BioEd Online

Tentative evidence has emerged to suggest that low doses of caffeine, equivalent to just one or two cups of coffee per day, can affect the development of unborn babies.

The findings are almost certainly too preliminary to prompt public health officials to change official advice to pregnant women, who at present are told only to avoid large amounts of caffeine. But the researchers involved, who have detected behavioural and cellular changes in rats whose mothers drank caffeine during pregnancy, say they themselves are advising pregnant women to avoid caffeine altogether.

Joseph Nunez and his colleagues from Michigan State University in East Lansing, who presented their results on 16 October at the annual meeting of the Society for Neuroscience in Atlanta, Georgia, say the findings came as a surprise. In an initial experiment, they examined brain cells from new-born rats whose mothers had been given a dose of caffeine, equivalent to one or two cups of coffee for a human, every day during pregnancy.

"I was a skeptic," says Deborah Soellner, a colleague of Nunez's. "I didn't expect to see this at such a low dose."

But in the exposed rats, Nunez's team found odd effects in brain cells of the hippocampus, a region of the brain associated with memory and spatial navigation. For example, the cells absorbed less glutamate, a molecule that makes brain cells more active. Whatever glutamate was absorbed also exited the cells sooner than usual.

Reduced inhibition

To see how the cellular changes were affecting behaviour, the Michigan team took baby rats whose mothers had been caffeined-up and ran them through a series of behavioural tests. Nunez says that the animals showed no cognitive defects, but were more active and less inhibited than those whose mothers had not received caffeine.

The rats were more willing to explore new environments, for example. When placed in a small dark space with an opening into a larger lit area, it took control animals around 4 minutes on average to emerge. But the caffeine rats left after an average of just 25 seconds.

Other tests showed similar, if less pronounced, changes. The rats were more likely to explore exposed environments, and spent more time interacting with other animals.

"You have an animal that doesn't know when to stop," says Nunez.

Safe not sorry

Although there is no reason to assume that these differences are negative or harmful, Nunez would like pregnant women to be advised to avoid caffeine as a precautionary measure. On his display was pinned a photograph of his four-month-old baby; he says his team's rat results started to emerge when his wife was pregnant, so he immediately advised her to stay away from caffeine.

Current public health guidelines say only that women should limit themselves to 300 millilitres or less a day, but that is equivalent to what Nunez fed his rats. He points out that caffeine is able to cross the placenta, and the developing fetus is known to take up to 4 days to clear out the caffeine from a single cup of coffee drunk by mum.

Nunez says that any effects of caffeine on humans may have been missed because it is so widely used and assumed to be relatively safe.

"No one has ever systematically done this research before," he says. Nunez's team plans to follow up their studies by looking in more detail at the effect that caffeine is having on brain cells.

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