ORIGINS unlocking secrets

A ground-breaking WA project to track the health of young children has notched up a significant milestone and is now playing a key role in global research.

Eric Martin reports

After setting out in 2017 to follow 10,000 children and their families for a decade, The ORIGINS Project has started celebrating their first five-year-olds coming through the program from July last year.

Professor Desiree Silva

And while the project hopes to continue following these children and their families into adolescence, Medical Forum caught up with ORIGINS co-director, paediatrician and director of research at Joondalup Health Campus, Professor Desiree Silva, to discuss the outcomes that have already been achieved.

“It is an absolute pot of gold for WA, which we have developed in a fairly short space of time,” Professor Silva said. “It really is a fabulous concept – the dream of helping every child reach their potential – and through ORIGINS we are actually giving children the opportunity to
reach it.

“We are collaborating with different researchers, both here and internationally, but I think we are taking the lead on this intervention-style of birth cohorts, certainly, from a national viewpoint. We already have over 16,000 individuals in our group, including the children, their mothers and some fathers or non-birthing partners.”

Professor Silva explained that while intervention birth cohorts have gained in popularity over the past few years, ORIGINS was one of the first to use the approach – a unique way of improving children’s health as they participate in longitudinal research.

“Normally you would observe a birth cohort and describe your findings, without necessarily following that group up until many years later, but with ORIGINS, we are actually creating a platform that enables us to perform intervention as well as observational studies,” she said.

Real-time change

“This means that we are actively trying to improve the lives of those children at different time points – to change their trajectory. If we find something that is not right or can be done better, then that is exactly what we will try to do for our participants.”

Real-time feedback is given to families if an issue is identified and, so far, the team has identified a broad range of concerns in some children, such as developmental delay, sleep problems, growth issues, allergies, iron deficiency and behavioural challenges.

“The main aim is that we want to look at ways to reduce the epidemic of non-communicable diseases,” Professor Silva said.

“It is not just the COVID tsunami that we are dealing with, we have a pandemic of chronic disease beginning with young children, right up to the elderly, and a significant proportion of these non-communicable diseases are pre-programmed early in life. 

“By providing a healthy start to life and improving our understanding of early pre-programming, we hope to help prevent some of this huge burden of chronic disease.”

Professor Silva said ORIGINS had a particular focus on epigenetics, the process by which an individual’s genes are activated by the environment, switching that gene on or off.

“What we are trying to understand is, what is causing these genes to switch on? What is it in our environment that has changed? What are we eating, what are we breathing that is different? We start looking at the environmental exposure of the mother during pregnancy and continue right through childhood because we know that early exposure probably does impact epigenetics.” 

Plastic not fantastic

A recent focus has been on the impact of microplastics building up in the placenta during pregnancy, a topic that has featured in several small studies but has been challenging to validate due to methodological difficulties. 

“These studies have attracted huge criticism because not only do we live in a plastic environment, but the samples were also collected using plastic gloves and placed into plastic tubes – maximising the potential for exposure,” Professor Silva said.

“So, we are now collaborating with the Minderoo Foundation, University of Queensland and University of WA looking into this, trying to ensure we collect our samples in a pristine way before they are transferred to the lab in Queensland – a predominantly plastic free environment, set up by the Minderoo Foundation.”

Similarly, the team has been collecting amniotic fluid using plastic-free materials to determine if it has also been contaminated by microplastics.

“You can see I get excited about all this! However, the main aspect is that we have created this incredible research platform that enables lots of projects to be established using our birth cohort,” Professor Silva said.

“For example, we have studies in allergies prevention, obesity reduction, how to improve children’s mental health, how
to improve fathers’ health.

“We expected about 25% of children to develop eczema by the time they turn one, but we are actually finding in our cohort that about 40% of them have got some level of eczema. But why is that the case? And why does that seem to be going up every year?”

Getting dirty

ORIGINS research has already suggested that there really could be something to the old adage that playing in the dirt will help to develop a strong immune system.

“We’re finding that nature is vital for our microbiome,” Professor Silva said. “The bacteria that we engage with outside is really important and we have a great intervention study collaborating with Nature Play WA, working with children about three years of age and bringing them out into nature, so that they can develop their resilience through various activities.

“Yet at the same time, electronic use has distracted people from being outside and we collect a lot of information on the impact that can have in both a positive and negative way, which provides balance to the research. 

“We are also asking parents about their children’s sleep, their attention span, and about their behaviour.”

As the ORIGINS study matures, it is demonstrating a growing ability to investigate transgenerational effects. It will look to enrol grandparents to explore behaviour and environment during a woman’s pregnancy and how that might affect their children’s fertility and egg quality.

“The Raine Study is already doing that. It is about recognising the if you really want to know about why someone has developed something, you have got to go back a few generations as well,” she said.

ORIGINS beginnings

An unlikely meeting with the former Mayor of the City of Wanneroo, Tracey Roberts – now the federal Member for Pearce, on a flight back from the UK, helped bring ORIGINS to life.

“We spent the entire flight plotting and planning,” Professor Silva said.

“In the Wanneroo area at the time, there was some information published on school readiness, which showed that this was a very high-risk area for schools, with pockets of poor performance compared to the national average.”

There were also high rates of developmental disorder, mental ill health, obesity and chronic disease. 

“It really was an ideal cohort of people because we wanted to capture the whole population of an area, identify problems as they arose, and direct individuals to the services they required, or try and prevent them from developing those issues in the first place,”
she said.

“At the same time, my co-director, paediatrician Professor Susan Prescott, had authored a book called ORIGINS – on the origins of disease – and it was a great fit to run this cohort at the Joondalup Health Campus in collaboration with the Telethon Kids Institute (TKI).

“Joondalup Health Campus is almost at a tertiary level with all the exciting research and teaching that is happening here. I have recently been appointed the inaugural Director of Research, where previously I was the Head of Paediatrics for over a decade.”

Professor Silva explained that through their collaboration with TKI, ORIGINS was assisting autism spectrum disorder expert Professor Andrew Whitehouse in developing new video technologies that could help parents better communicate with their infants.

“Andrew’s group is specifically looking at is this video technology which is helping to reduce the severity of some of the features of autism in an at-risk population, something that again, is quite unique,” she said.

“The work that will come out of this is really important because if you can actually prevent those features from developing, or reduce the symptoms of autism, that will have a huge impact for so many families.”

Professor Silva also highlighted the outcomes of another critical study run through Curtin University called Early Moves, which is using home videos to investigate certain movements in babies, as early as two weeks of age, to determine their risk of experiencing developmental difficulties.

“We know that at four months of age, an absence of certain movements in babies is almost 95% predictive of cerebral palsy,” Professor Silva said. 

“Those babies’ movements are like a video into their early brain development. If they do not have a particular movement then their risk of cerebral palsy is extremely high, and as a result they would be investigated very early on, rather than waiting to find out later in life that they have problems with their motor skills. 

“Knowing that you have over a million neuron connections occurring every second, you can really shape things differently if you intervene early. I never would have dreamt that you could find a way to increase the IQ of a population yet potentially, through Early Moves,
we do. 

“The benefits of these nested studies is that the researchers for Early Moves, for example, are doing quite detailed developmental checks at two years of age, before looking for more funding to do progress to early school years and we also get those results, which can then be compared with other studies.

“For example, once we know how to analyse microplastics in a manner where we are confident that the methodology is acceptable, we could combine that data with the analysis of children’s movements to further investigate microplastic’s impact on their development or allergy outcomes.”

The COVID effect

Significantly, ORIGINS is one of the only studies globally to have collected such a huge dataset both before, during and potentially after the pandemic, particularly in relation to Omicron.

This could have significant value for researchers looking at long-COVID in children because of the way that ORIGINS is structured, collecting data twice during pregnancy, with samples and measurements taken at the birth, followed up by questionnaires and more samples taken at one, three and five years of age. 

“Some participants would have had COVID while some wouldn’t, but opportunistically, we have also been collecting samples that can be looked at to evaluate whether there are changes in an individual’s metabolomics in relation to COVID exposure,” she said.

“A body of work was also undertaken to look at the health and wellbeing of our ORIGINS families at the height of the pandemic, including the impact of forced lockdowns and financial pressures, but our platform is collecting data, so we will have to find other funding to help with the analysis of that.

“We have this gem, this absolute pot of gold, and we need to find funding to analyse all of these samples – it is going to create a huge amount of discovery just from analysis.

“These samples are just sitting in freezers, and we need to look at them; we have dust samples collected during pregnancy that fill up rooms and rooms; we have over 300,000 samples in the biobank and that will grow to almost a million by the time we finish this project. 

“We want to source funding to scale and be able to analyse a lot more samples in multiple ways: what we’d like to do is to say, ‘OK, yes, you can analyse it, but then go on to investigate all these other aspects as well – don’t just do one thing’.”

Professor Silva said there had been a great deal of interest in ORIGINS from the international scientific community now that the data set has grown so substantially, and the project enjoys strong collaboration with Born in Bradford, another intervention birth cohort from a disadvantaged area of the UK. 

“We have done some comparative work with COVID and published a paper looking at the mental health effects of COVID in these two very different populations, which interestingly showed that even though we escaped in some ways, the mental health impacts were still comparable,” she said.

“The impact of the virus within families was still very, very high.”

As a paediatrician who works in the mental health space, Professor Silva pointed out that even before the pandemic, mental health was a significant issue.

“Pre-COVID I would see some children as young as seven, and it was not uncommon that they would present with suicidal ideation,” she said. “We are collecting measures very early and we have certainly seen several children at three and five who were extremely vulnerable.

“All the paediatricians in this area would concur with me that it is quite a frightening situation to be in, to see children that young and that vulnerable. And if they are also impulsive, they will do it if they can, without thinking it through, which is terrifying for families, especially when services are so difficult to access. 

“But over the pandemic, things have got significantly worse, and now, the issue is that a lot of these children are on wait lists, which is a real concern for parents as they do not know what to do. 

“Yet by being able to direct them to appropriate services at a very young age and support their parents, I think that is where many families have been very grateful for being involved with ORIGINS.”

Next phase

Recruitment for ORIGINS (mothers between 20-38 weeks pregnant) ended last December, and Professor Silva explained that due to the current shortage of paediatricians, ORIGINS asks parents to fill out a range of important questionnaires for review, to ensure that they capture any immediate concerns and provide this information back to families.

“We are certainly working on detecting issues in children at one year to 18 months old and directing them appropriately,” she said.

“But we are also using the information that we have gathered to develop technology that can help parents to identify an issue and then direct them to services. 

“We must find novel ways to achieve this, using the technology that we have now to create new models of care – there are just not enough specialists around to be able to see people in the way that we used to.”