Almost all babies who are born very prematurely have trouble breathing. For decades, doctors have treated them with the stimulant caffeine, even though there was little scientific evidence to justify it.

Breathing delivers oxygen to the brain, so when an infant's breathing is disrupted, it can have a critical impact on the child's development.

In an earlier stage of this study, some 2,000 premature babies in nine countries were randomly assigned to get caffeine or a placebo. At 18 months, researchers found numerous advantages for the caffeine group. Those babies had half as many cases of cerebral palsy as well as lower rates of blindness, deafness and delayed mental functioning.

Now, University of Pennsylvania researchers report on an additional three and a half years of follow-up, mainly to look for possible safety issues, which might take time to develop.

Lead researcher Barbara Schmidt says the new study confirms the effectiveness of the caffeine treatment, and underscores its lack of side effects.

"Not only is it safe, it is more effective than any other drugs we give to babies in the nursery when they are very preterm," Schmidt says.

There were some changes in the results between the two groups of children at age 18 months and then at five years, notably that the advantage children treated with caffeine had in mental development seemed to have evaporated.

"There is some residual benefit [to] the quality of the children's motor function - if they had impaired motor function - but there is no longer any effect whatsoever on the rates of cognitive impairment," she says.

Schmidt's research, published in the Journal of the American Medical Association, shows rates of cognitive impairment at five years were much lower than at 18 months - what she calls a potential for "remarkable catch-up" in the very premature babies as they get older, whether they get caffeine therapy or not.