INSPIRE Issue 30 - Advances in Paediatric Health and Medical Research by Research Australia

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HEALTH AND MEDICAL RESEARCH ADVANCES IN PAEDIATRICS CELEBRATING 20 YEARS OF CLINICAL RESEARCH EXCELLENCE AT THE RESEARCH AUSTRALIA 2023 HEALTH & MEDICAL RESEARCH AWARDS

Welcome to the Advances in Paediatric Health and Medical Research edition of INSPIRE

h i s i s s u e o f I N S PI R E c e l e b r a te s t h o s e healthcare professionals who are searching for answers to illness and disease that affects part of our most vulnerable population; that is our youngest. While all health and medical research is important, perhaps the one that most tugs at our heartstrings are those where an infant is involved. These researchers are working on solutions to answer medical challenges that impact our current and future generations. Yet as we come towards the end of 2023, we hear the same issues being raised year on year - hospitals waiting times are increasing, there are too many patients, too little funding and issues with staff recruitment and retention. These issues are systemic from ambulances spending more time ramping due to an inability to find beds, to longer waiting times to see GPs and specialists, in part because of an exhausted workforce and staff shortages.

paediatric asthma, as well as ways to improve sedation and infusion therapy techniques, and so much more! This issue is once again filled with inspiring stories from amazing individuals and aspirational teams. Equally inspiring are our Research Australia Award winners. Announced at the Annual Research Australia Awards night in Sydney on 2 November, these Awards celebrate contributions by individuals and groups across the spectrum of health and medical research, from researchers just starting in their career to the sectors leaders in research, philanthropy, and advocacy. These awards celebrated a milestone of 20 years recognising, rewarding, and celebrating those incredible quiet achievers, who make a difference in all our lives. It was a wonderful night, and a great privilege to be joined by 400 Research Australia members and their guests, many of the previous Peter Wills Medal recipients, local and state politicians, as well as senior government officials.

Health and medical researchers are not immune from these increased pressures. Yet they continue their quest to find answers, to translate research findings into tangible results that can ultimately be used to improve health outcomes for all Australians.

In closing, I wish you all the best for the festive season and for the year ahead. I look forward to continuing to work with each of you to advance our shared vision of health and prosperity through Australian Research and Innovation.

In this issue our members share their work to improve outcomes for children with cerebral palsy, diabetes, and

Best wishes Nadia and the Research Australia Team

Best Wishes for a safe and happy festive season from the Team at Research Australia. 2

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CONTENTS

Australian Health & Medical Research & Innovation

Events overview

20th Research Australia Awards

Gene patching potential explored for tackling childhood dementia

RESEARCH AUSTRALIA

PERRON INSTITUTE

Advanced immunotherapy may hold promise for children with brain cancer

Towards a universal gene therapy for SMA

Supporting children with cancer and their families in the era of precision medicine

WEHI

CMRI

UNIVERSITY OF NSW

Thirty years of funding kids’ cancer research

A genetic diagnosis enables precision medicine for cerebral palsy

Transforming the lives of children through rich, inclusive and resuable data

THE KIDS CANCER PROJECT

UNIVERSITY OF ADELAIDE

MCRI

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Publisher Research Australia Ltd Art Direction Matthew Ware p +61 403 844 763 e matt@objktive.com For Advertising enquiries please contact the Research Australia office on p 02 9295 8546 or e admin@researchaustralia.org researchaustralia.org

INSPIRE ONLINE issuu.com/researchaustralia

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INSPIRE is a publication of Research Australia Ltd ABN 28 095 324 379 CHRISTOPHE KEREBEL CHRISTOPHE Twitter : @chriskere KEREBEL 384 My Victoria Street Darlinghurst NSW 2010

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Who can submit articles? Any current member of Research Australia who would like to share a relevant story that affects their organisation including, philanthropic donations and their outcomes, research findings, and any other related health and medical research topic that affects the Australian population. Submission guidelines & deadlines For information regarding how to submit and publishing deadlines visit the Research Australia website. Disclaimer The opinions expressed in INSPIRE do not necessarily represent the views of Research Australia. Whilst every effort has been made to ensure accuracy, no responsibility can be accepted by Research Australia for omissions, typographical or inaccuracies that may have taken place after publication. All rights reserved. The editorial material published in INSPIRE is copyright. No part of the editorial contents may be reproduced or copied in any form without the prior permission from Research Australia. © Research Australia 2020.

20 Improving quality of life for children with Sanfilippo syndrome while we hunt for a cure SANFILIPPO CHILDREN’S FOUNDATION

The simple intervention designed to teach preterm babies the rhythm of life

Helping children with cerebral palsy to live their best life

Improving quality, access, and equity of childhood asthma care: ImpACT Childhood asthma

TELETHON KIDS INSTITUTE

UNIVERSITY OF MELBOURNE

UNIVERSITY OF NSW

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CONTENTS

Australian Health & Medical Research & Innovation

42 Baby CHiX FLINDERS UNIVERSITY

Airway smooth muscle growth trajectory and asthma

Giving children the mental tools to overcome medical trauma

UNIVERSITY OF WESTERN AUSTRALIA

TELETHON KIDS INSTITUTE

Early detection of type 1 diabetes

Luminesce Alliance: leading the deployment of precision medicine for children

TELETHON KIDS

LUMINESCE ALLIANCE

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60 Transforming children’s lives one gene therapy at a time SYDNEY CHILDREN'S HOPSITAL NETWORK

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44 Easing Pain and Ensuring Uninterrupted Treatment for Hospitalised Children UNIVERSITY OF QUEENSLAND

46 Sleep science plugs into new technology UNIVERSITY OF QUEENSLAND

52 A non-invasive bedside triaging tool for late pregnancy to prevent stillbirth and fetal distress UNIVERSITY OF NSW

Shaping healthier futures: the Activated OSHC program

Landmark Malawi trial boosts iron levels in pregnant women

UNIVERSITY OF SOUTH AUSTRALIA

WEHI

48 The common vitamin that could be the key to preventing some cases of heart birth defects and miscarriages VICTOR CHANG CARDIAC RESEARCH INSTITUTE

CONTENTS

Australian Health & Medical Research & Innovation

66 A gap in the system LA TROBE RURAL SCHOOL

64 Harvesting safe farmers: A comprehensive exploration of child farm safety

Making Moves: Empowering Paediatric Cancer Survivors Through Physical Activity

NATIONAL CENTRE FOR FARMER HEALTH

UNIVERSITY OF NSW

Specialist facilities opening doors to paediatric research

“Finding a Way”

TRANSLATIONAL RESEARCH INSTITUTE

UNIVERSITY OF NSW

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“FINDING A WAY”

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68 Mealtimes Matter UNIVERSITY OF QUEENSLAND BRAIN INSTITUTE

Giving Aboriginal and Torres Strait Islander families a voice through research

New early intervention options hold great promise for kids with CF

MATER RESEARCH INSTITUTE

TELETHON KIDS INSTITUTE

NEW MEMBER

80 Giving children the opportunity to design their care

CROHN’S COLITIS CURE

Luminesce Alliance

THE LAST WORD

84 Unlocking potential through philanthropy 2023 | INSPIRE 030 9

EVENTS OVERVIEW

UNIVERSITY ROUNDTABLE

The Research Australia University Roundtable on 22 November 2023 was hosted by the University of Wollongong at its Sydney CBD campus. At other Roundtables this year we have had a tour of a laboratory or facility. This Roundtable was preceded by a seminar which used the NSW RNA Bioscience Alliance as a case study in engagement between universities and government. Speakers were Professor Barney Glover AO, Vice Chancellor of Western Sydney University, Professor Patricia Davidson Vice Chancellor of University of Wollongong, Dr Darren Saunders, Deput y Chief Scientist NSW and Professor Pall Thordarson, Director of the UNSW RNA Institute and lead of the NSW RNA Bioscience Alliance. The Seminar explored how all

ABBVIE LAUNCH

Research Australia launched the new Fu t u re H e a l t h L e a d e r s p ro g r a m i n November at sponsor AbbVie’s 10-year anniversary event in Parliament House. Assistant Minister for Health and Aged Care, the Hon Ged Kearney MP officially launched the program alongside Senator the Hon Anne Ruston, Shadow Minister for Health and Aged Care. Dr Mike Freelander MP and the Hon Matt Thistlethwaite MP were also present at the event. This new initiative will pilot a program during the 2024 school year, aimed at year 11 girls interested in pursuing a career in life sciences. Connecting them with female leaders from research, education, policy and industry it will give practical exposure to the enriching and diverse career opportunities in health and medical research. Those wishing to learn more can register their interest in the program on the Research Australia website. 10

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L to R – Nadia Levin, CEO and Managing Director Research Australia, Hon Ged Kearney MP, Assistant Minister for Health and Aged Care, and Ms Nathalie McNeil, Vice President and General Manager, AbbVie ANZ

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universities in the ACT and NSW have collaborated with the NSW Government to further statewide capability in RNA research.

The Roundtable followed and the first presenter was Alicia Gregory, Deputy Chief Investment Officer at the Future Fund and Chair of the Australian Investment Council.

It was a great case study in collaboration between universities and government. The discussion over lunch reflected on how COVID had provided the crisis that galvanised the action at all levels of Government and at universities. This had enabled universities to demonstrate their value to the NSW Government, which was also evident in responses to floods and bush fires.

Ms Gregor y described some of the major venture capital (VC) funds investing in medical products, and the increasing role of ‘family offices’ (the private capital arms of wealthy Australian individuals and families) as a source of capital. Ms Gregory also provided a macro level view of investment markets in Australia and globally, showing how inflation and monetary policy affected the ‘cost of money’; as the return on bonds has improved with rising interest rates, the target rate of return on investment in start- ups has also risen, making it more difficult to secure funding. On a more positive note, the other major global trend driving changes in investment is the concern about sovereign manufacturing, leading to an increase in ‘onshoring’ and ‘friendshoring’ of investment, also driven by global security concerns. The ensuing discussion explored the implications of this for R&D at universities, and how it explained some of the change’s universities were seeing in investment markets, and potentially how to respond to them. Greg Mullins, Head of Policy, provided a policy update. The final presenter was Dr Julia Hocking, Research Development Manager at Stryker, where she leads the Brisbane R&D lab. The R&D lad is a collaboration between Stryker, the University of Queensland, QUT, Metro Health North and Queensland Health, with Queensland Government funding. Dr Hocking discussed some of the opportunities and challenges in collaboration between industry and academic researchers. The next Roundtable will be hosted by La Trobe University on 27 March 2024.

Nadia Levin, CEO and Managing Director, Research Australia with Alicia Gregory, Deputy Chief Investment Officer at the Future Fund and Chair of the Australian Investment Council

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Health & Medical Research

CONGRATULATIONS TO THE WINNERS OF THE 20TH RESEARCH AUSTRALIA AWARDS

he nation’s leading scientific minds and advocates have been recognised in Research Australia’s 20th Health and Medical Research Awards, celebrating the extraordinary researchers, philanthropists, and community champions who are transforming health systems and outcomes across Australia. Among the winners were researchers developing new vaccine technology to fight malaria, uncovering new information about brain function and disease through geometry, and breaking down barriers to healthcare in remote communities through innovative use of artificial intelligence (AI).

Research Australia CEO Nadia Levin said “the Awards were an opportunity to honour our outstanding medical research sector for its dedication to translating world-leading research into outcomes that can transform millions of lives. “We received a record-breaking number of entries this year, showcasing the depth and breadth of talent in Australian health and medical research,” she said. “Celebrating the 20th annual Awards is a proud moment for Research Australia, and we were honoured to have so many of our sector’s shining stars with us to mark this occasion. “The last few years have underscored the vital importance of medical research and demonstrated Australia’s

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leadership in many fields. But we must address the challenges before us – nurturing and supporting our researchers, strategically staff, and cooperating across disciplines must be our priority if we’re to make the most of Australia’s research talent and tackle global health challenges.”

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of medical research, most recently through his donation to establish the Cumming Global Centre for Pandemic Therapeutics within the Peter Doherty Institute for Infection and Immunity at the University of Melbourne.

Health & Medical Research

“We cannot rest on our laurels. We must continue to strengthen the sector to maintain our competitive advantages and drive better health outcomes for all Australians.” Former Australian of the Year and CSIRO chair Simon McKeon AO delivered the keynote address at the event, reflecting on his time as chair of the Strategic Review of Health and Medical Research in Australia and some of its findings which remain highly relevant today. Australian Chief Scientist Dr Cathy Foley AO PSM presented the prestigious Peter Wills Medal to Emeritus Professor Carol Bower AC (Telethon Kids Institute). Professor Bower has played a seminal role in birth defect research and advocacy, especially neural tube defects (NTDs) and fetal alcohol spectrum disorder (FASD). Among her achievements, Professor Bower confirmed the link between low dietary folate and NTDs before successfully advocating for fortification of wheat flour; established Australia’s first birth defects registry; and significantly developed the evidence base and diagnostic tools for FASD.

Mr Col Reynolds won the Advocacy Award (sponsored by AbbVie) for his decades of awareness-raising about the importance of medical research, particularly for children with cancer, through his charity The Kids’ Cancer Project. Professor Angus Turner (Lions Eye Institute) won the inaugural Digital Health Technology Award, recognising his team’s achievements in using artificial intelligence to detect eye disease in patients in remote communities in Western Australia. This new category recognises the best emerging innovative technology that advances healthcare delivery and/or enables improved health outcomes. Ms Levin said the standard of nominees this year had been exceptional, with remarkable achievements entered across all categories. “On behalf of Research Australia, I would like to thank all our nominees, nominators and members for helping us celebrate the world-class skill and talent within this sector,” she said.

Celebrating 20 years

Professor Jake Baum (UNSW) accepted the Frontiers Award (sponsored by Australian National University) for developing a new method of manufacturing malaria vaccine that could provide complete protection from future infection and greatly advance global responses to the disease.

“I would also like to thank the organisations who have supported the awards, including our premium event partners UNSW Sydney and CSIRO, and our award event sponsors Griffith University, Australian National University, AbbVie, the NSW Government, Digital Health CRC and GSK. We also thank our Awards Partner The University of Newcastle. Research is only made possible with the support of those who recognise its value, and we are always grateful to those who back its continued growth.”

Dr James Pang (Monash University) won the Griffith University Discover y Award, sponsored by Griffith University, for his discovery of the important role brain geometry has in brain function, health and disease. Professor Michele Sterling (The University of Queensland) won the Health Services Award (proudly sponsored by the NSW Government), recognising the impact of her research into traditional physical treatments for people with musculoskeletal road traffic injury.

Thursday 2 November Doltone House - Hyde Park 3/181 Sydney The DataElizabeth Innovation AwardStreet (sponsored by Digital Health

CRC) was accepted by Professor Georgina Chambers on behalf of the National Perinatal Epidemiology and Dress Unit at Black Tie Statistics UNSW for their YourIVFSuccess website which has improved the process Tickets $325 per decision-making person OR $2,950 perfortable of 10 those considering IVF.

Bookings Book Online Here

Mr Geoff Cumming won the Great Australian Philanthropy Enquiries Call 0434 325 909 Award, recognising his generosity and ongoing support

PREMIUM EVENT SPONSORS

AWARD SPONSORS

AWARDS PARTNER

PETER WILLS MEDAL

Named in honour of Research Australia’s Director, Peter Wills AC, a great leader whose work led to the inception of Research Australia. The Peter Wills Medal is the flagship award and recognises someone who has made an outstanding, longterm contribution to building Australia’s international reputation in areas of health and medical research and fostering collaboration for better health.

WINNER: Emeritus Professor Caroline Isabel Bower AC, Telethon Kids Institute, WA

FRONTIERS RESEARCH AWARD

Sponsored by Australian National University, this Award recognises the success of innovative health and medical research that extends existing knowledge, boundaries and/or understandings within health and medical research.

WINNER: Professor Jake Baum PhD, University of New South Wales

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GRIFFITH UNIVERSITY DISCOVERY AWARD

This Award, sponsored by Griffith University, recognises an early career researcher (anytime from qualification but no more than 5 years past PhD) whose paper/ patent /discovery has already demonstrated its importance or impact.

WINNER: Dr James Pang - Monash University, VIC

GREAT AUSTRALIAN PHILANTHROPY AWARD

This Award profiles personal philanthropy that is outstanding in its generosity, effectiveness, vision, high impact and transformative quality. The Award recognises and encourages personal philanthropic donations over a period of time by an individual(s) or family to Australian health and medical research.

WINNER: Mr Geoff Cumming - Karori Capital

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ADVOCACY AWARD

Sponsored by AbbVie, this Award recognises and congratulates exceptional contributions made by research champions who help raise community awa r e n e s s a n d u n d e r s t a n d i n g a b o u t t h e importance of health and medical research.

WINNER: Mr Col Reynolds OAM - The Kids’ Cancer Project, NSW

HEALTH SERVICES RESEARCH AWARD 2 Andrea Natoli

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DIGITAL HEALTH TECHNOLOGY AWARD NEW CATEGORY

This Award is presented for an emerging, innovative technology that advances healthcare delivery and/ or enables healthcare users and providers to improve health outcomes.

WINNER: Associate Professor Angus Turner - Lions Eye Institute, WA

GSK AWARD FOR RESEARCH EXCELLENCE

This Award is for an individual or team who has Awards Research Australia 2 Andrea Natoli provided leadership and made an outstanding lits of winners One of the most prestigious awards available to Awards Research Australia contribution to health services research; driven Australian researchers, thislitsprize has been awarded of winners research that has led to a significant improvement since 1980 to recognise outstanding achievements in healthcare; and/or has championed the in medical research with potential importance to development of the health services research human health. This year’s Award is accompanied field. Proudly sponsored by the New South Wales by a grant of $100,000 to further the winner’s Government. research. WINNER: Professor Michele Sterling PhD, The University of Queensland

WINNER: Professor David Komander – Walter and Eliza Hall Institute, VIC

DATA INNOVATION AWARD

This Award, sponsored by Digital Health CRC, recognises an individual or team whose innovation is considered to represent one of the most impactful new data innovations in the health and medical research sector within the past five years. WINNER: Professor Georgina Chambers - National Perinatal Epidemiology and Statistics Unit (NPESU), UNSW

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LEADING STRUCTURAL BIOLOGIST WINS THE 2023 GSK AWARD FOR RESEARCH EXCELLENCE FOR BREAKTHROUGH UBIQUITIN RESEARCH The ubiquitin research is an exciting and complex area that proved to be a rewarding experience for Professor David Komander, lead scientist at the Walter and Eliza Hall Institute of Medical Research (WEHI) Ubiquitin Signalling Division. Ubiquitin signals play a significant role in many biological processes. Any dysfunction in ubiquitin modification processes can lead to diseases such as cancer, inflammatory conditions and neurodegeneration.1 The breadth of impact this small protein can have on our health is significant and so is the need to increase our understanding of the ubiquitin systems full potential. The research driven by Professor David Komander has been instrumental in elevating global understanding of the ubiquitin system, including the processes by which ubiquitin chains assemble and disassemble. Professor Komander’s extensive research into the ubiquitin system won him the 2023 GSK Award for Research Excellence (ARE), one of Australia’s most longstanding and prestigious awards for the medical research community. He says that many areas of ubiquitination have been under-explored, which makes it a promising field to work in.

Professor David Komander

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“It’s an exciting time to be working within the field of ubiquitination. I am honoured to be named the 2023 recipient of the GSK Award for Research Excellence and have our work recognised in this way.” “Expanding our research into new substrates of ubiquitin will open an entire new realm of what ubiquitination might be able to do. The GSK ARE grant will provide us with

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critical support as we take our research to the next level and build new methods for measuring ubiquitin modifications.”

health outcomes for patients living with many currently incurable diseases, including cancer,” says Professor Komander.

THE ’KISS OF DEATH’ PROTEIN AND PARKINSON’S DISEASE

ABOUT THE AWARD

Ubiquitin is a protein that acts like a ‘tag’ to tell our cells which proteins to break down or recycle, an important ‘kiss of death’ process that helps our cells stay healthy and functional.2 Professor Komander and his team have been researching the link between early onset Parkinson’s disease and two proteins called PINK1 and Parkin as part of their studies into the ubiquitin system. Parkinson’s disease is a chronic and progressive disorder of the nervous system.3 It is estimated that over 200,000 people in Australia currently live with Parkinsons, with one in five being diagnosed before the age of 50.3 Professor Komander says his team’s work on the ubiquitin code is paving the way for the development of new therapies to treat Parkinson’s disease. “Early onset Parkinson’s can be caused by genetic mutations that alter the function of key proteins. By understanding the molecular structures of these mutated proteins and monitoring how these proteins become activated and function, we have gained powerful insights into how Parkinson’s disease develops. Along the way, we contributed to some of the most important breakthroughs in the field in the last decade,” says Professor Komander.

FUNDING THE FUTURE

According to Professor Komander, ubiquitin research is inherently disease agnostic as it regulates many distinct disease processes. The lab’s ultimate objective is to uncover new diagnostics and treatments to stop or delay incurable conditions, like Parkinson’s disease and other ubiquitin-based disorders. Professor Komander says the $100,000 AUD grant that comes with the GSK Award for Research Excellence will help take their ubiquitin research to the next level. “We are really getting out of the academic mindset and moving towards more translatable outcomes. Enhancing our knowledge in the ubiquitin area has the potential to drive transformative improvements in

The GSK Award for Research Excellence is one of the most prestigious awards available to the Australian Medical Research Community. It has been awarded since 1980 to recognise outstanding achievements in medical research and facilitates career development with potential importance to human health. “Professor Komander’s work is an outstanding example of how home-grown innovation is transforming our understanding and potential treatment of diseases like Parkinson’s that we once believed were incurable,” said Dr Alan Paul. “We are excited to support David and his team as they continue their critical research into the ubiquitin system.” The 2023 GSK Award for Research Excellence (ARE) was presented to Professor Komander at Research Australia’s Health and Medical Research Awards in Sydney in November.

About Professor Komander: David Komander is a biochemist and cell biologist, and a recognised leader in the field of ubiquitination. He generated new tools to unveil the complexity and specificity of the ubiquitin code, and uncovered fundamental principles in ubiquitin chain assembly, recognition and disassembly by deubiquitylating enzymes (DUBs). Professor Komander discovered OTULIN, a new protein that helps control inflammation, and described the human monogenic disease OTULIN-related autoinflammatory syndrome (ORAS). He determined the molecular basis for PINK1/Parkin-mediated mitophagy, a key ubiquitination pathway derailed in inherited Parkinson’s disease. His ultimate aim is the development of the first disease-modifying therapies for Parkinson’s and other ubiquitinbased disorders. He is now leading the Ubiquitin Signalling Division at the Walter and Eliza Institute of Medical Research (WEHI).

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GENE PATCHING POTENTIAL EXPLORED FOR TACKLING CHILDHOOD DEMENTIA

Every year in Australia, around one hundred babies are born with one of more than 70 rare genetic conditions that cause childhood dementia. Worldwide, this translates to around 700,000 children living with dementia symptoms such as confusion, loss of memory, loss of speech and more.

Dr May Aung-Htut and Prof Steve Wilton AO

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ost children with this devastating condition do not reach adulthood, but innovative new research in Australia is offering hope for an effective treatment applying antisense or ‘gene patching’ technology. This approach builds on ground-breaking WA-based research led by Professor Steve Wilton AO and Professor Sue Fletcher AO (developed at the Perron Institute) which has since resulted in US Food and Drug Administration approval for three drugs to treat Duchenne Muscular Dystrophy, via Sarepta Therapeutics. Professor Wilton and Dr May Aung-Htut co-lead the Molecular Therapies Laboratory based at the Centre for Molecular Medicine and Innovative Therapeutics (CMMIT) at Murdoch University, with a mission to develop therapies that modify gene expression to alleviate human suffering. As well as childhood dementia, their exploration of potential molecular genetic therapies is targeting a range of other conditions such as motor neurone disease, multiple sclerosis, and sepsis. The work on childhood dementia, embarking on a journey that could change the lives of children and families grappling with this cruel condition, is a collaboration with Associate Professor Tony Cook at the University of Tasmania and colleagues from Menzies Institute for Medical Research, the Tasmanian School of Medicine and Tasmanian Health Service, Perron Institute, and CMMIT, Murdoch University. Associate Professor Cook was awarded $599,977 from the Medical Research Future Fund for the project to develop new approaches for the treatment and care of children with dementia. “Many genetic diseases that cause childhood dementia involve accumulation of specific fat molecules within brain cells, causing them to become dysfunctional and die,” Associate Professor Cook said. “Inhibiting production of these fat molecules using traditional drugs has shown promise for these conditions in the laboratory, but these drugs have limitations and side effects that mean they are unsuitable as a therapy. “We believe the antisense or ‘gene patching’ drugs developed and successfully applied to Duchenne muscular dystrophy can be designed to reduce this fat accumulation with no or few side effects.” “Gene patching can correct or suppress abnormal gene expression that otherwise leads to rare inherited diseases,” said Dr Aung-Htut, who is leading the CMMIT, Murdoch University involvement. “The technique manipulates the cell machinery to trick cells into behaving as though there is no gene message, acting as genetic ‘white-out’.

“The flexibility of this technology allows us to modify gene expression in various ways increasing or decreasing gene expression, suppressing defective processes, and switching the type of protein produced. “Working collaboratively across Murdoch University and the University of Tasmania our focus is on improving outcomes for children with dementia by addressing the current limitations of traditional drugs,” Dr Aung-Htut said.

We will develop and conduct preclinical testing of a molecular genetic drug that we believe can overcomes these limitations, providing help where it is desperately needed.” The Centre for Molecular Medicine and Innovative Therapeutics is a joint research centre with the Perron Institute and is part of Murdoch University’s Health Futures Institute, bringing together a multidisciplinary team of scientists and the Western Australian community to transform how long and how well people live, not just in Australia, but around the world. “Building on successful antisense technology and a personalised medicine approach we believe precision medicine has the potential to transform healthcare on a scale equivalent to the way antibiotics transformed the fight against infectious diseases,” Dr Aung-Htut said. “As well as working to discovering more ef fective treatments, and treatments where there are currently none, our research teams are focusing on developing techniques for early diagnosis. “In WA, for example, where there are over 63,000 children with rare diseases, there is a pressing need to find novel antisense treatments for children with diagnosed and undiagnosed genetic disorders. “This can be challenging as it can take a long time to get a diagnosis for a child with a rare disease, during which time the disease progresses, often irreversibly. “If there is early molecular diagnosis of children with clinically diagnosed rare diseases, it becomes easier to precisely identify the underlying genetic defect so that antisense drug design can start as early as possible. “Funding received from the Telethon Channel 7 Trust has helped with this work on improving diagnosis and exploring antisense treatment,” Dr Aung-Htut said.

Author: This article was provided by the Perron Institute

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The family have provided their permission for this photograph to be shared with Research Australia

IMPROVING QUALITY OF LIFE FOR CHILDREN WITH SANFILIPPO SYNDROME WHILE WE HUNT FOR A CURE For individuals with a rare disease, seeking and receiving appropriate care and support can be filled with guesswork.

amilies often bear the brunt of educating each new health professional they encounter about the condition. It doesn’t need to be this hard and for Sanfilippo syndrome, the development of consensus clinical guidelines has been a game changer. As the Sanfilippo Children’s Foundation marked its 10th anniversary this year, we reflected on the advances made in our particular field of paediatrics. Our efforts, and those of 20

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our international sister organisations, to drive research into this devastating childhood dementia have spurred many advances. Promisingly, we are within reach of therapies that could halt the inexorable neurodegeneration that robs children of their ability to speak, walk, feed themselves and recognise their parents, and change the course of a disease that currently takes most lives before adulthood. While we continue to push for faster progress to realise these therapies, there is one achievement of which we are particularly proud that has made an immediate impact for families living with Sanfilippo—the development and publication of the global Consensus Guidelines for Sanfilippo Syndrome Clinical Care.

8 year old Jobe from NSW undergoes tests in the clinic to monitor his Sanfilippo syndrome symptoms.

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We are already seeing the difference that this resource is making in empowering families to seek and receive bestpractice care and optimise quality of life for their children. Children with Sanfilippo typically have an unremarkable infancy and toddler-hood, often marked only by frequent ear infections and/or enlarged adenoids and tonsils. Around two years of age a mild speech or developmental delay might be noted, but as the child gets a bit older other signs become more obvious like sleep issues, hyperactivity, and autistic behaviours. Viewed in isolation, these signs can lead to an incorrect diagnosis of ADHD or autism. Eventually, however, the diagnosis of Sanfilippo syndrome is reached. This devastating news is compounded by the knowledge that there is no treatment or cure, and clinical care and management are often pieced together and the subject of guesswork. Many families are simply told that there is nothing that can be done, to go home and love their children. But we can, and should, do better than this. Supportive and well-informed healthcare providers, and best-practice clinical care are vital to optimise the journey and quality of life for the child and family. And this is where consensus clinical guidelines can make all the difference. The Sanfilippo clinical guidelines were developed through a collaboration between Cure Sanfilippo Foundation (USA) and Sanfilippo Children’s Foundation (Australia) together with an international expert clinician steering committee. Robust consensus recommendations were established with input from more than 100 international clinicians with a range of specialist expertise and experience in caring for individuals with Sanfilippo syndrome. The two foundations ensured the patient perspective was also incorporated.

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significant source of concern for families caring for their non-verbal children. Despite the progressive and fatal nature of Sanfilippo, optimising education and development is also critical to maintain function, independence, and quality of life for as long as possible. The Guideline’s recommendations around these aspects have already been used by families around the world to secure and maintain appropriate educational and therapeutic supports and services, including via the NDIS here in Australia. As we move closer to the availability of disease-modifying therapies for Sanfilippo, it will be even more critical to identify children with Sanfilippo as early as possible. Emerging evidence from clinical trials suggests that treatment initiated after the age of two or three years in severe forms of the disease has limited impact on cognitive outcome measures, yet children are most commonly diagnosed between the ages of four to six years. While we wait for the implementation of newborn screening for Sanfilippo, these clinical guidelines can help all health practitioners to recognise the signs and symptoms, expedite a diagnosis and from there coordinate the best care for children with Sanfilippo syndrome and their families. Then they really can go home and love their children and better enjoy their precious time together.

Dr Lisa Melton

The greatest impact of this lysosomal storage disorder is on the brain, but the heart, gastrointestinal system, bones and joints, lungs, eyes, and hearing are also affected. As a re sult, suppor ting fa milie s to as se mble a multidisciplinary team around them and facilitating communication between members of the healthcare team can greatly help to ease the stress. Implementing regular monitoring as recommended in the guidelines will identify emerging issues before they lead to medical crises. Previous research has identified that caregivers’ greatest unmet needs are around the management of pain, distress, hyperactivity, and impulsivity; sleep; communication; mobility; and feeding and nutrition. More research is needed to enable effective management of the se sy mptoms, but the guide line s prov ide recommendations around the appropriate supports and therapies that are currently available. There is also a special focus on how to evaluate the potential causes of unexplained pain and distress – a

Author: Dr Lisa Melton, Head of Research, Sanfilippo Children’s Foundation

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ADVANCED IMMUNOTHERAPY MAY HOLD PROMISE FOR CHILDREN WITH BRAIN CANCER Diffuse Intrinsic Pontine Glioma (DIPG) is an aggressive brain tumour affecting 20 Australian children each year.

A histological image of a tissue sample studied in the research, which found the CART T cells persisted in the preclinical models post treatment, acting as a ‘living drug’ to fight the tumour if it returns. © WEHI researchers

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EHI researchers have found promise in treating DIPG with a new immunotherapy treatment, called CAR T therapy. In the study, CAR T cells were able to enter the brain and have an anti-cancer effect by reducing the tumour burden. An advanced immunotherapy treatment could hold promise for children with an inoperable type of brain cancer, according to new research.

AN AGGRESSIVE TYPE OF BRAIN TUMOUR

Usually occurring in children aged five to seven years old, Diffuse Intrinsic Pontine Glioma (DIPG) is an aggressive type of brain tumour that affects 20 children in Australia each year. The fast-growing tumour forms in the part of a child’s brain responsible for vital functions like breathing, swallowing and movement, meaning it is unable to be surgically removed. Children diagnosed with DIPG are unlikely to sur vive a year beyond diagnosis and there is currently no treatment for this devastating condition.

CAR T THERAPY HAS ANTI-CANCER EFFECT ON DIPG

WEHI researchers have found promise in treating DIPG with an innovative new immunotherapy treatment, called CAR T therapy. Published in Neuro-Oncology Advances, the research showed CAR T therapy was effective at targeting DIPG tumours. CAR T cell therapy involves isolating a patient’s immune cells, engineering them to become “super killer cells” and then re-infusing them into the patient to fight their cancer.

ACTING AS A LIVING DRUG

The research, led by Associate Professor Misty Jenkins, Laboratory Head at WEHI and The Brain Cancer Centre, showed in preclinical models these specifically-engineered CAR T cells were able to enter the brain and have an anticancer effect by reducing the tumour burden. ‘CAR T cells offer a possibility of cure, with no long-term side-effects. These genetically-modified white blood cells act as a “living drug”, which means the patient will retain a living memory in their body of the anti-tumour response that may also work to kill the tumour again if it ever returns. ‘The way these cells can completely eliminate the tumours and persist in the body into the future is what is so exciting

about CAR T cell therapy, and why immunotherapy is the future of precision medicine.’

NEW TARGET FOR FUTURE CLINICAL TRIALS

The study found DIPG brain tumours can be targeted using CAR T cells that recognise a cancer-specific protein called HER2. Once in the brain, the CAR T cells recognised this protein and signalled the T cells to kill the tumour cells. Associate Professor Jenkins said the use of CAR T cell therapy had effectively eliminated the DIPG tumours in the study’s preclinical models. ‘This paper shows that an approach to HER2 does work, and we hope to see this treatment incorporated into current and future clinical trials available to children in Australia. ‘While there are no long-term studies yet, this research builds on other work that has shown this treatment to be effective in reducing DIPG tumours and improving the quality of life for these patients, who currently have no treatment options. ‘Our hope is that this treatment will be included in future clinical trials and will eventually be used in combination with other drugs to treat DIPG.’

LAYING THE GROUNDWORK FOR NEW THERAPIES

The research was a promising step forward in treating DIPG, Associate Professor Jenkins said. ‘This lays the groundwork for us to interrogate thousands of potential therapies for anti-cancer immune cells to fight DIPG. Other studies have demonstrated this treatment approach is safe in children, so we are hopeful it won’t be long before it is clinically available.’ The research was made possible in part by funding from the Victorian Paediatric Cancer Consortium, Isabella & Marcus Foundation, Robert Connor Dawes Foundation and The Brain Cancer Centre. The study, “HER2 Chimeric Antigen Receptor T cell immunotherapy is an effective treatment for Diffuse Intrinsic Pontine Glioma”, is published in Neuro-Oncology Advances (DOI: 10.1093/noajnl/vdad024 ). Authors: Stacie Wang, Alexander Davenport, Melinda Iliopoulos, Hannah Hughes-Parry, Katherine Watson, Valeria Arcucci, Matthias Mulazzani, Ryan Cross and Misty Jenkins, WEHI.

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TOWARDS A UNIVERSAL G THERAPY FO In the first study of its kind, a team of scientists at Children’s Medical Research Institute is a step closer to developing a more universal gene therapy that can be used in all patients impacted by the devastating condition spinal muscular atrophy (SMA).

he work by lead author Dr Grant Logan and senior author Professor Ian Alexander was published in Molecular Therapy in July in collaboration with colleagues at the University of Florida, USA. SMA is an inherited neuromuscular disorder and a leading genetic cause of infant death in Australia. Children who are born seemingly perfectly healthy never gain the ability to crawl, walk, and sit up; eventually they even lose their ability to breathe, with the most severe cases dying within the first two years of life. However, gene therapy has proven to be a game changer for infants with SMA – the earliest treated patients are now reaching their seventh birthdays after receiving a single infusion in early life. NSW was the first state in Australia to start a gene therapy program for SMA, with more than 40 newborns having been

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successfully treated for this life-threatening condition since 2018. Gene therapy is a revolutionary approach to treating genetic and acquired diseases that most commonly involves replacing or repairing a faulty gene. The most efficient delivery systems are those based on viruses and the current SMA gene therapy uses a harmless virus named AAV that has a natural ability to carry genetic information into human cells. Unfortunately, a small number of infants with SMA are unable to receive the gene therapy because their body has immunity to the AAV vector as a consequence of exposure to the naturally occurring AAV virus circulating in the community. “Children who have antibodies to AAV, or pre-existing immunity, cannot currently receive the SMA gene therapy because the treatment will be neutralised by their antibodies,’’ Dr Logan said. “We are seeking to solve this problem so that all patients can access this life-saving technology.” Dr Logan and Professor Alexander’s team have been studying the immune response to the AAV vector in children diagnosed with SMA at birth, who were treated and have benefited from the gene therapy. Dr Logan said, ‘we find that AAV vector treated patients make a significant antibody response to the delivery system and have isolated a large panel of these antibodies. They are providing new insights into the complexity of the human response to the AAV gene therapy.’The teams in Sydney and Florida are now making a coordinated effort using different approaches

A GENE OR SMA

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Dr Grant Logan

to re-engineer the surface of the AAV delivery system so it can escape the antibodies that already exist in some patients and avoid neutralisation. ‘It is early days but we’ve made never before seen observations looking at how human antibodies bind to the surface of the AAV coat protein (capsid)’ Dr Logan said. ‘Our teams are extremely excited by this new information and we’re hopeful these novel human antibodies will be useful tools in the development of a new improved system.’’Mum Lykera, whose son Kalarny has SMA, described the research into his condition as “magic.’’ ‘It is no longer considered a palliative condition,’ Lykera said. ‘Whereas before, you were told to take your child home and nurture them. Now it’s completely changing the way that the SMA community think about things. Around the world, it’s giving everyone that glimmer of hope.’’It is hoped this work in SMA could also benefit other children who could be treated using AAV gene therapy for genetic disorders such as Sanfilippo syndrome and Duchenne’s Muscular Dystrophy.

Professor Ian Alexander

‘Completion of this study is like reaching base camp in our quest to develop better AAV delivery systems to get around the problem of pre-existing AAV immunity. We still have a way to go but it is very satisfying to reach this point in the journey and it would be incredible to see more infants and children having access to these life-changing technologies’. This has been a collaborative effort. Dr Logan and Professor Alexander also worked with scientists from the Garvan Institute, Westmead Institute for Medical Research and Sydney Children’s Hospitals Network.

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SUPPORTING CHILDREN WITH CANCER AND THEIR FAMILIES IN THE ERA OF PRECISION MEDICINE

Screenshot from BSUdeveloped animation resource for families enrolling in precision medicine for childhood cancer.

UNSW Sydney is conducting world-leading research into the psychosocial impact of precision medicine on children with cancer and their families.

y tracking the experiences of >400 families and >100 health professionals through Australia’s ZERO Childhood Cancer program, our work is driving initiatives to ensure scientific advances translate into improved outcomes for children and families. Precision medicine offers new hope for children with cancer and their families. Using genomic technologies along with in vitro and in vivo profiling, precision medicine programs have the potential

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to identify novel treatment options as well as inform a patient’s diagnosis, prognosis, and clinical management. Advances in precision medicine have increased our knowledge of genetics and childhood cancer risk and are expanding the therapeutic options for children diagnosed with cancer. Across Australia, precision medicine has been available to children with a poor prognosis cancer since 2017 through the Zero Childhood Cancer program, and by the end of 2023 will be available to all children diagnosed with cancer in Australia. Although the promise of precision medicine is great, it brings with it challenges for families and healthcare professionals alike. The Ethics and Genetics team at the Behavioural Sciences Unit (BSU) are conducting an ongoing program of research with the goal of better understanding these challenges, and a view to drive solutions through innovations in psychosocial care and workforce support. So far, through collaborations with our colleagues at the Children’s Cancer Institute and the Kids Cancer Centre, the team have captured the experiences of over 400

CHRISTOPHE KEREBEL

psychological challenges faced by families accessing families and 100 health professionals through the ZERO KEREBEL CHRISTOPHE My Twitter : @chriskere for poor prognosis Childhood Cancer program and the Luminesce Alliance precision medicineCHRISTOPHE KEREBEL cancer and found that most patients and parents reported symptoms of supported PREDICT trial1. anxiety and/or depression5, and 20% of parents reported One of the critical questions we continue to examine is needing further psychological support. To understand what parents hope for, and what they worry about, when how best to meet these support needs, our team are they enrol their child in a precision medicine trial. We examining barriers to accessing psychological support found parents tended to hold two hopes simultaneously: during the precision medicine process, and piloting the that participation would benefit their child, as well as future acceptability, uptake and impact of clinician initiated, 2 children . flexibly delivered telehealth for distressed families.

If it can’t save our daughter then it might help someone else” (Mother of child with a sarcoma).

Although parents told us about several worries, including the potential for a long wait for results, they generally expressed high levels of satisfaction with the trial and few regrets about their child’s participation. Importantly, this was true even for bereaved parents. With any treatment approach, it is important that families feel well-informed. Yet, parents often enrol their child in a precision medicine program at a time of crisis: whether it is shortly after the child’s diagnosis or at relapse. We hypothesised that emotional distress, combined with time pressures and the complexity of precision medicine concepts, might understandably impact parents’ and patients’ comprehension of the precision medicine process. To explore this, we asked parents and adolescent patients about their perspectives on the information given to them when consenting to a precision medicine trial and their understanding of the trial. Findings identified some gaps in understanding and participants provided useful suggestions for ways the information could be simplified and better formatted to foster engagement and understanding3. In a separate study, we focused on parents’ perspectives of having received information about their child’s genetic (heritable) cancer risk, a notoriously complex yet critical topic area for families to understand, with potentially significant implications for the wider family4.

Complementing our work with families, we have also conducted studies investigating the experiences of oncologists and other health professionals at the frontline of precision medicine care6,7. While attitudes toward precision medicine are generally positive, many describe how it adds complexity to their role and is resulting in changes, often navigated without formal training. “I hope we get to the stage… where you know…genetic knowledge becomes so integral to the treatment of patients that all members of the treatment group are familiar with it, but I don’t feel I have that understanding at the moment.” (Surgeon involved in precision medicine care). Findings highlight the need for health professional training, particularly for non-genetics trained professionals and models of care that promote multidisciplinary involvement. As we strive towards a world in which every child is free from cancer, precision medicine offers a new way forward. By listening closely to the perspectives of patients, parents, healthcare professionals and other key stakeholders, we aim to ensure all families are supported and empowered to participate in precision medicine, during what may be the most challenging time of their lives.

Dr Kate Hetherington

Our findings have informed exciting developments in the genetic counselling resources and supports available to families in the next stage of the ZERO program. Our team has also developed and piloted three short animation resources for patients and their parents to support understanding of key precision medicine concepts, which will eventually be available to families across Australia. Keeping equity at the forefront, we aim to adapt and translate these resources for families from culturally and linguistically diverse backgrounds and have commenced interpreter supported interviews so that all families may share their experiences of precision medicine for their child’s cancer. Developing models of psychosocial care for families participating in precision medicine is another pillar of our research. We documented the emotional and References can be supplied upon request.

Author: Dr Kate Hetherington is a Research Fellow and Clinical Psychologist at the Behavioural Sciences Unit (BSU) at UNSW Sydney. She leads the Ethics and Genetics team whose program of work is supported by Luminesce Alliance, ZERO Childhood Cancer, Cancer Institute NSW, and National Health and Medical Research Council (NHMRC).

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THIRTY YEARS OF FUNDING KIDS’ CANCER RESEARCH

Col Reynolds OAM

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CHRISTOPHE KEREBEL

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In the 1980s, Col Reynolds OAM was a tour bus driver, curious to know how he could help kids with cancer – his chance came one day whilst on a drive.

hirty years later, with Col in his 80s, his tenacity and passion to give kids with cancer the best chance of surviving and living long and healthy lives has only grown, with over $70 million being committed to research through The Kids’ Cancer Project, the charity he founded. Speaking about the moment that he stopped to let two children cross the road, a moment that changed his life’s purpose, Col says: “I knew that they had cancer because they were bald. I wanted to help them, so I went into the hospital and told the specialist I’d like to take the kids out on fun excursions. No one in Australia had done this before.” With the generous support of the fire brigade, mounted police, and navy to raise funds, the hospital and Col formed a partnership, and he was soon taking the sickest children on mini holidays to the snowfields, day trips on boats, and visits to wildlife parks – of course, with medical professionals on hand for any emergencies.

Kids’ Cancer Project has committed over $70 million to childhood cancer research and is still committed to investing in vital projects and researchers. To celebrate its 30th anniversary, and in honour of Col and his living legacy to kids’ cancer research, The Kids’ Cancer Project has established the Col Reynolds Fellowships to help future-proof the field of childhood cancer research. This $7.9 million funding commitment will ensure that 25 of the best young researchers in Australia can further their careers and, most importantly, their pioneering impact on childhood cancer long into the future. As Col says:

It takes time and money, but funding research will lead to 100% survival, after all, survival starts with science.”

Having spent several years trying to brighten the lives of kids with cancer, Col was tragically faced with the funerals of kids he knew over and over again. After a conversation with paediatric oncologist Professor Luciano Dalla-Pozza at Westmead Children’s Hospital, Col switched his focus to help save their lives. He says:

Luce informed me about three researchers working in a small back room at the hospital, adding that support was limited for research into saving kids’ lives.” Col decided to raise the funds needed to help give the researchers the resources they needed to develop better kids’ cancer treatments. He continues: “One of those scientists was Roger Reddell who went on to lead cancer research at the Children’s Medical Research Institute in Westmead. I bought Roger the first culture cancer cell counter in Australia. It was from Japan, and at minus 80 degrees it could freeze tissues and tumours better than the tucker box with a lift-up lid they’d been using.” Today, 30 years after Col first founded the charity, The

Author: Alison Muir, Trusts & Foundations Executive, The Kid’s Cancer Project

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Permission has been granted by the family to use this image.

A GENETIC DIAGNOSIS ENABLES PRECISION MEDICINE FOR CEREBRAL PALSY

While there are a number of known risk factors, for many people with cerebral palsy the cause is not clear.

ore than a decade of research by a team at the University of Adelaide has shown that genetic changes cause up to a third of CP. This research is now providing new opportunities for precision medicine.

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WHAT IS CEREBRAL PALSY?

Despite being studied for decades, there are still many “known unknowns” about cerebral palsy (CP), which is the most common cause of childhood disability in Australia, affecting 1 in 700 births. Children born preterm (<37 weeks), with low birth weight, or from multiple births (i.e. twins/triplets) account for up to one-half of cases, however the remainder come from pregnancies that reach full term with no obvious complications. Brain neuroimaging shows that 85% of people with CP display abnormalities which have occurred in utero or around birth. These abnormalities present most commonly as lesional injuries or maldevelopment in the areas of the

CHRISTOPHE KEREBEL Dr Clare van Eyk

Prof Jozef Gecz CHRISTOPHE KEREBEL

Dr Jesia Berry

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brain that control muscle movement. The remaining 15% have no obvious lesion or abnormality explaining their CP. CP disrupts control of muscle function, most frequently causing spasticity (contractions) or dyskinesia (involuntary movements). Severity varies from barely discernible, to severe activity limitation requiring a wheelchair. Depending on the area of the brain affected, people with CP also frequently have comorbidities such as intellectual disability, epilepsy and autism; or impairments in speech, vision, or hearing.

IDENTIFYING GENETIC CAUSES OF CP

Scientists at the University of Adelaide embarked on pioneering work to investigate the causes of CP more than a decade ago, with Emeritus Professor Alastair MacLennan establishing The Australian Cerebral Palsy Biobank (ACPB). More than 500 families have since enrolled and contributed blood or cheek swab samples for the group’s genetic research, as well as extensive clinical information. Landmark publications from the ACPB researchers and their international collaborators demonstrate that up to a third of people with cerebral palsy tested so far have an underlying genetic cause. In turn, around a third of those with a genetic cause are likely to benefit from a change in treatment as a result of this knowledge. Geneticists Prof Jozef Gecz and Dr Clare van Eyk lead the ACPB and are applying systematic genomic sequencing to identify genetic causes of CP. The group’s recent review of the genomics of CP, published in Nature Reviews Neurology, identified at least 190 genes reported multiple times with genetic changes in people diagnosed with CP. These genes overlap with those reported in other neurodevelopmental disorders such as intellectual disability, epilepsy and autism, as well as known causes of movement disorders such as hereditary spastic paraplegia.

INFORMING CLINICAL PRACTICE

Through the work of the Adelaide group, it is now clear that the presence of risk factors for CP such as prematurity and growth restriction do not rule out a genetic cause. In some cases, these risk factors may themselves have underlying genetic causes. With the benefit of their internationally unique ACPB resource, the Adelaide group are working to identify clinical and imaging findings which can be used to predict which people are most likely to have a genetic cause for their CP. As part

of this aim, epidemiologist Dr Jesia Berry is applying a standardised Magnetic Resonance Imaging Classification System (MRICS) to determine the association between patterns and timing of brain lesions or abnormalities visible on neuroimaging and genetic diagnoses.

GUIDING PRECISION MEDICINE

Early clinical diagnosis of CP and identification of ‘at risk’ infants is now possible through sensitive and specific movement assessments. Early diagnosis enables earlier intervention during the window of maximum neuroplasticity, thereby improving functional outcomes and patient and caregiver wellbeing. The Adelaide team are working to couple early clinical diagnosis with early genetic testing, which they hope will become part of the routine diagnostic workup in babies diagnosed with CP. There are many benefits to providing an early genetic diagnosis, including avoiding unnecessary and invasive investigations, enabling informed carrier testing and reproductive planning, providing prognostic information about future health needs, and informing the use of targeted treatments and physical therapies that can improve or even reverse physical impairment. Importantly, early genetic diagnosis will spur the progress of novel clinical trials and provide eligible individuals for recruitment, thereby aiding the development and honing of better precision medicines, including pharmaceutical, genetic, and rehabilitative therapies. Authors: Dr Clare van Eyk1,2 , molecular geneticist and Hospital Research Foundation Fellow; Dr Jesia Berry1,2 , epidemiologist, funded by the Cerebral Palsy Alliance and Channel 7 Children’s Research Foundation (CRF); Prof Jozef Gecz1,2,3 , molecular geneticist, NH&MRC Senior Principal Research Fellow, and Channel 7 CRF Honorary Chair for the Prevention of Childhood Disability 1 Adelaide Medical School, The University of Adelaide, Australia. 2 Robinson Research Institute, The University of Adelaide, Australia. 3 South Australian Health and Medical Research Institute, Adelaide, Australia.

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Over 115,000 people are taking part in GenV, if you are interested in collaborating please visit genv.org.au

TRANSFORMING THE LIVES OF CHILDREN THROUGH RICH, INCLUSIVE AND RESUABLE DATA Cell to Society’ approach is needed for researchers to tackle health and wellbeing problems facing today’s children.

ustralia’s largest-everchild and parent cohort, Generation Victoria (GenV) is already open for collaborations to enable new discoveries and test new approaches. Its data will soon be available to researchers to help transform the lives of thousands. The world has more children and adolescents than ever before – and they have the most to gain when it comes to building a healthier society. However, chronic disease, obesity and mental health conditions are on the rise, with more than 60 per cent of children over two years of age experiencing ongoing health or psychosocial problems. Myriad complex health, wellbeing and social issues affect Australia’s children and families, and their wellbeing is central to the nation’s health, social and economic outcomes. The current ‘one question at a time’ approach to research is simply not delivering answers at the speed and breadth needed. Over the last decade, life expectancy has fallen in many countries. Young children benefit most from preventive interventions but, right now, have the weakest evidence base of all age 32

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groups. Further, by the time children start school, their rates of developmental vulnerability are three times higher in lower income areas. This has not changed in the last 15 years. The opportunities to ensure all children, including our most vulnerable and disadvantaged youth, are given the best foundation for their health and development outcomes requires a whole-of-society approach. We will not break cycles of intergenerational disadvantage with the status quo. We need to know precisely which inventions work, for whom, when and where, and if they can work in tandem. Instead of one-off research projects, we need a rich, multipurpose, and inclusive whole-of-population research strategy. Children are key to measuring and tracking health and policy interventions and so we need more trials that focus on social, educational, and environmental factors. We especially lack large-scale trials that show how different groups may respond to the same intervention. Another challenge in the research space is that findings are often informed from a small cross-section of Australian voices. We must include young people who are living in

Professor Melissa Wake

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disadvantage, are from diverse cultural and linguistic groups or are First Nations people. Whilst numerous sectors may be involved in any given problem, getting different solutions from each one would not be tenable or sustainable. We need an approach that is holistic, yet targeted. Generation Victoria (GenV) is a modern cohort that represents the diversity of today’s children and their parents. Now reaching the end of its establishment phase, it has already enrolled over 115,000 participants (including 45,000+ babies), from right across Victoria. These babies have already provided a wealth of information, from their weight, height, and feeding habits, to cognitive and developmental milestones. Murdoch Children’s Research Institute (MCRI) has led the development of this new child and parent cohort that represents Australia’s rich cultural, geographic and social spectrum. Whereas Longitudinal Study of Australian Children (LSAC, or ‘Growing Up in Australia’) participants are now 20+ years old, the GenV resource can help address complex problems facing an entire new generation. Recruited across the COVID-19 pandemic in all 58 maternity hospitals in Victoria, this unique cohort collects information directly from participants, speaking to their experiences as parents, and tracks the development and milestones of their child. It collects diverse biosamples (including saliva, breastmilk, and stool samples) and links to existing administrative, service and place-based datasets to paint a rich picture of our children and families. It is a national asset, built in Victoria, for all Australians. GenV is guided by the concept of collecting population data once and using it many times over. This may be

Timothy Davies

for new discoveries (e.g., what levers could improve outcomes?) or for testing new interventions (e.g., which levers actually work and by how much?). These could be targeted (e.g., to disadvantaged or diverse communities) or ‘stacked’ with multiple interventions tested simultaneously or in succession. These mimic how children experience real life, save time and can ease the funding and family burdens that trials impose. As the GenV cohor t continues to grow, data and biosamples will be released in 2025 for approved researchers to analyse. Collaborations are already under way to enable GenV to support large-scale and longterm solutions. Over $30m of external grants has been awarded to researchers to use the GenV data and cohort to investigate areas such as hearing loss, pregnancy medications, maternal COVID-19 vaccines, hip dysplasia and skills loss, contributing to improved health and wellbeing of all Australians. These exciting early projects already demonstrate the future value of GenV. Tomorrow’s solutions will be unlocked with today’s children. Policymakers, services and researchers can leverage this resource to change trajectories for families, translating effective research into policy and practice. In order to find great solutions, we need great data. GenV is a research resource in Victoria for Australians. GenV has been enabled by generous funding from the Victorian Government, Paul Ramsay Foundation and The Royal Children’s Hospital Foundation. Expressions of interest for collaboration are welcomed via the GenV website.

Authors: Prof Melissa Wake is a paediatrician and population health researcher and is the Scientific Director of Generation Victoria (GenV) at the Murdoch Children’s Research Institute. Timothy Davies is a Project Officer for GenV at the Murdoch Children’s Research Institute.

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THE SIMPLE INTERVENTION DESIGNED TO TEACH PRETERM BABIES THE RHYTHM OF LIFE

We all appreciate the benefits of a good night’s sleep, but for premature babies that can be hard to achieve.

heir body clocks – or circadian rhythms – aren’t properly developed, potentially leading to physical and developmental problems. An inexpensive set of eye masks and ear plugs could hold the key to better lifetime outcomes. Most of us think of our circadian rhythm as the body clock that helps us to know when to go to sleep and when to wake up. In truth, the role played by circadian rhythms in our bodies is far more wide ranging, governing an extensive array of processes that contribute in critical ways to our overall health and wellbeing.

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“Circadian rhythms are vital for growth and development,” according to Professor Jane Pillow, a neonatologist from the Telethon Kids Institute and The University of Western Australia. “Nearly half of the genes of our body are expressed according to a 24-hour rhythm, so these circadian rhythms actually control many, many developmental processes.” These processes include sleep, body temperature, appetite, metabolism, and hormone release. Circadian rhythms are even thought to influence our ability to think, our mental health and our immune systems. On the flipside, disrupted circadian rhythms are associated with increased infections, cardiovascular disease, obesity, metabolic syndrome, motor problems such as cerebral palsy, behavioural issues, neuropsychiatric conditions, and cancer. Imagine, then, the impact of having no circadian rhythms at all – exactly the problem faced by babies born prematurely.

CHRISTOPHE KEREBEL Professor Jane Pillow

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“Full-term babies receive time-of-day signals from their mothers for most of a pregnancy but typically start to develop their own circadian rhythms late in the third trimester, shortly before birth,” Professor Pillow said. “Preterm babies are born before that intrinsic rhythm has developed, at a developmental stage when they’re normally still reliant on the mother’s circadian signals – and then suddenly those signals are not there anymore. “Some of these babies are then cared for in a noisy hospital environment with constant lighting for 3–5 months – and we know from recent studies that they don’t develop a circadian rhythm before they go home. That’s a concern because without circadian rhythms, development may not proceed normally. So it may be that the brain and other vital organs are not receiving the right signals for normal development. “Unless we help them experience the difference between night and day – effectively teach them to develop a circadian rhythm – they don’t develop one until 6–8 weeks after getting home.” Ke e n to s h o r te n thi s g a p a nd sup p o r t o ptima l development from the very start, a national research team led by Professor Pillow and Dr Peter Mark, a circadian biologist at The University of Western Australia, is now trialling an ingeniously simple, inexpensive solution that could get babies on track in as little as three days. CIRCA DIEM is a randomised controlled trial that aims to study nearly 1000 preterm babies – those born before 32 weeks’ gestation – across Australia and New Zealand. Half of the babies to be recruited will receive routine care. The other half will receive an intervention designed to kickstart their circadian rhythms – eye masks and earplugs applied between 8pm and 6am, with exposure to a comfortable level of lighting and noise during the daytime. Those receiving the intervention will do so until they are discharged from hospital. Just over 400 babies have already been recruited to the study across nine NICUs in Australia, with up to four other international recruiting sites potentially coming on in the future. A multi-disciplinary team – including neonatologists, neonatal nurses, developmental psychologists, perinatal health psychologists, speech pathologists, occupational therapists, biostatisticians, cell biologists, physiotherapists and data engineers from multiple institutions – will then follow the babies’ progress for two years to see whether the intervention leads to better outcomes, including around infection, sleep, social communication skills and brain development. “The big question the trial is trying to answer is whether earlier development of a circadian rhythm helps the brain to develop better,” Professor Pillow said.

“But we will also be able to answer other questions like whether earlier development of a circadian rhythm helps babies adapt to life in the early weeks after birth. For example, will they be less unwell in hospital, and will that help them to go home from hospital sooner? “We are so grateful to the families participating in this important study of such a simple intervention with the potential to change the outcomes of the more than 15 million premature babies born around the world every year.” The CIRCA DIEM trial commenced in 2019 at the King Edward Memorial Hospital within the WA Child and Adolescent Health Service, supported by a WA Child Research Fund grant. The study expanded to a multisite trial in 2021 after receiving funding from the National Health and Medical Research Council. Further funding from the Channel 7 Telethon Trust is helping to support a sub-study looking into the sleep habits of the babies and their parents following discharge and how these sleep habits influence parental mental wellbeing. A collaboration grant from Telethon Kids Institute will evaluate how the intervention affects hospitalisations for infection over the first two years. Recruitment is expected to continue until 2025. Participating academic institutions include Telethon Kids Institute, The University of Western Australia, Monash University, Curtin University, The University of Melbourne, the Murdoch Children’s Research Institute, and the University of Sydney. Author: Professor Jane Pillow is a clinical academic neonatologist, Senior Principal Research Fellow and NHMRC Leadership Fellow at the UWA School of Human Sciences and at the Telethon Kids Institute, where she is Research Theme Head, Early Environment, and Team Lead, Chronobiology.

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HELPING CHILDREN WITH CEREBRAL PALSY TO LIVE THEIR BEST LIFE From world-leading gait analysis to understanding gene faults and how to manage pain, University of Melbourne researchers are delivering life-changing treatments to children with cerebral palsy.

ach year, approximately two in every 1,000 children in Australia are born with cerebral palsy.

In some cases, the disorder is genetic; Professor David Amor, consultant clinical geneticist and inaugural Lorenzo and Pamela Galli Chair in Developmental Medicine at the University of Melbourne, are unravelling the gene faults that cause cerebral palsy to provide individualised, targeted treatments.

GENETIC CAUSES

‘The traditional paradigm is that cerebral palsy results from an accident during pregnancy or at birth, but over the past five to ten years we’ve shown that 20 to 30 percent of cerebral palsy is genetic,’ says Professor Amor, who also heads the Neurodisability and Rehabilitation Group at the Murdoch Children’s Research Institute.

‘Some cerebral palsy is caused by a single gene fault. Our team has discovered some of these genes and we can test children in our clinic who don’t have an obvious explanation for cerebral palsy. We sequence their genome with a simple saliva swab and look across hundreds of different genes known to be a potential cause.’ When there is cause for concern, Professor Amor’s vision is for a child to be tested within the first weeks and months of life. ‘We can then identify specific causes of cerebral palsy and tailor treatment, such as a new drug that targets a particular pathway. Implementing effective precision therapies at the earliest stage can alter the natural trajectory of cerebral palsy and change a child’s future.’

IDENTIFYING AND ASSESSING PAIN

Dr Adrienne Harvey, a paediatric physiotherapist and Senior Research Fellow at the Murdoch Children’s Research Institute who is funded through the Lorenzo and Pamela Galli Medical Research Trust, is focused on chronic pain management in children with cerebral palsy. ‘Many of these children have lived with chronic pain for as long as they can remember. It affects their ability to socialise, play sport, engage with school and sleep, and it affects their family,’ she says.

Image from the gait lab where software is used during assessment to recreate a child with cerebral palsy’s walk

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Dr Harvey is finding better ways to identify and assess pain, particularly in children with complex communication needs, and to improve and personalise pain management practices. This includes developing pain education resources in collaboration with Canadian researchers who’ve developed innovative online pain management platforms for children without disability. Dr Harvey believes these can be adapted for children with cerebral palsy in Australia. ‘A pillar of chronic pain management is first understanding it. Many children and families don’t want more medication — they want other avenues such as movement, relaxation, meditation, distraction and hydrotherapy. In another 10 years I’d like to be able to say that pain is identified, properly understood and managed effectively in children with cerebral palsy so the impact on their everyday lives is minimised.’

GAIT ANALYSIS TO IMPROVE TREATMENT

Australia’s first clinical gait analysis laboratory at The Royal Children’s Hospital Melbourne (RCH) is continuing its ground-breaking work for children with cerebral palsy. When Professor Kerr Graham arrived in Australia 30 years ago to introduce gait analysis technology for children with cerebral palsy, some medical professionals were sceptical. An accomplished orthopaedic surgeon who trained internationally, Professor Graham had seen the potential of gait analysis. The laboratory has since had worldwide impact on the assessment, treatment and management of cerebral palsy by pinpointing the specific muscles, tendons, bones and joints where surgical intervention is most effective. Alongside clinical assessment, the laboratory produces a blueprint for surgeons to operate with better outcomes. ‘Gait analysis has been a game changer in treating cerebral palsy. It allows us to make a diagnosis and prognosis, to select the best treatment and to follow up and ensure the treatment has worked. It has brought improvements in the quality of life of children with cerebral palsy that were never thought possible,’ says Professor Graham. The lab developed the Gait Profile Score used worldwide to help non-specialists decipher complicated analytic gait data and the Functional Mobility Scale used when assessing mobility in children with cerebral palsy. ‘That will allow us to easily assess muscle volume, how muscle is orientated, and the effects of lengthening or

Associate Professor Erich Rutz

shortening muscles on the structure and this better understanding will improve the outcomes for children,’ says Dr Rutz. ‘No cure is on the horizon but we want children to have the best quality of life and best level of functioning, without pain, so they can be independent young adults.’

Authors: Professor David Amor, Lorenzo and Pamela Galli Chair in Developmental Medicine, Department of Paediatrics, The University of Melbourne and Group Leader of the Neurodisability and Rehabilitation Group, Murdoch Children’s Research Institute Professor Kerr Graham, Professor of Orthopaedic Surgery, The University of Melbourne, Director of the Hugh Williamson Gait Laboratory, The Royal Children’s Hospital Associate Professor Adrienne Harvey, Associate Professor, Department of Paediatrics, The University of Melbourne and Team Leader/ Principal Research Fellow, Murdoch Children’s Research Institute Associate Professor Erich Rutz, Inaugural Bob Dickens Chair for Paediatric Orthopaedic Surgery, The University of Melbourne and Clinical Director of The Hugh Williamson Gait Laboratory, The Royal Children’s Hospital.

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IMPROVING QUALITY, ACCESS, AND EQUITY OF CHILDHOOD ASTHMA CARE:

ImpACT CHILDHOOD ASTHMA

THE PROBLEM

Sam, 5 years old, presented 6 times in 12 months to the emergency department of Sydney Children’s Hospital (SCH) with an asthma attack. Sam is not the only one. Asthma is the most common chronic condition in Australian children. One in every 10-school aged children in Australia has asthma which leads to 20,000 unscheduled hospital presentations and costs the Australian Health system ~AUD$300 million annually. This high rate of hospital presentation is not only associated with high cost to the healthcare system but results in school absenteeism, significant burden on families from days missed from work and psychological stress. Frequent asthma hospital presentation is also a marker of the quality-of-care children receive. Inequitable access to quality care due to socio-demographic disparity is 38

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a strong predictor of increased risk of asthma-related hospital presentation in children.

OUR AIM

The ImpACT Childhood asthma program aims to investigate determinants of poor asthma health outcomes and translate that knowledge to implementing and evaluating models of asthma care that can improve the quality of life in children with asthma and reduce the significant burden of avoidable asthma hospital presentations.

SIGNIFICANCE OF OUR PROGRAM

Our program has identified significant variations in existing paediatric asthma care in Australia: i). Children with asthma receive guideline-adherent care on <60% of occasions

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of care[1], ii). 3,500 Australian children aged <5 years are inappropriately dispensed fixed dose combination inhalers for asthma management annually, which is not adherent to guidelines[2] iii). Children hospitalised frequently with asthma have 33-51% higher risk of not completing year 12 of high school compared to peers[3] iv). Children hospitalised with asthma ≥4 times in 12 months have a 16 times higher risk of being hospitalised with lifethreatening asthma and[4] v). Post hospital discharge asthma management pathways vary between different LHDs highlighting the need for standardisation of care. On average 4-6 different asthma clinical practice guidelines and asthma action plans were used in each local health districts (LHDs), between hospitals in the same LHD and within departments in same hospital.

online staff training for first aid asthma and uptake of the School & Child Services Action Plan for Asthma Flare-Ups. 3. Post-discharge care coordination to ensure continuity of asthma care: Work with families post-discharge to develop a person-centred shared asthma care plan for the child to ensure ongoing asthma review, promote asthma safe home environments and enhance asthma self-management knowledge and medication adherence. The successful evaluation of the model of care led to 3 competitive grants from NSW MoH Translational Research Grant Scheme, Asthma Australia, and Sydney Children’s Hospitals Foundation and the model is being evaluated in underserved communities including Southwest Sydney and 4 rural health districts in NSW.

Additionally, asthma education provided in hospitals was often non-formal and rarely involved key topics such as knowledge of asthma, asthma control and regular medical review. vi)

OUR TEAM MEMBERS

There was no system to ensure subsequent follow-up with GPs post-discharge from hospitals and linkages with community-based services was almost non-existent[5] highlighting the need for a comprehensive integrated model of paediatric asthma care.

FUNDING PARTNERS

IMPACT OF OUR PROGRAM

Systematic review and meta-analysis from our team have shown that a multicomponent comprehensive communitybased model of asthma care that includes evidencebased interventions can lead to improvement in paediatric asthma quality of life and reduction in asthma hospital presentations by 80%[6].

Dr Nusrat Homaira, Dr Louisa Owens, Melinda Gray, Prof Adam Jaffe, Nicole Campbell, Dr Mei Chan, Dr Ryan mackle, Dr Mahbubur Rashid. NSW Ministry of Health, Asthma Australia, Rotary Club of Sydney Cove, and Sydney Children’s Hospitals Foundation.

Dr Nusrat Homaira

Subsequently in 2016, we evaluated an integrated comprehensive model of asthma care (in collaboration with Asthma Australia, local health par tners, and consumers) that led to 60% reduction in the number of children presenting frequently with asthma to The Sydney Children’s Hospital (SCH)[7]. The model of care has been adopted as standard of care at SCH which cares for 1,000 children with asthma /year. Our model of care has three essential components: 1.

Standardisation of asthma discharge plan: Provision of standardised asthma action plan and written discharge instructions; asthma self-management education and asthma educational resources. In addition, streamline follow-up appointments with GPs/ paediatricians.

2. Integration with community services: Enhance communication with schools/childcare and promote

Author: Dr Nusrat Homaira, Senior Lecturer and Respiratory Researcher, UNSW Sydney and Sydney Children’s Hospital, Randwick.

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AIRWAY SMOOTH MUSCLE GROWTH TRAJECTORY AND ASTHMA Asthma is a common chronic respiratory disease; 1 in 9 Australians were diagnosed with asthma in 2020-21 (1).

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here is considerable morbidity associated with asthma, as well as mortality, totalling 417 deaths in Australia in 2020 (2).

In 2019-20, an estimated ~$900 million of expenditure in the Australian health care system was allocated to asthma (3). Asthma is characterised by symptoms of variable shortness of breath, wheeze and cough, and pathological features of inflammation (often allergic) (4) and thickening (remodelling) of the airway wall, including the airway smooth muscle layer (5). Airway smooth muscle remodelling is related to asthma severity (5) by increasing the capacity for airway narrowing (6) that in turn makes breathing more difficult.

NORMAL GROWTH OF THE AIRWAY SMOOTH MUSCLE

Given the detrimental effect of airway smooth muscle remodelling in asthma, it is important to understand the structural mechanism underpinning normal airway smooth muscle growth in order to identify periods of susceptibility that may lead to abnormal airway smooth muscle thickness (remodelling). While it was known that airway smooth muscle layer thickness increases during early life (7), the compositional changes governing this growth were unclear. Funded by the National Health & Medical Research Council of Australia, respiratory physiologists Dr Kimberley Wang and Associate Professor Peter Noble from the School of Human Sciences, The University of Western Australia, in collaboration with national and international colleagues, used morphological and stereological techniques to establish that ontogenic airway smooth muscle growth is initially due to hypertrophy (increase cell size) and subsequently hyperplasia (increase in cell number) and proportionate expansion of the extracellular matrix (8).

examined the structural composition of the airway smooth muscle layer in infants born at a low birth weight. Results demonstrated that in low birth weight infants, the structural composition of the airway smooth muscle layer is abnormal, where there is an increased number of airway smooth muscle cells and proportionally greater extracellular matrix (11). These findings outline a structural basis for the relationship between reduced birth weight and increased risk of asthma.

AIRWAY SMOOTH MUSCLE REMODELLING AND DEVELOPMENTAL ORIGIN OF ASTHMA

What have we learnt so far? The first nine months in the womb is critical in laying the foundation of our lifelong respiratory health. Normal airway smooth muscle growth is vulnerable and may become structurally abnormal early in the clinical course of asthma. Air way smooth muscle remodelling may therefore be considered a precursor to disease, rather than a consequence of asthma where patients are often exposed to inflammatory insults. Efforts to detangle the interrelationship between airway smooth muscle remodelling and the developmental origin of asthma will provide new directions for future interventional research. Prevention of disease is likely to be a more effective strategy than ‘cure’ (if at all possible), from both an economic and health perspective.

Left Dr Kimberley Wang, below Associate Professor Peter Noble.

This new knowledge of identifying normal mechanisms of airway smooth muscle growth raises the question as to whether abnormalities in these specific growth processes contribute to the onset of asthma later in life.

ABNORMAL GROWTH OF THE AIRWAY SMOOTH MUSCLE

An association between low birth weight (defined as <2.5 kg) and asthma in later life has been repeatedly documented in epidemiology studies across the globe. In Australia, 6.3% of liveborn babies were low birth weight in 2021 (9), who then have a 65% greater risk of developing asthma compared with individuals born at a normal weight (10). An intriguing possibility is that at least some cases of asthma can be traced back to abnormalities in fetal growth and development that manifest as structural and functional respiratory abnormalities, predisposing these individuals to future disease. The same team at The University of Western Australia

Authors - Dr Kimberley Wang and Associate Professor Peter Noble, School of Human Sciences, The University of Western Australia.

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BABY CHIX A DIFFERENT TYPE OF ANAESTHETIC TO MAKE HERNIA SURGERY SAFER FOR BABIES

Baby having his inguinal hernia surgery performed with the Baby CHiX anaesthetic technique. Parental permission to use photograph.

Baby CHiX feasibility study, a multicentre project using a different anaesthetic technique to avoid general anaesthesia in babies having hernia surgery 42

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nguinal (groin) hernia surgery is the most common surgery performed in babies, who are often born preterm with high anaesthetic risk.

Current practice in Australia and New Zealand (and worldwide) appears to most commonly involve general anaesthesia, which has significant risks of lung problems during and after surgery, as well as concerns for the

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and dexmedetomidine sedation) is a feasibility study of an anaesthetic technique that aims to avoid general anaesthesia and the invasive procedures of intubation and mechanical ventilation that can damage babies’ delicate lungs. The study involved performing anaesthesia with the Baby CHiX technique, which is not routine practice in Australia or New Zealand. The infants had sedation with dexmedetomidine to provide a gentle sleep but allow the babies to breathe by themselves, high flow nasal oxygen to support them breathing by themselves, and a caudal anaesthetic. A caudal is like an epidural, so provides numbness below the umbilicus, so that the surgery is pain free. This feasibility study was carried out at three hospitals: Flinders Medical Centre, Adelaide; Women’s and Children’s Hospital, Adelaide; and Christchurch Hospital, New Zealand in 50 babies undergoing inguinal hernia surgery. Anaesthesia was performed by 22 different anaesthetists. Nearly 60% were born preterm (less than 37 weeks gestational age) and were on average 9 weeks old on the day of surgery and weighed 4.1kg.

Over 80% of babies had successful surgery without needing a general anaesthetic, including long and complex operations. There was a low rate of breathing problems during and after the operation, and no babies in the study needed intubation after surgery. Parents were surveyed anonymously and 90% reported they were either satisfied or very satisfied with their baby’s anaesthetic. These early results show that this technique is possible as an alternative to general anaesthesia, in three different hospitals with a large number of different anaesthetists. We hope to do further research with this technique and disseminate these results to change anaesthesia practice and improve outcomes for babies undergoing inguinal hernia surgery.

impact of anaesthesia on the developing brain. The most common alternative, spinal anaesthesia has much lower risks of breathing problems, but is technically difficult and can’t be performed on all babies. The overall goal of this research is to improve respiratory outcomes for these infants when inguinal hernia surgery is required. Baby CHiX – (caudal, high flow

Author: Dr Fiona Taverner is a paediatric anaesthetist at Flinders Medical Centre, Adelaide, South Australia. She has a keen interest in research, being Deputy Director for Research and Chair of the SPANZA research sub-committee. She has a special interest in avoiding general anaesthetics in neonates and infants and is doing a PhD on improving respiratory outcomes for infants undergoing inguinal hernia surgery at Flinders University, College of Medicine and Public Health.

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EASING PAIN AND ENSURING UNINTERRUPTED TREATMENT FOR HOSPITALISED CHILDREN

In partnership with The Queensland Children’s Hospital, The University of Queensland has led the world’s first clinical trial to establish the effectiveness of midline catheters as a superior and gentler alternative to traditional intravenous treatment methods. 44

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eripheral intravenous catheterisation (PIVC) is a routinely performed medical procedure yet is one of the most distressing experiences for hospitalised children. Despite the necessity of vascular access devices, up to 50% can fail due to complications such as dislodgement, extravasation, infection, device occlusion, pain, phlebitis, and thrombosis. However, simple changes can make a big difference to a child’s health experience. Nurse Researchers, Tricia M. Kleidon and Professor Amanda Ullman from The University of Queensland’s Paediatric Nursing and Patient Safety group have found an effective alternative, promising

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a more comfortable and uninterrupted experience for children in need of intravenous treatment such as antibiotics.

IMPACT OF INTRAVENOUS DEVICE FAILURE

When PIVCs fail, it often requires the insertion of additional vascular access devices to complete treatment. This leads to increased healthcare costs, heightened patient discomfort and anxiety, and contribution to vessel depletion. Device failure in children is a multifactorial issue tied to patient factors (e.g., age, comorbidities, diagnoses), device specifics (e.g., catheter-to-vein ratio, both gauge and length), and insertion techniques (e.g., site of insertion, use of ultrasonography), however only some of these elements are modifiable. “Our research has shown that we can prevent discomfort, treatment disruption and unnecessary costs, all with the introduction of a longer peripheral IV device – the Midline Catheter.” – Tricia Kleidon

MIDLINE CATHETERS AS AN ALTERENERATIVE

Midline catheters are a longer alternative to PIVCs. These are inserted into an upper arm vein, with the tip terminating at or distal to the axillary vein, outside the thoracic cavity. While midline catheters have been available since the 1950s, past complications, including hypersensitivity reactions to outdated catheter materials reduced their popularity in the 1990s. However, technological advances in their design, including the use of biocompatible polyurethane materials, have led to a recent resurgence in their clinical popularity. While multiple cohort studies and a recent systematic review in adult populations have shown promising results, there has been a notable gap in research when it comes to evaluating the clinical effectiveness and performance of midlines compared to PIVCs in children.

THE PUBLISHED RESEARCH

The research, now published in JAMA Pediatrics, answered the question: does the use of midline catheters in patients requiring peripherally compatible intravenous therapy for four days or longer improve patient, catheter and cost outcomes compared with PIVCs? Their results provide some of the earliest evidence to support midline catheter use in the paediatric population. Not only did their research demonstrate that children who received the alternative, longer midline catheter, encountered significantly fewer device failures, less inser tion attempts, and longer treatment stability compared to those receiving traditional PIVCs, it also demonstrated improved financial outcomes from a health service perspective.

The two-year, randomised clinical superiority trial, which included an embedded internal pilot study, enrolled children aged one to 18 years requiring peripherally compatible intravenous therapy for four days or longer. Among the 127 participating patients, 65 children were randomly allocated to receive PIVC treatment, while 62 children received midline catheter treatment. One catheter was studied per patient. All insertion and maintenance procedures were performed by a medical officer or nurse practitioner with competence in PIVC and midline catheter insertion, in accordance with the existing local hospital policy and international guidelines. Devices were monitored daily, and records was entered into the hospital database for analysis. Notably, the trial upheld rigorous standards, including prospective trial registration, allocation concealment, statistician masking and minimal attrition.

A MORE COST-EFFECTIVE SOLUTION

The research unveiled a substantial cost difference of of AUS $151.67 per child, resulting with a total cost of $390.27 per child for midline catheters, compared to $541.95 per child for PIVCs. The cost of device insertion was largely influenced by use of operating room time; therefore, the use of midline catheters can be further minimised where a reduction in operating room time use for device insertion is possible.

THE PATH FORWARD

Future research should focus on implementation in cohorts most likely to benefit, such as children with vascular access-dependent conditions. Additionally, longterm outcomes, including vessel patency, require further examination. “In response to these findings, we are putting together a project to implement midlines into everyday clinical pathways in paediatrics, and other vulnerable populations.” – Tricia Kleidon The journal article was published in JAMA Pediatrics and is available here on open access.

Authors: Tricia M. Kleidon, Registered Nurse and Nurse Practitioner from the Department of Anaesthesia and Pain, Children’s Health Queensland Hospital and Health Service. Professor Amanda Ullman is the Professor and Chair of Paediatric Nursing at the University of Queensland. Linda N. Nguyen is a Clinical Research Assistant at the University of Queensland, School of Nursing, Midwifery and Social Work

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The patient's mother has given permission for these images to be used.

SLEEP SCIENCE PLUGS INTO NEW TECHNOLOGY Sleep studies are essential for those with disordered breathing, but some children do not tolerate traditional methods of analysis. A new contactless approach has yielded promising early results. 46

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r Jasneek Chawla understands the vital role that sleep plays in a child’s development better than most.

Dr Chawla is a respiratory and sleep specialist at the Queensland Children’s Hospital, and an associate professor with The University of Queensland’s Child Health Research Centre, leading the Kids Sleep Research team. Her recently completed PhD combines world-first investigations into how the sleep monitoring process can be improved for children with neurodevelopmental disorders.

Contactless sleep monitoring aims to support the development of our children.

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SEARCHING FOR ANSWERS

The inspiration for Dr Chawla’s doctorate came from questions that came up in her day-to-day practice in the sleep clinic. “We see a lot of children with Down syndrome. And that’s because sleep problems are about six times more common in children with Down syndrome than they are in the general population,” Dr Chawla explains. “There’s a combination of reasons that can contribute to poor sleep patterns, including differences in facial anatomy and low muscle tone which can cause breathing problems. Intellectual disability can also contribute to difficulties with healthy sleep patterns.” From her initial research questions, the scope of the studies quickly grew. “We did some qualitative work looking at what the families’ sleep was like and how having a child with a sleep problem really impacted on them. There are negative consequences for the child, but if a child’s not sleeping, the family’s not sleeping, the siblings are not sleeping. And so, we interviewed children’s parents and siblings and that was the first time that’s actually been done.” Dr Chawla and her colleagues have recently published research within the Journal of Clinical Sleep Medicine that focuses on children’s tolerance for polysomnography – the “gold standard” test to evaluate sleep-disordered breathing. The method requires an overnight stay in a sleep lab, monitored by a nursing team, with an extensive array of leads and sensors connected to the patient’s face, head, torso, and limbs. The lengthy set up time and highly tactile nature of the equipment can be particularly challenging for children with neurodevelopmental disorders, including Down syndrome. If the leads and sensors do not stay in place overnight, adequate sleep data cannot be captured, and important clinical measurements are missed. “These are the kids that we really need the sleep monitoring results for, and we’re not getting great results,” Dr Chawla said.

AUSTRALIAN INNOVATION TO THE RESCUE

In newly published research, Dr Chawla and partners investigate the efficacy of an innovative, contactless Australian-made device to capture sleep data. It is known as the Sonomat, and was created by Dr Colin Sullivan, the inventor of continuous positive airway pressure (CPAP) therapy. The Sonomat has sensors built into it that measure movement and sound and is placed on top of a mattress for ease of use. An SD card captures the data, which can then be downloaded and scored.

I approached Colin because I saw him present about this device and I thought, for children who really struggle with sleep monitoring, this is the kind of thing we need,” Dr Chawla said. “We decided that it was really important to look at the Sonomat compared against the gold standard sleep study monitoring method. “This study was about testing the Sonomat in a group of children with Down syndrome. And we got some really promising results. We had a sample of 60 children and the Sonomat was able to detect obstructive sleep apnoea or sleep disordered breathing in the majority.”

EXPANDED STUDY UNDERWAY

The findings have led to a larger, multi-site project that is currently in progress with children with a variety of neurodevelopmental disorders. Funding from the Medical Research Future Fund (MRFF) was secured in 2022, with participants recruited at the start of this year. The project’s lead site is the Queensland Children’s Hospital, with the Children’s Hospital at Westmead and the Royal Children’s Hospital Melbourne also taking part. The new study once again tests the Sonomat in a sleep lab environment alongside traditional processes, but also allows participants to take the device home for additional monitoring. Dr Chawla’s wider research has been supported by the MRFF, the Children’s Hospital Foundation, Sonomedical (who are supplying the Sonomats in kind), and the Queensland Children’s Hospital SERTA Scheme. Dr Chawla says the potential for contactless sleep monitoring for younger patients and their families is immense. “It’s really game changing for these families. It changes the amount of times they have to come up to hospital. It changes the stress they go through with their kids. It means that we could potentially monitor them even more frequently than we do right now. “We will be able to understand so much more about their disease course by being able to use these Sonomats repeatedly at home. And we haven’t even scratched the surface with their potential.”

Authors: Cameron Pegg, University of Queensland, with contributions by Dr Jasneek Chawla 2023 | INSPIRE 030 47

NADIP study clinician Jennifer Goth with pregnantwoman

THE COMMON VITAMIN THAT COULD BE THE KEY TO PREVENTING SOME CASES OF HEART BIRTH DEFECTS AND MISCARRIAGES In Australia, some 2,400 babies are born each year with congenital heart disease- four babies die every week. In at least 80% of these cases the cause of the heart defect is unknown. 48

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Dunwoodie NADIP Research Team

CHRISTOPHE KEREBEL

CHRISTOPHE KEREBEL Twitter @chriskere cientists from the Victor Chang Cardiac recruited almost 250 women between theMy ages of :20 and CHRISTOPHE KEREBEL Research Institute are hoping to change that. 40 years to take part in the clinical study in Sydney.

Professor Sally Dunwoodie and her team have found a genetic cause for various heart and other birth defects and crucially, a possible way to prevent some cases.

The Nicotinamide Adenine Dinucleotide in Pregnancy (NADIP) Study is measuring the NAD levels of five groups of women, including both pregnant and non-pregnant women, by screening urine and blood samples.

THE NAD BREAKTHROUGH

The team are assessing and comparing NAD levels between pregnant and non-pregnant women with or without diabetes, and those having babies with congenital conditions or having had previous miscarriages.

In 2017, Professor Dunwoodie and her team at the Institute discovered that a deficiency in a vital molecule, known as NAD, prevents a baby’s organs from developing correctly in the womb. The study published in the New England Journal of Medicine1 involved 97 people with congenital heart disease. Their whole genome was studied, along with that of their parents, and in some cases their siblings too. This research was a mammoth undertaking that included analysing six billion pieces of genetic code per person and identifying what is often just a single change that disrupted embryogenesis. Professor Dunwoodie and her team found mutations in two genes known as KYNU and HAAO. These mutations resulted in babies with defects of the heart, kidneys, and vertebra, as well as other birth defects. KYNU and HAAO usually help convert an amino acid called tryptophan into a substance called NAD, which plays a crucial role in energy production and repairing DNA. After KYNU and HAAO’s role was identified, the same mutations and defects were reproduced in mice. Adding vitamin B3 to the pregnant mouse’s diet was found to prevent the defects appearing in offspring. Professor Dunwoodie says: “It’s very rare to find a mutation, and then to find the mechanism behind it and understand it. It’s even rarer to identify a possible preventative.” “NAD is a vital substance that is required in every cell in our body. For women who have low levels of NAD we believe this can play out disastrously during pregnancy because the growing baby also needs NAD to develop. We believe this explains not only why some babies have birth defects, but also why some women are prone to miscarriage.”

CURRENT CLINICAL STUDIES INTO NAD AND PREGNANCY

Since 2017 the team has been scrutinising NAD and vitamin B3 in painstaking detail. With this information, the researchers have developed a diagnostic test that can accurately measure NAD and vitamin B3 levels in women. The Institute, in collaboration with the Royal Hospital for Women at Randwick and the University of Sydney, has 1 https://www.nejm.org/doi/10.1056/NEJMoa1616361?url_ ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20 %200www.ncbi.nlm.nih.gov

The results of the study will reveal whether low levels of NAD are more likely to occur in mothers who have a baby with birth defects or women who have recurrent miscarriages. This will help identify how best to increase and stabilise NAD levels during pregnancy. As well as measuring levels of NAD, the team are also measuring 25 other metabolites that are associated with NAD. The study is expected to be completed in 2024, with data already being analysed.

TESTING THE EFFECTS OF VITAMIN B3 SUPPLEMENTATION

Once the team has established the healthy range of NAD in women and identified a link between low NAD levels and adverse pregnancy outcomes, the next stage is a clinical trial to measure the effects of vitamin B3 supplementation to bring NAD to normal levels. Professor Dunwoodie says: “We really want to take this to a point where women can benefit from our years of research and our important findings. This will take more dedicated time and of course much more funding.” This will be a world-first study conducted here in Australia. Author: Professor Dunwoodie heads the Congenital Heart Disease Research Program at the Victor Chang Cardiac Research Institute (VCCRI). She is Deputy Director of VCCRI and Director of the VCCRI Innovation Centre. Professor Nassar is a perinatal and paediatric epidemiologist and the Financial Markets Foundation for Children Chair in Translational Childhood Medicine at the Children’s Hospital at Westmead (CHW) Clinical School, University of Sydney. Dr Shand is an Obstetrician and Gynaecologist and RANZCOG-certified subspecialist in Maternal Fetal Medicine. She is Head of the Department of Maternal Fetal Medicine at the Royal Hospital for Women, in Randwick. She is also a Visiting Medical Officer in the Department of Maternal Fetal Medicine Department at Royal North Shore Hospital.

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GIVING CHILDREN THE MENTAL TOOLS TO OVERCOME MEDICAL TRAUMA

Burn injuries are one of the leading causes for hospitalisation amongst Australian children, yet the impact of this medical trauma on the child’s mental health and wellbeing is so often overlooked. 50

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Play is a key aspect of wellbeing interventions for children

eceiving a burn is one of the most distressing injuries a child can experience, often involving a long and painful recovery period.

Our previous research revealed that children and young people who sustain a burn are vulnerable to short- and long-term mental health problems following the injury. For instance, anxiety is commonly found in children who may be fearful of hospitalisations, painful treatments, or appearance concerns through scarring. Thoughts of re-experiencing the injury, avoidance of thoughts or situations, and heightened anxiety associated with the injury are also common. Worryingly, these problems can develop regardless of the burn size or severity and can persist well into adulthood.

CHRISTOPHE KEREBEL Dr Alix Woolard

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But our research also found factors that can promote resilience after injury, including strong social supports, optimism, problem-solving skills, and autonomy. Some patients experience post-traumatic growth following their injury, encouraged through coping mechanisms and positively reframing the accident.

EARLY INTERVENTION

My team and I are currently piloting an early intervention program called the Wellbeing Project, which we designed after consulting and working with children who have experienced a burn injury, their parents, and hospital staff from the Perth Children’s Hospital Burns Unit. We spoke to caregivers of children aged 4-12 who had experienced this kind of injury, and to adolescents and clinicians, about how burn injuries impacted on the young people’s mental health, what supports they used or needed, and what mental health supports they felt should be made available. One thing noted by the young people we consulted was how much the burn and recovery process disrupted their day-to-day living, negatively impacting their mental health. Caregivers described observing fear and anxiety in their child following the accident and noted their own feelings of guilt and shame around their child’s accident. They also felt unwilling or unable to reach out to peers and family for support for fear of judgement. Some children and young people also noted positive outcomes – such as developing resilience during their recovery period – as well as the importance of developing coping strategies through accessing support services. Based on this consultation process, we developed a sixsession program for children and young people to improve resilience and wellbeing by helping them to overcome concerns about the burn, the stress around recovery, and their perceptions of the scar once healed. The idea is to make sure they learn healthy thoughts and behaviours for when they encounter difficult situations. Results so far have been promising: we’ve found families who have taken part in the sessions have an improved outlook on injury and illness, while young people’s stress and coping mechanisms are stronger. Young people have reported improved self-esteem and confidence; and anecdotally, we have found young participants are using the skills learned in a transferable way, teaching their peers and family members.

ADAPTING THE MODEL FOR OTHER MEDICAL TRAUMA

We recently began consultation to adapt the Wellbeing Project for children and young people with Type 1 Diabetes. The issues these children and young people are dealing with are universal for people who are experiencing medical trauma, meaning we can easily transfer learnings from one group to another. Medical trauma typically has a three-pronged impact on mental health that can be grouped into: the event (an accident or diagnosis); ongoing management (including rehabilitation and recovery, and stress symptoms related to painful treatments); and a diminished quality of life following medical trauma. This loss of quality of life can lead to grief for the life a child used to have as compared to their life now. Medical conditions also often come with their own set of stigmas and self-stigmas that the child must endure. The universality of these impacts, consistently felt by children who have experienced different forms of medical trauma, means the Wellbeing Project can be easily adapted from acute conditions such as burns, to chronic conditions like Type 1 Diabetes and cancer. It is a medical trauma intervention designed to help not just the individual but the entire family, equipping kinship systems, parents and other caregivers with the tools to provide support to a child who has experienced the trauma. The Wellbeing Project is funded by a research grant from Embrace @ Telethon Kids Institute and Telethon Trust. It is led by researchers at Embrace @ Telethon Kids Institute, in partnership with the JDRF Global Centre of Excellence, Rio Tinto Children’s Diabetes Centre, the Fiona Wood Foundation and Perth Children’s Hospital. Author: Dr Alix Woolard is a senior researcher for Embrace @ Telethon Kids Institute’s childhood trauma team.

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A NON-INVASIVE BEDSIDE TRIAGING TOOL FOR LATE PREGNANCY TO PREVENT STILLBIRTH AND FETAL DISTRESS. A multidisciplinary team of engineers and medical professionals are working together to develop novel imaging techniques that may be applied to the human fetus in utero.

his team have developed ultrasound tools to non-invasively quantify perfusion and to evaluate large regions using infra-red camera tracking technology.

PROJECT LEAD:

Alec Welsh, Professor in Maternal-Fetal Medicine, Division of Women’s Health, School of Clinical Medicine, University of New South Wales, Sydney. Alec is a researcher clinician with subspecialty training in Maternal-Fetal Medicine based at the University of New South Wales and the Royal Hospital for Women. He holds a PhD in Fetal Imaging, MSc in Digital Imaging and MBA in Digital Technology and supervises a team of postgraduate and undergraduate researchers.

COLLABORATING TEAM:

Welsh AW1,2, Barber T2,3, Thomas S1,2, Li S4 , Wang D4. 1. School of Clinical Medicine, Medicine and Health, Discipline of Women’s Health, University of New South Wales, Sydney, Australia. 2. Perinatal Imaging Research Group, Royal Hospital for Women and University of New South Wales, Sydney, Australia. 3. School of Mechanical and Manufacturing Engineering, Engineering, University of New South Wales, Sydney, Australia. 4. Materials and Manufacturing Futures Institute, University of New South Wales.

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BACKGROUND

Around 40-60% of stillbirths are identified as having intrauterine growth restriction secondary to ‘placental insufficiency’ highlighting the central role of the placenta as a fetal life support system (1). Fetuses failing to reach their true growth potential as a consequence of placental dysfunction may be described as showing ‘fetal growth restriction’ (2). These fetuses frequently are within a normal gestational centile range though they may be redistributing blood preferentially to conserve development of vital organs (3); undetectable using conventional surveillance methods (4), yet a fetus under such conditions is at high risk of stillbirth. Ultrasound tools have only provided indirect crude measurements of umbilical blood flow that have not improved in the last 30 years (5, 6) and no current tool is used to evaluate blood flow to different fetal organs.

RESEARCH TEAM COLLABORATION

The Perinatal Imaging Research Group (PIRG) at the University of New South Wales combine expertise in Engineering and Medicine and have collaborated for over a decade in development of novel ultrasound imaging tools. The digital information available in conventional ultrasound scanning is markedly underutilised. Our group works on novel algorithms, with a focus on flow information (Doppler ultrasound) to optimise the outcomes for unborn babies.

TECHNOLOGICAL DEVELOPMENT

Our research team have created a non-invasive ultrasound tool to quantify perfusion called Three-Dimensional

Figure 1. a) Current third trimester fetal surveillance; b) Proposed surveillance system for late pregnancy showing: 1. A Third trimester scan at 32-36 weeks gestation to triage care and optimise level of surveillance and 2. A full-term scan at 39-40 weeks gestation to determine the placental capacity and ability to continue ‘post-dates’.

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Fractional Moving Blood Volume (3D-FMBV). We have previously validated 3D-FMBV experimentally and have proven it to show excellent correlation with perfusion (7). There is no other validated ultrasound tool for perfusion quantification. A limitation in feto-placental evaluation is evaluation of perfusion within the placenta, as the placenta is a large organ and its vascularity is heterogenous. A second technological advance from our group has been development of infra-red camera tracking to globally ‘map’ multiple volumes of acquired data into a larger geometrical space, facilitating stitching together of ultrasound to recreate the entire placenta. This is the first such tool internationally.

CURRENT FUNDING MODEL

The primary funder of our research group is Wellcome Leap and their In Utero international 3 year competitive grant fund (https://wellcomeleap.org/inutero/). Our project with Wellcome Leap ‘Detecting the ‘at risk’ fetus by noninvasive bedside assessment of fetoplacental blood flow’ aims to develop a novel triaging system to determine the fetus at risk of stillbirth or intrapartum distress by means of ultrasound in the late third trimester. Additional team funding comes from the Royal Hospital for Women Foundation (https://www.royalwomen.org.au/).

THE CORE PROJECT

With the support of Wellcome Leap we are undertaking a number of research activities. These include a clinical study to determine normal ranges for regional fetal perfusion and for total and regional placental perfusion during pregnancy. We are developing integrated software to automate image acquisition and regional analysis and are working towards cloud capability for this system. We

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intend to progress towards development of a novel lowcost automated perfusion device for evaluation of the human fetus in diverse environments.

FINDINGS TO DATE

We have shown so far that it is technically feasible to measure fetal renal, cerebral and hepatic perfusion in the second and third trimesters of pregnancy. The perfusion values are repeatable with ICCs >0.90. We have also shown that it is technically feasible to not only recreate the entire vascularity of a human placenta in the second and third trimesters of pregnancy, but to measure total and regional perfusion. Data are under preparation for peerreviewed publication.

INTENDED OUTCOMES

We intend to develop a system that could be used to ‘triage’ the human fetus in the late third trimester, with the potential for a second ‘post-dates’ scan around 40 weeks to determine those cases where pregnancy could continue further. The figure above outlines this. It is likely that if successful, our triaging tool will be combined with other methods for non-invasive surveillance to be applied to the pregnant woman during the late third trimester. Within the Wellcome Leap In Utero program there is a strong focus on collaboration, with other teams working on a number of biomarkers, including blood samples, wearable technology and novel ultrasound. Whilst following this pathway to development of a noninvasive stillbirth and fetal distress screening tool we intend to manufacture a hand-held 3D ultrasound system capable of perfusion evaluation, under ISO13485 compliant conditions. This device should have potential applications throughout the fields of medicine. 2023 | INSPIRE 030 53

Professor Sant-Rayn Pasricha (L) and Professor Kamija Phiri (R) are exploring new ways to fight anaemia in Malawi. © WEHI

LANDMARK MALAWI TRIAL BOOSTS IRON LEVELS IN PREGNANT WOMEN The World Health Organization (WHO) currently recommends oral iron taken twice daily as the standard of care in developing nations, but adherence to this treatment is poor.

world-first study by a collaboration between Australian and Malawian researchers exploring new ways to fight anaemia in developing nations has found a single iron infusion can significantly reduce iron deficiency in pregnant women, compared with daily tablets. It paves the way for more effective health policies to reduce the global health burden of anaemia, which remains one of the most avoidable causes of illness and death in resource-poor nations.

THE RESEARCH IS PUBLISHED IN THE LANCET.

Iron deficiency is a major public health burden in resourcepoor countries and a key precursor to anaemia – a 54

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condition affecting nearly half of all pregnancies in Africa. It occurs when a person lacks oxygen-carrying red blood cells (haemoglobin) and iron. While the WHO recommends daily iron tablets for pregnant women in sub-Saharan Africa, less than 30% of the population consumes this recommended dose. Ferric carboxymaltose (FCM) is a 15-minute iron infusion treatment widely given to iron-deficient pregnant mothers in developed countries. In efforts to find more effective ways of treating irondeficient patients, WEHI researchers worked with Malawian scientists at the Training Research Unit of Excellence and Kamuzu University of Health Sciences to compare FCM to standard-of-care oral iron. Half of the Malawian women (431) in their second trimester received FCM, while the other half took standard-of-care oral iron. Professor Sant-Rayn Pasricha, a leading anaemia expert and Division Head in WEHI’s Population Health and Immunity Division, said the trial was four times larger than the one conducted to bring FCM onto the market. ‘We proved FCM can not only be safely administered in a complex resource-limited setting like Malawi, but can also reduce the iron deficiency component of anaemia by around 60% – a significantly better result than the oral iron currently recommended in these populations. ‘Women who received FCM throughout the trial had a substantial reduction in iron deficiency and iron deficiency anaemia during their third trimester, at delivery and 4-weeks post-partum. ‘This will open a whole new field of research that was previously thought impossible and could help transform health policies in vulnerable communities. ‘I’m tremendously excited that a medicine widely used in high-income nations might have an application to help women in Sub-Saharan Africa and other resource-poor settings. Our next task is to identify those women who have the best chance of benefiting from the IV treatment.

UNIQUE HEALTH CHALLENGES

Pregnant women with anaemia are at elevated risk of complications, including post-partum haemorrhage, stillbirth and low birthweight. Despite the substantial improvements in iron levels, the trial found FCM was not superior to oral iron in reducing the overall burden of anaemia in pregnant women and did not reduce incidences of low birthweight or anaemia in women at the time of delivery.

This is because anaemia can be driven by more than irondeficiency in developing nations. ‘For example, conditions like malaria and HIV, which are common in parts of Sub-Saharan Africa, can drive up inflammation in the body and prevent access to stored iron, Professor Kamija Phiri, a leading epidemiologist and Director of the Training and Research Unit of Excellence, said. ‘Additionally, haemoglobinopathies – a group of inherited blood disorders predominantly affecting red blood cells – are common in the region and cause anaemia. Professor Pasricha says the results emphasise the urgent need for new mechanisms to address these unique health challenges. ‘Over half of participants had inflammation in their bodies, despite testing negative for malaria. With some parasites able to hide in the placenta during pregnancies, it is likely that current tests are not sensitive enough to help us understand a mother’s complete health status and flow-on risks to her unborn child. ‘While you can do a blood test to detect determinants of anaemia, like ferritin, in developed nations, there is no such tool in place for these parts of the world to measure iron status.’ With FCM remaining an expensive treatment option, researchers hope the promising results of the trial can encourage philanthropic efforts to further research the intervention and make it more accessible to women in low-income settings. The research team is currently tracking the mothers involved in this study and their babies to assess whether the intervention will impact on anaemia prevalence, postpartum depression and child neurodevelopment. The study, “Ferric Carboxymaltose versus standardof-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial,” is published in The Lancet (DOI: 10.1016/). The research was funded by the Bill & Melinda Gates Foundation and a National Health and Medical Research Council (NHMRC) Investigator Grant awarded to Professor Pasricha.

Authors: Sant-Rayn Pasricha, Ricardo Ataide, Rebecca Harding, Danielle Clucas, Sabine Braat.

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EARLY DETECTION OF TYPE 1 DIABETES About 130,000 Australian children have type 1 diabetes, and an average of three children are diagnosed every day. These children need lifelong daily insulin treatment to stay alive. 56

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ype 1 diabetes (T1D), one of the commonest chronic conditions of childhood, is an autoimmune condition in which immunemediated destruction of the pancreatic beta-cells results in insulin deficiency, and the need for lifelong insulin replacement therapy to stay alive. The number of children developing T1D around the world has been increasing, and despite intensive research efforts, the cause for this increase and cause(s) of T1D

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remain unknown. Multiple genetic and environmental factors are thought to play a role, but the exact nature of these is still not understood. Although, the cause of T1D remains unknown, there have been significant advances in the understanding of its natural history over the past decades. Longitudinal, prospective cohort studies of babies and young children at genetic risk of T1D have shown that the peak age of islet autoantibody detection, which signal that the autoimmune process underlying T1D is underway, occurs during very early life, between 9 and 30 months of age. Furthermore, children with ≥2 islet autoantibodies detected on ≥2 occasions at least 3 months apart, who are defined as having persistent multiple islet autoimmunity, have a ~70% 10-year, 85% 15-year, and ~100% lifetime risk of developing clinical, insulin-requiring T1D. These children are now considered to have Stage 1 T1D, or pre-symptomatic T1D. Individuals with persistent multiple islet autoimmunity and some evidence of abnormal glucose levels or patterns, without the usual symptoms or signs of T1D, are said to have Stage 2 T1D which is another stage of pre-symptomatic T1D. Symptomatic or clinical T1D is referred to as Stage 3 T1D and is when clinical onset and diagnosis is usually made and insulin therapy commenced. How and when children at risk of T1D progress from Stage 1 to Stage 3 is highly relevant to providing appropriate care and interventions to them and their families. By detecting early changes in glucose patterns and levels, we can provide families of such children with tailored education, support and advice to ensure that their child is diagnosed before they become severely unwell in those who are progressing towards clinical onset and offer interventions to delay progression as they become increasingly available.

NEW RESEARCH TO DETECT EARLY CHANGES IN GLUCOSE LEVELS

We are conducting an Australia-wide study using continuous glucose monitoring (CGM) technology in children identified with Stage 1 T1D being longitudinally followed in the Environmental Determinants of Islet Autoimmunity (ENDIA) study (www.endia.org.au). This is a world’s first study focussed on monitoring very young, preschool aged children, who are thought to progress more rapidly, from detection of persistent islet autoimmunity, or Stage 1 T1D. By using CGM, we can look at the pattern of 5-minutely glucose levels across 24-hours for up to 10-days in a row, whilst children are at home, going about their usual activities. This detailed information enables researchers to identify early changes in glucose patterns in these children who are known to be at risk of developing insulin requiring clinical T1D. Importantly, such changes occur months

to years before children may be diagnosed or have any symptoms of T1D. This information is incredibly useful for families and clinicians responsible for taking care of them. Being able to identify whether a child’s glucose levels are changing enables families to be educated and supported according to whether or not their child is progressing or not. For those who are progressing, it provides an important opportunity for them time to learn more about T1D symptoms and when to seek medical help, thereby avoiding late presentation with diabetic ketoacidosis at the time of clinical onset.

THE NEXT STEPS

For the first time ever, there is now a drug licensed for use to delay the progression from pre-symptomatic T1D to insulin requiring, or clinical T1D. A landmark trial of a drug called teplizumab showed that a single 14-day intravenous course can delay progression to clinical onset by a median of three years. This drug received FDA approval in the US in November 2022 with approval anticipated in other countries, including Australia, in the near future. The potential to delay progression of pre-symptomatic T1D to insulin requiring clinical T1D has resulted in the urgent need to identify individuals at risk who may benefit from such interventions as they become available. The use of CGM to monitor Australian children at risk of developing T1D using CGM is a vital step in the path to delaying, or potentially preventing, progression to insulin requiring clinical T1D, as this, and newer therapies become available in Australia. Author: Dr Aveni Haynes, BA (Hons), MBBChir, PhD, is a Senior Research Fellow at the Rio Tinto Children’s Diabetes Centre, Telethon Kids Institute and Adjunct Research Fellow in the Centre for Child Health Research at the University of Western Australia

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LUMINESCE ALLIANCE: LEADING THE DEPLOYMENT OF PRECISION MEDICINE FOR CHILDREN.

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Precision medicine deliversCHRISTOPHE KEREBEL My Twitter : @chriskere CHRISTOPHE KEREBEL personalised, targeted medical bring our leading researchers, practitioners, and children and families together to tackle problems is at the core of care to patients by studying translational research. We are seeing new discoveries in a child’s individual genes, practice sooner, so all our children can live healthy and behaviours, and environment to productive lives.” Luminesce Alliance Executive Director, Anastasia Ioannou, understand what is causing their is passionate about the importance of collaboration to the success of the Alliance. disease, and how to treat it.

hildren benefit significantly from precision medicine, with genetic conditions contributing substantially to admissions in New South Wales (NSW) paediatric hospitals (40-50%), and a ppr oximately 15 -2 0% of childhood ca nce r s appearing genetically predisposed. In just four years, a quiet achiever called Luminesce Alliance has driven world-leading research into paediatric precision medicine, turning a $24m investment into leveraging an additional $294m in funding. Luminesce Alliance has secured an additional $20 million in funding for the next four years (2023-2027).

Luminesce Alliance is a not-for-profit cooperative joint venture between the Sydney Children’s Hospitals Network, the Children’s Medical Research Institute, the Children’s Cancer Institute, the University of Sydney, and the University of New South Wales Sydney. It has been established with the support of the NSW Government to coordinate and integrate paediatric research. By bringing together specialists across many fields and with different sets of skills, Luminesce Alliance is contributing to the discovery and development of medical and technological innovations that deliver tangible outcomes to sick children. Many diseases of adulthood start in childhood, so advances in detection and treatment benefit the whole community. Luminesce Alliance launched the Paediatric Precision Medicine Program in 2019. The program enhanced NSW’s capacity and integrated cutting-edge technologies into personalised clinical care, exclusively focussing on early diagnosis and treatment for children, limiting long-term effects and reducing the burden on the healthcare system. To date, Luminesce Alliance has established over 140 new STEM jobs, facilitated over 20 pharma and investigatorled clinical trials, collaborated with over 450 national and international organisations, shared paediatric precision medicine findings with more than 150 peer reviewed publications, and given over 190 presentations across Australia and internationally. Insert image at the end of this article if possible. Luminesce Alliance Chair, Kathryn Greiner AO, says that “ensuring the wellbeing of the future generations is one of the most important challenges for us all. Finding ways to

“Our aim is to support the collaboration needed to deliver better health outcomes for children, particularly those impacted by cancer, rare genetic diseases, and neurodevelopmental disorders.”

“Despite medical advances, cancer, and rare genetic diseases are the leading causes of death in children worldwide. At least one in 20 babies is born with a rare genetic disease or neurodevelopmental disorder and around 1,000 children and young people are diagnosed with cancer annually in Australia.” The current four-year funding commitment allows Luminesce Alliance and leading researchers from the partner organisations to build on their success with the development of five Enabling Platforms: 1. Functional Genomics: identifying and understanding disease-causing genes and new treatments 2. D ata: translating rich and complex data into new treatments, new prevention strategies and clinical impact 3. Precision Therapy: delivering new drugs and novel medical technologies that will support early-phase clinical trials 4. P sychosocial: developing world-leading best practices for psychological, emotional, social, and educational support of patients and their caregivers 5. Health Systems Implementation and Economic Research: translating research discoveries into new models of care. “Enabling platforms add significant value” says Anastasia Ioannou. “They galvanise and intensify collaboration; encourage multi-disciplinary thinking and fresh perspectives; join research translation capabilities into an end-to-end commercialisation pathway; complement geographical precinct strategies by supporting linkages within and across precincts; fill gaps, accelerate translation and create efficiencies; and reinforce competitive advantages. “The Enabling Platforms take collaboration to the next level, to make a difference to children, while fostering longterm health and economic benefits to the community.”

Author: This article was provided by Luminesce Alliance.

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TRANSFORMING CHILDREN’S LIVES ONE GENE THERAPY AT A TIME In 2018, the Sydney Children’s Hospitals Network administered the first gene therapy for SMA in Australia.

ince then, over 50 patients with rare conditions have been treated successfully. Through the Kids Advanced Therapeutics program, a whole system approach enabled a significant increase of advanced therapeutics clinical trials to be implemented in the network. The Sydney Children’s Hospitals Network (SCHN) through the Kids Advanced Therapeutics (KAT) program, successfully conducted several advanced therapeutic clinical trials and is now an accredited treatment provider for Zolgensma (Onasemnogene abeparvovec) for SMA and Luxturna (Voretigene neparvovec) for children diagnosed with inherited retinal blindness. Now we are recognised as a leader in advanced therapeutics, locally and internationally, and the workforce continues to gain experience in these rapidly emerging

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therapies. These successes are attributed to our own paediatric and scientific experts, in addition to the wholesystem approach we continue to implement and refine.

THE KAT PROGRAM

The KAT program supports advanced therapeutics in both industry sponsored trials and investigator-initiated studies. Workforce education and health system readiness were critical pillars established to ensure the safe and efficient delivery of advanced therapeutics. A team was set up to lead clinical trials, focus on study start-up processes and drive the educational resources for the workforce, patients, and their families.

HEALTH TRANSLATION TIMELINE ON WARP SPEED

Previously, drug development took 10-15 years for therapies to move through clinical trials to post-market sur veillance. Locally, therapeutic goods authority (TGA) approval and subsidised funding through the Pharmaceutical Benefits Scheme (PBS) added up to an additional two years. However, through continuous consultations with industry partners, patient advocacy groups and key government officials, gene therapy

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investigational products have crossed the health translation timeline in less than 5 years. It is predicted that this will be the model for succeeding gene therapies that have proven efficacy in clinical trials.

IT STARTS AT DAY 0

Newborn screening is a recognized tool to identify conditions to enable early intervention. A bold initiative was led by Professor Michelle Farrar and Dr Sandi Kariyawasam, in partnership with NSW Health, wherein 400,000 babies were screened for SMA. Results showed that early diagnosis enabled pre-symptomatic treatment, which changed SMA from a lethal disease to being treatable. This paved the way for NSW and the ACT to be the first state and territory to offer routine SMA newborn screening, with subsequent expansion of screening to all of Australia.

EDUCATING THE MASSES ABOUT ADVANCED THERAPEUTICS

The first educational drives were through webinars, which featured the scientific basis and clinical application of advanced therapeutics. Since December 2020, the program has facilitated 13 webinars, attracted over 1200 attendees, including interstate and international attendees. The KAT program will soon launch video resources on gene therapy, along with various fact sheets to further educate patients and families. Face-to-face teaching sessions are being conducted to upskill the multidisciplinary team who provide care to gene therapy patients. Online training via the Sydney Child Health Program will be available in 2024 for the workforce to learn more about AAV-mediated gene therapies.

IMPROVING EFFICIENCY IN REGULATORY PROCESSES THROUGH PROACTIVE ENGAGEMENT

The adeno-associated viral (AAV) vectors used in currently approved gene therapies are considered genetically modified organisms (GMOs), warranting proactive engagement with the Office of the Gene Technology Regulator (OGTR). The KAT program initiated various health system readiness activities such as clinically focused biosafety training to orient staff dealing with GMOs in line with the requirements of the OGTR. New hospital policies were required to ensure the workforce adheres to consistent and high-quality practices for GMOrelated procedures. As subsequent trials were proposed to the network, it was noted that each OGTR license had similar requirements, regardless of the target condition. Through the guidance of Professor Ian Alexander, SCHN partnered with the OGTR to procure an overarching

license to conduct clinical trials involving AAV therapies. This innovation streamlined clinical trial start-up, removing the 90-day application process, increasing SCHN’s reputation as an attractive site for international gene therapy trials.

LEADING CLINICAL TRIALS GLOBALLY

In 2023, through the expertise of Clinical Professor Kristi Jones and Dr Michelle Lorentzos, three boys diagnosed with Duchenne Muscular Dystrophy received gene replacement therapy. They are the youngest in the world to take part in this clinical trial for boys under the age of four. A multi-disciplinary team approach was taken, ensuring holistic care was provided to the participants, inclusive of long-term monitoring.

Due to the successful delivery of previous clinical trials, various industry sponsors have approached the network to conduct first-in-human trials, recognising the capacity of our hospitals and our ever-expanding expertise in advanced therapeutics. VISUALIZING THE FUTURE OF VIRAL VECTORS

As advanced therapeutics continue to change the landscape of medicine, scientists from our partner agency, the Children’s Medical Research Institute (CMRI), continue to find ways to develop and manufacture gene therapies locally. The multi-million dollar funded viral vector manufacturing facility, currently in construction will accelerate NSW’s capacity to produce viral vectors, essential in gene therapies, at a commercial scale. This will keep NSW at the forefront of advanced therapeutics research, development, and translation.

THE WORK KEEPS GOING

As the pipeline for advanced therapeutics expands, CAR-T cell, bacteriophage and gene therapies are being implemented across the network. This would not be possible without the support of Luminesce Alliance and Sydney Children’s Hospital Foundation, helping us to ensure children and young people are living their healthiest lives possible.

Authors: Kristine Concepcion, Laura Fawcett, Michelle Lorentzos and Lani Attwood Kids Advanced Therapeutics Team

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SHAPING HEALTHIER FUTURES:

THE ACTIVATED OSHC PROGRAM Paving the way for healthier Australian kids: The Activated OSHC program’s mission is to elevate standards around children’s physical activity and screen time in Outside School Hours Care service.

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hildren’s daily habits, including physical activity and screen time, significantly influence their health, wellbeing and academic performance.

Yet, in Australia, less than half of children meet the recommended physical activity guidelines, and only a third stick to screen time limits. Out of School Hours Care (OSHC) settings, serving nearly half a million Australian children weekly, present a vital opportunity to positively impact these lifestyle habits. Recent Australian studies have revealed notable inconsistencies in OSHC practices concerning physical activity and screen time, partly due to the absence of clear policy guidance. This inconsistency ranges from no screen time to over five hours daily, with varied physical activity opportunities. Surprisingly, few OSHC directors are aware of the government’s 24-hour physical activity and screen time guidelines. To tackle this issue, stakeholders, including OSHC staff and child health experts, collaborated to develop the first evidence-based physical activity and screen time guidelines for the Australian OSHC sector. Endorsed by the Australian National Out of School Hours Services Association (NOSHSA), these guidelines are a significant step forward but require effective implementation and evaluation to truly transform OSHC practices.

ACTIVATION

This is where the Activated OSHC program comes in. We’ve developed an accreditation process to encourage and support OSHC services to implement the OSHC physical activit y and screentime guidelines. The accreditation process involves the following key steps: Policy Submission and Assessment: OSHC services are required to submit a physical activity and screen time policy for assessment. This policy must meet the OSHC Physical Activity and Screen Time guidelines, ensuring that it aligns with the established standards for promoting healthy physical activity and responsible screen time management among children. 2. Staff Training: A significant component of the accreditation process is staff training. At least 50% of the staff at an OSHC service must complete the online training modules provided. This training is crucial to ensure the staff are well-versed in the guidelines and can effectively implement them in their daily interactions with children. 3. Accreditation and Recognition: Once an OSHC service has successfully submitted its policy and met the staff training requirement, it will be accredited as an Activated OSHC service. Accredited services receive signage to display at their location, highlighting the ir status as a n Acti vate d OSHC se r v ic e. 1.

Additionally, they will receive an email signature to promote their Accredited Activated OSHC status, further recognising their commitment to the program’s goals. The Activated OSHC program is currently being evaluated in a 12-month Type 2 hybrid effectiveness-implementation randomised controlled trial. Spanning Adelaide, Newcastle, and Perth, and regional SA, NSW and WA, the study will involve 192 randomly selected OSHC services, with half randomly allocated to receive the Activated OSHC program. The trial focuses on the program’s effectiveness, cost-effectiveness, acceptability, and feasibility, employing thorough observation and survey methods. Looking ahead, we plan to roll out the guidelines and the Activated OSHC accreditation program nationally in 2025, aiming to reach all 5000 OSHC services. This ambitious study is a collaborative effort, supported by numerous state and national partners: YMCA; National Outside School Hours Service Alliance; The Australian Children’s Education and Care Quality Authority; Outside School Hours Council of Australia; the University of Newcastle; University of Western Australia; Flinders University; University of Wollongong; and University of Nevada Las Vegas. It is funded by the National Health and Medical Research Council, the Medical Research Future Fund, the SA Department for Education, Healthway, and Hunter New England Local Health District. The Activated OSHC program, positioned as a sustainable enhancement to current care practices, aligns with existing policy-based accreditation systems, offering a dual benefit of promoting healthier behaviours in children and providing a mark of quality for OSHC services. The insights gained from this trial will be instrumental in understanding the complexities of large-scale implementation and the potential for national scaling. The trial’s outcomes may have significant policy implications, particularly if the guidelines prove to be both feasible and sustainable. If successful, this program and its guidelines could serve as a model for international initiatives, demonstrating the effectiveness of strategically designed, policy-aligned interventions in improving the developmental environments for children globally.

Author: Carol Maher is a Professor of Population and Digital Health at the University of South Australia. Dr Jacinta Brinsley is a postdoctoral research fellow at the University of South Australia.

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HARVESTING

SAFE

FARMERS:

A COMPREHENSIVE EXPLORATION OF CHILD FARM SAFETY

Research undertaken at the National Centre for Farmer Health has explored crucial insights into the challenge of keeping children safe on farms.

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griculture is a key industry in Australia and utilises over half of the country’s landmass. However, the work environment is one of the most dangerous—the Australian agriculture, forestry and fishing industry is responsible for the highest rate of worker fatalities per capita. Adding to this is the fact that farms often serve as both a home and a workplace, meaning family members are also exposed to the hazardous work environment. Children are frequently present on the farm worksite, often due to family traditions and values, lack of childcare, enjoyment, provision of labour, exposure and learning of

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family work. As farming is one of the most dangerous occupations for adults, risk of injury is only increased with the presence of children in the farm work environment. This is highlighted by the statistic that children under 15 years have consistently represented approximately 15% of all farm-related fatalities in Australia over the last 20 years1. The National Centre for Farmer Health conducted research to explore the behaviours and attitudes that influence the risk of fatal and non-fatal injuries of children (aged 5 to 14 years) on Victorian farms. Following a literature review, a modified Delphi method was undertaken to develop surveys to explore children’s exposure to farming hazards, risk-taking behaviours and the use of, and attitudes towards, safety measures. A diverse group of subject experts (child farm safety specialists, injury data specialists, child farm safety educators, farm safety researchers, farming parents and agricultural industry and government body representatives) rated questions for inclusion/exclusion over three rounds. This resulted in the development of a child and a parent survey. Surveys were completed by 107 farming parents and 62 children from across rural Victoria.

WHY ARE CHILD FARM-RELATED INJURIES STILL OCCURRING?

The survey results confirmed the blurred distinction between the farm as a home and a worksite. The farm is a place where families live, work and play, often with no official distinction between where the worksite begins and the home ends. This leads to children being engaged with the farm worksite. The traditions and values of farming families are a key contributor to children’s engagement with the farm worksite; specifically, the enjoyment of involving and teaching children on the farm, family bonding and enjoyment. Further, while on the farm worksite children are regularly exposed and interact with the hazards that have been identified as the leading causes of child farm-related fatalities (including water bodies, quad bikes, tractors, utes and cars, motorbikes and horses). Survey results also demonstrated children are involved in and contributing economically to the family farm business. Unlike most other industries, farming culture often relies on and expects family members to assist with labour. This was highlighted with over 90% of children surveyed beginning work on the farm before 10 years of age. While children are regularly interacting with the farm worksite, the use of safety measures to protect them from injury was low. The two key safety measures relied on 1 Peachey K, Lower T, Rolfe M. Protecting the future: Fatal incidents on Australian farms involving children (2001-2019) The Australian Journal of Rural Health 2020;00:1-9.

by parents were supervision and rules. These two safety measures are identified as lower order controls on the hierarchy of control2 and largely rely on there being no human error. Parents seek assistance from their children with farm work, express the desire for their children’s safety and acknowledge the inherent hazards of the farm environment. However, they may not consistently create the safest possible environment for their children. Finally, the generational transfer of farming knowledge, behaviours and attitudes was evident. Parents want to involve and teach their child about farming from a young age; it is part of the lifestyle of growing up on a farm. This generational transfer can result in (potentially unsafe) methods being passed down through generations without any change.

ACTIONS FOR FARMING COMMUNITIES

The findings highlight the need for a shift in the culture in farming communities to prioritise safety. As high engagement of children on farm worksites is unlikely to change, future work must focus on how children’s engagement with the farm can be as safe as possible. For this to be achieved, a whole of system approach is required. There must be increased implementation of higher-level strategies from the hierarchy of control. Farm safety education for the whole family and farming communities is one element that could assist in normalising the use of safety measures and ensure children undertake developmentally appropriate tasks. Better enforcement of safety regulations has the potential to improve safety for children on farms. Finally, the portrayal of farming families by agricultural industry bodies often displays the idealistic farming lifestyle. The industry has a duty to assist farmers in creating safe worksites to protect themselves and family members from injury. The risk of injury should not be accepted or viewed as inevitable. Children have little agency over their own safety on farm worksites. Embedded traditions must be collectively challenged to improve safety for the next generation. 2 Worksafe. The hierachy of control 2020 [Available from: https:// www.worksafe.vic.gov.au/hierarchy-control.

Author: Jessie Adams, PhD Candidate, Associate Research Fellow, National Centre for Farmer Health, Deakin University

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A GAP IN THE SYSTEM 66

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Associate Professor Virginia Dickson-Swift

Better training for paediatricians is needed to address a widening oral health crisis for CHRISTOPHE KEREBEL vulnerable kids in the bush.

n many parts of regional Victoria, it’s dental decay - not injury or respiratory issues - that lands most children in hospital. This often results in traumatic and completely avoidable interventions, such as tooth extraction under general anaesthesia. Water fluoridation, which is still lacking in more than 60 towns with populations over 1000, is part of the solution, but with more support, rural paediatricians can play a more active role in bridging the gap.

MOST AT RISK: RURAL CHILDREN IN OUT OF HOME CARE

Dental caries (dental decay) is one of the most common chronic conditions affecting children. Children in rural areas experience poorer oral health than children in cities due to limited access to dental services, longer distances and a lack of oral health promoting infrastructure improvements such as water fluoridation. This disproportionately impacts children in out-of-home care (OOHC) who are up to six times more likely to experience dental decay. Since 2017, the number of Australian children in OOHC (ie; foster, kinship, or residential care) has grown by 7.3%, with higher rates in rural communities (14.6 per 1000 children) compared to metropolitan areas (6.7 per 1000 children). Children in OOHC have higher needs than other children across physical, mental, and oral health domains. According to The Royal Australasian College of Physicians, these inequities are ‘unjust, unnecessary, systemic and preventable.’

THE TOLL OF TOOTH DECAY

As the number of rural children in OOHC grows, so does the urgency to address their poor oral health. Each year, almost 23,000 Australian children are hospitalised due to preventable dental conditions. Pain and swelling from dental decay negatively impact a child’s eating, sleeping and school attendance. For children in OOHC, poor oral health can be exacerbated by poor diet and living conditions, low incomes, and fragmented care arrangements. This compromises their capacity to lead healthy and fulfilling lives.

THE ROLE OF THE PAEDIATRICIANS IN CHILDREN’S ORAL HEALTH

Despite the traditional divide between medicine and dentistry, paediatricians can play a role in improving oral health in children through early intervention and prevention. The role of paediatricians in providing screening, anticipatory advice, and referrals to dental services before 12 months of age has been identified for well

CHRISTOPHE KEREBEL

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over a decade. The Royal Australian College of General Practitioners and the Royal Children’s Hospital have well established guidelines around oral health assessments and referrals. These are suppor ted by The Royal Australasian College of Physicians who describe the integration of oral health awareness into training for paediatricians as an ‘important step that can improve early intervention and support prevention strategies, particularly in vulnerable populations.’ Recent Australian and international studies highlight a lack of training across the paediatric medical curriculum as well as knowledge and practice gaps, including limited knowledge about clinical signs of dental caries, the recommended age for first dental visits, fluoride uses and available oral health services. Without sufficient exposure to, or training in, oral health, paediatricians working with children in OOHC naturally triage their time to other acute health issues and may assume that ‘someone else’ will deal with their oral health. With limited access to public dental care in rural areas, we know this is often not the case for rural children in OOHC.

THE NEED FOR BETTER EDUCATION AND TRAINING

The Australian Government has committed to reduce inequities in oral health through the National Oral Health Plan Healthy Mouths: Healthy Lives 2015-2024. For rural children in OOHC - arguably the nation’s most vulnerable cohort - improving oral health knowledge and practice of paediatricians through education and training is vital. This can be achieved through mandatory pre-registration oral health modules for those specialising in paediatrics as well as dedicated and readily available modules to complete as part of their continuing professional development. This, in turn, will build awareness among paediatricians that oral health is not an ‘add-on,’ but part of their core practice. As experts in trauma-informed practice, paediatricians are best placed to address all the health needs of children in OOHC. More support to access training and integrate oral health into their practice will minimise hospitalisations for vulnerable children and enable them to lead happier and healthier lives.

Author: Associate Professor Virginia DicksonSwift is a Senior Research Fellow in the Violet Vines Marshman Centre for Rural Health Research (VVMCRHR) based at the La Trobe Rural Health School.

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MEALTIMES MATTER

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Bonnie Searle

esearchers at the University of Queensland CHRISTOPHE KEREBEL examined mealtimes in Early education and care (ECEC) services located in communities ex p e r i e n c i n g h i g h l e ve l s o f s o c i o e c o n o m i c disadvantage.

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They found a problem of child hunger, low quality food provision and interactions that were sub-optimal in supporting child learning and positive food choices. The findings call for a system level overhaul to meal provision and mealtime practices in ECEC. One in six children in Australia live in poverty and 27% of families with children at home experience severe food insecurity (Foodbank Hunger Report 2023 - Foodbank Reports), defined as inconsistent access to adequate nutritious food. Multiple risk factors place these children at high risk of sub-optimal social-emotional, physical, and academic development (Shankar 2017). Early Childhood Education and Care (ECEC) services are a policy investment that have been shown to avert developmental risk and promote optimal development in the crucial early years before formal schooling (White 2015) Most Australian children (95%) attend ECEC services, ideally placed for interventions to support child development, and especially for those who live in circumstances of disadvantage. Child nutrition is an important focus. Mealtimes at ECEC provide opportunities to provide good nutrition to support healthy brain growth and, through interactions with educators, to learn about new food and food preferences. Yet, recent research in Queensland, focused in disadvantaged communities, demonstrated that the quantity and quality of food children consumed in their ECEC services generally did not meet dietary recommendations. Children were hungry, food available was poor and quality of interactions with educators limited. Our research at Queensland Brain Institute found that most meals, whether provided by services or brought from home, did not provide enough food, with vegetables and meat/alternative protein sources particularly low. In ECEC that served families with the lowest incomes and highest levels of food insecurity, children arrived hungry daily and were reminded not to eat too much in the morning, to ensure their lunchbox food lasted all day. In these services we also found that educator-child interactions at mealtimes were low quality with high levels of conflict.

in fees charged. An ECEC place in Winton, remote Queensland, costs a family around $80 a day before subsidies. Leafy Chapel Hill in the Western suburbs of Brisbane, on the other hand, costs significantly more, around $145 per day. In locations in which family ability to pay is constrained, it is it is highly likely that ECEC food budgets are low, making it difficult or impossible to provide nutritious food. Services in the most disadvantaged areas are those which are more likely to require families to provide food. A recent Foodbank report illustrated the extent of worsening hunger and food insecurity (Foodbank Hunger Report 2023 - Foodbank Reports). Government policies in countries such as Sweden, the United Kingdom and the United States, provide universal or subsidised meals to ECEC and schools, providing a safety net for children and reducing the financial burden of food for families. For example, Head Start and Child and Adult Care Food (CACFP) Programs in the United States provide subsidies directly to ECEC and have demonstrated effectiveness in reducing family food insecurity (Drennan 2019). Robust monitoring and support systems are required to ensure that food provided to children is adequate and nutritious. As the cost of living continues to rise, it is time for strong policy action to ensure that the most vulnerable children are assured equitable access to nutritious food in the developmentally crucial years before school.

FEWER MEALS WHERE MOST NEEDED

In Australia, ECEC exists as a mixed market system consisting of for-profit and not-for profit services. Services set their own fees and make their own decisions about whether to provide food. Previous research from our team determined that services in areas of high disadvantage across Queensland were less likely to provide meals, and charged lower fees. The exception to this occurred in Metropolitan areas, in which meals were provided in response to high market competition, without increases

Author: Bonnie Searle is a dietitian and researcher, at the Queensland Brain Institute (University of Queensland) within the Child Development, Education and Care Research Group. Bonnie has a background in education and clinical paediatric dietetics and is completing a PhD examining mealtimes in Early Childhood Education and Care.

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NEW EARLY INTERVENTION OPTIONS HOLD GREAT PROMISE FOR KIDS WITH CF

Cystic fibrosis (CF) is the most common, life-limiting genetic condition affecting Australian children, with around 3,500 young Australians living with CF. In the 1960s, the life expectancy for a baby born with CF was just five years but thanks to research, a baby born with CF today can expect to live beyond the age of 50. 70

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Eight-year-old Connor, pictured with his dog Bonnie, lives with CF – he needs better treatment options so that he has a chance at a longer, healthier life. New research is giving him this chance. Connor’s mother has given permission for this image to be used by Research Australia.

CHRISTOPHE KEREBEL

CHRISTOPHE F causes an abnormal build-up of thick and KEREBEL as sick as they otherwise would have in the few: @chriskere years Myfirst Twitter CHRISTOPHE KEREBEL stick y mucus in the lungs, air ways, and of their life. digestive system. “These kids weren’t going into hospital as frequently, and Treatment requires intensive daily physiotherapy to clear therefore didn’t need to have stronger medications to treat the lungs and airways, countless medications, and infection flareups,” Professor Stick said. frequent hospitalisations. “Those that did present to hospital had fewer days of M e dic ations such as modulator the ra pie s have strong IV antibiotics, so they were able to get back to transformed treatment in older children and adults with being kids faster. CF because they change the way the CF gene works at “Importantly, we found that this treatment reduced a cellular level, making the body more efficient at clearing inflammation in the lungs of young children, which is mucus so it doesn’t build up – in turn giving the body incredibly significant because there are no other antia better chance at fighting infection. But the majority of inflammatory medications currently available to treat the young children in the world don’t have access to these lung inflammation that we see in these kids.” transformative therapies. SHIP CT, the second trial led by Professor Stick, showed Two long-standing international trials led out of Perth – that hypertonic saline – a saltwater solution that has a COMBAT CF and SHIP CT – looked to find better ways to higher concentration of salt than normal saline – is a safe, treat lung disease in younger children with CF. Both have cheap, and effective treatment option to reduce structural resulted in new early intervention options that hold great lung damage in children with CF aged three to six years. potential for reducing progressive lung damage in these kids. This is the first evidence of a treatment that alters structural Co-led by Professor Stephen Stick, Director of the Wal-yan lung disease in children with CF in this age group. Respiratory Research Centre at Telethon Kids Institute, the COMBAT CF trial found that when used as a preventive Structural lung disease has already developed in a large therapy, azithromycin – a commonly prescribed broad- population of children with CF by this age, leading to spectrum antibiotic –helped reduce the inflammation negative effects on their health and overall quality of life. associated with progressive lung disease in young children Effective and affordable therapies are needed to prevent with CF and resulted in fewer days in hospital. or slow development of structural lung disease in these The decade-long multi-site trial followed 130 children from children. 10 CF clinics across Australia and New Zealand, from the By using images of the lung from chest CT scans as the time they were diagnosed with CF at birth until they turned main way to measure results, this study showed that three years old, to see if using azithromycin reduced treatment with inhaled hypertonic saline, twice daily for 48 lung inflammation and therefore altered the course of weeks, resulted in less structural lung damage compared the disease. The children were either given the antibiotic with children who inhaled isotonic saline – a saltwater treatment or a placebo. solution with the same salt concentration as the body. The 60-plus researchers in the COMBAT CF team Professor Stick said the results from both trials hold the found long-term use of azithromycin was safe, improved potential to pave an early path for altering the disease’s respirator y symptoms, reduced hospital stays for progression in a cohort of children who currently don’t respiratory needs, and reduced the number of courses of have access to modulator therapies. IV antibiotics required to treat the infection. “As interventions, we now know that both azithromycin Professor Stick said using azithromycin as a preventative and hypertonic saline hold great promise in terms of treatment meant kids involved in the trial hadn’t become reducing the progressive lung damage we see in early CF,” he said.

Professor Stephen Stick

“They therefore give doctors another weapon to treat these kids until they are old enough and eligible for modulator therapies.” Author: Professor Stephen Stick is a respiratory clinician, clinical researcher and Director of the Wal-yan Respiratory Research Centre – a powerhouse partnership between Telethon Kids Institute, Perth Children’s Hospital Foundation and Perth Children’s Hospital.

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MAKING MOVES:

EMPOWERING PAEDIATRIC CANCER SURVIVORS THROUGH PHYSICAL ACTIVITY

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CHRISTOPHE KEREBEL

My Twitter : @chriskere CHRISTOPHE KEREBEL

In Australia, around 1000 children and adolescents are diagnosed with cancer annually. Today, 85% of children and adolescents will survive their disease.

hile these numbers are certainly encouraging, the cost of cure is substantial. Survivors may face a range of physical, emotional, and psychological challenges, both as a child and adult. One of the most pressing concerns is survivors’ increased risk of developing cardiovascular disease, as they are eight times more likely to experience compared to their peers. Understanding and addressing their modifiable risk factors are critical to ensure these young survivors enjoy a healthy and active lifestyle.

PHYSICAL ACTIVITY: A VITAL COMPONENT OF SURVIVORSHIP

Physical activity is a crucial factor in mitigating the risk of cardiovascular disease. It plays a pivotal role in improving overall health, reducing the risk of obesity, enhancing cardiovascular fitness, and promoting well-being. Yet studies have shown that 70% of paediatric cancer survivors do not meet physical activity recommendations, making them more susceptible to the long-term health consequences. To date, there are limited age-appropriate physical activity programs available to young people affected by cancer.

THE MAKING MOVES PROGRAM

‘Making Moves’ is an Australian first novel digital health education program that aims to empower paediatric cancer survivors by educating them on the therapeutic role of exercise in cancer survivorship. It’s designed to encourage home-based physical activity for survivors and equip them with the knowledge and motivation needed to maintain an active lifestyle. One of the primary advantages of Making Moves is that it is delivered online, addressing distance barriers of accessing health services often experienced by more than 30% of survivors living in rural and regional areas. With the program accessible via the internet, survivors from all corners of Australia can participate and benefit from the program.

CO-DESIGNED WITH SURVIVORS

Youth is a significant stage of life, with many young people shaping their social, physical, and psychological aspects of health. Yet, young people are often neglected in health research and research is mostly done ‘on’ young people or their data. Youth participation in research is critical to improve their health outcomes now and into the future. Making Moves was co-developed in partnership with survivors, parents, and healthcare professionals, ensuring that it caters to the specific needs and concerns of paediatric cancer survivors. By involving the lived experience and expertise of the very individuals who have experienced the challenges and unique aspects of childhood cancer, the program becomes more relevant and relatable.

PRIOR WORK

The effectiveness and feasibility of Making Moves have already been put to the test. The pilot study demonstrated that the digital health program achieved 70% feasibility. This success was the first step to ensuring that this program was feasible to deliver in a home setting and used by survivors. The next stage of conducting a hybrid effectiveness-implementation trial is made possible through the generous support of The Kids’ Cancer Project, a dedicated organisation that has been at the forefront of paediatric cancer research and support. This trial will investigate the effectiveness of Making Moves on survivors’ health outcomes, and concurrently explore the potential for scale-up and implementation in a real-world setting. Making Moves represents a crucial step forward in the role of exercise oncology and digital health interventions. By focusing on the importance of physical activity, this digital health education program empowers survivors to take control of their own well-being, reducing their risk of cardiovascular disease and enhancing their overall quality of life. Author: Dr Lauren Ha is an accredited exercise physiologist and post-doctoral research fellow at the Behavioural Sciences Unit, School of Clinical Medicine, University of New South Wales, Sydney.

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GIVING ABORIGINAL AND TORRES STRAIT ISLANDER FAMILIES A VOICE THROUGH Australian Aboriginal RESEARCH and Torres Strait Islander

communities have survived the harsh but beautiful lands of Australia for over 65,000 years.

Indigenous Research Assistant Loretta Weatherall with an IndigenousQueensland Family Cohort (I-QFC) First 1,000 days study participant

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espite the ravages that colonisation has caused for their communities, they continue to survive, and Mater Researchers are working to close the healthcare gap to help them thrive. Associate Professor Kym Rae and her research team are determined to improve healthcare outcomes for Aboriginal and Torres Strait Islander people. By partnering with communities, the research team is forging strong alliances and focusing on improving understanding of the serious health issues identified by community members to support the growth of strong families in communities. The team has spent the past two years visiting more than 10 Aboriginal and Torres Strait Islander communities throughout Queensland, engaging with over 230 people to hear their stories and talk about the importance of early life - from pregnancy, throughout the perinatal period and the first 1,000 days of a child’s life. ‘We always ask the question, “what do you believe is important for families?”, and everyone we speak to agrees that the perinatal period is critical for future health,’ A/Prof Rae said. ‘Despite the communities identifying its importance, there are currently no studies using a co-designed approach to investigate the critical importance of the first 1,000 days in the development of Aboriginal and Torres Strait Islander children to healthy adults.’ Yarns held with communities to date have identified other important factors impacting health outcomes including social and emotional wellbeing, exposure to trauma, grief and loss and impacts of racism and poor access to basic healthcare interventions, such as hearing, eyes and dental care. ‘Community members identified how challenging this was for those with issues such as autism, fetal alcohol syndrome and cerebral palsy to access early interventions, particularly when living in rural or remote regions,’ A/Prof Rae said. ‘To respond to community feedback, we will combine the longitudinal study with a range of immediate healthcare interventions to improve outcomes for families now. ‘This will enable parents who join the study to self-refer to the PACT program, led by Dr Koa Whittingham, to support parenting and social emotional wellbeing, and all babies born into the study will be screened early in life to determine if they are at risk of poor neurodevelopmental outcomes.’ Babies who are identified as at risk of these poor outcomes will be referred into the LEAP program led by Dr Kath Benfer and Prof Roz Boyd, where parents will learn about everyday play activities that can promote neurodevelopment and improve outcomes for children. This will be supported via an Aboriginal Health worker in their community and via telehealth, enabling easy access to those outside of metropolitan areas. Each of these

The Indigenous Health Research Group at Mater Research lead by Associate Professor Kym Rae

programs will meet a priority set by the Aboriginal and Torres Strait Islander communities of Queensland. The research team are now finalising plans to co-design the elements of the longitudinal study of parents and their children for the first 1,000-2,000 days of life for Aboriginal and Torres Strait Islander families. This ambitious research project to close the healthcare gap is the product of a Strong Families Study grant, funded by the National Health and Medical Research Council. Working with Aboriginal researcher co-leads Professor Maree Toombs and Associate Professor Anne-Marie Eades, as well as Aboriginal researchers Professor Sandra Eades, Professor Rhonda Marriott, and researchers from the Children’s Health Research Centre, the team will also soon formalise an Indigenous Steering Committee. A/Prof Rae said that community members are well aware that what happened in the previous generation can have significant implications for the generations to follow. ‘The people we speak to in these communities speak out about the intergenerational trauma that is still being experienced through colonisation and systemic racism. For this reason, self-determination of research priorities and practices can only be delivered using a co-designed approach. ‘Having a strong culture improves health and resilience for Aboriginal and Torres Strait Islander people, and our team is determined to walk hand in hand with Aboriginal and Torres Strait Islander communities to create a better today, a better tomorrow and a stronger future for their families.’

Author: Associate Professor Kym Rae is a Principal Research Fellow leading the Indigenous Health Research Group at Mater Research and is internationally recognised for her extensive expertise in successfully developing cohort studies with Aboriginal and Torres Strait Islander families.

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SPECIALIST FACILITIES OPENING DOORS TO PAEDIATRIC RESEARCH How children are welcomed into Translational Research Institute facilities to drive studies and clinical trials

Associate Professor Samudragupta (Sam) Bora with a young study participant.

TRIC opens doors for children and their parents, offering a welcoming environment for participating in leading edge research into healthcare improvement and life saving treatments.

Tertiary and quaternary services are provided at the flagship Queensland Children’s Hospital in South Brisbane.

Facilities include laboratory spaces; consult, testing, interview and observation rooms; phone booths and a calm room.

Leveraging the expertise of the hospital’s clinicians is TRIC, the Translational Research Institute’s clinical research facility at the Centre for Children’s Health Research (CCHR).

Experts provide services including biological sample collection and processing, and participant recruitment for community-based population studies, as well as measuring and observing vital signs.

CCHR is CHQ’s dedicated research building, adjacent to the hospital and operated in partnership with TRI, The University of Queensland (UQ) and Queensland University of Technology (QUT).

Services are designed to support low-risk studies involving outpatient babies, children and adolescents – from qualitative, quantitative and epidemiological to observational, Phase III and Phase IV.

hildren’s Health Queensland (CHQ) is the only state-wide hospital and health service dedicated to paediatrics, meeting the diverse needs of children from metropolitan, rural, remote and First Nations communities.

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The facilities and ser vices have underpinned and progressed clinical research into diabetes, foetal alcohol spectrum disorder and premature births – and can accommodate treatments for rare diseases.

‘O u r r e s u l t s s u p p o r t p u b l i c h e a l t h g u i d e l i n e s recommending abstinence from alcohol when you’re pregnant or planning a pregnancy; and add to the growing body of evidence for early diagnosis and medical support.’

CAUSES AND PREVENTION OF TYPE 1 DIABETES

BETTER TOOLS TO DIAGNOSE NEURODEVELOPMENTAL DELAY

A major national research initiative has used TRIC in a bid to find the causes of – and prevention for – type 1 diabetes. The study has recruited 1500 babies from around Australia who have a close relative with type 1 diabetes, such as a parent or sibling. Researchers will use TRIC facilities to investigate environmental factors that may contribute to the development of type 1 diabetes in children. Associate Professor Tony Huynh, Director of the Department of Endocrinology and Diabetes at Children’s Health Queensland, says type 1 diabetes in Australian children is twice as common as it was 20 years ago because of our changing environment.

Neurodevelopmental researcher Associate Professor Samudragupta (Sam) Bora has used TRIC to improve Australian diagnosis of neurodevelopmental delay or deficit – especially for premature babies. The research has developed a tool that can accurately test Australian children and guide healthcare workers. TRIC facilities and expertise has been used to assess infants and toddlers during a play-based session, while their parents completed questionnaires. Associate Professor Bora conducted the study for Mater Research Institute and UQ, with colleagues from Monash University in Melbourne and Pearson Clinical Australia.

‘We are looking at an autoimmunity disease that causes the immune system to destroy insulin-producing cells.

‘This is regarded as a seminal contribution to neonatal and developmental medicine in Australia and New Zealand,; Associate Professor Bora says.

‘Factors linked to children developing type 1 diabetes that way may include genetics, bacteria, viruses, nutrition, weight gain during pregnancy – or even breast feeding during early life.

‘It had a significant impact on healthcare delivery by improving the diagnostic accuracy of a standard of care assessment that has been in use since 1969.’Preventing early-onset pneumonia in children

‘It’s important to identify the factors and develop prevention strategies before the autoimmune process begins.’

QUT and Menzies School of Health Research are using TRIC to study early onset pneumonia in children.

UNDERSTANDING BODY COMPOSITION IN CHILDREN WITH ALCOHOL EXPOSURE

The PneuMat ters study is investigating whether vaccinating pregnant First Nation mothers reduces acute lower respiratory infections in their infants. Such infections, including pneumonia, are a major cause of childhood death and illness and are linked to chronic lung disease into adulthood.

UQ researchers have used TRIC in the first study of its kind to report on outcomes in children with fetal alcohol spectrum disorder (FASD). UQ Child Health Research Centre researcher Dr Natasha Reid says the study included a psychologist, paediatrician and an occupational therapist. They conducted body composition assessments on children from four to 15 years of age, recruited through UQ’s neurodevelopmental clinic at CCHR. TRIC exper ts collected clinical samples and measurements, including saliva, cheek swabs, urine, blood pressure and heart rate. Clinical rooms were provided at TRIC, along with administrative support, equipment and lab resources. ‘The study suggests adolescents with FASD are at risk of having a lower lean tissue mass and bone mineral content,’ Dr Reid says. ‘That can lead to serious conditions including osteoporosis and bone fractures.

Vaccination aims to protect both mother and child in the months before the baby’s immune system provides adequate protection. Chronic cough researcher and QCH consultant paediatric respirator y physician Professor Anne Chang says PneuMatters has used TRIC for several years. ‘The study wouldn’t be feasible without the rooms and laboratory. We need a space for the study visits,’ Professor Chang says. ‘The samples are critical for to examine mechanisms and we wouldn’t be able to do it without the facilities.’ Author: Erik de Wit, Media and Communications Manager, Translational Research Institute

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“FINDING A WAY” A world-first suite of positive psychology videos codeveloped with families of children with rare and severe neurodegenerative conditions

evere neurodevelopmental conditions, with devastating comorbid psychiatric, behavioural, and medical challenges have profound impact on children and families. Achieving a genetic diagnosis is critical for improving patient outcomes, as it can inform optimal therapies, provide early access to information about developmental comorbidities, and potential opportunities to participate in clinical trials. Outside the specialist setting, these conditions are poorly understood, and our research has demonstrated that families can experience high levels of distress and uncertainty while undergoing genetic testing and receiving a genetic diagnosis for their child. Challenges can be manifold and include the highly emotional impact of new-onset life-threatening seizures, developmental comorbidities, coupled with an overwhelming amount of complex information families endeavour to absorb during this intensely emotional crisis period. There is a glaring lack of accessible psychosocial care and evidence-based psychological resources for families. Between 2018 and 2022, a team at UNSW and Sydney Children’s Hospital partnered with families to conduct a translational, codesign program of work. The team

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conducted several independent and sequential high-quality research studies including a systematic review, priority setting workshops, in-depth mixed-methods interviews. The research generated novel insights that were used to inform the scope and content of ‘Finding a Way’, a suite of positive psychology resources tailored to address specific psychosocial challenges families face. The current study describes an online mixed-methods pilot evaluation of the co-developed psychological resources. The online pilot evaluation included the perspectives of 167 parents from 18 countries. Data showed that Finding a Way is highly acceptable and relevant to families’ experiences. The coping strategies recommended were considered practical and achievable. Families valued that ‘Finding a Way’ provided a balanced representation of their experiences. In both the quantitative and qualitative data, parents reported that the resources normalised their emotional experiences and provided helpful suggestions about managing their personal relationships, seeking support and accepting help from others. “They put into words exactly how I felt through this journey. I actually nearly cried in the second video as I felt someone gets it. That’s me. I also loved how it describes how others cope with the diagnoses and gave me a better understanding of my husband’s role.”

CHRISTOPHE KEREBEL

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“I was looking for answer on this topic since my son was born, but I couldn’t find them. I really appreciate there is enough money and effort for parent’s mental health.” Our research revealed that the resources appeared to be of highest relevance to parents’ social-emotional support needs following their child’s initial diagnosis. Frequently reported emotional responses after viewing the resources included feeling “comforted”, “hopeful”, “connected” and “reassured”. Importantly, social support can empower individuals to maintain optimal mental health and parents noted that the content and the quotes in the resources validated their emotional experiences and provided them with a sense of social-emotional connection. Our results offer preliminary evidence that framing adaptation to a genetic and rare neurodevelopmental condition as a shared challenge has the potential to increase parent and family social-emotional connection and to empower families who feel isolated following their child’s genetic diagnosis. “I found myself very alone, very afraid and very distraught in the beginning and I still feel the same to some extent. There’s very little focus on helping the families cope. I find the advice in the videos very helpful and approachable” “They were beautiful. I’m literally in tears as I write this, I wish I’d had access to something similar 4 years ago when we got our child’s diagnosis, but I’m grateful for them today, they’re still just as relevant today as they would have been back then.” Insights provided by families highlighted the need to broaden the accessibility of psychological resources using a holistic lens, to support families throughout different stages of their child’s rare disease trajectory. Suggestions for improvement included increasing the accessibility of positive psychology resources, reducing barriers to implementation and embedding the resources with links to specialised family services and online platforms. Psychologic al re source s are incre asingl y be ing disseminated online and via smartphone applications as a strategy to improve the accessibility and sustainability of available psychological support. Studies consistently show that individuals are unlikely to engage in psychological resources that drive a notion of positivity without validating their experiences as real, relevant and painful. Finding a Way includes positive psychology resources tailored to satisfy parents’ social-emotional needs, while gently nudging them towards an adaptive solution, harnessing their cognitive abilities and perspectives. Following family recommendations, Finding a Way is now freely accessible and available to families via the Paediatric Epilepsy Network New South Wales (PENNSW) website (https://pennsw.schn.health.nsw.gov.au/families/ resources/finding-way-video-series).

PENNSW is an openly accessible website developed by specialists in epilepsy and paediatrics, embedded with educational resources designed to optimise the care of all children and families living with neurological conditions. Hosting the resources online improves the accessibility, enabling engagement with families living in rural or remote locations who are unable to access other services. In view of the current research findings, we are conducting further research to investigate the feasibility and acceptability of incorporating ‘Finding a Way’ into clinical practice. This research has increased awareness and provided high-quality, innovative, and freely available psychological resources (https://pennsw.schn.health.nsw. gov.au/families/resources/finding-way-video-series) for families of children living with severe neurodevelopmental conditions. This family-led body of work suggests that positive psychology resources may prove valuable in the context of rare and multifactorial genetic conditions, when used to complement other treatments and the suite of existing clinical psychology services. Equipping clinicians with accessible evidence-based resources will promote the delivery of integrated and sustainable best practice care, paving the way for improved quality of life for these families. Finding a Way can be accessed via this link: https:// p e n n s w. s c h n . h e a l t h . n s w. g o v. a u / f a m i l i e s / resources/finding-way-video-series

Author: De Suzanne Nevin is a Research Fellow, within the School of Clinical Medicine, UNSW Medicine & Health, Randwick Clinical Campus, Discipline of Paediatrics, UNSW Sydney and the Behavioural Sciences Unit, Kids Cancer Centre, Sydney Children’s Hospital CoGENeS is a collaborative group of researchers and multidisciplinary health professionals from Sydney Children’s Hospital Network and the School of Paediatrics and Child Health, UNSW. Members of the CoGENes team who contributed to this research project include Professor Ann Bye, Professor Kenneth Nunn, Fleur Le Marne, Erin Beavis, Rebecca Macintosh, Dr Rani Sachdev, Dr Elizabeth Palmer.Sources of support: The authors would like to thank Manildra Corporation and NSW Kids and Families for generous funding support. This work was also supported by Luminesce Alliance - Innovation for Children’s Health. Dr Suzanne Nevin is supported by the Sydney Children’s Hospital Neurology department and the Behavioural Sciences Unit

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GIVING CHILDREN THE OPPORTUNITY TO DESIGN THEIR CARE A way to improve adherence and outcomes

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CHRISTOPHE KEREBEL

round 10% of people with inflammatory bowel diseases (IBD) are diagnosed as children, so shouldn’t they receive the same quality of care as adults? Crohn’s Colitis Cure, an Australian not-for-profit dedicated to improving care for people with IBD certainly think so! Find out about their cloud-based software, now with paediatric functionality! Crohn’s disease (CD) and ulcerative colitis (UC), collectively referred to as ‘Inflammatory Bowel Diseases’ (IBD), affect around 1 in 290 Australians. Around 10% are diagnosed before they turn 18 years old, which is important considering IBD has been shown to be more severe and progressive in children. As with many diseases, clinical manifestations dif fer in children with IBD compared to adults. Therefore, paediatric gastroenterologists often employ additional measures of treatment success compared to adult physicians, including pubertal progress, growth, school attendance and bone metabolism, while standard outcomes also remain important; including symptomatic, biochemical, endoscopic and radiologic remission. IBD is lifelong and carried with it a high burden of disease. Notably, all children with IBD eventually transition to an adult clinic, however issues with efficient and complete medical record transfer between sites are not uncommon. Therefore, care consistency and quality during the transition process is paramount. Crohn’s Colitis Care (CCCare) is a world-leading, cloudbased IBD-specific electronic medical record and patient

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management platform. It is used by clinicians at the point of patient contact to perform clinical assessments and build management plans. It is also used by people with IBD who can complete questionnaires and report symptoms anytime via a linked consumer portal. Notably, all data feed into a de-identified clinical quality registry which can be used for research. This is important, given there are relatively limited real-world data available pertaining to people with IBD. Up until recently, CCCare included functionality solely relevant to care for adults with IBD. Therefore, its use in paediatric settings was impractical. This raises the question – what process needed to be followed to ensure adequate and appropriate incorporation of paediatric functionality into the existing CCCare platform? Our article, entitled “Co‑design and Consultation Ensure Consumer Needs Are Met: Building an eHealth Platform for Children with Inflammatory Bowel Disease” was recently published online in Digestive Diseases and Sciences. The aim of this study was to develop and implement a consensus method between clinicians, parents, and children with IBD to vote on paediatric metrics to be included in CCCare prior to software build. The objective was to ensure consumer and clinician needs were met. Overall, the article underscores the importance of involving consumers in the design and consultation process to account for differing perspectives and create a system that supports both consumer and clinician needs. We invite you to reach this article in further detail here Further information can be found at info@c-c-cure.org.

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NEW MEMBER BECOME A MEMBER OF RESEARCH AUSTRALIA

For more information on Research Australia and how you can join contact us at admin@researchaustralia.org

L-R Anastasia Ioannou, Executive Director and Kathryn Greiner AO, Chair

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CHRISTOPHE KEREBEL

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term effects and reducing the burden on the healthcare system.

LUMINESCE ALLIANCE: EMBEDDING PRECISION MEDICINE INNOVATION FOR CHILDREN’S HEALTH. Since the NSW government funded an initial proof of concept for the Centre for Paediatric Precision Medicine in 2019, the Luminesce Alliance research powerhouse has established five Enabling Platforms to accelerate the translation of precision medicine research into the healthcare system. Luminesce Alliance is a not-for-profit joint venture between the Sydney Children’s Hospitals Network, the Children’s Medical Research Institute, the Children’s Cancer Institute, the University of Sydney, and the University of New South Wales Sydney. Established with the support of the NSW Government to coordinate and integrate paediatric research in NSW, nationally and internationally, the alliance enhances capacity and integrates cutting-edge technologies i nto p e r so n a li s e d c l i n i c a l c a re, focussing on early diagnosis and treatment for children, limiting long-

With the generous additional support of $20 million from the NSW government in 2023, Luminesce Alliance established five Enabling Platforms: • Functional Genomics: identifying and understanding disease-causing genes and new treatments; impact; • Precision Therapy: delivering new drugs and novel medical technologies that will support earlyphase clinical trials; • Data: translating rich and complex data into new treatments, new prevention strategies and clinical • Psychosocial: developing world-leading best practices for psychological, emotional, social, and educational support of patients and their caregivers; • Health Systems Implementation and Economic Research: translating research discoveries into new models of care. The Enabling Platforms accelerate the collaboration of leading researchers, practitioners, and children and families together to enable us to see new discoveries in practice sooner. For more information: www.luminesce.org.au info@luminesce.org.au

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THE LAST WORD

UNLOCKING POTENTIAL THROUGH PHILANTHROPY It can take up to 17 years for research to translate to clinical care – that’s an entire childhood.

outcomes. By leveraging the power of philanthropy, we can aim for radical advancements in children’s health. But it means galvanising the community behind the cause.

ydney Children’s Hospitals Foundation CEO, Kristina Keneally, discusses how the power of philanthropy can fast-track transformative care from the bench to the bedside and change the lives of sick kids and their families sooner.

With the help of generous donors, SCHF invests in research that accelerates the ability to take crucial discoveries and turn them into innovative treatments, prevention strategies and cures to make a bigger impact on children’s health, sooner.

Sydney Children’s Hospitals Foundation (SCHF) exists to help provide all children with access to the best possible healthcare, whenever and wherever they need it. We are proud to be the exclusive philanthropic partner of the Sydney Children’s Hospitals Network, the largest kids’ health network in Australia, encompassing two major children’s hospitals, specialised care services and cuttingedge paediatric research. After working in public service for 20 years – in elected roles at state and federal levels, as well as several years as a member of the press gallery at Parliament House – one of the things that excited me most about joining SCHF was the chance to support the clinicians and cutting-edge researchers at the Network. I began my career 30 years ago in the philanthropic sector at the Society of St Vincent de Paul. I know that philanthropy is key to delivering the best possible 84

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It can take up to 17 years for research to translate to clinical care – that’s an entire childhood.

Through the power of philanthropy, we are fast tracking transformative care from the bench to the bedside, and back again. And with government and philanthropy working hand in hand, advancements will come faster than we ever thought possible. A researcher recently shared with me that the job can sometimes feel like you’re standing alone in a room, surrounded by a lot of different doors. Each door represents a new treatment, theory or line of investigation. Alone, it can feel overwhelming and hopeless to explore every single door and what lies beyond. What they said next struck me. They said that philanthropy makes it so you’re no longer alone. You now have the space, the people and the resources to open those doors and search for lifesaving, and life-changing, answers. The researchers at SCHN are at the forefront of their fields, delivering groundbreaking research projects and

Kristina Keneally

CHRISTOPHE KEREBEL

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SCHF funds crucial clinical trials infrastructure and key clinical trial research staff across the Network, such as clinical trial centre managers, nurses, and pharmacists. These spaces and support staff are essential for the Network’s researchers to participate in high-quality clinical trials each year.

providing the best possible care to young patients. With critical philanthropic backing, we have been able to unlock unrealised potential of outstanding researchers, support lifesaving clinical trials, explore new ideas, and provide the necessary infrastructure and environment for the Network’s expert hospital teams and researchers to thrive. We are giving researchers the support they need to open new doors and make ground-breaking discoveries. We have seen this already with the world-first clinical trials led by former SCHF-funded Fellow, Professor Michelle Farrar, Paediatric Neurologist at Sydney Children’s Hospital, Randwick. Professor Farrar completed a Neurology Fellowship in 2007-09 and has since spearheaded diagnostic and treatment advances to help babies born with the devastating genetic condition, Spinal Muscular Atrophy (SMA). Until recently, the average life expectancy of a child with SMA was just nine months. With the support of government and philanthropic funding, Professor Farrar’s efforts were instrumental in creating two life-saving outcomes for babies with SMA. A new gene therapy is now listed on the Pharmaceutical Benefits Scheme (PBS), saving families hundreds of thousands of dollars each year, and NSW Health has permanently added SMA to the newborn bloodspot screening in NSW and the ACT to ensure early diagnosis. Without philanthropy, this simply would not have been possible.

But research does not happen in a vacuum, and it cannot exist on project-based funding alone. To make tangible, transformative change come faster, our researchers need sufficient resources to operate. They need ongoing funds to support vital infrastructure, equipment and positions.

The incredible success of the SMA clinical trials is proof that by using philanthropic funds to invest in the specialists of the future, and the dedicated teams and purpose-built environments that enable their work, we can put clinical trials into practice for sick kids and their families faster than ever before. With critical philanthropic backing and government support, we have been able to unlock unrealised potential of outstanding researchers, support lifesaving clinical trials, explore new ideas, and provide the necessary infrastructure and environment for the Network’s expert hospital teams and researchers to thrive. Philanthropy truly can transform children’s health in Australia and around the globe. Where existing government and grant funding can’t stretch, committed philanthropists are filling the gaps and making our good Australian hospitals great. The SMA Newborn Screening Pilot and its economic analysis were proudly supported by Luminesce Alliance.

Author: As CEO of Sydney Children’s Hospitals Foundation (SCHF), Kristina leads the strategic direction, vision and purpose of the organisation. With a career spanning nearly 30 years across both public and not for profit sectors, Kristina has dedicated her life to making a positive impact in the lives of individuals and communities. During her time as Premier of NSW and an Australian Senator, Kristina worked several front bench portfolios including Home Affairs, Immigration, Planning, Disability Services, and Ageing. Kristina is married and the mother of two grown sons and a daughter, Caroline, who was stillborn. Kristina was Patron of Stillbirth Foundation Australia for many years and is well-known for her advocacy to reduce stillbirth in Australia.

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