Treating prem babies with caffeine improves later lung function

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Premature babies treated with caffeine have better lung function in mid-childhood than preemies not treated with caffeine, according to an Australian randomised controlled trial.

“Previous studies have shown that caffeine, which belongs to a group of drugs known as methylxanthines, reduces apnoea of pre-maturity, a condition in which the baby stops breathing for many seconds,” said lead study author Dr Lex W Doyle, professor of neonatal pediatrics at the Royal Women’s Hospital in Melbourne and head of the Australian National Health and Medical Research Council’s Centre of Research Excellence in Newborn Medicine.

Doyle added that caffeine, one of the most widely used drugs in neonatal intensive care, shortens the time premature infants require help breathing after birth. It also reduces the chances that the newborn will develop lung injury or abnormal lung development, a condition called broncho-pulmonary dysplasia, which can lead to higher rates of breathing problems later in life.

Doyle and colleagues’ study is to determine if the lung benefits of caffeine in premature babies persist in mid-childhood.

At age 11, 142 children living in Australia who had been part of the international Caffeine for Apnea of Prematurity randomised controlled trial had their expiratory flow rates measured. Slightly more than half the children had been enrolled in the caffeine intervention; the others had been given a placebo.

The researchers found expiratory flows were significantly better in the caffeine group by approximately one-half a standard deviation for FEV1 (the maximum amount of air that can be forcefully blown out in one second), FVC (the amount of air that can be forcibly exhaled after taking the deepest breath possible) and FEF25-75% (the average flow from the point at which 25 percent of the FVC has been exhaled to the point at which 75 percent of the FVC has been exhaled.) FEV1/FVC (a measure of obstructive lung disease) was better by a lesser amount but still statistically significant.

The researchers said that caffeine appeared to improve long-term breathing by reducing lung injury and abnormal development during the newborn period, “rather than the caffeine molecule having any direct effect on the lung itself.”

Study limitations include the fact that respiratory function tests measured only expiratory flows and the children were from only one of the Caffeine for the Apnea of Prematurity trial sites.

“It would be desirable to repeat lung function more extensively later in life, and at more sites to identify those participants at highest risk of developing severe breathing disorders in adulthood,” Doyle said. “If it were possible to repeat lung function at one time only, the best time would be around age 25, when lung growth peaks.”

Rationale: Caffeine in the newborn period shortens the duration of assisted ventilation and reduces the incidence of bronchopulmonary dysplasia, but its effects on respiratory function in later childhood are unknown.
Objectives: To determine if children born <1251 g birthweight who were treated with neonatal caffeine had improved respiratory function at 11 years of age compared with children treated with placebo.
Methods: Children enrolled in the Caffeine for Apnea of Prematurity randomized controlled trial and assessed at the Royal Women’s Hospital in Melbourne at 11 years of age had expiratory flow rates measured according to the standards of the American Thoracic Society. Values were converted to z-scores predicted for age, height, ethnicity and sex. Parents completed questionnaires related to their child’s respiratory health.
Results: 142 children had expiratory flows measured. Expiratory flows were better in the caffeine group, by approximately 0.5 SD for most variables (e.g. forced expired volume in one second; mean z-score -1.00 vs. -1.53; mean difference 0.54, 95% confidence interval [CI] 0.14, 0.94, P=0.008). Fewer children in the caffeine group had values for the forced vital capacity <5th centile (11% vs 28%; odds ratio 0.31, 95% CI 0.12, 0.77, P=0.012). When adjusted for bronchopulmonary dysplasia, the differences in flow rates between groups diminished.
Conclusions: Caffeine treatment in the newborn period improves expiratory flow rates in mid-childhood, which it seems to achieve by improving respiratory health in the newborn period. Follow up lung function testing in adulthood will be vital. Future placebo-controlled randomized trials of neonatal caffeine are unlikely.

Lex W Doyle , Sarath Ranganathan , Jeanie L Y Cheong

American Thoracic Society material
American Journal of Respiratory and Critical Care Medicine abstract

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