Help for Fetal Defects : Why Not Try to Fix What Is Wrong?

Doctors over the last five years have watched the fetus draw ever closer to them. What was once a vague presence inside a patient’s womb has become, itself, a patient.

On the increasingly sophisticated ultrasound screens, arms wave, feet kick, hearts beat. Doctors study the fetus’s kidneys, bladder, spine, bowels. They take blood samples and examine the fetus’s enzymes, proteins, genes.

Once they could see their patient so clearly, it was no surprise that the doctors began to wonder: Why not try to fix what’s wrong?

Michael R. Harrison, a pediatric surgeon at the University of California, San Francisco, used to look at babies emerging from the womb with lesions and malformations. If we were just here a little bit earlier, he would tell himself, we could fix them.

The first efforts have been experimental, tentative and not always successful, but they have begun. Fetal medicine no longer means simply prenatal diagnosis and selective termination.

Doctors pass fine hollow needles through mothers’ abdomens and aim straight for the fetus, watching their target on ultrasound screens. They drain blocked bladders, kidneys and urinary tracts. They implant small tubes to draw off fluid gathering in chests, abdomens and heads. They inject proteins and medicines.

Staggering Notion

A few pioneers have gone further. The notion was staggering but unavoidable. Why not lay hands directly on the patient? the doctors asked themselves. And so they have.

Harrison is part of a team at UCSF that since 1981 has several times opened a pregnant woman’s abdomen and uterus, partly removed a fetus from the womb, unblocked a urinary tract, returned the fetus to the womb, and sewed up the mother.

The unborn patient. That is the title Harrison and his colleagues, perinatologist-geneticist Mitchell S. Golbus and ultrasonographer Roy A. Filly, gave their textbook on prenatal diagnosis and treatment. Harrison and Golbus are professors at the UCSF medical school and co-directors of the university’s vaunted Fetal Treatment Program.

When Harrison, 43, talks of his field, he is visibly excited about the future, even while candidly cautious about the present.

“When we first started doing this work I would go and talk about it to all kinds of people, but often to pediatric surgeons and people who deal with kids only after birth,” he said. “They’d say, ‘That’s really stupid, you don’t want to do that. You’ll have to make all these hard choices.’ I feel that is absolutely wrong. That’s just being afraid of knowledge. I think you ought to have a choice. It’s never better not to know.”

The medicinal solutions came first. Anemic fetuses missing red blood cells got transfusions. Fetuses with underdeveloped lungs got steroids. Fetuses with unbalanced metabolisms got vitamins and medications. Fetuses with retarded growth got nutrients.

Getting the medicine to the fetus was easy. Sometimes it was fed to the mother and it floated across by way of the placenta. Or doctors dropped it into the amniotic fluid and the fetus ate it. Or they injected it directly into the fetus.

The surgical solutions came more recently. Three maladies got the most attention, because they presented clear dangers and solutions.

In hydronephrosis, obstructed urinary tracts cause fluid to build up and damage the kidneys and lungs. In hydrocephaly, cerebrospinal fluid building up at high pressure inside the brain produces severe retardation. In diaphragmatic hernias, a hole in the diaphragm, which separates the abdomen from the chest, allows the growing intestines to spill into the chest cavity and stunt the lungs’ growth.

Uncharted Territory

In April of 1981, Harrison, with Golbus and Filly, stepped off into uncharted territory.

The mother, Rosa Skinner, was 17 weeks pregnant and carrying twins, an apparently healthy girl and a boy with a blocked urinary tract. The doctors knew the condition could be deadly. A blockage in the urethra, which passes urine from the bladder, causes a backup and swelling into the fetus’s abdomen. The kidneys can balloon and suffer permanent damage, or the amniotic fluid--consisting mainly of fetal urine--can disappear, causing severe abnormalities of the face, limbs and lungs.

To reduce the risk to the healthy fetus, the doctors waited until that twin’s lungs were mature enough to survive a premature birth, knowing surgery might trigger just such an event.

When the fetuses were 30 weeks old, Harrison passed a needle through the mother’s abdomen and uterus and into the male fetus’s bladder. The doctors watched on the ultrasound screen as fluid drained into the amniotic sac.

Attached to the end of the needle was a spaghetti-thin, hollow plastic tube with a one-way valve allowing fluid to flow from but not into the fetus’s bladder. The doctors pushed the tube off the needle, leaving it implanted halfway into the bladder. This shunt would keep the bladder drained until birth.

Fifteen days later, the twins were born by normal vaginal delivery, six weeks prematurely. The shunt was removed from young Michael Skinner, a healthy newborn boy.

Not everyone applauded. The procedure came only two weeks before delivery, so some doctors wondered why the risky procedure was done at all. If the fetus had survived to 30 weeks with an obstruction, they suggested, it could have made it to 32 weeks.

A good point, Harrison agreed--in retrospect. But they didn’t know the baby would be born so early. The rationale, the hope, was for a later delivery, a full-term delivery.

Procedure Repeated

Besides, the procedure had worked, and to Harrison that was the key. He and Golbus repeated the procedure on a number of other fetuses, becoming known as specialists in the field. Teams at medical centers throughout the world have followed after them. Worldwide, doctors have unblocked urinary tracts 79 times, according to the latest tabulations. Among those cases, 34 infants survived the neonatal period, all but two without long-term problems. Among the 45 deaths most came after birth because of lung problems, and 11 were aborted therapeutically before delivery because of chromosomal abnormalities and lack of kidney function. Three deaths were linked to the attempts at fetal therapy.

Some doctors also began using much the same technique to drain fluid in fetal brains. Results with these hydrocephalus cases were much more discouraging.

Doctors found they could not pick the right fetuses to operate on. They could not tell which had fluid on the brain because of an obstruction that would benefit by decompression, and which simply had a massive fluid buildup that would not be helped by a shunt.

Shunt Tried 45 Times

Doctors also found that draining fluid did not always mean the fetal brain would rebound and resume development. Fetuses often were operated on and then born severely retarded.

Doctors have tried the brain shunt 45 times, according to the most recent tabulations. Although 38 fetuses survived, two-thirds of them have serious brain damage.

Harrison and Golbus decided against trying operations for hydrocephalus.

Harrison had something even more ambitious in mind. Even as he began experimenting with shunts inserted through the abdomen, he felt dissatisfied with the limits of that procedure.

“Little tubes stuck in by needle were clearly not going to work over the long run,” he said. “It’s going to fall out, it’s going to fall in, it’s going to get plugged up with something. The kids are going to grab them and yank them out. These things are all going to happen. Little tubes don’t work very well long-term.”

Operating on Fetus

What would work, Harrison decided, was to open up the abdomen and uterus and operate directly on the fetus.

The mother was 18 years old, and her 21-week-old fetus had an enlarged bladder and kidneys, indicating a severe urinary tract blockage. Because of the position of the fetus and the mother’s unusually small uterus, Harrison decided that implanting a shunt was impossible.

He felt scared facing that first case, scared to death. There was a very real risk to the mother. Harrison had experimented with animals, but nobody had done this with a human patient. They were groping in the dark.

The doctors explained the risks to the mother. She or her baby could die from the surgery. The fetus could spontaneously abort. A hysterectomy might be necessary, or she could be rendered sterile. The fetus could have other undetected defects. The surgery just might not work, and even if it did, the kidneys and lungs might be too damaged or undeveloped for the baby to survive.

Save my baby, the mother said.

Open-Womb Surgery

On April 20, 1981, the UCSF team administered a general anesthetic to the mother. They also gave her crucial drugs, not available until recently, to relax the uterus and prevent premature labor--the most immediate danger in such open-womb surgery.

Then the doctors made an incision in the mother’s uterus and lifted the bottom half of the fetus out by its legs, still attached to the umbilical cord. They made two small incisions on his flank. The ureters were brought out, opened, and sutured to the skin so urine could drain directly out the lower back into the amniotic fluid.

The fetus was returned to the uterus. Doctors sewed up the uterus and abdomen. The operation took less than half an hour.

Monitors offered encouraging signs. Ultrasound showed the urinary tract had completely decompressed and fluid was draining. The fetal heartbeat was normal.

Kidneys Malfunction

However, the amniotic fluid, low to begin with because of the blockage, was not reaccumulating and this indicated that the kidneys were not functioning well. Too much damage had been done before surgery.

The baby was born at the 35th week. Because of the diminished amniotic fluid, his lungs had not matured enough to support life. He died after nine hours.

In an article in the New England Journal of Medicine reporting this case, Harrison and his colleagues wrote: “The ability to treat a few fetal disorders gives new importance to prenatal diagnosis and raises complex ethical questions about risks and benefits. . . . Although surgery offers new hope for the fetus with a correctable defect, the risks are high and there is considerable potential for doing harm.” Such surgery must be undertaken “only with great trepidation.”

Still, the operation had worked. Harrison marveled at the technical accomplishment even as he felt sad about the outcome. The mother went on to have two normal pregnancies, allaying his fears about the damage he might have done to her. The real challenge was to select a suitable fetus. The first one had been too sick to begin with.

Refinement of Science

So the UCSF team members worked on greatly refining their ability to pick fetuses. Without fanfare, they have now performed similar open-womb procedures several times. Until they publish their accounts in scientific journals, they will talk about only two of them. The results indicate both the increasing refinement of the science and the remaining potential for harm.

A family had traveled to San Francisco from the Midwest, seeking help for a fetus with a badly obstructed urinary tract. Harrison’s associates knew they were getting better but had not yet mastered the art of evaluating each case.

The family accepted the not inconsiderable risks and agreed to the surgery. Harrison opened the mother’s abdomen and uterus and operated directly on the fetus.

Thinking about it even now, when he is well aware of the final outcome, Harrison cannot help but remember that the procedure went beautifully. The technical accomplishment was all they could have hoped for.

The family returned to the Midwest and the baby girl was born three months later. Not until then did doctors discover that the urinary tract blockage had been only part of bigger, multiple anomalies. The kidneys, the intestines, most of her organs were defective.

The doctors had missed it all.

“This nice young family then went through a lot of agony with this kid over months and months, and then finally she died. . . . If we had done nothing, it’s awfully hard to know. Probably it would have died in the womb or at birth. Then they would have saved all the months and months of agony.”

There might have been an even worse result, Harrison believes. The baby might have survived, in a severely damaged state.

“That’s probably the scariest part, particularly with kids with central nervous system problems like hydrocephalus. Really the worst tragedy might not be that you intervened and screwed up and killed a kid. You could argue that it might be a worse tragedy to take a kid who would have died and then you convert him into a kid who is terribly damaged. That is the one thing I would fear the most. No, that’s the second. The worst fear would be to hurt the mom.”

Best Results to Date

The third fetus, a boy operated on in July of 1985 at 22 weeks, yielded the best results to date. He recently celebrated his first birthday in relatively good health, although he has only 50% function in one kidney and none in the other.

Harrison next will treat a fetus with a diaphragmatic hernia. For the surgeon, it is a bigger challenge, a more difficult procedure. It is also a more pressing malady, for these fetuses all die needlessly.

“The anatomical problem is a hole in the diaphragm and through it goes the intestines and various things that live down there,” he said. “That’s easy to fix after birth. We operate, put it back, close the hole. But the problem is, the lungs’ growth have been stunted by the intestines and are too small, haven’t developed. You need your lungs at birth, so the babies die.”

The only solution, Harrison knows, is to open the uterus and correct the defect before birth. He has experimented over and over on lambs and other animals, successfully. He has been looking for the right human patient.

He almost had one recently.

Counseling Families

When he counsels families, Harrison notices most seem to have reached decisions, one way or another, from the start. Some are going to do everything they can, and some, given the slightest hint of bad news, are going to get out. Neither type is nearly as anguished as the ones who cannot decide.

Such a couple came to Harrison from out of state. The woman was carrying a fetus with a diaphragmatic hernia. Harrison thought it was a good candidate for surgery and told them so, his words positive and encouraging. Yet in such situations, the UCSF team provides counseling from several people, and other counselors were not as supportive.

Harrison understood. The matter was full of ambivalence. He is the surgeon, after all, and a surgeon wants to operate. But decisions are difficult when you hear so many different voices.

“Sometimes it just floods the circuit. This particular couple had a hard time and eventually decided to terminate. It was a tough decision for them.”

The couple still call, long distance, to talk about options they no longer have.

“I am not a psychologist,” Harrison said, “but I think even if they had elected to try this operation, and it was a total failure and the kid just died right in the operation, they would have been happier.”

He considered the matter.

“Whether that is worth the risk, I don’t know.”

There are other types of risks. Harrison could diagnose a problem where there isn’t one, leading to a healthy fetus’s abortion.

One morning recently a woman came to him carrying a fetus with gastroschisis--its intestines were hanging outside the body. Harrison knew he could handle this easily after birth. Just stuff the guts back in and sew him up.

“But this woman came in very early, the earliest one I’ve ever seen, and we thought since the thing was already out, the guts were already out at 14 weeks or some god-awful early time, the kid would almost certainly be on the very severe end of bowel damage. It seemed like it just had to be a disaster because the survival with gastroschisis depends on the extent of bowel damage. If it’s a good bowel they do great.”

This was not the type of defect that allows for treatment before birth. The doctors’ task was to provide an accurate prognosis, so the mother could decide whether to continue the pregnancy.

What will my baby be like? she asked, just as they all do. What should I do?

Harrison considered. He didn’t know if the baby was going to be born with an unfixable situation. They might operate on the fetus 10 times and then it would die anyway. That would be devastating, a heavy number.

He was negative, openly so, in what he told the couple. So were the other doctors. The couple refused to listen.

‘Last Chance for a Child’

“The family were extremely good people,” Harrison said. “They were at the age where this was probably their last chance for a child. They had been childhood sweethearts who had married other people; each had two children by different mates, then they split up and got together and were very happy and this was their first child together. This family had their mind set that they were going to keep this child. I think we really sort of tried to talk them out of it.”

The doctors, surprised at the couple’s decision, continued to monitor the fetus, checking to see if the bowel was deteriorating. They figured the family might still have a chance to terminate before 22 or 24 weeks if things got worse.

The bowel did not get worse. Instead, it got better and better.

“It was an absolute total surprise to us,” Harrison said. “Her bowel was just great. Delivered her at 37 weeks. Stuffed it all back in with one shot--it was the easiest thing. It was just wonderful. The kid is perfect. I saw her last week and she’s absolutely adorable. It was just a good example of how sometimes there is some sort of unspoken wisdom that sort of defies everything else.”

Clearly Delighted

Harrison was clearly delighted, rather than alarmed, by his story.

“I just told them what I thought at the time. That’s all you can do,” he said. “You just have to be as honest as you can and know that you’re going to look back on a lot of these things and say I was flat out wrong. . . . People who actually deal with problems like this don’t have a philosophic bent. We just say, we’re not very good at this. We’re really pretty stupid at this. I’m sorry but you’ll have to decide.”

Harrison’s team has performed abortions. Faced with cases of twins, where a monstrously defective and doomed fetus is threatening the life of a healthy one, they have opened uteruses and removed the damaged twin.

Normally, doctors who abort sick fetuses stick needles in, shoot air into the heart, inject medication into the blood. Yet a problem arises, not infrequently, when they are handling identical twins who are sharing circulation. Inject something in that situation and it goes to the healthy fetus.

Some time ago, thinking about this, Harrison told his colleague Mitchell Golbus what they should do.

“Well, Mickey,” he said, “don’t screw around. Just take the kid out.”

At first the team members felt they could not dare intervene in this manner. The doctors preferred to wait long enough during the pregnancy for the healthy one to be viable outside the womb, then do an early Caesarean section. The least evasive approach is always the first choice.

They tried that with several cases. They would get far enough into the pregnancy to deliver, then wait. As soon as the healthy twin turned bad, their hand would be forced, but they did not want to do anything unless they had to.

The problem was, the healthy fetuses never turned bad--they just died.

“The mother would come in one day, you’d look at the kid, he’d be perfectly happy and his heart would be beating,” Harrison said. “They’d come back the next day and he’d be dead. They died just like that. It was incredible and it happened several times while we were following and planning to intervene as soon as he looked bad.”

More Direct Action

So the doctors decided they should take more direct action. First they thought they might just open the uterus and put a clip across the umbilical cord of the damaged fetus.

“But if you’re going to do that you might as well take him out,” Harrison said. “And that’s in fact what we did a couple of times recently.”

Harrison will talk philosophy, even though he does not feel it counts for much in his field. The father of three, he is a practicing Catholic. Sitting in his office one afternoon, he pointed to the picture of a fetus on the cover of his textbook.

“Our science makes this guy a patient, that’s all. This enterprise can be viewed in a lot of different ways. For example, we could be the darling of the right-to-lifers. You know, prenatal diagnosis before was aimed at search and destroy and killing all these kids. Now we come along, we can treat them, so, oh my God, we’re in there and they’re patients; therefore, they’re people. And there is truth in that. That’s sort of my own slant. . . .

“In practice, though, the thing is, prenatal diagnosis more often than not turns up bad kids. The problem is, we don’t have answers for them. I mean, in the big picture these little things we do are for diseases that are exceedingly rare. The vast majority we don’t have answers to. Many of the things we see, the families choose to abort the pregnancy and that seems to me to be the right decision. So, you know, you could argue where that’s on the other side of the coin. . . .

“We’re not going to save all these little babies. Some of them were not meant to be saved at the present time. The fact that families can abort and start all over again and avoid five months of hopeless pregnancy seems to me to be the right thing to do.”

Harrison looked mildly pained.

“Don’t tell my church,” he said.

If he thought out and defined all the issues his work kicks up, Harrison suspects he would be out of the Catholic church. He says he would rather just admit there are conflicts, unsolvable ones, and exist in a state of ignorance.

Yet he has, in fact, thought about it all a good deal.

“I look at those guys hopping ‘round on the sonogram, having a good time, and I think, they’re just the same as we are,” he said one afternoon. “But that’s just the point. I don’t think that being in the womb or out has anything to do with it. There are some sick fetuses and there are some not sick ones, some that live and some that don’t. . . . Or one has this terrible problem and one has a pretty good problem, so this one we refuse to operate on and that one we are happy to try to fix. The thing is, fetuses are no different than we are.”