It's one of those odd twists of medicine: One of the substances that women are told to limit during pregnancy can actually help premature babies breathe better once they're out of the womb.
A Canadian-led international study has confirmed that treating very preterm infants with caffeine improves their ability to breathe with less help from ventilators and lowers the incidence of abnormal lung development compared with preemies given a salt-and-water placebo.
"This is a treatment that has been used for many years, even though it's not actually licensed in Canada," said principal investigator Barbara Schmidt, a professor of pediatrics and clinical epidemiology at McMaster University in Hamilton.
"But everybody uses it because of the known short-term benefit, which is that it reduces the problem that preterm babies have with irregular breathing, or interrupted breathing."
That irregular breathing, known as apnea, occurs in about 85 per cent of infants born at less than 34 weeks gestation (a full-term pregnancy is 37 to 42 weeks long) and is believed to arise due to dysfunction in a portion of the brain that regulates respiration.
Caffeine -- the stimulating chemical in coffee, tea and colas -- is believed to neutralize a neurotransmitter that slows down lung activity too much in the newborns. The agent is administered intravenously or through a nasal-gastric feeding tube. The treatment is used worldwide "off-label" by doctors; it has regulatory approval only in the United States.
In the nine-country study of more than 2,000 premature infants -- born on average after 28 weeks gestation and weighing from 1 pound 2 ounces to 2 pounds 8 ounces -- researchers found that 47 per cent of the infants on placebo still needed extra oxygen at a postconceptual age of 36 weeks. Among babies given caffeine, only 36 per cent needed a ventilator to provide additional oxygen.
"The main finding up to this point is that the children who received the caffeine had less problem with chronic lung disease . . . which is essentially scarring of the lung in response to being preterm [and]being given oxygen on the ventilator," Dr. Schmidt said.
What is not known, however, is the medium- and long-term effects of caffeine on babies' developing brains -- and that's what the research group hopes to determine as it follows the children's progress up to the age of 5.
"We don't yet know whether the caffeine will be safe with respect to the child's behavioural development, the child's cognitive development, whether or not there will be more or less cerebral palsy," Dr. Schmidt said. "Because all of these drugs do affect the brain, which is developing very actively during this period."
The 2,006 youngsters, born between October of 1999 and October of 2004, are being tested at about age 2 to assess their cognitive development, hearing and vision. That data -- from centres in Canada, the United States, Europe, Australia and Israel -- should be collected by the end of the year.
A second phase will assess the children at age 5 with a new battery of tests that will look at a number of developmental markers, including behaviour and IQ, said Dr. Schmidt, whose study is published in today's edition of the New England Journal of Medicine.
"It would be nice to be able to show in a few years that caffeine is beneficial not only in the short term, as we have shown now, but also in the long term. And that would be pretty much one of the first, if not the first, treatments that we use in neonatology that would have been shown to do that, to have a long-term beneficial effect."
Commenting on the study, neonatologist Doug McMillan of the IWK Health Centre in Halifax said the most important outcome of the research "will be a year from now" when doctors learn whether early use of caffeine will prove to be safe for the developing child.
In an editorial accompanying the study, neonatologist Eduardo Bancalari of the University of Miami said that after searching unsuccessfully for almost 40 years for an effective means of preventing apnea-related lung damage in premature infants, "it would be a welcome surprise if a simple pharmacologic intervention proved to reduce its incidence."
But Dr. Bancalari urged doctors to be judicious in using caffeine until the results of the Canadian-led study are known. "Assessment of the long-term effects of caffeine is needed before this therapy can be routinely recommended."