Cheating Death

by Sanjay Gupta

  Until the mid-1990s, virtually all fetal procedures were done outside the mother’s body. Virtually all of these patients ended up being born prematurely. Anyone who’s been around for a delivery can understand the basic problem. When the sac in which the fetus grows is torn or punctured, the amniotic fluid that surrounds and cushions the baby leaks out. Or pours out, as the case may be. When a mother’s water breaks, it signals that labor is close at hand. The tearing of the sac, also called the rupturing of membranes, is more than a side effect. According to Michael Harrison, the amniotic fluid actually triggers a complex biological response, which itself induces labor. That’s why a physician who wants to induce birth will simply rupture the membranes.

  To do anything to the fetus surgically, there’s no way to avoid this fact of biology. You have to go through the lining of that sac. Says Harrison, “If you poke this little thin lining with a needle, you make an opening that does not heal. Fluid leaks through the hole, gets between membrane and muscle, and it’s a metabolically active fluid.” It turns out that even a tiny amount of that fluid is enough to cause a baby to be born several weeks before it’s due. You might think it’s a soluble problem, but Harrison says the human anatomy has proven trickier than expected.“We used to say, ‘Oh, just make a smaller hole.’ But it’s a discouraging thing; we’ve found that using smaller instruments doesn’t offer a big advantage.”

  A few developments have made fetal intervention far less risky, to both mother and child, than it was in the early 1990s. As we’ve seen already, sometimes the most important medical breakthroughs are the simplest. In the case of fetal surgery, the biggest thing making it safer and more effective was the simple ability to see the patient. The first fetal surgeries, at UCSF Children’s Hospital and a handful of European hospitals, were crude. Surgeons had to open the mother’s abdomen to reach the fetus. But the mid-1990s saw the development of tiny fiber-optic cameras, which could be inserted on a small instrument and send back pictures to a viewing monitor that would guide the surgeon. Michael Harrison and his colleagues at UCSF dubbed the technique Fetendo, because it reminded them of watching their kids play Nintendo video games. 7 (Dr. Hanmin Lee, the current director of fetal therapies at UCSF, smiles at the mention of Fetendo but says he prefers to talk about fetal endoscopic surgery. 8 )

  Another breakthrough came with the improvement of ultrasound imaging, which got to the point where the ultrasound could make out fine distinctions in a heart the size of a grape. A lot of expectant parents have watched in wonder as an ultrasound technician sends back pictures of their growing baby. This is the same technology that made possible the operation on Anders Wiley. “This is where the whole field is going,” Dr. Lee told me. “We are trying to make this a minimally invasive surgery.”

  Making fetal intervention minimally invasive hasn’t solved all the problems. Even for procedures like the one that Sally Wiley went through, the proportion of preterm births is about one in three. Preterm delivery and labor remains the Achilles’ heel of fetal surgery. Says Harrison, “We’ve been trying for thirty years, and we’ve failed [to prevent preterm birth].”

  For such a miraculous-seeming medical procedure, fetal surgery has seen its share of disappointments. One of the biggest involved early efforts at UCSF to repair congenital diaphragmatic hernias. CDH was one of the first problems identified as something which might be fixable in utero. Of babies born with the defect, about a third die and many more have lifelong, severe, and debilitating problems caused by stunted lung development.

  Unfortunately, in the first group of UCSF patients, the babies who had surgery did even worse. 9 “We found it was probably too much of an operation,” Lee says now. “It didn’t really work. We just had too many problems with preterm birth and the delicacy of the fetal body at that stage.”

  A group of younger UCSF doctors decided to take another tack, trying a complicated procedure that involves blocking the trachea of the fetus, which causes the developing lungs to secrete fluid. They hoped that the added pressure inside the chest would push the lungs to grow. Early results were promising, but a larger study fizzled. It’s not the end of the story; efforts are now under way to refine the technique, using smaller surgical tools and leaving the trachea blocked for a shorter period of time. A team in Belgium has found promising results. But even after twenty-five years of research, for a relatively simple anatomical problem, there is still no reliable fix. 10

  Of the study that didn’t pan out, Lee told me, “Of course, it’s disappointing that something you put a lot of work into doesn’t show the benefits, but you still have a group of sick patients you have to take care of. We need to think about ways of making care better for these patients. It just makes you roll up your sleeves and say to yourself, ‘You still have more work to do.’ ”

  It’s a pretty tough ledger. On one side, there are modest successes, along with a few patients stolen from the clutches of fatal illness. On the other side, there is a high risk of preterm birth, not to mention the dangers of any major operation: bleeding, infection, and complications with anesthesia—for the mother as well as the developing child. With this daunting calculus in mind, these operations are almost never done unless doctors think there is no other option—if the condition looks so debilitating that the child can’t wait until he’s born.

  THERE ARE THOSE who say the lure of technology—the sense that “we can do it, so why not?”—has been too seductive.

  One of the loudest critics, a sociologist named Monica Casper, says the biggest risk is placing too much emphasis on the health of the fetus as opposed to the mother’s. In 1998, Casper wrote a book, The Making of the Unborn Patient, based on extensive research and interviews with participants in the UCSF fetal surgery program. In a recent article, she writes that too often, doctors ignore the fact that there’s a second patient in the mix: “After all, it is only with women’s consent that fetal surgery can proceed at all; it is women’s bodies that surgeons must traverse to access the fetus, and it is pregnant women who assume principal risk on behalf of their fetuses. Fetal surgery is not, I argued, ‘fetal surgery’ at all; rather, it is more aptly maternal-fetal surgery, or just maternal surgery.” 11

  Casper notes that an early logo of the UCSF program was the hand of a tiny fetus reaching out for help with no mother in sight. More importantly, she says she found a cultural disconnect between the fast-track, aggressive approach of the surgeons and the delicate emotional condition of the women who came to the center. Casper says, “I’d sit down with a surgeon, and he’d be talking about why they leave the fetus inside the woman after the procedure, and he’d say, ‘The mother is the best heart-lung machine available.’ ” 12

  It’s not that Casper thinks fetal surgery is a bad idea. “I mean, the woman is the best heart-lung machine available. It’s just that by thinking that way, they turn her into a machine,” she says. Casper thinks the risks and benefits are not always fully discussed—it’s safe to say that few patients are as well informed as an ob-gyn like Sally Wiley. When the situation is a life-threatening defect—like Anders’ heart condition or a total urinary blockage—the benefits are pretty clear. But the calculus started to shift with the first surgical attempts to cure spina bifida in the womb. No one would argue that curing or lessening the crippling results of that disease isn’t worth some risk, but it has shifted the debate beyond the realm of cheating death.

  Around the same time, a handful of surgeons reached into the womb to repair cleft palates. By intervening early, they could minimize or eliminate scarring and get a better result. Still, that meant major surgery and all the attendant risks for a condition that is not life threatening by any stretch of the imagination. For Casper, it’s too much. “Clearly, anything that’s cosmetic, I think it’s insane to go through an intervention that could be handled postnatally.”

  Over the last decade since her book’s publication, Casper says there’s been a growing appreciation that two vulnerable patients are involved. Just l
ook at the UCSF logo: today, it’s a more realistic silhouette of a fetus cradled by two stylized hands. Needless to say, Casper does have critics, including Michael Harrison who calls her “a stealth radical who set out to undermine the whole process.” 13 Casper’s critics also include a number of antiabortion activists. She told me that after the book was published, many of these passionate activists called local radio shows to bash her and showed up to protest when she gave talks at bookstores.

  From its very beginnings, it was clear that fetal surgery would become an issue in the abortion wars. A 1981 Time magazine article describing Harrison’s first case suggested that “if fetal surgery fulfills its potential, the right-to-life argument—heretofore wielded by antiabortionists—could be used in favor of medical intervention, rather than against it.” 14 More recently, research by a Vanderbilt medical ethicist, Mark Bliton, found that pregnant women who are philosophically opposed to abortion are far more likely to pursue medical intervention to save their fetus. 15

  Meanwhile, the same technology that made fetal intervention possible has been adopted—in spirit—by the antiabortion movement to try and encourage women to bring their pregnancies to term. More than a dozen states have passed laws requiring doctors who provide abortions to do an ultrasound reading on any woman who comes for an abortion. 16 Some states require doctors to show those images to the expectant mother. A spokesman for Care Net, an antiabortion group that runs 1,100 “pregnancy centers” around the country, says that 75 percent of the women who see such pictures ultimately decide not to have an abortion. 17

  Not everyone accepts that number, but there’s no doubt: the visual image of a fetus, almost a miniature baby, is a powerful one. When we see a tiny image on the screen, fingers curled or reaching out, human nature tells us that’s a person. Even a pragmatic surgeon feels the tug of that emotion. Before the refinement of ultrasound, Michael Harrison says, “We’d never seen inside the uterus before. We never saw the kid having troubles.” 18

  Intellectually, doctors knew that birth defects developed in the womb. But it took an image to trigger the sense that something might be done about it. As Harrison observed to me, “The conceptual thing was to see that, hey, we’re seeing the same problems as in babies after birth. ‘Oh my gosh! You can predict there’s going to be a severe malformation. Hey, you can prevent that!’ And it makes sense. It’s just like the early diagnosis of cancer. The sooner you catch a problem, the better the results are in treating it.”

  Michael Skinner, Harrison’s first fetal patient to survive the surgery, is alive and well today in his mid-twenties and living in Florida. He suffered a few complications from his prebirth urinary blockage, but he has good kidney function and leads a normal life. He even came to a twenty-fifth reunion celebration of the UCSF transplant program. 19 Without the operation, there’s a good chance he would have been stillborn.

  When he talks about that first operation, Harrison’s tone is matter-of-fact. “It was really exciting. But we’d done our homework—and we thought it was the right thing to do.” By that time, the homework included more than one thousand operations on fetal lambs and nearly five hundred on fetal monkeys. “We were working like mad in the lab, and this case was just desperate enough to try it.”

  Harrison says the nascent fetal intervention program “was an extremely shaky and vulnerable enterprise” but adds that failures have to be expected with a brand-new, experimental surgery. It’s trial and error, literally. In terms of the team’s broad approach, it was crucial to choose both the right patients and the right condition to treat. Fetal hydronephrosis—the urinary blockage—was easy to detect, and as a pediatric surgeon, Harrison knew that in newborns it was relatively easy to fix. But that wasn’t enough to go on. “We had to prove our thinking was correct, that if you could unobstruct the urinary tract, the kidneys and lungs would recover,” he explains.

  The team also had to figure out a way to diagnose the severity of each case. They didn’t want to risk an experimental surgery on an in utero patient when the problem could just as easily be repaired in a newborn; at the same time, they didn’t want to work on hopeless cases. Not only would that be a poor use of time, there were cold pragmatic reasons, too. If the surgery didn’t save lives, it would be harder to find permission and funding for further research. Diagnosis was difficult, because these were patients, in the womb, whom doctors couldn’t physically examine. The San Francisco group spent years developing diagnostic tricks, studying crucial markers on the sonogram and biochemical markers in the fetal urine that would signal a more severe problem. 20

  * * *

  AS WITH ANY potentially lifesaving procedure, there were heated discussions over when its use was appropriate. Monica Casper, who studied the proceedings of the hospital’s independent review board, quotes a hospital social worker and a nurse as saying that there were cases when the medical team went ahead with surgery without waiting for approval from the hospital’s internal review board. 21 In medical ethics, this is a serious violation of procedure.

  In her book, the hospital is given the pseudonym Capitol Hospital, and Casper declines to say which hospital she refers to—but it seems likely that the fetal surgery program in question is the University of California, San Francisco.

  HARRISON INSISTS—VIGOROUSLY—that his team has always fully weighed the risks and shared the information with potential patients. Hanmin Lee says that caution continues to this day: “There was always work done first to prove it could be done safely for the mother [lab animal], and, number two, that we could successfully fix a potentially lethal anomaly. We always have to prove those things are true, before we even try it in humans.”

  Some programs that began with high hopes—like fetal surgery to prevent the lung problems that come with CDH—have proven disappointing. For others, the jury is still out. There is no definitive study showing that the operation performed on Anders Wiley is more likely to fix his heart condition than the traditional course of waiting until birth. When I first met the Wileys, fewer than one hundred such operations had ever been performed. Even now, the oldest survivor is just six years old. There are still major hospitals and accomplished prenatal and neonatal surgeons who do not think the benefits are proven and certainly not worth the risk to both mother and child.

  After returning to Austin to organize their affairs, the Wileys flew back to Boston to wait out the final months of Sally’s pregnancy. Wilkins-Haug thought she had corrected Anders Wiley’s heart problem, but it would be months before anyone would know the actual outcome. It was an excruciating wait. Jay Wiley describes a miserable winter, schlepping back and forth to the hospital through the frigid Boston streets. He manages a laugh, recalling it now: “We’re from Texas. We weren’t used to that weather!” Sally was exhausted with the pregnancy. Jay told me, “The worst part was just being in a holding pattern week after week. We desperately wanted a better picture of his long-term prospects, but we wouldn’t know that until he was born.”

  It was four months later that everyone got their first real look at the patient. Unlike Dyson’s arrival, Jay Wiley remembers the birth of Anders as a “joyless” event. There were few smiles and many tense faces in the delivery room. It’s not that he is a heartless dad; it’s just that it was hard to think of this as the beginning of life, when so much work had already gone into helping this infant to cheat death.

  Born a week before Valentine’s Day, Anders was small, and before the day was out he faced daunting complications. “It was grim,” says Jay. “I went with Anders while Sally recovered, and I could tell from the look on [the doctors’] faces and the urgency with which they moved that everyone was concerned about him not doing well.” Just hours after coming into the world, Anders was rushed to the cath lab. There, cardiologists who had used a tiny balloon to stretch his heart in the womb did an almost identical procedure, inserting a small catheter to further stretch the valve inside the left side of Anders’ heart.

  I paid a visit the very ne
xt day, as he was being monitored in the Children’s Hospital Intensive Care Unit. Any intensive care unit is a bit intimidating, with all the cold-looking, massive technology, but it’s especially jarring when the patients are so tiny. The ICU at Children’s Hospital is huge, full of dozens of patients at any given time. The patients, mostly newborns and preemies, are barely visible beneath the mountains of wires and machines surrounding each bed. I found Sally Wiley by Anders’ bedside, squeezing his tiny hand. Right away I noticed one remarkable thing: the skin around the ribs, where the needle had passed through when Anders was just a fetus, bore no scar. But the picture-perfect exterior was misleading. Anders Wiley faced a fight for his life.

  Those first weeks took a major toll. With all her medical training, Sally says she was prone to imagine the worst. “They’d tell me something, and I’d go down the pathway. If his eye looked like it drooped, I’d wonder, ‘Did he have a stroke?’ They’d take him off for tests, and my husband wouldn’t know why, but I would know just what they were concerned about, and it terrified me.”

  “There was almost a shorthand between Sally and the doctors,” says Jay. “Sometimes I would come away [from a meeting with the doctor] with a good feeling about our prospects, but Sally would throw cold water on that because she could read between the lines much better than I could.”

  Jay was getting his own crash course in pediatric medicine. “Jay said I drove him crazy, because I was so worried about everything,” Sally told me. “He wishes he’d have stayed naive.”

  Anders struggled mightily that first month. His breathing was so weak that doctors performed open-heart surgery when he was just three months old. It succeeded in helping his breathing, but doctors couldn’t say what the surgery meant for the long-term prognosis. At six weeks, Anders was well enough to be transferred to a hospital in Austin, where he spent another six weeks before going home. Even then, he wasn’t out of the woods. At eight months, Anders’ heart still wasn’t developing properly, and he had to be flown back to Boston for another open-heart surgery.