Today

NHMRC’s history in developing dietary advice during pregnancy, lactation and early infant feeding dates to the 1980s where early recommendations were made to those providing direct care to pregnant and lactating women to meet the nutrient requirements for both the mother and their baby.

Adelaide based research into the fatty acid composition of human colostrum found that, among other things, colostrum includes a high percentage of long chain polyunsaturated fatty acids including the 4 types of omega-3 fatty acids.

What followed was decades of high quality research into the differential effects of omega-3 fatty acids in infancy and pregnancy that would later underpin national health advice, programs and policies.

Watch and listen to our latest Speaking of Science with an integral research leader in this area, Professor Maria Makrides of SAHMRI, below.

Recorded on Thursday 20 August 2026 from 10:00AM–11:00AM AEST.

Video transcript

0:01 Professor Steve Wesselingh
We’ll be a little bit quiet, Maria, while everyone joins.

1:35 Professor Steve Wesselingh
OK, I think we might start.

1:37 Professor Steve Wesselingh
I can still see people joining us, but we can get through what I've got to say first and then hopefully everyone will have joined us in time for Maria to talk.

1:47 Professor Steve Wesselingh
Thank you for joining us for today's Speaking of Science.

1:52 Professor Steve Wesselingh
Importantly, I'd like to start by acknowledging the Traditional custodians of the lands which we each are on today. I would personally like to acknowledge the Ngunnawal people as the traditional custodians of the ACT. I acknowledge and respect their continuing culture and the contributions they make to the life of this nation. I pay my respects to their elders past, present and emerging and I extend this respect to all Aboriginal and Torres Strait Islander people joining us online today.

2:23 Professor Steve Wesselingh
Before we start, I'd just like to remind everyone again that there's an opportunity to ask questions of our guest speaker towards the end and so I encourage you to ask questions you'd like answering by entering them into the chat function.

2:37 Professor Steve Wesselingh
Another bit of housekeeping, if you're unable to attend a webinar or would like to go back and rewatch, all the recordings are available on NHMRC's website.

2:48 Professor Steve Wesselingh
On a personal note, it is a bit sad, but this is my last time hosting Speaking of Science as my tenure as NHMRC CEO comes to an end.

2:59 Professor Steve Wesselingh
When I started in 2023, our Speaking of Science series was just an idea as a way to recognise Australia's health and medical research powerhouses that were, or had, made waves in their chosen fields.

3:15 Professor Steve Wesselingh
I'm really thankful to the team for coming up with really great ideas and great people to give the Speaking of Science and, and I'm really proud of the people we've had, the questions we've had and the conversations we've had on Speaking and Science.

3:34 Professor Steve Wesselingh
I'm really excited to see the series continue and expand under new leadership in the future.

3:44 Professor Steve Wesselingh
In addition, as NHMRC continues to celebrate 90 years of improving health through research, so does our reflections on NHMRC funded discoveries that have led to the greatest impact. From shaping policy, strengthening healthcare, developing public health advice, to improving the lives of all Australians, this milestone celebrates the researchers, the ideas and breakthroughs that continue to drive better health outcomes.

4:15 Professor Steve Wesselingh
NHMRC's history in developing dietary advice during pregnancy, lactation and early infant feeding dates back to the 1980s, where early recommendations were made to those providing direct care to pregnant and lactating women to meet the nutrient requirements for both the mother and their baby.

4:35 Professor Steve Wesselingh
Parallel to this, Adelaide based research into fatty acid composition of human colostrum found that, among other things, colostrum includes a high percentage of long chain polyunsaturated fatty acids, including the four types of omega-3 fatty acids.

4:53 Professor Steve Wesselingh
What followed was decades of high quality research in the differential effects of omega-3 fatty acids in infancy and pregnancy that would later underpin national health advice programs and policies.

5:07 Professor Steve Wesselingh
Really exactly the sort of research that NHMRC values the highest, and that is going from discovery all the way to policy and guidelines.

5:17 Professor Steve Wesselingh
Today I'm really happy that the last speaker that I'll introduce for Speaking of Science is a really close friend of mine, a fantastic researcher, and that is Professor Maria Makrides.

5:31 Professor Steve Wesselingh
Maria is the Executive Director of SAHMRI, having previously served as the Deputy Director and Theme Leader for Women and Kids. As a clinical nutritionist, Maria is committed to improving the nutrition and health of mothers and their babies through the conduct and translation of high quality research.

5:51 Professor Steve Wesselingh
Maria is an NHMRC Leadership Fellow and has been responsible for changes into international policy regarding the safe composition of infant foods and national and international guidance on diet supplementation during pregnancy and infant feeding guidelines to minimise the risk of childhood allergies.

6:12 Professor Steve Wesselingh
She's also been elected as a Fellow of the Australian Academy of Science and the Australian Academy of Health and Medical Science and was in addition awarded the Australian Scientist for the Year in 2022. An amazing person and an amazing scientist.

6:28 Professor Steve Wesselingh
Thanks Maria for coming today and giving this speech. Really looking forward to it. Thank you.

6:34 Professor Maria Makrides
Thanks Steve for the wonderful introduction. It's an absolute pleasure to be here, to be able to share one part of the story and the journey to do with pregnancy and fatty acids which we've titled From Bench to Birth.

6:55 Professor Maria Makrides
Oops, did we? Did we lose the slides?

7:04 Professor Maria Makrides
I too acknowledge that the Aboriginal and Torres Strait Islander peoples of all parts of Australia as the custodians and owners of the lands.

7:19 Professor Maria Makrides
I'm on the Kaurna land and acknowledge the Kaurna elders and the Kaurna people for their strong connection to the land and the fact that they lead such wonderful science, particularly the scientists that are here at SAHMRI and acknowledge all other Aboriginal peoples that may be listening today and for your great contribution to science.

7:52 Professor Maria Makrides
I also acknowledge the many supporters and collaborators that have contributed to this story and to this journey of pregnancy, improving pregnancy outcomes for maternal and pregnancy outcomes for children, particularly in the omega-3 area as a clinical trial participants.

8:16 Professor Maria Makrides
There's been many thousands of them that have engaged around the country as a trial leaders and collaborators. The people who actually did the work and the many collaborators that range from the fields of epidemiology, biochemistry, statistics, neonatology, obstetrics, pathology and implementation science. It's actually been a wonderful journey and they've all played an important role.

8:52 Professor Steve Wesselingh
Maria, can I just check? Are you pushing your slides forward?

8:56 Professor Maria Makrides
Yes, I am and I'm seeing them change, right? Are you not seeing them change?

9:02 Professor Steve Wesselingh
I'm not, but I'm maybe. Tash, are you seeing them change?

9:08 Natasha Ness
No, I'm not. We're just trying to work out what's happening on our end. Bear with us.

9:20 Professor Maria Makrides
Do you want me to keep going or wait, Just perhaps wait.

9:25 Professor Steve Wesselingh
Might wait 30 seconds, but we can, we are offering others. Can everyone?

9:34 Audience
If you go to the bottom of your slides, you can actually move them forward yourselves until we get it to Maria.

9:41 Professor Steve Wesselingh
I've moved forward to seeing the pictures of Bob and everyone else on the screen, thanks to the many supporters, partners and collaborators.

9:52 Professor Maria Makrides
Yep, I'm just now going to start on slide 4.

9:56 Professor Steve Wesselingh
Excellent.

9:57 Professor Maria Makrides
Some 30 years ago, I started out thinking that if we could actually get better understanding of omega-3 fatty acid requirements, we would actually be able to make an important contribution in optimising the developmental outcomes of young children.

10:19 Professor Maria Makrides
Clearly that journey hasn't been a simple one, but I still feel it's still true and there's been many contributions that have been made through that.

10:32 Professor Maria Makrides
Originally, a lot of the work was around understanding the requirements for term babies and what we learned there was that the parent or essential fatty acid, of which is alpha linolenic acid, was actually enough and that there was no additional requirement for the long chain omega-3 fatty acid DHA for the developmental outcomes of the term babies.

11:02 Professor Maria Makrides
But all the action really was for preterm babies who missed that last trimester of pregnancy where there probably is a specific requirement for preform DHA and this is most important for the babies that are born at the earliest gestations. Those that are less than 29 weeks and miss that whole of that last trimester and their requirement is probably about three times the level that is currently in human milk.

11:35 Professor Maria Makrides
Trying to match what they would normally be exposed to in the womb in order to optimise their developmental outcomes from a nutritional point of view.

11:47 Professor Maria Makrides
But along the way, there was this amazing diversion in terms of when we were looking at pregnancy requirements in terms of omega-3 fatty acids also being an important contributor to being a risk factor for preterm birth and that we could actually make a contribution there to correct that.

12:16 Professor Maria Makrides
Just a little bit of orientation for people who don't know a lot about fatty acids.

12:23 Professor Maria Makrides
When we talk about the omega-3 fatty acids, we're talking about one family of polyunsaturated fatty acids, alpha linolenic acid. That is the primary essential omega-3 fatty acid that is largely in plant based foods walnuts, some oils, flax, soy.

12:40 Professor Maria Makrides
But it's biological activity is largely, because it gets metabolised to these longer chain fatty acids, eicosapentaenoic acid and docosahexaenoic acid. These long chain fatty acids are also of course in fish and fish oils and breast milk and eggs and the lean tissues of red meat. That's where we as adults mostly get our long chain fatty acids from.

13:18 Professor Maria Makrides
The complexity around understanding nutritional requirements for omega-3 fatty acids is that we can get the long chain ones directly from our diet, or we can synthesise them and make them from the parent essential fatty acid. That has made understanding those requirements a little bit more challenging.

13:45 Professor Maria Makrides
In the early 2000s, when we had roughly worked out that a healthy term baby who had the full in utero requirement of DHA, and probably didn't need extra DHA to optimise their development, attention turned to what was going on in pregnancy.

14:11 Professor Maria Makrides
At that time, there were lots of epidemiological studies that were being published suggesting that women who had greater intakes of fish during pregnancy had children who had advanced development or higher IQs into childhood.

14:34 Professor Maria Makrides
Many supplements started to appear in the market for pregnant women with low dose DHA added to them with advertisements like the one that you see on the on the slide suggesting that perhaps there was ultrasound development for children in utero.

14:59 Professor Maria Makrides
It was around this background that we actually wanted to establish whether there was truly a critical period for DHA in the last trimester of pregnancy in terms of improving the development of children.

15:18 Professor Maria Makrides
With NHMRC funding, we undertook the DOMInO trial, which was around trying to answer this question, and see whether we could optimise maternal infant outcomes.

15:34 Professor Maria Makrides
We randomly allocated almost 2,500 women single pregnancies to an omega-3 supplement, which was rich in DHA and the dose that was chosen here was really matching those epidemiological studies where you would think you would get the best neurodevelopmental outcomes, providing around 800 milligrams of DHA per day.

16:05 Professor Maria Makrides
For the dietitians who may be listening, about 3 fish meals a week equivalent compared to a control group, a blend of 3 vegetable oils that were designed to match the background diet of the Australian population with no DHA.

16:24 Professor Maria Makrides
We did exclude women who happened to be taking any fish oil. We intervened from around 20 weeks of gestation until birth.

16:38 Professor Maria Makrides
So what did we find? That there was absolutely no effect of giving DHA during pregnancy on developmental quotients or intelligence quotients of the children regardless of whether they were measured at 18 months of age, 4 years of age or 7 years of age.

16:58 Professor Maria Makrides
This did conclusively suggest to us that children who were born at term who are largely breastfed following guidelines after birth, that their pregnancy nutrition was adequate and a supplementation wasn't needed for improving developmental outcomes of the babies.

17:27 Professor Maria Makrides
We were of course aware that earlier studies in the 90s and the late 80s from Shura Olson and others were suggesting that long chain omega-3 fatty acids did have a role to play in extending the duration of gestation.

17:50 Professor Maria Makrides
Being aware of this, we made sure that we measured pregnancy outcomes and we were also very keen to make sure that we were addressing the concerns of people around supplementation, around bleeding risk, around the time of pregnancy.

18:11 Professor Maria Makrides
This was really the most amazing finding or secondary outcome out of the study is that we did see that with supplementation the risk of early preterm birth, that's birth before 34 weeks, about halved risk of preterm birth less than 37 weeks was trending to be lower.

18:38 Professor Maria Makrides
The frequency of the need for obstetric intervention for either a post term induction or a post term caesarean section because the pregnancy that was progressing beyond term was higher in the omega-3 group.

19:02 Professor Maria Makrides
Adding all of this together, there was this sense of replication of some of those earlier epidemiological studies where much higher doses of fish oil were used and there was this suggestion that pregnancy, there was a shift of, of pregnancy duration.

19:25 Professor Maria Makrides
The intervention was also associated with fewer admissions to neonatal intensive care and fewer perinatal deaths.

19:35 Professor Maria Makrides
It was with this background that we thought there was a really important pivot that we needed to think about in terms of omega-3s and their role in a pregnancy duration, preterm birth.

19:53 Professor Maria Makrides
What was really important about the DOMInO study when it was first published in 2010 was that at that time, it was the largest supplementation study that had that had assessed pregnancy outcomes.

20:10 Professor Maria Makrides
It did support that observation of DHA and DPA extending a duration of gestation. The amazing thing was that we'd only used about 1/3 of the dose of previous studies, and mostly only as DHA because we were interested in perinatal development.

20:29 Professor Maria Makrides
Of course, it's DHA that's largely accumulated in the brain and forms about 1/3 of the lipids in the brain, which was a bit at odds with earlier studies that use mainly EPA, which the rationale there was that it's thought to interfere with the production of the 2 series prostaglandins that are of course involved in initiating part tuition.

21:05 Professor Maria Makrides
The fact that we had both a bit of EPA and DHA leading to other potential mechanisms, but a very clear signal of changing gestation as the important factor here was that we weren't increasing bleeding risk.

21:25 Professor Maria Makrides
This was a bit of a pivot point for us. Although we continued the work on development, this whole new branch of work started around trying to understand and deal with a preterm birth.

21:45 Professor Maria Makrides
In terms of pre term birth being a major global challenge, we have 15,000,000 pre term births globally. In the industrialised world, they're the greatest cause of death and disability in children under 5 years of age.

22:02 Professor Maria Makrides
In the Australian context, 26,000 pre term births each year, of course with severity being worse for the outcomes of the baby as gestational age decreases. Surprisingly, about 2/3 of all preterm births still occur without known risk factors and here we thought, right, we've got a risk factor that might be new that we can do something about.

22:39 Professor Maria Makrides
This led us onto a new path. As I said, so the path to try and reduce pre term birth through a nutritional pathway.

22:49 Professor Maria Makrides
What does one do? One goes back and does a synthesis of the available data to understand where we're at around omega-3 fatty acids and understanding the duration of gestation.

23:06 Professor Maria Makrides
But we of course needed to conduct a new modern intervention study whose aim was really to be specifically designed to try and retain the benefit of reducing the risk of early birth, early preterm birth, while minimising any risk associated with post term birth.

23:33 Professor Maria Makrides
I'll talk a little bit about the Cochrane Review that we updated.

23:39 Professor Maria Makrides
Much to our surprise at the time, we found about 70 randomised trials that had intervened with omega-3 fatty acids in pregnancy involving almost 20,000 women and Philippa Middleton led this review, which took a long time to knit together because of the complexity of the studies, which were mostly from high income studies of high income countries.

24:09 Professor Maria Makrides
Although there was a smattering of studies from low and middle income countries, most trials only included singleton pregnancies. Most were originally designed to look at this issue of developmental outcomes for babies and the dose of omega-3 fatty acids could have ranged anywhere from 200 milligrams per day to almost 3 grams a day.

24:37 Professor Maria Makrides
The interventions were largely with capsules, but there were some studies that used fish or eggs or other supplemented foods, with the interventions mainly being in the second half of pregnancy.

24:54 Professor Maria Makrides
What did we find in the Cochrane Review? Birth less than 34 weeks. We saw a 42% reduction from about 4.6% to 2.7% for preterm birth, less than 27 weeks an 11% reduction from around 13.4% to 11.9%.

25:30 Professor Maria Makrides
Again, this evidence of increasing birth beyond 42 weeks. This was largely from the older studies because modern practice of course wouldn't allow pregnancies to progress beyond 42 weeks.

25:41 Professor Maria Makrides
What was important about this Cochrane Review was that it did include a range of women with different risk profiles, but almost all the women included were only from singleton pregnancies.

25:59 Professor Maria Makrides
Most studies did give a decent dose of about half a gram a day of long chain polyunsaturated fatty acids.

26:08 Professor Maria Makrides
We were of course a little bit worried about potentially reporting biases whether we over or underestimated the effect of omega-3 fatty acids, largely because although there were many studies say involving almost 20,000 women, you would have noted from the previous slide that not all of those studies reported pregnancy outcomes. We did conduct sensitivity analysis on the high quality studies and the effect was definitely consistent of omega-3 supplementation on reducing prematurity.

26:49 Professor Maria Makrides
In the meantime, we had designed and started our ORIP trial, which we thought you're right. This is the trial that really needs to nail this.

27:04 Professor Maria Makrides
Again, grateful for NHMRC funding to be able to have conducted this study with 6 centres around Australia. We recruited over 5,500 women regardless of pregnancy risk and including both singleton and multiple pregnancies.

27:27 Professor Maria Makrides
The study design here was that supplementation started before 20 weeks, but we asked women to stop supplementation at 34 weeks with the idea that we would preserve.. the hypothesis was that we would preserve the effect of reducing the risk of early preterm birth and prevent the need for obstetric intervention because pregnancies were running beyond post term.

28:04 Professor Maria Makrides
We had a very broad strategy. We did include women who were already taking low dose omega-3 supplementation and by this stage many prenatal supplements were already including a low dose of omega-3 fatty acids largely as DHA.

28:23 Professor Maria Makrides
And because of this, we thought it was actually really vital that we understood the fatty acid status of women who are coming into the trial.

28:34 Professor Maria Makrides
Also during the course of the study, and thanks to Bob Gibson and our other biochemical collaborators, we were able to develop a dried blood spot method for measuring omega-3 fatty acids so that we could easily afford to do these measurements without sending us broke basically and be able to easily collect and measure the fatty acids.

29:11 Professor Maria Makrides
What did we find? Much to our surprise, because we thought this was going to be the study that was going to absolutely nail this, the primary outcome of early preterm births, there was no difference between the treatment and the control group.

29:28 Professor Maria Makrides
There was also no difference in secondary outcomes of pre term births and we didn't also increase the need for intervention post term. That bit worked.

29:44 Professor Maria Makrides
Why did we end up with differences between what we were expecting so strongly given the Cochrane Review with the single largest trial?

30:01 Professor Maria Makrides
I think it's important to just reflect on what was different about the ORIP study and what was different about the studies that were included in the Cochrane Review.

30:16 Professor Maria Makrides
If we just recap, the studies in the Cochrane included more selective populations, they're often limited to singleton pregnancies and most often women who had high omega-3 intakes or were already supplemented were excluded from those studies.

30:41 Professor Maria Makrides
On the other hand, was actually testing a broad based population based strategy because we wanted to test whether we should be supplementing everybody in the same way. We were starting to supplement everybody with folic acid, so we included everybody regardless of omega-3 risk, sorry, everybody regardless of their risk of pregnancy outcomes. Whether they were already taking supplements or not and regardless of multiplicity.

31:17 Professor Maria Makrides
We thought we needed to go back and better understand how that baseline omega-3 fatty acid status might explain what was going on.

31:32 Professor Maria Makrides
When we just looked at the control group of the ORIP study, we did see that the risk of early preterm birth did vary by the baseline status. If you had a low omega-3 status as you were starting the trial at the end of the first trimester or early in the second trimester, your risk of early preterm birth was around 2.5%. If you had a high status of omega-3, your risk of early preterm birth was basically less than 1%.

32:21 Professor Maria Makrides
We then went on to see whether omega-3 status at baseline predicts the response to supplementation.

32:31 Professor Maria Makrides
This graph shows the relative risk of treatment versus control of preterm birth mapped along the status at study entry. What you actually see for women who start off with a low status and if that status is below about 4.2, you see that confidence interval doesn't cross the one line.

33:02 Professor Maria Makrides
In those women, there's about a 77% reduction in early preterm birth from about 3.2% to 0.7%. But for women who already have a high status, their risk of early preterm birth is already low. It's around that 1% mark and if your status is above 4.9%, that risk, you might inadvertently increase your risk from 1% to 2.2%.

33:37 Professor Maria Makrides
That really led us to this understanding that perhaps it's only the women with low status in early pregnancy that helps identify those women who are going to benefit from supplementation and that this broad based strategy of supplementation that we were testing that supplementing everybody isn't going to be effective at reducing the risk of prematurity.

34:08 Professor Maria Makrides
Rather, what we do need is a targeted approach where we're looking for women who are depleted in omega-3 fatty acids, that's probably the risk factor and by correcting that depletion, we can also correct the risk of prematurity.

34:31 Professor Maria Makrides
Now, as a nutritionist, that seems perfectly logical that you only need to correct depletion. At about the same time, the pregnancy care guidelines were being updated around diet and lifestyle, and for the first time there was advice for pregnant women who happened to be low in omega-3 fatty acids to supplement with around a gram a day.

35:03 Professor Maria Makrides
Since that time, there have now been other studies, particularly one out of the US that has compared supplementation of around 200 milligrams per day with around a gram a day and again, in that study the effect is most notable in the women with a low status.

35:29 Professor Maria Makrides
Again, we're correcting a depletion, we now have international guidance from an international consensus group, as well as other learned societies, to support the advice that actually NHMRC endorsed pregnancy care guidelines were the first to nominate internationally.

35:55 Professor Maria Makrides
You sort of think, well that's great, our work is done, we've got it into policy, but who knows about omega-3 fatty acids out in the real world. A guideline is not the same as changing practice and how do we actually create an operational pathway to make sure that we can actually test something like this in practice and see that it is feasible and adoptable?

36:30 Professor Maria Makrides
There was no test, no way to work out who was low in omega-3 fatty acids. We couldn't really do it by diet because there's a combination of diet and metabolism that's involved so testing it, it was the most accurate way of screening status.

36:51 Professor Maria Makrides
Obviously, new information for health professionals and relatively low awareness for women and clinicians about what they might need to do.

37:02 Professor Maria Makrides
In talking with a colleagues from both the consumer perspective as well as the clinical perspective, what was actually going to be needed to operationalise a guideline was an easy way to measure omega-3 fatty acids as part of routine pregnancy testing to be able to identify who is low in omega-3 fatty acids, that we can specifically provide tailored advice around supplementation only for those women who need it and to ultimately lead to a reduction in early preterm birth for those women.

37:54 Professor Maria Makrides
What was the best way to do this? Obviously for us in SA, a partnership with our colleagues at SA Pathology who routinely cover 80% to 85% of women who have their joint early trimester screenings through SA Pathology and tested before about 16 weeks. We wanted to find a way that we could do this in partnership without an additional blood draw at no cost to the women.

38:35 Professor Maria Makrides
In working with our colleagues in SA Pathology, I was obviously very excited about the blood spot technology that we had developed and being able to just use that. But it was very clear that our colleagues at SA Pathology said to me, look Maria, we've got our laboratory workflows and they are all about serum. If you can make sure that your test fits with serum and you can convert the dried blood spot into a serum test to our pathology standards, we'll partner with you and add a screening test to the SA Pathology form and then we can test out the implementation study.

39:30 Professor Maria Makrides
There we were, back to the drawing board, trying to work out… back to the laboratory and make sure that we can actually have a valid way of measuring total omega-3 fatty acids to pathology standards in serum and make sure that the cut offs work.

39:54 Professor Maria Makrides
This is a lovely graph that has now been published but is probably one of the publications that gets the fewer citations. But probably the most key piece of work in terms of able to bridge that translational pathway. You can see that as a standard validated method from the dried blood spot, it can be with a serum method.

40:26 Professor Maria Makrides
We could measure the fatty acids in a way that they're absolutely correlated between the saturates, mono unsaturated, the total omega-6s, and of course the total omega-3s. But that wasn't enough, we wanted to make sure that we weren't getting any misclassification between what we were measuring in a blood spot versus what we were measuring in serum.

40:50 Professor Maria Makrides
We happened to have about 450 bloods from ORIP, from both whole blood and a plasma serum in the freezer so we could validate.

41:02 Professor Maria Makrides
There was strong agreement just beyond the methods that we weren't getting any misclassification between women who had low status and women who had sufficient status. That was the absolutely vital thing so that we could actually translate things into clinical action.

41:25 Professor Maria Makrides
With our new serum cut offs, the low status below less than now 3.7%, we could confidently advise these women that needed supplementation to reduce their risk of early preterm birth and for the women who were sufficient and already at low risk of early preterm birth that they didn't need extra supplementation.

41:55 Professor Maria Makrides
In fact, from extra analysis of our study, as well as the studies out of the US, these women didn't really need anymore and shouldn't be supplementing beyond the 200 odd milligrams of DHA that may be in standard perinatal supplements.

42:17 Professor Maria Makrides
We then started a program of making sure we could pass on the information to clinicians.

42:26 Professor Maria Makrides
We had information for families. We had a community campaign largely on social media to be able to share the information about the program we were about to embark on with SA Pathology.

42:43 Professor Maria Makrides
Consistent with the NHNMRC endorsed clinical guidelines, we launched this program in May 2021 with SA Pathology and as part of this, there was also a mass media advertisement which I will share for you on community service announcements on TV. Then with progressing with that evaluation for the first few couple of years, we assessed the program in terms of fidelity, reach, feasibility and worked out that it was feasible. We saw a steady increase of uptake over time.

44:20 Professor Maria Makrides
We were able to reach a significant number of women and there weren't major differences in socioeconomic status in terms of who we were reaching and those who we weren't and the program was able to be applied as we intended.

44:37 Professor Maria Makrides
About 99% of the referrals occurred at the right time and that was actually, and they were measured and returned within 72 hours.

44:51 Professor Maria Makrides
By the end of May this year, the program had reached 40,000 women in South Australia. About 17% were identified as having low status. This 17% number is really important for a couple of reasons.

45:10 Professor Maria Makrides
Firstly, it exactly matches the number from the ORIP study in terms of those who are testing low, so that's been well validated. From a nutritional point of view, if you think about how we define depletion, it's generally those that are 1 standard deviation below the population mean and that's about 17%, so that was very validating from both those points of view.

45:48 Professor Maria Makrides
All of the referrals that SA Pathology was getting for their combined early pregnancy screening, omega-3 testing was being requested by May this year in 68% of those referrals, which means that when we were now covering about 50% of pregnant women in South Australia.

46:13 Professor Maria Makrides
We were doing this with amazing funding and support from the Hospital Research Foundation and an MRFF grant to show that we could actually implement in the real world.

46:30 Professor Maria Makrides
But if we were going to take that next step and extract that funding, because that funding was actually essentially for paying for the testing, we needed to convince people that this was of value to do and could be sustainable without funding.

46:49 Professor Maria Makrides
If we took the numbers out of the program and out of the trials, we could conservatively estimate that if this was applied nationwide that we would prevent about 640 early preterm births a year and that would give about a 3 to 1 return on investment and about 1167 or more than half of those costs would be in savings to direct healthcare and that's with a test cost of about $50 per test.

47:26 Professor Maria Makrides
We've now managed to get the cost of the test down to about $20.00. We would expect even greater savings because of those 2 things with hopefully greater uptake and lower cost of test.

47:42 Professor Maria Makrides
With this background and preparing for the health system to take over in SA and an agreement from SA Pathology to add this to their standard screening, we've set up a group that's chaired by Health Translation SA to look at local health system priorities to ensure that there is appropriate ownership from the health system.

48:18 Professor Maria Makrides
That means that, and the local priorities are really making sure that the testing can be integrated into the electronic medical record, that the resources for clinicians and consumers become clearer and are very concise and consistent.

48:37 Professor Maria Makrides
We take away the research language for in terms of equity that there's access to appropriate supplementation for women who can least afford it and with our national partnerships looking at a more sustainable funding for omega-3 testing through an MSAC type approach.

49:02 Professor Maria Makrides
On the 13th of May, there was a ministerial announcement of SA Pathology officially taking over and incorporating the program from the 1st of June into their standard serum screening. We actually support that through all of the work in the background and the consumer testing and the provision of advice of course in terms of thinking about long term sustainability and what those foundations need to be for true national scale up.

49:47 Professor Maria Makrides
Now as we think about the next steps and using a tool around scalability assessment, you can see that on about 10 criteria this works and where we need to keep an eye out with as many other interventions do is of course how the evidence space is incorporated with current and contemporary and changing practice.

50:20 Professor Maria Makrides
What that means for example, as practice changes and evolves, making sure we have equity looked after and that we of course keep monitoring outcomes in terms of stewarding scale. That's about, as I mentioned, the integrity of the program, adapting to local health systems, ensuring viability and maintaining equity.

50:46 Professor Maria Makrides
We have a national partnership that we are looking at scaling as the next steps.

50:55 Professor Maria Makrides
We're very grateful for the engagement of health services across the nation and particularly from organisations like Gpex, because one of our big learnings has been embedding this testing.

51:12 Professor Maria Makrides
The program starts with the GPs and the obstetric GPs that do a lot of ordering in that first and second trimester screening and it also allays the worries of our colleagues in the maternal foetal medicine space that we're not creating a lot of extra work for them. Obviously, the testing and the pathology services, the other industries involved and the learned societies.

51:50 Professor Maria Makrides
It has been quite a journey and obviously isn't quite finished yet because we do need to do the national scale up and we do need to make sure that integration with contemporary practice works well.

52:08 Professor Maria Makrides
Learnings from this translational journey, it definitely is a journey and understanding that one cannot predict the outcome. It's important to stay true to the quality of the process, and that is linked to the quality of the research outcomes.

52:27 Professor Maria Makrides
It's important not to assume that you know too much and that you need to engage with everybody early and often, because all of those learnings that come from everybody else become hugely important, as do the friends that you make along the way and the more diverse they are, the better.

52:51 Professor Maria Makrides
It’s often surprising about who ends up being your biggest supports and help along the way. It is a tough journey often, so it's important to have those friends and be kind to each other and importantly yourself, and not to take things to heart when things don't work out. There will be another way, so that's why it's important to celebrate the wins when you have them and have the fun and enjoy the journey.

53:23 Professor Maria Makrides
As I look forward and we look to the excitement of the national scale up with our implementation science scientists like Acushla Lyndale, with our clinical leads like Karen Best, and our laboratory people and chemists in Michael Mugford, David Jeffrey, who are creating new ways to assess the biomarkers and the oxy lipons from not just the prostaglandin pathways, but the leukotrienes and the cytochrome P450 derivatives that are probably all involved in understanding those pathways for part tuition.

54:14 Professor Maria Makrides
Then we will understand how our omega-3 fatty acids do interfere with things like aspirin, who also interfere with similar pathways, so that we can make sure that contemporary practice is actually rooted in evidence based care.

54:36 Professor Maria Makrides
In closing, I pay tribute to my partner in science and in life in terms of the huge journey that we've been on together, in terms of knitting together the biochemistry with the clinical impact to get better nutritional outcomes for maternal child health.

55:00 Professor Maria Makrides
If you are interested in the omega-3 Test and Treat Program and do want to stay abreast of developments, you can use the QR code, sign up for newsletters and if you're interested in becoming involved, please let us know.

55:15 Professor Maria Makrides
I thank you for your attention.

55:23 Professor Steve Wesselingh
Thanks so much, Maria. What an amazing story and lots of accolades on the chat and the Q&A and lots of clapping going on there and we don't normally see that by the way.

55:33 Professor Steve Wesselingh
I think the reason we're seeing that is just the story going from that discovery work all the way through to implementation science and also the ups and downs.

55:44 Professor Steve Wesselingh
When you've got a hypothesis and you test it and you actually get a different answer, it takes you back to discoveries of penicillin and things when people didn't expect what they got and I think also, sorry, I'm talking too much, but it really goes to we've been talking a lot about trust in science lately and if people could listen to this and understand the process of science and how all of that testing and process to make sure that we actually get to the right answer.

56:14 Professor Steve Wesselingh
The right answer is different to the question you asked, right? All the way back, we're in a different place, but with all of the evidence behind it.

56:22 Professor Steve Wesselingh
So, so much positivity on the screen in front of me, I guess one, one question that came up. I'll put a couple of questions from the screen to you.

56:33 Professor Steve Wesselingh
One was, are there any commonalities in the people who are low in omega-3 fatty acids? Was there something, what is common about that population other than their low omega-3 fatty acid status?

56:49 Professor Maria Makrides
We don't know. It could be because of low intake and that might be because of poor diet. That might also be because of long term vegetarianism or poor diet, led with poor social circumstance or it might be a combination of not quite enough and being a poor metaboliser of alpha linolenic acid into long chain omega-3.

57:20 Professor Maria Makrides
We've done a whole lot of other things to see whether there are other predictors that change that relationship with preterm birth, but it just seems to be that it's low status.

57:39 Professor Steve Wesselingh
The next question is from Agnes, who runs our clinical guidelines process. I'm sure you know Agnes. But anyway, Agnes is asking what do you think of the most key facilitators? And I guess this goes to implementation science, doesn't it? To get this to roll out nationally. What are the key things we need or you need to achieve in order to make this truly national?

58:06 Professor Maria Makrides
A test that everybody can access with no or little cost, and very clear advice about what to do with supplementation. The other limitation has been that the supplements available haven't been easy to decipher in terms of getting the right dose, so we're looking at what levers we have in terms of also working with the TGA to make sure that women who are low can have much easier visibility and access, but also clinicians about what's low.

59:00 Professor Maria Makrides
Coming back to Agnes, if we're thinking about guidelines, we need to get as many people as possible having a healthy intake of omega-3 acids early on to avoid the need for supplementation. But the really nice thing about this is that if you if you are low, we can actually identify people in the first half of pregnancy and correct that lowness.

59:32 Professor Maria Makrides
Unlike, for example, folic acid, where by the time you find out you might have been depleted, it's actually too late because the neural tube's closed and we needed a different implementation strategy that we needed to actually fortify the whole food supply.

59:51 Professor Maria Makrides
So, the nice thing here is that we can test during pregnancy and we can do something about it. It’s actually about making the test available and having the right supplement linked.

1:00:07 Professor Steve Wesselingh
The next question, goes a bit to the journey. So were there times during the journey, and I'm sure there was when the results came back and you said that actually isn't what we wanted to see, and how you got the team… how did you deal with the issues of sort of feeling a bit low about that, the team feeling low, but we got to keep going sort of scenario it.

1:00:36 Professor Maria Makrides
We've always had this, this thing and some very strong reminders from our statistical colleague and I will call out Phil Ryan here, who basically was always wary of us falling in love with our hypothesis and, and that grounding right through the whole journey has been important.

1:01:09 Professor Maria Makrides
The other thing, and this is why I mentioned the colleagues and the friends that you make during the journey is that particularly our clinical colleagues who were truly interested and are interested in the science, the desire to have a conclusive answer on which to base clinical practice, and having that conclusive answer and being able to regroup and say, well, it's not, we're not going to go down this pathway collectively, we're going to go down that pathway and having the conclusive answers also meant that the journals took the studies seriously.

1:01:57 Professor Maria Makrides
Even though we were publishing null findings, you know, JAMA and the New England Journal of Medicine thought that it was an important enough study that conclusively answered a question.

1:02:11 Professor Maria Makrides
We were able to actually draw some strength from that and that was a way of importantly regrouping and reshaping the direction.

1:02:25 Professor Steve Wesselingh
Great, thank you. We're a bit over time, but I'm going to do 2 more questions.

1:02:30 Professor Steve Wesselingh
I'm going to do Emma and Cath. Cath says what a terrific presentation as everyone does. But how did you get government decision makers on board the journey when there are so many competing important causes?

1:02:46 Professor Maria Makrides
Start early is the and make sure that they're on the journey too. For example, SA Pathology was instrumental in pointing us towards what we needed to do to plea it to meet pathology guidance and they were on the journey for that 5 years with us on the MRFF grant, and with the Hospital Research Foundation, where the research was actually essentially paying for the test.

1:03:28 Professor Maria Makrides
It was that journey that allowed us to share, see the importance, get up to speed with the literature, understand what was going on, feed it up their chain and for them to actually have ways and have the time to establish how it fits in with their funding model with all of the other serum screening and how to knit that together.

1:04:00 Professor Steve Wesselingh
Last question from Emma. Again, thanks for presenting your wonderful work.

1:04:05 Professor Steve Wesselingh
But her question is quite a good one, I think to end us up. Do you see with supplementation of people with low omega-3 fatty acids an increase in the number of people who go late and need intervention?

1:04:20 Professor Maria Makrides
No, and we have actually as the advice in the program has been to stop supplementation at 37 weeks.

1:04:33 Professor Maria Makrides
Once you've passed the risk for preterm birth and also in the ORIP study, but also with the other studies out of China now and the European work that if you stop at the right time, you do get that wash out.

1:04:58 Professor Steve Wesselingh
Fantastic.

1:04:59 Professor Steve Wesselingh
That just leads me to, I said I was going to ask another question, but internationally, so this is rolling out internationally now as well?

1:05:06 Professor Maria Makrides
There's a lot of interest internationally in different ways, both obviously different health systems work in different ways. We've had a lot of interest from the NHS in the Manchester Liverpool area and we've been working with them in terms of how that works there in Rochester, NY, in parts of Europe. I think the Netherlands have set up their own system which is largely a private one.

1:05:47 Professor Maria Makrides
People are also looking at private versus public type systems and how that works. Are lots of questions coming up about do I need to retest? There's obviously a whole new lot of questions that will need to be answered from an implementation point of view.

1:06:12 Professor Steve Wesselingh
Alright, we better, we could go on for a while, but we are now well over time.

1:06:16 Professor Steve Wesselingh
Just we've had so many accolades on the screen. Thanks so much for a really great presentation and a great story. A really important story in terms of when we think about our National Strategy for Health and Medical Research and how we really are looking for impact.

1:06:33 Professor Steve Wesselingh
This is a real story from discovery out to impact, and I know N HMRC uses case studies as well, which is terrific and a great reminder of the importance of nutritional science and nutrition.

1:06:49 Professor Steve Wesselingh
Again, that's not something you have to remind NHMRC on. We're about to release our nutrition guidelines for public consultation and so really exciting, great presentation, great work.

1:07:04 Professor Steve Wesselingh
Thank you very much, Maria.

1:07:06 Professor Maria Makrides
Thank you. It's an absolute pleasure.

1:07:11 Professor Steve Wesselingh
Thank you. Bye.

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