Using caffeine to treat premature newborns for apnea - dangerous pauses in breathing during sleep - does not have long-term harmful effects on their sleep or breathing patterns, according to research led by Children's Hospital of Philadelphia.
But the new study also found that prematurity itself is a risk factor for sleep disorders years later. Children born preterm had high rates of obstructive sleep apnea and periodic limb movement during sleep, whether or not they had caffeine therapy in the neonatal intensive care unit.
The very idea of caffeinating fragile preemies may sound misguided. But eight years ago, an international study that compared the stimulant to a placebo found it had benefits, including relieving sleep apnea.
Still, there were lingering concerns. Caffeine works in the brain, blocking a molecule that promotes sleep. Animal studies suggest that such early biochemical tinkering can lead to permanent sleep and breathing abnormalities.
"I think we all know from daily life the effect that caffeine has on us," said lead author Carole L. Marcus, a pediatric pulmonologist and director of the sleep center at Children's Hospital. "We give the equivalent of six cups of coffee a day for a week or more - and these are little babies whose brains are still developing."
The new study, published Friday in the American Journal of Respiratory and Critical Care Medicine, tracked down 201 of the original 2006 premature babies, now ages 5 to 12. Half had gotten caffeine therapy, the other half a placebo.
For two weeks, the children wore a noninvasive sensor at night to monitor their sleep. The parents also filled out questionnaires.
There were no differences in the children's sleep patterns, including how long they took to fall asleep and how soundly they slept.
But both caffeine and placebo groups had high rates of sleep disorders. Overall, about 10 percent had periodic limb movement disorder (episodes of involuntary movement, usually of the legs), and 14 percent had obstructive sleep apnea. In general, less than 4 percent of school-age children have apnea, and 5 percent to 8 percent have the limb movement disorder.
Obstructive sleep apnea is different from the apnea of prematurity. In the obstructive form, the throat airway collapses or becomes blocked. In preemies, breathing stops because their immature nervous systems cannot yet enable continuous respiration.
Obstructive apnea can lead to daytime sleepiness, learning problems, high blood pressure, and heart disease. Limb movement disorder is less understood but has been linked to attention deficit hyperactivity disorder and a serious sleep problem called restless leg syndrome.
If caffeine isn't a culprit, why are sleep disorders common in former premature babies?
One possibility, the researchers noted, is enlarged tonsils. About a quarter of the children had already undergone tonsillectomies, the primary treatment for childhood obstructive sleep apnea.
"We're thinking the rate of apnea would have been even higher if not for the tonsillectomies," Marcus said.
The limb movement may be related, at least partly, to iron deficiency. Low blood iron levels were found in the children with the movement disorder who underwent testing.
All the children with apnea or limb movement disorder were referred for more testing and treatment, but most former preemies are not even checked for such problems. The study suggests that should change.
"We should be screening these children," Marcus said. "Then we could prevent problems, or treat them earlier."
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