Drug's ability to ease one type of post-birth lung disorder studied
Dr. William Walsh is testing a new drug to treat lung infections in newborns. Photo by John Howser.
For countless tiny premature babies suffering from lung disease, treatment with a substance called surfactant has been a lifesaver.
Now it¹s the big babies¹ turn.
Researchers at Vanderbilt Children¹s Hospital and nine other medical centers are studying whether treatment with a new man-made version of surfactant can help full-term babies with a different lung disease called meconium aspiration syndrome.
"Surfactant has proven very effective at treating hyaline membrane disease, the lung disease that we often see in very premature babies," said Dr. William F. Walsh, professor of Pediatrics and director of the Nurseries.
"This study targets full-term babies who have been unfortunate enough to do two things before birth have a bowel movement inside the amniotic fluid and then gasp hard enough to breathe in some of that substance. It¹s that combination we call meconium aspiration syndrome."
Surfactant is a naturally occurring substance in the lungs that helps reduce surface tension and prevent the lungs from collapsing. The lungs of premature infants often do not have adequate amounts of surfactant, leading to hyaline membrane disease.
Neonatologists began treating babies with synthetic surfactant in the 1980s, greatly reducing the number of deaths from the disease most famous for claiming the life of President John F. and Jacqueline Kennedy¹s prematurely born son in the early 1960s.
A newborn¹s very first bowel movement ‹ which normally happens during the first few days after birth ‹ is a thick, sticky, tar-like substance called meconium. However, when the meconium is passed before birth and an infant breathes it into the lungs, it sets up an aggressive inflammatory response and can lead to infection.
"Meconium is very thick and very tenacious," Walsh said. "It¹s difficult for the body to clear it on its own, and we¹d like to get it out of the lungs as quickly as possible."
In the 1970s, researchers attempted to wash out the meconium with saline, Walsh said. It worked, but with the meconium also came all the infant¹s natural surfactant.
"It took babies with meconium aspiration and changed them to babies with hyaline membrane disease," Walsh said. "It ended up making babies sicker."
In the 1980s, while he was in the U.S. Air Force, Walsh conducted animal studies using surfactant to wash meconium from the lungs. The animals¹ condition improved.
Currently, the most effective surfactant available is extracted from cow¹s lungs, but the process is expensive and presents a slight concern of disease transmission and initiation of allergies to beef products, Walsh said.
"Bovine surfactant costs about $600 per dose, and a baby usually requires four doses," Walsh said. "This man-made surfactant, called KL4, is potentially as good as the bovine surfactant but doesn¹t present even the slight safety concerns. It¹s also really cheap to produce."
The pharmaceutical company that makes KL4 sponsors the study. It is randomized and controlled, which means that babies with meconium aspiration are randomly assigned to receive either the KL4 surfactant or the standard treatment, which can include high frequency ventilation, ECMO or nitrous oxide.
"We have a safety net for babies who don¹t get the new surfactant or if the surfactant doesn¹t work," Walsh said. "The study is also designed so that a baby in the control group or who doesn¹t do well with KL4 can receive the bovine surfactant instead."
Nationwide, 30 babies treated with KL4 will be compared to 30 babies in the control group. Enrollment is expected to take about a year, Walsh said.
Vanderbilt is the largest center participating. About 2-3 percent of babies admitted to the Neonatal Intensive Care Unit at VCH have meconium aspiration syndrome, Walsh said.
"We see about two a month," Walsh said. "It¹s not that common.
"A bowel movement in the uterus is very common, occurring in about 10-12 percent of all deliveries. The longer the pregnancy continues, the greater the chances. In pregnancies that go beyond 42 weeks, about half of the babies have passed meconium into the amniotic fluid. But the proportion who breathe the meconium into their lungs and who are sick enough to be in an neonatal intensive care unit is much smaller."
The bovine surfactant is so effective and so expensive, Walsh said he does not expect a private company to support a head-to-head comparison of the two versions. However, if KL4 is proven safe and equally effective in this and other studies, its cheaper production costs may ultimately make it the surfactant of choice, he said.