Dad's age, diet and lifestyle may cause birth defects

2:45pm Monday 16th May 2016

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"Men are being warned to become fathers by 40 or face a greater risk of having children with serious illnesses," the Daily Mail reports after a new review looked at some of the evidence about paternal influences on the risk of childhood diseases.

The review discusses several research findings found previously, including some reports that children born to fathers over the age of 40 have higher rates of conditions like autism spectrum disorder - and that stress, smoking and alcohol may also cause heritable changes.  

But this is an opinion piece. We don't know how the researchers selected the evidence they reviewed, and it is possible that not all relevant research was considered.

The review should not be taken as firm evidence that there is such a thing as a "male biological clock" and fathers are putting their children at risk by delaying fatherhood until middle age.

Still, men trying for a baby should avoid smokingexcessive alcohol consumption and eating a poor diet. It may not boost your sperm's health, but it will definitely improve your health.  

Epigenetics

The review explores a branch of science known as epigenetics. Epigenetics is the study of how external and environmental factors can affect gene expression - essentially, turning some genes "off" so they are not "read" by the body and have no effect on biological processes.

 

Some epigenetic changes can be beneficial. For example, there is a tentative body of evidence that good parenting may trigger genetic changes that protect against chronic mental health conditions.

 

Other epigenetic changes, such as mothers drinking alcohol or smoking during pregnancy, can be harmful.

Where did the story come from?

The study was carried out by researchers from Georgetown University Medical Centre in the US, and was funded by the US National Institutes of Health.

It was published in the peer-reviewed American Journal of Stem Cells. This is an open-access journal, so the study can be downloaded for free as a PDF.

Neither the Daily Mail nor The Times recognise the important limitations of this review: namely, that is it is not a systematic review, so it carries far less weight in terms of evidence.

Also, the Mail talks about men being "warned" about delaying fatherhood - but, as far as we can tell, the only people actually issuing any warning based on this review is the Mail itself.

What kind of research was this?

This appears to be a narrative review discussing whether how a man's age and environmental exposures may alter his genes and so be passed on to his offspring.

The article centred on epigenetics, the idea that, though a person's DNA sequence may not change, their exposures over the course of a lifetime may lead to changes in their gene activity and expression that can be passed on to their children.

This happens through mechanisms such as DNA methylation, where methyl groups (types of molecules) are added to the building blocks of the DNA, or where small RNA molecules (miRNA) are added to the DNA - both of which alter gene activity.

This review discusses how epigenetics in the father have an effect on the offspring, focusing on age and environmental exposures. The researchers discuss these theories, referencing various publications, but this does not appear to be a systematic review. 

The research team did not provide any information about how they identified and selected the evidence they reviewed. As such, it is possible that not all relevant research has been examined and so this must largely be considered to be an opinion piece.      

What does the research say about a father's age?

The researchers say that past research has shown that a father's age has a significant effect on a child's characteristics and the likelihood of them having congenital abnormalities.

Some studies have linked increasing paternal age (over 40 or so years) with higher rates of conditions like autism and schizophrenia. Others have observed increased rates of birth abnormalities, such as heart defects, musculoskeletal abnormalities, and Down's syndrome.

Mouse studies also support this. Studies have shown that mice born to "old" fathers (over two years old) performed poorly on tests of learning and memory, and also had a reduced lifespan and less reproductive success themselves. Mice with slightly younger fathers (10 months old) were less social.

The researchers say that although the mechanism behind this is not established, most evidence points in the direction of DNA methylation. Animal studies have shown higher rates of DNA methylation in the sperm cells of older rats compared with younger rats.

What does the research say about environmental exposure?

The effect of environmental exposures on offspring is less clear, although there is some evidence of this. Some studies have shown that people with little available food have demonstrated some changes that can be passed on to their children, though not necessarily bad ones.

It's reported that children born to fathers who had low food availability during pre-adolescence were less likely to die from cardiovascular disease. And those whose grandparents had little food were less likely to have diabetes.

Other studies have suggested stress induces DNA changes that could be passed on. Mouse fathers who were subject to the stress of food deprivation before mating had offspring with lower blood glucose levels.

Mice exposed to other psychological stressors - such as cage changes and fox smell - had offspring that displayed blunted stress responses, indicating some form of behavioural defect.

Smoking and alcohol may also have effects. Smoking has been shown to alter the DNA in sperm.

And three-quarters of babies with foetal alcohol syndrome - birth defects normally associated with maternal consumption of alcohol during pregnancy - are reported to have fathers with alcohol use problems.

Chronic alcohol use in the father is said to again affect DNA methylation. In rats, offspring from fathers given alcohol were more likely to have a low birthweight or spatial learning problems when put in a maze test.

Studies in mice also found those whose fathers were given alcohol were more likely to have cognitive and mobility problems. 

How did the researchers interpret the results?

The researchers say their review findings support the concept of the epigenetic inheritance of paternal experiences across generations.

They say their review highlights "the possible links between birth defects and paternal age, environmental factors, and alcohol consumption" and the need for future research in this area.

Conclusion

This narrative review summarises past research on DNA changes that may occur as a result of a father's age and exposures that could be passed on to his children.

In particular, the review discusses animal and human studies that have linked changes in offspring with increasing paternal age, stress and substance use.  

But this review must largely be considered to only be an opinion piece. We don't know how the researchers identified, appraised and selected the studies they discussed.

As such, there is a strong possibility that not all animal and human research relevant to the issue of paternal epigenetic inheritance will have been reviewed and discussed here.  

There are also no clear methods or results provided for the studies that are discussed, with only a few brief sentences given for each study. We are not able to critique the quality and strength of evidence linking a father's age or any other exposure with the outcome reported. 

For example, people would likely be concerned by reports that increased rates of autism or congenital defects have been observed in children born to fathers over the age of 40. But we have nothing more to go on than this - no firm risk figures are given.

And the observational studies themselves are likely to have been influenced by various unknown sources of bias and confounding, like the report that three-quarters of babies with foetal alcohol syndrome have a father with alcohol use problems.

This doesn't tell us anything about what the mother is doing. It could be that many of these babies had a mother who also had alcohol use problems - alongside her partner - and used alcohol during pregnancy, and has directly exposed the developing baby.

This study will add to the research on how parental exposures may be passed on to a child through epigenetics.

However, given the limitations of this review and the lack of methods given, this opinion piece should not be taken as firm evidence that fathers are putting their children at risk by delaying fatherhood.

These limitations aside, advice that men hoping to become fathers should avoid known bad lifestyle behaviours, such as smoking, drinking too much, not exercising and eating a poor diet seems sensible.

Read more about what both men and women can do to protect their fertility.

Summary

"Men are being warned to become fathers by 40 or face a greater risk of having children with serious illnesses," the Daily Mail reports after a new review looked at some of the evidence about paternal influences on the risk of childhood diseases.

Links to Headlines

Men's biological clock kicks in after 40, too: Warning to start a family early to cut risk of fathering sick children. Daily Mail, May 16 2016

Drinking dads can harm babies just as much as mums who drink alcohol. Metro, May 15 2016

Older fathers can raise risk of birth defect in children. The Times, May 16 2016 (subscription required)

Links to Science

Day J, Savani S, Krempley BD, et al. Influence of paternal preconception exposures on their offspring: through epigenetics to phenotype (PDF, 243kb). American Journal of Stem Cells. Published online May 15 2016

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