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Michael Douglas is said to have seduced Catherine Zeta-Jones, 25 years his junior, with the unforgivable line “I’d like to father your children”. When she acquiesced, Zeta-Jones paid a price she was probably unaware of – a higher risk of health problems for those children.
It turns out that at least some of the risk of problems ranging from Down syndrome, schizophrenia and autism to obesity and poor social skills can all be linked back to the father’s age and environment around the time of conception. And yet most couples have never heard of these findings.
Similarly, a current public health campaign in Britain warns fathers not to smoke around their pregnant partners, but it doesn’t mention anything about the risks of men smoking themselves at the time they are trying to conceive.
“It’s not as though the scientific community has kept quiet about this, but the popular media has not picked up on it,” says Mary Cannon, a psychiatrist at the Royal College of Surgeons in Ireland. “My hunch is that the area of reproducing, especially fertility and the health of offspring, is somehow seen as women’s business.”
Cynthia Daniels at Rutgers University, in New Jersey, USA, agrees. “It’s a function of gender bias that we haven’t focussed more attention on the role of men in healthy pregnancy outcomes,” she says. “We continue to see reproduction as the exclusive responsibility of women – and we’re reluctant to recognise men’s responsibilities as well.”
When it comes to fertility, most women know that it’s best to avoid alcohol and too much caffeine, to maintain a healthy weight and to have children earlier rather than later. But what kind of influence does the would-be father have on the success, or otherwise, of conception – and how exactly are these environmental factors inherited?
For men, it seems that caffeine might actually help. One Brazilian study found that the sperm of men who drank one or more cups of coffee a day were much better swimmers than the sperm of men who avoided caffeine.
But other drugs are bad news. A U.S. study found that marijuana smokers have fewer sperm, and these sperm have swimming problems: they move too fast too early, potentially leading to burn-out before they get near an egg. Excess body fat can also cause problems for wannabe dads as it lowers testosterone levels, which in turn reduces a man’s sperm count. Meanwhile, smoking and drinking can harm a man’s ability to conceive by damaging the DNA of his sperm.
Of course, smokers and drinkers do father children. But that doesn’t mean that a few good sperm escaped the toxic chemicals in pristine condition.
The cause of some 60% of birth defects isn’t known, but sperm abnormalities caused by a father’s heavy drinking may be one important factor and should be urgently investigated, says political scientist Daniels. “The research that has been done shows that men’s excessive alcohol use can cause increased rates of low birth-weight babies, as well as increased rates of sperm abnormalities.”
But researchers who have found associations between paternal alcohol use and harm have had a difficult time getting funding for further work, she says. “As a result, public attention is focussed exclusively on women’s use of alcohol – even though women who consume alcohol during their pregnancies are highly likely to be partnered with men who abuse alcohol.”
If more work needs to be done on alcohol, there is clear evidence that other environmental factors can leave an unpleasant legacy for the next generation. The children of Vietnam veterans exposed to Agent Orange have a higher risk of spina bifida. Men who work with pesticides have kids who are more likely to develop certain cancers, such as Hodgkin’s lymphoma.
Cigarette smoking, too, has an effect. Clinical geneticist Marcus Pembrey at University College London, in England, and colleagues analysed British couples who’d had babies in the early 1990s. More than 5,000 of the fathers were or had been smokers, and 166 had started smoking before they were 11. In 2006 the team reported that, while there was no effect on daughters, the men who had started smoking before puberty had fatter-than-average sons.
Other work on animals has also uncovered unpleasant effects of drug use by fathers. One study at the University of Maryland found that the pups of male mice that had inhaled cocaine inherited their father’s memory problems.
But even if a father has led a vice-free life, his age alone can affect his child’s health. In fact, it seems to have a potentially broader impact than the mother’s age. “When you look at the range of disorders associated with advanced paternal age, there certainly seem to be a greater number and range of possible adverse consequences,” says Cannon.
Back in 1912, a German doctor called Wilhelm Weinberg noticed that an inherited type of dwarfism was more common in the last-born child of big families. With incredible insight, he concluded that the parent’s age was to blame. Forty-three years later, though, scientists discovered that only the father was responsible.
Since Weinberg’s discovery, a long list of disorders has been associated with fatherhood later in life. Progeria – a rare condition in which children ‘age’ rapidly and usually die in their teens – is one. Marfan syndrome, which leaves sufferers with unusually long arms, legs, fingers and toes, is another.
While a mother’s age has long been known to affect her child’s risk of Down syndrome, it turns out that so does the father’s – but only if both parents are over the age of 35 at the time of conception.
Harry Fisch, director of the Columbia University College of Physicians and Surgeons’ Male Reproductive Centre in New York, led a team which found that among mothers older than forty, about half of the incidence of Down syndrome could be put down to the sperm.
Older dads are also more likely to have children with a range of psychiatric problems.
For schizophrenia, a father who is 40 or older has a 2% chance of having a child with the disorder, a risk that is twice that for a man under 30. The work on schizophrenia has been confirmed in several studies looking at large numbers of people, and in which the researchers have been careful to control for many other factors that might influence the results. “On a league table of believability of the risks associated with advanced paternal age, I’d put schizophrenia at the top,” says John McGrath at the Queensland Brain Institute, in Brisbane, who works in this field.
For autism there have been fewer studies, but findings suggest an even stronger effect. Avraham Reichenberg of the Mount Sinai School of Medicine in New York City analysed data on about 130,000 Israelis born in the 1980s who were medically assessed at 17 to determine their eligibility to serve in the military.
They found that a mother’s age at conception had little influence on her child’s risk of autism, but the risk for someone fathered by a man who was 40 or older was a massive six times greater than those whose fathers had been under 30. For children of dads over 50, that risk leapt to nine times higher.
Even if a child isn’t diagnosed with autism or Asperger’s, paternal age can increase their chances of displaying one of the key characteristics of the disorder – poor social skills.
Again, the work is based on Israelis being assessed by the army. Males aged 16 and 17 were asked: “How many good friends do you have? Do you have a girlfriend? Do you generally prefer to be with or without a group of friends? How often do you go out on Friday evenings? Do you tend to be at the centre of a party?” And the researchers found that boys fathered by men aged 45 or older were 50% more likely to have what was classed as poor social functioning. The most dramatic effects came with dads who’d been in their fifties.
In September 2008, Swedish researchers also revealed that a child’s risk of developing bipolar disorder (formerly manic depression) increases when the father is aged over 29. When the mother’s age, the family’s socio-economic status and its history of mental disorders were all taken into account, a child born to a man who’d been 55 or older was 1.37 times more likely to be diagnosed than the child of a man aged 20 to 24.
Then, in March 2009, John McGrath revealed that kids of older men score worse on intelligence tests, including tests of learning, reasoning, concentration and memory. The differences are slight – an average of two IQ points separate the children of a 20- and a 50-year-old dad – but they are startling, McGrath says. “It is widely accepted that the offspring of older parents have better socio-cultural opportunities [because] the parents earn more, they have better health literacy, the kids are vaccinated, the pregnancies are planned.”
In theory, this should all help create a more nurturing environment that actually boosts a child’s mental performance. But while the children of older mothers did perform better on intelligence tests than those of younger mothers, the reverse was true for dads.
So how can environmental factors such as a man’s age and lifestyle have such an impact on his child?
In some cases, social factors could be to blame. Mark Weiser at Tel Aviv University, who led the work on social skills, points out that men with poor social skills might get married later, and pass this characteristic onto their sons. However, genetic damage could account for many of the findings.
Alcohol, nicotine and other toxins are known to directly damage the DNA of sperm. The good news is that sperm is completely renewed about every 10 weeks – so a little clean living before conception should help boost his child’s chances.
But when it comes to older dads, the story is different. McGrath, and others, suspect that an age-related accumulation of genetic mutations in the cells that make sperm might be responsible. For a man aged 20, these cells have divided about 150 times. By age 50, this number has leapt to 840. Every time the cells divide, there’s a chance they’ll make a mistake. And these mistakes could lead to defects in the sperm.
But there is another possible explanation. It concerns epigenetics, which deals not with DNA, but with which genes are active within a cell. While your liver and skin cells contain exactly the same DNA, they look very different, and do a very different job, thanks to their epigenetic settings.
Scientists know that certain epigenetic settings acquired by a mother during her lifetime can be passed to her children. Now there’s good evidence that the same can happen with fathers.
As Marcus Pembrey and his team published their work on smoking and body fat, they also published results from another study, this time of historical records from Sweden, dating back three generations.
They found that the grandsons of men who had been short of food between the ages of nine and 12 (when sperm are first produced) lived longer. A similar effect was found in women too, but the vital time window wasn’t when the grandmothers went through puberty, it was while they were in the womb or shortly after birth (when eggs are made).
Other work on animals has also found that ‘epigenetic marks’ on cells, acquired as a result of exposure to a fungicide for example, can lead to health problems not only for the exposed animal’s offspring, but for at least two successive generations.
If some of these health problems are due to errors in copying part of the DNA code, these errors could also be passed through the generations, McGrath notes. In developed countries, there is a trend towards delaying fatherhood. “If these errors are accumulating, we need to be alert to that,” he says.
So, what does all this work mean for men and women planning to have children?
Since the evidence on age and increased risks for men is so compelling, some researchers suggest that men consider banking their sperm while they’re still young. Women might also want to be more careful when choosing a partner.
“If I were a young woman planning my family, I would consider not only the age of my partner, but also his possible exposures to workplace and environmental toxins, excessive use of drugs and alcohol and cigarette smoking,” says Daniels. “And I would be quite angry that we as a society haven’t paid more attention to this possible risk of harm.”
OFF LIMITS
Women are generally aware of the things to avoid during pregnancy. Here is the most up-to-date evidence on the major things to be careful about.
Alcohol
Women who are pregnant or planning a pregnancy should not drink any alcohol, according to the Australian National Health and Medical Research Council guidelines released in March 2009. Alcohol is toxic to a foetus. And recent research on Australian women found that those who consumed more than two standard drinks on any one occasion in their first trimester were more likely to have a premature baby.
Coffee
Pregnant women who drink 200 mg of caffeine (roughly equivalent to two cups or one mug of coffee) a day in their first trimester are at twice the risk of having a miscarriage as women who avoid caffeine. And women who consume just one cup of coffee a day are more likely to have a baby who is underweight, which carries health risks later in life.
Tea
Black tea contains about 40 mg of caffeine a cup, so intake should be restricted. There isn’t much data on the effects on foetuses of many herbal teas, including peppermint and chamomile, so pregnant women are advised to drink these only in moderation. Teas that should be completely avoided include ginseng, liquorice, hawthorn berry, St Johns Wort and dong quai.
Fish
Swordfish, shark, king mackerel (all of which can contain high levels of mercury), any raw fish, shellfish and cold smoked fish should be avoided. But 300 to 450 g of other types of fish every week is recommended. One recent study found that the children of mothers who had consumed less than 340g of fish and seafood a week were more likely to score poorly in verbal intelligence tests.
Cheese
Pregnant women should avoid unpasteurised cheese. Camembert, brie and blue cheese are OK to eat if they’ve been thoroughly cooked. Other sorts of cheese (hard cheeses such as cheddar, processed cheese, cream cheese and cottage cheese) are good to eat, because they are excellent sources of calcium. The recommended daily intake of calcium during pregnancy is 840mg.
Peanuts
There is ongoing debate about whether eating peanuts during pregnancy affects a child’s risk of developing a peanut allergy. However, a recent British study concluded that even if there is a family history of food or other allergies, pregnant women do not need to avoid peanuts.
Smoking
Smoking during pregnancy increases the risk of miscarriage, stillbirth and sudden infant death syndrome (cot death). It can also lead to birth defects, such as cleft palate, and cause complications with the placenta. Even passive smoking seems to increase the risk of having a low birth-weight or premature baby.
Artificial sweeteners
These are added to a range of products, including soft drinks, desserts, sweets and pastries. Aspartame is considered safe during pregnancy, except for women with certain rare medical disorders. Some previous studies have suggested that saccharin might potentially be harmful to foetuses, but this is now thought to be unlikely.
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Emma Young is a Sydney-based science journalist.
