Thursday March 15 2012
Can our time in the womb really 'programme us to be fat'?
The Daily Mail today put a dampener on the approaching Mother's Day by telling us that it is our mum’s fault if we are “losing the fight against the flab”. The newspaper said that a new study has shown that our mother’s lifestyle may leave us “programmed to be fat”.
Thankfully for our relationships with our mums, the research does not actually say this. The study in question aimed to investigate whether DNA modifications in early life are linked to our size and body composition in later childhood. The modification in question does not change the underlying genetic code but it does decreases the amount of proteins the body makes using the instructions in our genes.
After stringent testing the researchers found only one significant link, between the modification of one gene and height rather than weight. None of the links between DNA modification and body mass index (BMI) stood up to stringent testing, and even the study’s authors note the study cannot prove that the DNA modification at birth definitely directly affected height. For the time being, it is probably best to work on improving our health by addressing the lifestyle factors that we can change.
Where did the story come from?
The study was carried out by researchers from Newcastle University and other research centres in the UK. It was funded by the Biotechnology and Biological Sciences Research Council, Special Trustees of Newcastle Hospitals, the UK Medical Research Council, the Wellcome Trust, the University of Bristol, Asthma UK, the medical nutrition firm Nutricia UK, and the pharmaceutical company Novo Nordisk.
The study was published in the peer-reviewed open access scientific journal PLoS One.
The story was covered by articles from the BBC News and the Daily Mail, which both featured headlines focusing on how factors in the womb might influence obesity. However, the study found only one outcome to be statistically significant – a link with height.
The BBC did state that only one link stood up to rigorous testing but did not say this was a link with height rather than BMI or body fat levels.
The study did not look at obesity itself, rather it looked at BMI and fat mass. It did not classify the children into weight categories such as ‘overweight’ or ‘obese’ in its analyses, nor did it look at ability to lose weight, as suggested by the Daily Mail’s headline about ‘losing the fight against the flab’.
Both sources mention factors that might influence these DNA modifications in the womb, such as diet, exercise, smoking or drinking alcohol. However, it is important to note that the study did not look at why the DNA modifications might have occurred, so they cannot be attributed to these or any other factors based on this study.
What kind of research was this?
The body uses DNA as the blueprint for producing a range of important proteins. Sections of DNA produce individual proteins are known as genes.
In this study, researchers looked at a type of DNA modification called ‘methylation’, where a chemical compound called a methyl group becomes attached to the outside edge of a DNA strand. This process does not change the underlying genetic code, but it does reduce the amount of protein the body produces using nearby genes. It is one of the ways the body can control how much of each protein is produced.
The study looked at whether the levels of DNA methylation shortly after birth had any relationship to body size later in childhood. To examine the issue it analysed information collected in two cohort studies: the Preterm Birth Growth Study (PBGS), and the Avon Longitudinal Study of Parents and Children (ALSPAC). The level of methylation after birth was calculated using analyses of umbilical cord blood.
What did the research involve?
The researchers initially wanted to identify which genes might be related to BMI composition in childhood. To do this they looked at a group of 24 children in the PBGS study whose BMIs had been measured when they were aged between 11 and 13 years (average 12.35 years). They then looked at how active various genes were in the children with the highest BMIs and those with the lowest BMIs. They did this to identify genes that could be affecting BMI, to target these genes for investigation in the next phase of the study.
A selection of the genes identified through this first phase of the study were then assessed in a second phase of the study, to see whether these differences in gene activity in later childhood, and changes in BMI, might be related to the level of DNA methylation that was in place from the time of birth. The genes selected for this second phase were selected because they could be assessed with the technology the lab had available.
In this second part of the study the researchers looked at the levels of DNA methylation in blood collected from the umbilical cord of 178 babies taking part in the ALSPAC study. These babies had been followed up through childhood, and had data on their body composition, including BMI, fat mass, lean mass, and height at about age nine (average age 9.8 years). Methylation was measured in up to three places within the selected genes.
The researchers analysed whether the level of methylation of these genes at birth was related to body composition at age nine.
What were the basic results?
In the first part of their study, looking at children aged about 12 years, the researchers found that 514 genes had different levels of activity in those with higher BMIs and lower BMIs. From the genes they identified they selected 29 of these genes to look at in the second part of their study.
They found that four of these 29 genes were not methylated in the 178 cord blood samples tested, so they did not study these genes any further. The methylation levels of nine of the remaining genes were each related to at least one measure of body composition at age nine.
However, once the researchers took into account the number of statistical tests they had performed, the methylation level of only one gene was found to have a statistically significant association with a body composition measure. The gene in question was called ALPL, and higher levels of methylation of this gene in umbilical cord blood at birth were associated with being shorter at age nine. Each 1% increase in DNA methylation of ALPL was linked with a 0.15% decrease in height at age nine.
How did the researchers interpret the results?
The researchers conclude that the patterns of DNA methylation in cord blood showed some association with body size and composition in childhood. However, they note that their study is not able to say whether the changes in DNA methylation seen actually cause the differences in body size and composition in childhood, and further research is needed to investigate this.
In recent years there has been a lot of scientific and public interest in how events early in the womb may relate to our health in later life. In this vein, the national press have picked up on this study, which investigated whether DNA modifications during early life might impact on body size and composition in later childhood.
While these press narratives have given the impression that this study linked particular environmental exposures in the womb such as maternal smoking and drinking can lead to DNA modifications and later obesity, this is not the case:
- The news sources mention factors that might influence these DNA modifications in the womb, such as the mother’s diet, exercise, smoking, or drinking alcohol. However, it is important to note that the study did not look at how or why the DNA modifications might have occurred, so they cannot be attributed to these or any other factors based on this study.
- The study did not look at obesity, rather it looked at BMI and fat mass. It did not classify the children into weight categories such as ‘overweight’ or ‘obese’ in its analyses. It also did not look at whether participants had difficulty losing weight, as suggested by the Daily Mail’s headline about why some people may be ‘losing the fight against the flab’.
- The study was relatively small, and only looked at methylation of a small number of genes. Only one association between methylation of one gene at birth and height remained statistically significant after stringent testing. However, the authors themselves note that their study cannot prove that the DNA methylation pattern at birth caused the differences in height seen.
- None of the links between DNA methylation at birth and BMI or fat mass remained statistically significant in stringent tests. This means that they cannot be said to be real associations, as they may therefore have just occurred by chance.
If the results of the current study can be confirmed in other studies, researchers will need to try and work out if the link is causal. Even if the link is confirmed and found to be causal (and it is a big IF), it is not clear what, if anything, could be done to alter this.
For the time being, we are probably best working on improving our health by addressing the factors that we know we can change, rather than blaming our Mums for making us ‘programmed to be fat while in the womb’. Not a nice sentiment in the run-up to Mother’s day.
Analysis by Bazian