explore the influence of various factors, including rurality and area-level disadvantage on caries experience and use novel data analytics to develop prediction.
Infant2Child: Optimising nutrition in early life to reduce childhood dental caries
Dietary and dental habits are established early in life, particularly during the first 2000 days. This period offers a unique, time-limited opportunity for early intervention. In partnership with The Melbourne Dental School, the University of Melbourne and Deakin University’s Institute for Physical Activity and Nutrition, this project seeks to provide early oral health promotion through INFANT, an early-life nutrition intervention that is currently being rolled out across Victoria. The program offers a unique opportunity to harness synergies between preventive strategies targeting diet-related chronic disease including obesity, diabetes and dental caries to effectively and efficiently improve both oral and general health outcomes.
Funding
- National Health and Medical Research Council (NHMRC)
- National Institute of Health (NIH)
- Canadian Institutes of Health Research (CIHR)
- Jam and Jelly Foundation
- DHB Trustees
- Medical Research Future Fund (MRFF)
- Murdoch Children’s Research Institute
- Monash Health
- Dutch Heart Foundation
Collaborations
Institutions
- The Royal Children’s Hospital, Melbourne
- Baker IDI, Melbourne
- Centre for Multicultural Youth, Melbourne
- Deakin University, Victoria
- Barwon Health, Victoria
- University of New South Wales (UNSW)
- The University of Sydney
- Telethon Kids Institute, Perth
- University of Queensland
- Australian National University (ANU)
- Radboud amc, The Netherlands
- Integrative Epidemiology Unit, Bristol University, UK
- Finnish Institute of Health and Welfare, Finland
- Turku University, Finland
- Aarhus University, Denmark
- University of Copenhagen, Denmark
- University College Dublin
- UC San Diego
- Nightingale Health, Finland
- 3Shape, Denmark
- Norwegian Institute of Public Health
- Estonian Biobank
Studies/Cohorts
- Barwon Infant Study (AUS)
- Longitudinal Study of Australian Children Child Health CheckPoint (AUS)
- VITALITY study
- Growing Up in Singapore Towards healthy Outcomes, GUSTO
- Medical Research Council National Survey of Health and Development
- Physical Activity and Nutrition in Children Study
- Southall And Brent Revisited, SABRE
- Avon Longitudinal Study of Parents and Children, ALSPAC (UK)
- Born in Bradford (UK)
- Cardiovascular Risk in Young Finns Study (Finland)
- Special Turku Coronary Risk Factor Intervention Project, STRIP (Finland)
- Northern Finnish Birth Cohort (Finland)
- UK BioBank (UK)
- Norwegian Mother, Father and Child Cohort Study, MoBA (Norway)
- Danish National Birth Cohort, DNBC (Denmark)
- Drakenstein Child Health Study (South Africa)
- CHILD study (Canada)
- Kaiser Permanente (US)
- THL Biobank (Finland)
- Estonian National Biobank
Featured publications
Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries. 2023.
Immune responses to SARS-CoV-2 in three of parents with symptomatic COVID-19. 2020.
Genetic and Early Life Environmental Influences on Dental Caries Risk: A Twin Study. 2019.