Wednesday July 20 2011
The study did not look at how the babies behaved as they grew up
“Being stressed in pregnancy genetically programmes the developing baby to be more susceptible to anxiety and behavioural problems in life,” reported The Daily Telegraph.
The news story is based on a very small study of 25 adult women and their children aged between 10 and 19 years. It found that children of women who had been subjected to domestic abuse during pregnancy were more likely to have a specific chemical modification of a gene that codes for a protein involved in response to stress. This chemical modification, called methylation, is a common mechanism used by the body to regulate how active genes are.
As noted, this is a very small study and it does not provide robust evidence that maternal stress during pregnancy can influence the genetics of the offspring. The study looked at the DNA of blood cells; it is not clear whether these changes would also be found in other cells of the body, such as nerve cells in the areas of the brain that influence anxiety and behaviour.
Although the media reported that these findings suggest that children with the methylated version of the gene were more likely to have behavioural problems or are less likely to be able to deal with stress, these suggestions are not supported by the research. The study did not investigate whether the children had any behavioural problems or how they responded to stress.
Where did the story come from?
The study was carried out by researchers from the University of Konstanz and was funded by the German Research Council (DFG).
The study was published in the peer-reviewed medical journal Translational Psychiatry.
The newspapers generally overstated the conclusions of this research by suggesting that it showed that the unborn children of mothers who are subject to domestic violence are “genetically programmed” to have behavioural problems and to be susceptible to stress. These suggestions are not supported by the research, which did not look at whether the observed genetic changes were related to the children’s behaviour or their response to stress.
What kind of research was this?
The authors report that previous research has found an association between prenatal exposure to maternal stress (for example, due to food shortages or natural disaster) and later behavioural and emotional problems in the child. They say that one way that this link could occur is if maternal stress in the womb leads to changes in the activity of genes relating to behaviour and stress response in the offspring.
The current study aimed to investigate whether unborn children of mothers who are subject to domestic violence have genetic changes that could affect the activity of genes involved in stress response. The researchers looked at a chemical change to the DNA called methylation, which reduces the activity of genes. The pattern of methylation can be passed on in the DNA from parent to child, but can also be modified in cells during their development.
They aimed to look at methylation of a gene encoding a hormone receptor (called the glucocorticoid receptor) in children aged 10 to 19, and whether this was affected by their mother’s experience of domestic violence in and around pregnancy. The glucocorticoid receptor binds to the stress hormone cortisol.
What did the research involve?
The study recruited 25 mothers who had at least one child aged between 10 and 19 years. Both the mother’s and child’s DNA were analysed from blood samples to assess the methylation status of the ‘promoter’ area of the GR gene that controls the gene’s activity. The methylation status of the promoter region affects the activity of the gene.
The mothers were interviewed about their exposure to intimate partner violence (IPV) (a marker for stress) at three separate times, each focusing on a different period of their lives: before, during and after pregnancy. For the periods before and after pregnancy, the participants were asked to report acts of domestic violence whenever these happened.
IPV was defined as “any behaviour within an intimate relationship that causes physical, psychological or sexual harm to those in the relationship”. The interview assessed the degree of domestic violence experienced by the mothers in four areas: severe combined abuse, physical abuse, emotional abuse and harassment. The frequency of the abuse, ranging from daily to never, was also assessed and the measures combined into an overall score for exposure to IPV.
The researchers compared whether there was an association between exposure to IPV and the presence of methylation in either the mothers or the children.
What were the basic results?
Of the 25 mothers who were interviewed, three were exposed to IPV before pregnancy, eight during pregnancy, and nine in the period following pregnancy. Some women experienced IPV during more than one period, and not all women provided information on IPV for each time period.
The methylation status of the GR promoter was assessed in all 25 women and in 24 of the children. The researchers made the following findings:
- There was no association between the mother’s GR promoter methylation status and that of her child.
- There was no association between a mother’s exposure to IPV and their own GR promoter methylation status.
- There was no association between maternal exposure to IPV before or after pregnancy and the presence of methylation of the GR promoter in the offspring.
- There was a significant association between maternal exposure to IPV during pregnancy and the presence of methylation of the GR promoter in the offspring.
- The authors tested the influence of 15 other variables, including mode of birth and maternal marital status on the methylation status of the GR promoter in the offspring but did not find any significant relationships.
How did the researchers interpret the results?
The authors conclude that “maternal stress-induced changes [in the womb] can have an impact on the methylation pattern of the children’s GR gene”.
They also highlight an important limitation of their study - that their data represents associations and “cannot prove a causal relationship between changes in methylation and adverse experiences”. The authors also point out that it is still unclear whether methylation in blood cells reflects methylation in the brain cells, specifically in areas of the brain affecting stress and behaviour.
The study looked at whether there is an association between exposure to intimate partner violence (IPV) in and around pregnancy and the presence of methylation (a chemical change that affects gene activity) in the glucocorticoid receptor (GR) gene in either the mothers or their children. The glucocorticoid receptor is involved in response to the stress hormone cortisol.
While this study has shown some association between exposure to IPV in the womb and methylation, there are significant limitations:
- The researchers looked only at the methylation status of the GR gene in blood cells, rather than looking directly at brain cells. The authors acknowledge that it is not clear whether the methylation status of the gene in blood cells is linked to its methylation status in the brain.
- The study did not investigate whether children with different methylation levels or those exposed to IPV in the womb were able to deal with stressful situations or exhibited any different behaviour from those who did not. One of the news articles about this study suggested that the investigators had assessed the behaviour of the children, but this was not reported in the main publication that was appraised by Behind The Headlines. Hence, the effect of these small-scale genetic changes on adult behaviour and ability to deal with anxiety is not known.
- Mothers were asked to recall events of IPV 10-19 years in the past. Given the amount of time that had passed since the event, there may be some error in accurately reporting the severity and frequency of the IPV, and some mothers may have been unwilling to report IPV events.
- This study looked at extreme levels of stress associated with IPV. This level of stress is not likely to be experienced by the majority of women during pregnancy and so the conclusions of this research may not be applicable to the majority of pregnant women.
- As the authors themselves note, they cannot judge from this cross-sectional study whether maternal exposure to IPV directly lead to the changes in methylation seen in their offspring.
Further research is needed to investigate whether maternal stress during pregnancy influences gene expression in the brain, and whether this leads to any behavioural differences in those individuals.
As the authors acknowledge, this study suggests “a potential mechanism” whereby maternal stress can influence psychological function, but stops short of providing evidence to prove this.