Caffeine Helps Premature Babies' Lungs
Study's Early Results Show Less Need of Supplemental Oxygen With Caffeine Therapy
Reviewed by Louise Chang, MD
May 17, 2006 -- A new study shows that caffeine therapy may help the lungs of premature babies weighing 1 or 2 pounds at birth.
So far, the researchers only have early results from the study. They've published that data in The New England Journal of Medicine.
The key finding is that premature babies who started caffeine therapy during the first 10 days after birth needed supplemental oxygen less often at 36 weeks after their mothers' last menstrual period, compared with premature babies who didn't get caffeine therapy, without a higher risk of death or intestinal inflammation/infection before leaving the hospital.
However, babies receiving caffeine therapy temporarily gained less weight than those that didn't get caffeine therapy.
The long-term safety results aren't in yet, write the researchers. They included Barbara Schmidt, MD, of Canada's McMaster University in Hamilton, Ontario, Canada.
It's also not known if the results apply to premature babies who start caffeine therapy later, after "most of the lung damage has occurred," states a journal editorial.
Why Caffeine?
Caffeine, a stimulant, is "one of the most commonly prescribed drugs among premature infants," writes editorialist Eduardo Bancalari, MD.
Bancalari was not involved in Schmidt's study. He works in Miami at the University of Miami's neonatology division.
In his editorial, Bancalari explains that caffeine is mainly used in premature infants to reduce the incidence of episodes of apnea -- in which breathing temporarily stops -- associated with an immature central nervous system.
Caffeine is also used to help wean babies from mechanical ventilation, Bancalari notes.
"Despite the widespread use of caffeine for these indications, the evidence to support its use is based on the results of a few relatively small and short-term studies," Bancalari writes.
"Information is lacking on possible long-term effects of prolonged administration of caffeine on the development of the brain and other organs," he adds.
Caffeine Study
Schmidt's study included 2,006 babies. Each baby weighed 1.1 pounds to 2.8 pounds at birth.
With the parents' permission, the researchers randomly assigned 963 babies to get caffeine therapy starting during the first 10 days of life. On average, they started caffeine therapy 28 weeks after their mother's last menstrual period. For comparison, the other infants got a placebo lacking caffeine.
The babies in the caffeine group got an initial intravenous dose of caffeine, followed by a smaller daily maintenance dose of caffeine.
Schmidt's team tweaked the daily maintenance doses as the babies gained weight, using oral doses when the babies could tolerate it. On average, the babies received 37 days on caffeine therapy.
All babies got nondrug therapies as needed to help with breathing. Nondrug therapies included supplemental oxygen, continuous positive airway pressure (CPAP), and assisted ventilation through a tube inserted in the trachea (endotracheal tube). The trachea is the part of the airway also known as the windpipe.
Caffeine and Weight Gain
The early results cover the babies until they left the hospital.
Of the babies that lived to 36 weeks after their mothers' last menstrual period, fewer of those that got caffeine therapy needed supplemental oxygen. Those babies also stopped needing CPAP, an endotracheal tube, and supplemental oxygen one week earlier than the babies in the comparison group.
The babies in the caffeine group also temporarily gained less weight than those in the comparison group, the study shows. The average weight difference between the two groups was greatest at 23 grams (0.05 pounds) after two weeks.
However, there were no significant differences in weight gain between four and six weeks after the start of therapy. And there was never a significant difference in average head circumference, which doctors also use to track babies' growth.
"Caffeine had the potentially adverse effect of diminishing weight gain for the first three weeks after the start of therapy," the researchers write. They add that caffeine didn't seem to affect death before the first discharge home, signs of brain injury as shown on ultrasound images, and infection and inflammation of the intestines (necrotizing enterocolitis).
Long-Term Results Not Out Yet
A longer follow-up is currently underway.
The study was designed to check whether premature babies that got caffeine therapy starting during the first 10 days after birth differed from those without caffeine therapy in death, cerebral palsy, cognitive delay, deafness, or blindness when they were approaching their second birthday.
The researchers write that the long-term results, including a follow-up when the babies are about 5 years old, "is needed before one can confidently recommend the standard use of methylxanthine therapy for apnea of prematurity."
Methylxanthines are chemicals that include caffeine.
Bancalari's editorial notes that the babies in Schmidt's study got caffeine therapy earlier than many premature infants, who may have already suffered lung damage by the time they're started on caffeine. "It is unknown whether caffeine would protect against lung injury in this clinical setting, but it seems unlikely," Bancalari writes.
