Many Infant Transplant Questions Unanswered : Loma Linda’s Bailey--A Bold Pioneer

Seven months ago, Dr. Leonard Bailey, Loma Linda University Medical Center’s pioneering pediatric heart surgeon, stood virtually alone in the medical world in his determination to pursue experimental heart transplants on newborn babies.

Today, with five surviving patients out of five attempts--the youngest of whom was only 4 days old at the time of his transplant--Bailey has become, for the public and the profession alike, the man in the vanguard of an area of surgical experimentation that is fraught with unique medical and ethical difficulties.

Following Bailey’s lead, a hospital in Louisville last week gave a new heart to a 23-day-old boy, and surgeons at other transplant centers at Stanford, Tucson, Minneapolis, Philadelphia and elsewhere say they are ready to enter the heady new field as soon as the right candidate--and donor--comes along.

“Bailey is a pioneer and we’re following his results very closely. What other surgeons do will depend very much on what Bailey learns,” said Dr. Jack Copeland, chief transplant surgeon at the University of Arizona at Tucson.

Dr. W. Steves Ring of the University of Minnesota said he had considered heart transplants several years ago but was reluctant to take the chance. “Bailey’s experience has stimulated us to rethink it,” he said.

But many surgical researchers still regard newborn heart transplantation as a super-specialized field and they are willing to watch--and learn from--Bailey’s efforts rather than join in them.

“It’s an exciting clinical research area, but a new experience rather than an established theory,” said Dr. Hillel Laks, UCLA’s chief heart transplant surgeon. “We may be interested in doing infants in a couple of years.”

Transplant surgeons around the nation say that although Bailey has five surviving patients, the oldest of whom is 7 months old, there are many questions still unanswered about the length and quality of life ahead of the newborn heart transplant recipients.

- What will be the long-term effects of the anti-rejection drugs these infants must receive, perhaps for life? Cyclosporine, the chief among these medications, is known to cause kidney damage. Will baby kidneys be able to withstand its toxic effects? Will its use lead to the need for a kidney transplant?

- Will the heart grow as the baby grows? Will the side effects of steroids, another anti-rejection medication, stunt the growth of the transplant infants and slow their normal development? These concerns rank high among the reasons that very few youngsters under 18 years of age have received heart transplants.

- In adult patients, doctors gain early signs of an upcoming rejection episode by periodically removing a small piece of heart tissue for examination, a procedure that has helped to increase survival. This technique, called heart biopsy, is too risky in infants. Does this mean that rejection in infants will be harder to detect?

- Will the drugs’ effect on the immune system seriously impair the baby’s ability to fight the usual infectious diseases that every child encounters and usually fights off? What effect will that have on the rest of the family and the child’s ability to live normally?

Difficulties of Care

Last week, the mother of one of Bailey’s earlier transplant patients, Baby Rachel, now 5 months old, told reporters that Rachel’s three siblings must wear sanitary masks at the first sign of an infection and that no other children under age 10 are allowed in the house. Children of visiting family and friends have to wait outside.

“If she has a sniffle or a fever, you immediately begin to worry because she’s so susceptible (to rejection of her new heart),” said her father.

- How many of the babies will survive one year? Five years? Surgery to extend the life of an adult for five years is often considered a good risk by physicians, but should the same standard apply to newborn infants?

“The prospect of adding small amounts of life to an infant’s existence is very different than for adults,” said Arthur Caplan, specialist in medical ethics at the Hastings Center, a think tank near New York City.

Something close to normal maturation and development should be reasonably certain before a procedure can be considered a success, and hospitalization for treatment of acute rejection episodes should be infrequent, Caplan said.

Bailey was unavailable for an interview, but he indicated at a press conference last week that the seven months since he performed the world’s first successful newborn heart transplant on Baby Moses is insufficient time to answer those questions. But he said the results of years of experimentation on newborn animals that preceded his human trials convince him that the potential benefits to the babies are worth the risks of a series of human experiments.

Unknown Factors

Dr. William Frist, a senior fellow at Stanford University Medical Center who is active in the transplant program, said the unknown effects of anti-rejection drugs on growth and similar concerns will be carefully considered when Stanford selects its first newborn heart transplant patient.

“We’re geared up and ready to go (on younger children) if an appropriate candidate comes along,” he said, but added that candidates will have to meet very strict criteria, especially the kind of supportive family structure that is required to meet the baby’s needs after discharge.

A factor that weighs in favor of newborn transplants is that the survival rate of the 18 patients under 18 years who have received heart transplants at the center since 1981 is higher than that of adults, Frist said.

The head of Stanford’s program, Dr. Norman Shumway, widely regarded as the top authority on heart transplants, said last December that it is likely that an increasing number of children will receive transplants in the future. He credited drugs like cyclosporine and special techniques with dramatically expanding transplant possibilities.

Shumway said that the thinking at Stanford about trying heart transplants in children changed when a colleague, Dr. Philip E. Oyer, implanted the heart of a 12-year-old boy into an adult man. Although the boy’s heart was considerably smaller than the man’s, it eventually grew large enough to supply the adult’s needs, Shumway said.

“So we know that a transplanted heart will grow and develop along with the patient. That made it feasible to consider heart transplants in younger patients.” Shumway said.

Youngest Recipient

The youngest Stanford heart transplant recipient so far is a 2 1/2-year-old girl who received a heart in late 1984.

Copeland, the chief heart transplant surgeon at the University of Arizona at Tucson, summarized the dilemma faced by surgeons contemplating heart transplants on dying infants. Transplants so far have been done on newborns with hypoplastic left heart syndrome, a rare but always fatal birth defect, and cardiomyopathy, which fatally weakens the heart muscle.

To begin with, he noted, every heart transplant represents a tremendous investment in time, effort and money--all of which could be expended on other hospital work with more certainty of success.

“We are not dealing with a proven therapy. We don’t know the outcome,” Copeland said. “And we are reluctant to put these uncertainties on the shoulders of a young family unless they seem to be very responsible individuals. Although we’d like to be assured that the children will grow and be able to overcome all the usual childhood diseases, we have no such assurances.”

Having said all that, Copeland concludes, “But we will have to try it anyhow and see what happens.”

It was the demoralizing experience of watching newborn babies suffer and die of hypoplastic left heart syndrome that stimulated Bailey more than 10 years ago to begin research on infant heart transplants, he told reporters two years ago.

Baboon’s Heart

Bailey, 42, a graduate of Loma Linda University Medical School who has spent all but two years of his surgical career there, first gained national prominence in October, 1984, when he implanted the heart of a baboon into a 2-week-old infant known as Baby Fae. Baby Fae, who suffered from hypoplastic left heart syndrome, died 21 days later.

Last week he indicated he has not given up plans to do more baboon heart transplants, although he does not have the hospital’s institutional review board approval for another such operation at this time.

His most recent infant-to-infant transplant was last week on 16-day-old Jesse Dean Sepulveda. Two of the others were back in the hospital battling rejection episodes.

Although Bailey and his transplant team have not yet published in medical journals their findings on the infant-to-infant transplants, Bailey has made numerous appearances at surgical meetings across the country. His talks at those meetings have enabled other cardiac surgeons to benefit from what he has learned to date.

The medical community, however, also is watching for Bailey’s publications, one of which reportedly is pending.

Alternate Procedure

One reason for the growing interest in transplants for children is a disenchantment with another surgery developed by Dr. William Norwood of the University of Pennsylvania as a correction of hypoplastic left heart syndrome. The Norwood procedure requires two operations, separated by an interval of a year or so, that are aimed at repairing the baby’s defective heart rather than replacing it.

Norwood could not be reached for comment.

“The problem with the Norwood procedure is survival,” said the University of Minnesota’s Ring. While about 66% of the babies survive the first-stage operation, only a handful of Norwood’s patients live past the second stage, he said.

Ring and Dr. Jeff Dunn of Temple University’s St. Christopher’s Children’s Hospital in Philadelphia, who also said he has had poor results with the Norwood operation, said they have been encouraged by Bailey’s early successes to consider doing transplants instead. Both surgeons said they are now prepared to use transplants on newborns.

Recalling the low survival rate during the early days of adult heart transplants, which subsequently have increased substantially, Ring said, “If we could get a 50% survival over four or five years (for newborns), it would be worthwhile.”

Meanwhile, at Loma Linda, hospital officials are preparing an effort to try to convince the state and health insurance companies that infant heart transplants are no longer experimental.

Until now, Loma Linda University has borne the cost of all five infant transplants, which range from $60,000 to $100,000 each. But Baby Jesse, who received a new heart last Tuesday, marks the turning point in that policy, according to administrators and researchers at the university.

“Two years ago we agreed (with Bailey) to do five infant-to-infant heart transplants at our expense with the idea that with five under our belt we would have a viable track record from which to find outside funding to continue such work,” said Dr. John Ruffcorn, president of Loma Linda Medical Center.

“With Baby Jesse,” Ruffcorn said, “we are there now.”

Seeking Acceptance

Ruffcorn said the next step will be to “put a team together to approach the state to accept this procedure as viable” and make it eligible for reimbursement by Medi-Cal, the state-paid insurance program for the poor.

“We are a private institution. There is no free lunch for us,” he said.

Acceptance by the state, he said, would also “give us a better chance of being accepted by private, third-party (insurance companies).”

Bailey agreed. “I think we should present the state with a track record,” he told a reporter. “I think it should be soon.”

Dr. Bruce Branson, chief of surgery at Loma Linda, added that the problem of financing more infant heart transplants “will have to be settled within the next year.”

Meanwhile, Loma Linda has hired a team of private consultants to work on long-term fund-raising proposals to pay for new expansion projects at the medical center. The consultants, Steve Jacobs and Kent Dove of the marketing and development firm of Barton-Gillette Co., said Bailey and his widely reported accomplishments will be a major selling point for their efforts.

“I think Bailey is a marvelous commodity,” Dove said. “He is also a marvelous man and that is more important.”