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AQUA Study Updates

Almost 1600 Victorian women participated in AQUA from early in their pregnancy, many of whom drank varying levels of alcohol before they realised they were pregnant. Participants provided detailed information at three stages of pregnancy on demographics, obstetric history and pregnancy complications, diet, use of folate, health and lifestyle, and family/personal drinking history.

Samples from placenta, cord blood and cheek brush swabs were collected to test for genetic and other markers thought to be important indicators of an alcohol effect. Over 500 babies had a 3D photo taken of their face at 12 months looking for potential early subtle signs of alcohol effects. Then, at two years of age, mothers again brought their children to the Royal Children’s Hospital for a comprehensive developmental assessment, done by a trained psychologist. At both time points, all AQUA mothers also reported on their baby’s development and aspects of family environment.

For example, a small 100ml glass of wine or a stubby of mid strength beer are equivalent to 1 standard drink. A glass of champagne would typically be 1.4 standard drinks. ‘Low’ level pregnancy alcohol consumption was classified as no more than 2 standard drinks per occasion or up to 7 drinks per week. ‘Moderate’ pregnancy drinking was 3-4 standard drinks per occasion, and still a maximum of 7 per week. More than 7 drinks per week was classified as ‘high’ level pregnancy drinking and if a woman consumed 5 or more standard drinks at a time, this was considered to be a ‘binge’ episode. 

What have we found?

Of the 1570 women who completed all this information, 41.3% did not drink alcohol at all while they were pregnant. Almost one third drank alcohol in the first trimester only, most of whom stopped as soon as they found out that they were pregnant. A similar number of women drank alcohol at some level throughout their pregnancy, around half of whom never drank more than at low or moderate levels.

Women who drank alcohol throughout their pregnancy tended to be in their early to mid-thirties, smoke, have a higher income and be well educated.

Overall, almost one in five women (18.5%) who had binge episodes, told us that this was on a special occasion.

Women who told us that they had their first alcohol intoxication before they were 18 old were much more likely to drink in pregnancy and have binge episodes early in pregnancy.

What does this mean?

It is important to know about these common drinking patterns. It helps researchers, health professionals and policy makers to develop more meaningful and directed health messages on the importance of abstaining from alcohol in pregnancy. We are about to publish our findings in a public health journal.

What will we do next?

We will be using our detailed pregnancy alcohol consumption patterns to look at any possible effects on the child. For example, we are interested in low level drinking throughout pregnancy and early pregnancy binge drinking (before the mother knew she was pregnant), because these patterns are quite common and there are many unanswered questions about possible harmful effects of this.

We plan to compare birth outcomes, such as birth weight, facial shape at 12 months of age and child development at 12 months and two years. We are also looking to see if different pregnancy alcohol consumption patterns are related to the mother’s genes or affect how some genes in the child function.

518 AQUA study mothers brought their child to the Royal Children’s Hospital to have a 3D photo taken around the time of their first birthday.

Our main outcome of interest in terms of facial imaging was to see whether or not different patterns of alcohol consumption in pregnancy are associated with the development of facial shape.

What’s new in 2017?

We have now examined the images on the computer and compared the facial shape of children whose mothers consumed no alcohol at all while pregnant with those whose mothers consumed some alcohol. 

We saw subtle changes to the mid-face – the nose, lips and eyes – of babies who were exposed to any amount of alcohol from the first trimester of pregnancy. The changes were only small, less than 2mm, and are not visible to the naked eye, seen only by cutting-edge computer modelling (see picture). This is an interesting finding because children who are diagnosed with Fetal Alcohol Spectrum Disorder have larger visible changes in these same mid-face regions.

Our findings show that when analysing the detailed images in our study, any alcohol in pregnancy, even low amounts can subtly influence how the face is formed in the womb. We have now published these findings in a scientific journal so that other researchers working in this area can benefit from this new knowledge.

What does this mean?

Our study shows that alcohol in pregnancy can subtly influence the way a baby’s face is formed in the womb. This does not mean that unborn babies have been harmed if the mother consumed some alcohol while pregnant. We don’t know if the small changes in the children’s facial shape are connected in any way to differences in their development and we plan to look at this as the children grow. 

What will we do next?

We are now looking whether or not the changes we observed in facial shape are associated with the children’s development at age two. We have also applied for funding to follow the children up again as they turn 6 and 7 years old to check in again with their development as they enter school-age and more complex skills are required.

What else have we found when studing the children's facial shape?

While doing this research we found that even though it is not as obvious as in older children, the faces of boys look different from the faces of girls, even at 12 months. The difference was mainly seen in the forehead and around the cheeks (see picture). This had not been documented before and we published this finding in a scientific journal in 2016.

85% of mothers in the study provided extensive information on their child’s health and development on the questionnaires sent at one and/or two years of age. 564 mothers also brought their two-year old child to the Royal Children’s Hospital for a clinical developmental assessment, which looked at thinking, reactions, learning, recognition of sounds and words, communication and body movement. A child psychologist did these assessments.  

What have we found?

Many aspects of the mother’s pregnancy, the child’s early health and their family environment influence a child’s learning and behaviour, especially in the early years. We looked at all these factors carefully and found that the development of the two-year old AQUA children was the same whether they were exposed to alcohol before birth or not. There were some differences in one aspect of toddler behaviour. Mothers of children exposed to binge drinking early in pregnancy were more likely to report that their child used disruptive behaviours, such as temper tantrums, when trying to cope with stressful situations.

What does this mean?

We think that follow up to two years may not be long enough to detect any differences in child development, as they may not be apparent until the children start school and have to develop more complex social, academic and physical abilities, like fitting in with their peers and class room routine, physical education, or literacy and numeracy skills. 

Blood Samples

Many AQUA participants also gave us permission to collect samples from their placenta, umbilical cord, or their baby’s cheek cells. Our study midwives attended as many births as possible and mothers also sent us cheek swabs from their baby where we missed the birth. We have over 200 placenta and cord blood samples and around 730 cheek swabs from babies in the AQUA study. In the cheek swabs of babies, we have been studying a process called DNA methylation. DNA methylation regulates whether or not particular genes are being used (i.e. switched on). This is important in growth and development as not all the thousands of genes we have are always active in every cell of our body all of the time.

What have we found?

In mothers so far, we looked at 59 DNA coding changes in and around genes that are involved in metabolising alcohol and are in the process of analysing whether any of them might have influenced the drinking patterns of pregnant women. For example, we found one genetic marker more likely to be present in women who feel the effects of alcohol slowly than in women who feel the effects quickly. We are planning further study to understand what this means.

In the placenta of babies, we have studied the overall methylation across the genome to see if levels might be changed by alcohol consumption. We found that in boys, overall methylation levels were different when alcohol had been consumed, but in girls there was no difference. This means that alcohol exposure changes the activity of some genes in the placenta for boys. We now need to look at these findings more in-depth, because changes in gene activity can influence later health and development. 

What will we do next?

We have a lot of work left to do in our study of genes and DNA methylation in mothers and babies. We aim to include quick or slow metabolism of alcohol when we look at alcohol effects on the child, but we have not finalised which genes might be important. In children, we now plan to study the same genes we looked at in mothers, because the baby also helps to clear alcohol from their body, especially later in pregnancy when their organs are quite developed. 

We asked all participants about their diet with a Food Frequency Questionnaire and also if they were taking any vitamin supplements, such as folate, and when they started taking these. We will take this information into account when we look at any possible effects of drinking alcohol on the baby’s development.

What have we found?

Over half of women were taking supplements before pregnancy and almost all women took some when they were pregnant (91%). Mostly these were multivitamins, but many women also took Vitamin D and/or iron later in pregnancy. Women who planned their pregnancy were more likely to take pregnancy-specific multivitamins or folate preparations in the 3 months before they became pregnant. We also took into account any vitamins and minerals from the women’s diet as well as any supplements taken. Here, we found that even though many women increased their iron intake over the course of their pregnancy, 70% of pregnant women did not reach the recommended dietary intake for this nutrient by the third trimester.

What will we do next?

We have published these findings in a public health nutrition journal because it is important for midwives and doctors to know whether pregnant women consume enough micronutrients for their health and wellbeing, as well as that of their baby. We will further look into the diet of pregnant women and compare this to the Australian Dietary Guidelines recommendations to better understand what women in Australia eat. This will give us important information to take into account when looking at possible negative effects of pregnancy alcohol consumption on the child (as some nutrients and diet types may lessen any harm). It will also help target healthy-eating programs to positively change food choices.