Rare Treatment for Premature Infants
Rory Clark still gets goose bumps talking about a moment two years ago when he heard the news: His daughter Jennifer, a premature baby with respiratory disease syndrome (RDS), had been chosen for a new treatment with a rare and experimental substance. Doctors “were literally drawing names out of a box,” Clark said. Then one came “waving a card saying ‘She’s going to get it! She’s going to get it!’ ”
“It” was human surfactant--a complex aggregate of proteins and lipids (mostly fats) found in the amniotic fluid of mature fetuses. Victims of RDS (also known as hyaline membrane disease) lack the sticky, soaplike substance, which in full-term infants has prepared the lungs for birth by lubricating them and keeping fluids out.
Rory and his wife, Karen, had been visiting her mother in Escondido when Karen went into labor two months prematurely. Palomar Memorial Hospital sent them to the UC San Diego Medical Center, where Jennifer was born.
Little Hope for Survival
She weighed less than 3 pounds; her delicate lungs had collapsed and were filling with fluid. No one had given the parents any hope that their first child would survive.
Doctors had explained to the Clarks that Jennifer had a severe case of RDS, which afflicts the youngest and smallest 15% of the 380,000 premature infants born in the United States every year--including the three Frustaci septuplets who died at Childrens Hospital of Orange County in recent weeks.
To help Jennifer live, UCSD specialists had started with what has become standard treatment for RDS--hand-pumping oxygen into her lungs and attaching her to a sophisticated mechanical ventilator.
But they had also told the Clarks their daughter could be helped to breathe on her own by an emerging therapy available through the center’s randomized research project. In the treatment--first used on infants in 1981--doctors use surfactant from the amniotic sacs of healthy, full-term babies, dripping the substance down the windpipes of sick premature babies in the first few hours after birth.
Not Widely Accepted
Champions of surfactant treatment--which is not yet widely accepted--say it instantly increases an infant’s oxygen intake by as much as 10 times and reduces the need for artificial ventilation.
The treatment was an instant success, Rory said. After receiving the surfactant, Jennifer “immediately started breathing on her own,” he said. After a single treatment hours after birth, she remained in the hospital for two months--returning periodically to the mechanical ventilators--and was then released.
Today the only reminders of her early brush with death are scars and lumps on her hands and feet where she received blood transfusions for her low blood pressure. The strawberry blond toddler, who alternates between seriously scrutinizing the world and reacting joyously to it, is “happy and healthy because she has no (medical) problem,” according to Dr. T. Allen Merritt, associate professor of pediatrics at UC San Diego Medical Center, who administered the surfactant to Jennifer and monitors her development every six months as part of the ongoing project. “Her development has always been normal,” he added.
Now under intense study at a handful of hospitals, surfactant therapy is one of the latest in recent advances--including medication, monitoring equipment and surgical techniques--aimed at saving younger and smaller infants.
Still many, including Donald McNellis of the National Institutes of Health and doctors at the Childrens Hospital of Orange County, believe the jury is still out on surfactant. “We don’t have enough data on its effectiveness and safety,” said McNellis, who is special assistant for obstetrics in the pregnancy and perinatology branch of the National Institute of Child Health and Human Development.
“It’s a very exciting approach, and it will probably be effective in the most severe cases.”
Enthusiastic Supporters
The Clarks, however, are enthusiastic proponents of surfactant therapy, and credit it for their daughter’s survival and healthy recovery. In particular, they note, it allowed her to avoid prolonged dependence on the mechanical ventilator.
Though there is disagreement among neonatalogists, some researchers say the use of mechanical ventilators is associated with a high incidence of lung injury. Among them are Merritt and Louis Gluck, director of neonatal/perinatal medicine at UC Irvine Medical Center and founder of the first neonatalogy unit at Yale University in 1960. “Although some infants are able to have excellent recovery after assisted ventilation, a 20-year experience now indicates that perhaps one-third of all infants ventilated for RDS develop a debilitating chronic lung disease--bronchopulmonary dysplasia,” Merritt said. The disease can be fatal within the first year; it is also associated with lower (physical) development scores and recurrent infections in the lung, he said.
About 7% of all live births are premature, according to the March of Dimes Birth Defects Foundation, which has labeled preterm birth the leading unresolved issue in obstetric health care. Prematurity is the cause of death in the first month of life for 75% to 90% of all otherwise normal newborns and also the cause of 50% of all neurological handicaps among the survivors.
Developmental Problems
While some preterm babies have no problems, those born before 32 weeks of gestation (about the same time surfactant appears in the amniotic fluid) or those weighing less than 1,500 grams (3 pounds, 5 ounces) are prone to a number of problems associated with immature development, said McNellis.
“They die from problems related to brain, heart, intestines, liver, kidney. In addition, they have a limited caloric reserve,” Merritt said.
However, it is the lack of surfactant that is “the straw that breaks the camel’s back,” said Alan Jobe, director of the neonatal intensive care unit at Harbor UCLA Medical Center and a surfactant researcher.
Since 1980, seven papers in English have documented the benefits of surfactant, Merritt said. The UCSD study, published last month in The Journal of Pediatrics, followed 45 infants over a two-year period. Of the 23 who did not receive surfactant, 14 died of RDS. Of the 22 who received surfactant only one died of RDS. In addition, Merritt said, “we have no evidence of any long-term adverse consequences owing to surfactant administration.”
According to Merritt, 42 infants have been treated with human surfactant at UC San Diego Medical Center since 1981. In addition, Gluck, formerly of UC San Diego, has treated two infants with human surfactant since moving to UC Irvine last year. Tests are also under way in Toronto, the United Kingdom, Japan and Finland. Other institutions in the United States treating preterm infants with surfactant are the University of Rochester, University of Buffalo, University of Vermont and Boston Children’s Hospital, according to the National Institutes of Health. These programs use surfactant derived from cow lungs or artificial surfactant.
Only San Diego and UC Irvine are known to use human surfactant. Both have been issued an investigational drug number for use of human surfactant from the Food and Drug Administration. The surfactant is obtained from the amniotic sacs of volunteer women who have undergone Caesarean sections--a more sterile procedure, researchers say, than amniotic fluid that has been delivered vaginally.
After being isolated from the fluid, the surfactant is given to infants who do not respond to conventional therapy. After it is administered through a tube inserted in their windpipes, the tiny newborns are gently rocked back and forth to coat the lungs with surfactant.
Hospital regulations governing such tests vary but usually require informed consent from both donors and recipients, and professional committees that review the risk to the subjects. Parents currently cannot obtain surfactant treatment for their children on demand, Merritt said.
Recently, he administered surfactant to one of twin boys born 14 weeks early to Ann and Scott Kubichek, a couple from Brillion, Wis., who had been vacationing in Orange County. At birth, one baby, Joey, weighed 980 grams (2 pounds 3 ounces); the other, Michael, weighed 900 grams (2 pounds.) “We felt we had to,” Gluck said. “One baby was responding beautifully (to conventional treatment), the other was getting sicker.”
Ten weeks after birth, Joey weighs 4 pounds, 2 ounces and Michael weighs 3 pounds. “There’s no question he’ll do very well,” Gluck said.
‘A Different Breed’
Doctors at other hospitals, such as Childrens Hospital of Orange County, are content with conventional treatment. “Newborns are really a different breed, “ said Ralph Rucker, assistant director of the neonatal intensive care unit at CHOC. “You can’t use medication on these babies without good controls and safe drugs.
“As far as surfactant goes, we are certainly eager to see a good, available, studied preparation that would be safe,” he said. “It’s not appropriate to use surfactant in midsummer 1985. Maybe in midsummer 1986. You have to make sure the new way is better than the old way.”
The March of Dimes is currently funding studies into the prevention of preterm labor at medical centers in six cities: Birmingham, Chicago, Columbus, Nashville and San Francisco as well as San Diego.
