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Standing Committee on Social Policy and Legal Affairs
22/06/2012
Foetal alcohol spectrum disorder

HALLIDAY, Associate Professor Jane, Principal Research Fellow, Murdoch Children's Research Institute.

MUGGLI, Ms Evi, Senior Research Officer, Murdoch Children's Research Institute.

Subcommittee met at 10:10

CHAIR ( Mr Perrett ): Good morning. I now declare open this hearing of the inquiry into the incidence and prevention of foetal alcohol spectrum disorder. I would like to acknowledge the traditional custodians of this land and pay our respects to the elders past, present and future. The committee also acknowledges the present Aboriginal and Torres Strait Islander people who now reside in this area and thank them for their continuing stewardship of this land.

Please note that these meetings are formal proceedings of parliament and everything said should be factual and honest. It can be considered a serious matter to attempt to mislead the committee. This hearing is open to the public and is being broadcast live and a transcript of what is said will be placed on the committee's website. I welcome representatives from the AQUA Study at the Murdoch Children's Research Institute. Thank you for taking the time to come and give us some evidence. Would either of you like to make an opening statement before we live in questions?

Prof. Halliday : We have prepared some material here about the study to explain it, and some points that we would like to raise.

CHAIR: My understanding is that a lot of this will be about you telling us what you are currently doing rather than us grilling you for information.

Prof. Halliday : Probably we will raise questions in the process of telling you about the study.

CHAIR: Please do.

Prof. Halliday : We are conducting a longitudinal cohort study to investigate the association between low and moderate prenatal alcohol exposure and the effects on the foetus. The AQUA Study—and AQUA stands for 'Asking QUestions about Alcohol'—is a large collaboration involving researchers from all over Australia and it is funded by the National Health and Medical Research Council for four years. We started last year so it is in the early phases.

Our research aims to observe and accurately record what women are drinking at three stages of pregnancy—very early, before 18 weeks gestation; in the middle of pregnancy; and late pregnancy—and then to follow up the children for two years.

CHAIR: When was the third one? They are all pre-birth—

Prof. Halliday : The third one is at 36 weeks.

CHAIR: And no breastfeeding?

Prof. Halliday : We have another questionnaire at one year of age and that has several questions on breastfeeding, yes. At one year of age, we do a clinical review of the children—and I will explain that in a minute—

CHAIR: So there would be no necessary physiological exploration of breastfeeding and alcohol consumption from birth to one year?

Prof. Halliday : No. Our primary aim is to look at exposures in pregnancy. We began recruiting pregnant women in June last year at six hospital antenatal sites. We have research nurses employed at each site, who busily walk around the room recruiting people. We currently have over 1,900 women recruited before 18 weeks and they have completed the first of the three questionnaires. We have subsequent numbers for the other two questionnaires, and we even have some first births. The questionnaire asks about drinking habits during the current pregnancy and about drinking in the years before they become pregnant—so exposure in the teenage years. It asks about the father's drinking around the time of conception. It asks about family history, body type—BMI, eating habits; there are detailed dietary questions. It asks about medication and supplements, smoking, pregnancy complications, general health and more. The three questionnaires cover a huge range of potential what we know as confounders, which are things that can influence the effect of alcohol. It is a major limitation of many studies that they do not have these detailed measures. We have spent a year developing these questions, with funding from VicHealth, so we had a lot of pilot work before we even started putting the questionnaire out there to women. We ran focus groups with pregnant women in that year to find out what would be the best way to ask these questions.

We provide the women with a coloured chart that we developed with them in that focus group period and we ask women to report their drinking in terms of the amount, the frequency and then the timing—so when they have been drinking. We consign women to one of eight categories of exposure, using the information they provide, on drinking both before they knew they were pregnant and then after they knew they were pregnant, and that is very important—that pre- and post-aware drinking period. We have got women that have never had a drink—the teetotallers. We have women who are abstinent right from before pregnancy through pregnancy.

CHAIR: Who have made a considered choice to abstain?

Prof. Halliday : Yes, we presume that. Then we have a number of women drinking low, moderate and high levels pre- and post-aware. We have this question that we think has yielded some really important data, which is what we call our special occasion question. Again, this came out of the focus group testing, where women said that sometimes they just had a special drink, and it has given them permission to put that into the questionnaire and it has revealed a lot of very important information. I will come back to that in a minute.

The children are going to be followed up at one and two years of age, and we are using some new research ideas to do this. In one-year-olds we are going to be taking 3D photographs of their face. This is looking for subtle neurological signs because, as I am sure you know, foetal alcohol syndrome has these rather major facial effects, but there has been some preliminary work coming out of the States and other places that show there may be subtle signs of facial dysmorphology.

CHAIR: So it is a continuum?

Prof. Halliday : It could well be. We have got some data to compare what we are seeing in the different exposure groups. We will have the data on the non-exposed to those that have had varying levels of exposure. So we will have enough statistical power to look at differences in average widths of this and heights of that. That is a novel and early potential sign of foetal alcohol spectrum disorder.

CHAIR: You said there is some US work in the facial recognition or in this area as well?

Prof. Halliday : I think there were two studies—I am straining my memory a bit—and that one was American. It gives some average measures in children that have been exposed to high levels.

Ms Muggli : Certain points in the face were measured. That showed that even with low to moderate levels of alcohol they found there were some differences in the facial measurement, in the bridge here and the philtrum here. This is quite experimental work. At the children's hospital they have a very large normative database, a normal population base database of this 3D photography. They have this resource that we can compare it to a population based facial measurement database, not just our own cohort.

CHAIR: Unwashed, sort of?

Ms Muggli : That is right. So we would be able to compare it to a large children's facial database as well. It is quite experimental but it has the potential to possibly show some small differences as well.

Prof. Halliday : So we bring the women in with their child at one year of age. We have been funded. This is not cheap. It is about $150 per photograph, but that has been part of the funding. Women have expressed great interest in doing that, so we believe that is going to be an important outcome to look at. At two years of age, we are bringing in the same children for the three Bayley Scales of Infant and Toddler Development, and the Infant/Toddler Sensory Profile. Some are arguing that this is too early to pick up neurodevelopmental problems, but the people that we work with in child psychology at the Children's Hospital use this a lot and they believe that it is very predictive.

CHAIR: It is a peer reviewed, well-respected tool, is it?

Prof. Halliday : Yes, they are real experts in this area. This is their collaborator, Chief Investigator Peter Anderson's field of expertise and he will be training up to psychologist to do this testing specifically and they are dedicated to that task.

Ms Muggli : We are looking at cognition, behaviour and social adaptation.

Prof. Halliday : We are also collecting biosamples at birth so we will have placenta, cord blood and the cheek brush swab—not on all the children; we are trying to get 35 in each exposure group. This is to do epigenetic testing, which is a very novel approach that is growing all the time. We started off just looking at a couple of particular genetic regions—

CHAIR: So epigenetic—below the genetics?

Prof. Halliday : It means sitting on top of. It is changes in genetic action that is mediated by non-DNA activity.

CHAIR: But doesn't 'epi' mean below?

Prof. Halliday : Epidermis—on top of the skin; it means on top.

CHAIR: Epicentre—it means below.

Prof. Halliday : I am not sure of the Latin derivation; I have forgotten my Latin. It could be below—it is around the DNA—

CHAIR: You are right; it is above.

Ms Muggli : It influences if the gene is activated or not. It does not change the actual gene but it influences if the gene becomes active or stays inactive.

Prof. Halliday : There is quite a lot of animal evidence of epigenetic actions, which is the methylation of the DNA coding regions that is altered in the presence of alcohol. We are specifically going to look at some of the areas of the genome where this was thought to be occurring. We are now going to, as the technology has progressed a bit since we started, be able to do more sophisticated epigenetic analysis, so we are collecting enough samples to do that. You need different tissue types to do that effectively, so that is why we are getting placenta, cord blood and cheek. We are also doing genetic analysis, looking at the alcohol hydrogenated, genes and others of the mothers. We have collected cord blood from the mothers, so we have got biomarkers in there as well.

CHAIR: Is it costly to do the testing? Are some parents not keen to do the testing? Why not have all 1900?

Prof. Halliday : The 35—that is a very good question. It is very expensive to do epigenetic testing.

Ms Muggli : It is also difficult to be able to attend all the births and it is very costly.

Prof. Halliday : There are 35 in each of these eight exposure groups, and so we have got the midwives on call going to the delivery suites and picking up the samples. Women get a bit upset if we have missed their births.

CHAIR: It is a bit hard to schedule them in.

Prof. Halliday : It is a bit. We have just got some extra funding from the McCusker foundation in WA to help fund this on-call part of the project. That is something that has emerged since we got the NHMRC funding and which has been very exciting for us.

I suppose there are three points—do you want me to keep talking like this?

CHAIR: Yes, please. This is the best introduction we have ever had.

Prof. Halliday : Is it?

CHAIR: You are answering all of our questions before we get to ask them.

Prof. Halliday : Probably our most important point that we are dealing with is the fact that many pregnancies are unplanned. Women are drinking before they recognise they are pregnant and, obviously, better pregnancy planning would assist in reducing exposures in this pre-aware period. Reducing the rate of risky drinking in the whole population would also contribute to that, but the reality is that there were about 50 percent of women in our study who were drinking before they knew they were pregnant, drinking in the pre-aware period.

CHAIR: Does that mean that 50 percent of pregnancies are unplanned?

Prof. Halliday : Yes. We assume; there has been data about that.

Ms Muggli : There are prevalence studies in Australia that show that around 47 percent of pregnancies are unplanned, and we are finding in our most current recruitment—in the last 12 months—of pregnant women that that is still the same. So our exposure data on drinking is showing that that is exactly what is happening with women. Because we are separating the exposure periods into, 'Did you drink before you knew you were pregnant?' and, 'Did you drink when you found out you were pregnant?', you can see the pattern that many women stopped drinking when they found out they were pregnant. Many women did not drink before then, but it is exactly that situation of planning versus accidentally falling pregnant.

Ms SMYTH: Do you think those figures, and more broadly, are an understatement, given that you are asking women to think about what has happened previously and answer questionnaires? Do you sense that the data that you are likely to derive will be quite representative but, perhaps, still an understatement because some women will be aware that it is regarded as socially undesirable that they not drink and might be a bit revisionist about their consumption?

Prof. Halliday : Certainly people have made that sort of commentary around asking these questions about alcohol. But we would like to think that, because of the way this has been designed and because of the way that the research nurses approach the women—they are saying, 'We're not here to monitor what you are doing; there is no judgment aspect to this; we are not looking for risky drinking'. People who are drinking low and moderate levels of alcohol and who have been drinking accidentally are very keen to get answers to this question because, at the moment, there are a lot of women and a lot of health professionals out there who are obviously very concerned about this issue.

Ms SMYTH: You mentioned special occasion drinks.

Prof. Halliday : Special occasion drinking is revealed a lot.

Ms SMYTH: Is that revealing a higher proportion of people?

Prof. Halliday : Yes. It is revealing high levels of drinking in that pre-conception period, the pre-awareness period.

Ms Muggli : It allows women to be really honest about what they are doing. Most other studies ask about their usual drinking and you have to put down whether you drink one glass of wine a week, or they may have less than one glass of wine a week. But if you have had only a Christmas drink or a party drink, a drink when you were upset or even you had a drink or two, you cannot fit that into that sort of category and you might leave that out altogether. We did focus groups with women and they said to us exactly that: 'We can't put that down so we leave it out.'

CHAIR: But the placenta does not, so it is a brilliant investigative tool.

Ms Muggli : We thought that maybe that is one of the reasons why many studies come up with conflicting results. Some say that it has no effect, some say that it is protective, or some say, 'We have detrimental results.' We thought we might give them that extra opportunity and ask: 'Did you drink on any special occasion, say at a party or when you were upset?'

CHAIR: Or happy.

Ms Muggli : Yes. We found women saying, yes, they did drink. We do not know what to make of that yet; obviously we are not analysing the results.

Prof. Halliday : But they are a particular exposure group that we will be looking at with great interest.

Ms Muggli : We are categorising them separately.

Prof. Halliday : In thinking around this point it is worth mentioning what happened with folate and how difficult it has been to get women to take folate before pregnancy and in the first three months. There have been huge health promotion campaigns to get women to take folate to prevent neural tube defects. Primary prevention of birth defects by asking women to do something is challenging. We could learn a lot from the folate story, and we could probably learn even more from the listeria story, which has been successful but does not have the pre-pregnancy—

CHAIR: Is that from cheese?

Prof. Halliday : Yes. So I think that what we want to get across is that this population is always going to exist. The strategies need to be put in place to educate people and health professionals in the much broader community so that people of child-bearing age are thinking about this, not just people that are considering that they might get pregnant. I think that is what the folate study did. They had these two populations—those who were planning a pregnancy and those who were not but could get pregnant. I think that, if anyone is developing educational campaigns, they should take into account those two populations. That is, I suppose, one of the main messages we want to have put into the equation. It is all right to say, 'Zero tolerance—no drinking is the safest option.' We would totally agree with that, but it is not the reality. So what are we going to do about that?

CHAIR: You have 1,900 women that have already engaged with health services.

Prof. Halliday : Yes.

CHAIR: There would be people who have a different process in terms of having birth that do not engage with the health services in the prebirth process.

Prof. Halliday : Early on, yes—not many. There are some that do not turn up until 20 weeks. They do not get in to have pregnancy care in that first few months, for sure, but I think the majority—

CHAIR: It is just hard to find them because they are not engaged. Where do you go looking for them?

Prof. Halliday : I would suspect that that is a small proportion. I think the biggest challenge is around getting information around pre-conception to everyone. I do not think there is a particular risk group. I suppose they could be the people that are engaging in more risky behaviours.

CHAIR: Yes, that is what I was thinking—or people who are not aware of our health system. There might be some cultural groups or ethnic groups that are not aware of our health system.

Prof. Halliday : There is certainly a lot of data out there on the number of women having babies, say, in Victoria through our Department of Health mandatory collection of births. There would be fairly good information about whether they have sought care and what proportion have sought care. In some study I did years back we found, I think, that it was only about 20 per cent that had not accessed care before 20 weeks gestation. So the majority—

CHAIR: Yes.

Prof. Halliday : I think there is this idea about the conflicting results around low and moderate levels of drinking. You may well have seen reports in the press yesterday about the study coming out of Denmark. If you look carefully at that, there is some—

CHAIR: What paper was that in?

Prof. Halliday : It was in the British Journal of Obstetrics and Gynaecology, and it hit all the press yesterday, saying that low and moderate levels do not lead to cognitive problems in five-year-olds. I was in Adelaide till midnight, but I just managed to have a look at it online before I came in, and it looks like they only had 50 per cent participation among the people that they wanted to participate. Anyway, there are methodological problems in a lot of these studies, and they are all conflicting, so I think the story is still not fully told and there is a lot more research that needs to be done to try to address what are the true risks associated with low and moderate levels of drinking, which is what we are focused on.

The third and final point is this idea that we are dealing with a spectrum of severity with foetal alcohol spectrum disorder and the possibility of early detection of an affected child to allow for appropriate intervention. I guess that we would like to think that our study has the potential to pick up particular risk factors in the mother—individual risk factors that might put one woman at greater risk than another. It might be her genetics, her body mass, her family history or what she drank as a teenager. So we are hoping that we will be able to get a more targeted message out there which people might take a bit more notice of. We also hope that this clinical review we are doing, with the 3-D photography, might lead to some kind of early appropriate intervention.

Ms Muggli : Identification.

Prof. Halliday : Yes. So I think they are the main points in relation to our study that are relevant.

CHAIR: Ms Smyth touched on the social expectation about pregnancy and the behaviour of women. There is, as Ms Smyth suggested, a wowserism in our society about pregnancy in particular—a higher expectation of change in the behaviour of women who are pregnant than of the husbands of those women. When you ask women about their behaviour, when they fill out the questionnaire—even though it is anonymous—there might be that inclination to tell the story they think people should here.

Prof. Halliday : It is not anonymous, for a start.

CHAIR: It's not anonymous?

Prof. Halliday : No. We follow these people up for two years.

CHAIR: But we are not going to hear of Jane Smith of such and such a place and how she drank?

Prof. Halliday : Oh, heavens no.

CHAIR: So it will be anonymous data.

Prof. Halliday : The privacy issues around it are enormous and are addressed very carefully. The ethical issues and the committees we have had to go to! We are working at six sites, and you have to go through an ethics committee at each. There is anonymity to the general public. When we come to write this up it will all be aggregate data. I really think one of the most important things about this study is the fact that we have developed questions that we think women are answering well. It is not like lots of studies, whereby people are just suddenly approached in a clinic or somewhere and asked, 'How much did you drink in pregnancy?' We have put in an enormous amount of work to cope with that potential problem.

CHAIR: Yes. And I am sorry I am asking this when you have done all that hard work, but I just wanted to—

Prof. Halliday : No, I think we are going to have to keep justifying it, obviously. We have not been out and talked about his much yet, so I think it is early days, and we have a lot of work to still do.

CHAIR: And there is camaraderie, because of the questions being asked—you are not going through Customs; the relationship is different. It is a health professional who is asking the questions.

Prof. Halliday : They sit in a setting that is very private. They fill out the questionnaire without anyone seeing what they are writing, and it just has an ID number on it. The person who has recruited them is not actually involved in that process. We have a kit that people can look at in their own time, and she just leaves that with them. They read about it and give consent, and then they either fill out the questionnaire while they are waiting in the clinic or take it home and fill it out.

Ms SMYTH: I am interested in revisiting that question of epigenetic issues and the kinds of things you are expecting to come out of some of that research. You mentioned that there are some things that are, I suppose, at this stage known in terms of epigenetic consequences for the child, as well as things you are looking at in terms of the mother. I was just wondering what the next thing is that is being focused on, or whether there is research that you are particularly interested in around new epigenetic consequences from alcohol consumption pre-pregnancy and for the foetuses as a result of pregnancy.

Prof. Halliday : That is a very good question. The developmental origins of health and disease is the buzz thing now. What happens in utero and early development can have longer-term impacts on people's health. So it is not just about what is happening to the baby and the young infant; it is about people's cardiovascular disease, diabetes and so on. It is very well recognised now that, if a baby is born with a low birth weight, that correlates with later adult disease. What causes the low birth weight may well be epigenetic factors—methylation errors on the growth factor genes and placental genes. There is so much research going into this area, and not much is known yet. It is still early days, but certainly the epigenetic group that we are working with is going to be looking for changes in methylation patterns that relate to the different exposures. They might see a different methylation pattern in people who have low exposure compared with those who have a higher exposure. Then they can look to see if those methylation changes relate to particular genes that might be influential in growth and development

The study that comes to mind came from a group in Sydney with Emma Whitelaw. They looked at mice. The agouti mice have a particular coat colour, and their coat colour changes if there are epigenetic methylation changes. So she gave some of the mice alcohol and some of them no alcohol and looked at their coat colour changes, then looked at the foetuses of the ones where the coat colour had shown those methylation patterns that were different. They had distinct changes in their skull shape. I can picture those. So they were showing there were epigenetic errors, and that was associated with the skull shape.

Ms SMYTH: I think it is probably of particular interest to the committee because we have had evidence about the long-term generational impacts for particular communities.

CHAIR: To touch on that, though I know you came to talk about the AQIS study—and you do not have to answer this question at all—a hotel has a duty of care to the people it serves alcohol to, and there have been court cases on how far that duty extends. If an obviously pregnant woman is standing at the bar and orders one drink, one would assume they are allowed to be served. A responsible service would not prevent them being given one. Would you like to comment on when they should not be given a second, third, fourth, fifth, sixth or seventh drink?

Prof. Halliday : You do not stop very pregnant looking people who walking down the street smoking, do you? You do not stop them and say, 'Sorry, you shouldn't be doing that.'

CHAIR: There is no duty on a retailer for that, but there is a duty—

Prof. Halliday : Do they sell cigarettes to pregnant women?

CHAIR: As I said, you do not have to answer the question.

Prof. Halliday : I do not think we live in a society where that kind of policing is expected of civil—

CHAIR: I am sorry, but there is actually a duty.

Prof. Halliday : Is there?

CHAIR: Arguably there is not, because the foetus does not legally exist as a human being.

Prof. Halliday : What do you think?

Ms Muggli : He is saying that they are not allowed to serve alcohol to inebriated people?

Prof. Halliday : No, you are not allowed to serve to inebriated people.

CHAIR: You are not, but that is probably a question for another day.

Ms Muggli : So he has a duty not to serve alcohol to inebriated people. Unless it is written into the law like it is with inebriated people, he cannot refuse alcohol to pregnant women.

CHAIR: I apologise for asking.

Prof. Halliday : I do not mind at all. It is probably good to think about these things.

CHAIR: And maybe at the end of your studies you might be able to answer that question.

Ms Muggli : It is an ethical debate.

Prof. Halliday : That is what it is: an ethical debate.

CHAIR: We might have some empirical data in three, four or five years time.

Prof. Halliday : And it is for the lawmakers to change the law, I guess. But other than that it is an ethical debate and depends on where everyone stands with their moral opinion.

CHAIR: Yes.

Ms SMYTH: Forgive me if this was alluded to in your introductory remarks, but I wanted to get a sense of the method of selection of those who are participating, the demographics and how you have gone about ensuring that those are as representative as they can be in a study of this kind.

Prof. Halliday : We are using six public hospital sites. One might think, 'Where are the private patients?' We recognise that socioeconomic status is not an issue in this context. It is not going to alter the effect of alcohol on the foetus. So we chose to work at these sites because we could get large numbers—

Ms Muggli : And there is a system for ethical approval in place as well. There is no clear system for ethical applications and approval for the private system as there is in the public system. It is easier for us to go through a chain of approvals and everything in the public system.

Prof. Halliday : But it was a very deliberate process of recruitment and we had to think carefully about whether we were missing an important group of people. I think we will have a range of people of different socioeconomic status within that anyway. Lots of people from all walks of life use the public hospital antenatal setting.

CHAIR: And do you have the capacity to have some partly paid in public hospitals in Victoria?

Prof. Halliday : Yes.

CHAIR: So for some people it is a private hospital experience in a public hospital.

Ms SMYTH: I would certainly be fascinated by the outcomes of the research. I do not know whether it is possible for us to see some of the questions—

Prof. Halliday : We will leave you the kit—

Ms SMYTH: Great.

Prof. Halliday : as long as you do not hand it around—

CHAIR: No, it will not be a public document.

Prof. Halliday : No, definitely not. Obviously there is a lot of IP in here.

Ms Muggli : We have got some study brochures on the site here and the material that we hand out to the participants including the questionnaires.

CHAIR: That will be a confidential submission. Thank you very much and good luck. We hope to sit down again in five years time or however long—

Ms Muggli : Thank you for letting us present.

Prof. Halliday : We look forward to the outcome of all of this.