Premature infants with lung disease may continue to require replacement substance to ease breathing

Physicians have known for decades that many premature babies suffer respiratory problems stemming from insufficiency of a lung substance called surfactant during their first few weeks of life.

The standard treatment has been to provide replacement surfactant immediately after birth. A new study has found that even after infants begin producing their own surfactant, it often fails to function properly in premature infants who continue to have lung disease after their first week.

The study also raises the question of whether additional replacement surfactant treatment may benefit such infants, just as it does in the week after birth.

Neonatology researchers from The Children's Hospital of Philadelphia and the University of Pennsylvania published the study in the October 20 online edition of the journal Pediatric Research. It was the first study of surfactant dysfunction in infants beyond the first week of life.

"We studied premature babies who require mechanical ventilation to breathe after one week of age," said Philip L. Ballard, M.D., Ph.D., director of Neonatology Research at The Children's Hospital of Philadelphia. "We found that three-quarters of these high-risk infants have episodes of surfactant dysfunction, and these episodes are associated with worsening of their respiratory status."

Surfactant is a naturally produced mixture of proteins and lipids (fats) that lowers surface tension within alveoli, the tiny air sacs within the lungs. By doing so, it prevents the alveoli from collapsing during exhalation, and eases the work of breathing. Premature infants have underdeveloped respiratory systems and do not produce enough of their own surfactant. Therefore, physicians have found that supplying replacement surfactant may improve infants' lung function during the earliest period after birth.

Replacement surfactant is discontinued after babies begin to produce enough surfactant on their own. However, infants with persistent lung disease may develop a condition called bronchopulmonary dysplasia (BPD), in which chronic respiratory distress makes it necessary for infants to breathe through a mechanical ventilator. BPD can cause long-term disability or death.

In this study, the researchers analyzed samples of fluid from the windpipes of 68 premature infants who had breathing tubes between one to 12 weeks after birth. Seventy-five percent of the infants on at least one occasion had abnormal surfactant function, and diminished amounts of an important component of surfactant, called surfactant protein B. In addition, these surfactant abnormalities were significantly more likely to occur during periods of respiratory infection and worsened respiratory status.

Babies are defined as premature if they are born before 37 weeks of gestation. Most premature babies have symptoms of respiratory distress, with the risk increasing with greater prematurity. The infants in this study were very premature, having been born at 23 to 30 weeks gestation.

"Premature infants with continuing respiratory failure and abnormal surfactant may benefit from treatment with replacement surfactant - or from strategies to increase their own production of surfactant," said Dr. Ballard, who has been studying infant lung development for more than 30 years. He and his colleagues are currently carrying out a pilot trial of surfactant therapy in preterm infants older than 7 days, and they are planning a clinical trial to investigate short- and long-term safety and effectiveness of surfactant treatment in these infants.