In 1969, at the Massachusetts General Hospital, after helping fix a hernia in a newborn’s diaphragm and then watching the baby die following an all-night vigil, surgical intern Michael Harrison had a big idea: repairing CDH in utero. The hole in the diaphragm wasn’t the real problem; rather, it was the abdominal organs that squeezed into the chest cavity, leaving no room for lungs to develop, so surgery on the fetus might allow the lungs to grow normally. At the time, the only fetal procedures that had been attempted were blood transfusions for Rh disease. Yet the thought that a fetus could be a patient never left Harrison, and in 1978 he joined the staff of the University of California, San Francisco, attracted by the research of pediatric cardiologists who were using a fetal sheep model to study the physiology of a newborn’s congenital heart defects. “But when I said, ‘Why don’t we think about fixing the heart in utero?’ they about fell off their chairs,” Harrison recalls.

Harrison pressed ahead, and in 1984, after 2,000 operations on fetal sheep and 500 on fetal monkeys, he tried a CDH repair on a human fetus. The surgery was radical—“I would just cut and sew in a big, terrible, open operation,” Harrison says—and no fetuses survived until 1989. But once he’d had a few successes, Harrison applied for funding from the National Institutes of Health for a randomized controlled trial to compare fetal surgical repair of CDH with postnatal surgery. The results, based on interventions involving just 11 fetuses and newborns, were “disappointing but interesting,” as Harrison reported in 1997. Those treated in utero had a 75% survival rate, compared with 86% for repair of CDH after birth. In such a small study, those outcomes were statistically indistinguishable.

With such questionable benefits, Harrison and other surgeons stopped doing that surgery but continued their research. As minimally invasive surgical techniques were developed for adults, fetal surgeons miniaturized endoscopes and other instruments, adapting them for their own use. Improvements in ultrasound made it easier to diagnose fetal problems and visualize the surgery, and doctors discovered that deeper anesthesia for the mother relaxed the uterus during surgery and helped prevent preterm labor. Surgery became less invasive and safer for both mother and child.

Still, CDH interventions in the womb have yet to prove as beneficial as operating on a newborn. From 1999 through 2001, a second NIH randomized trial involved 24 fetuses and newborns. But once again, the results favored the neonatal approach, which had a 77% survival rate compared with 73% for the fetal intervention. Further tipping the scales was that fetuses undergoing the procedure were delivered at 31 weeks, six weeks earlier than babies who were operated on after birth. As experiments continue, particularly in Europe, U.S. surgeons have largely abandoned fetal CDH repair.

Results have been much better for twin-twin transfusion syndrome. Compared with the conventional treatment of amnioreduction, selective laser ablation is less likely to prompt preterm delivery; fetuses are typically born at 33 to 34 weeks vs. 28 to 31 weeks with amnioreduction. Those extra weeks in utero reduce the risk of neurologic and cognitive problems—including mental retardation, cerebral palsy and muscle weakness disorders—that afflict as many as a third of babies who have amnioreduction. “Those risks fall to 7% or 8% with the laser procedure,” Johnson says. “That’s a significant difference.”

In the early 1990s, when surgeons first performed TTTS treatments, their tools were large and clumsy, but European researchers demonstrated that laser treatment of TTTS in the womb is significantly better than amnioreduction. The results reported in a 2004 European trial were so striking that a clinical trial under way in the United States was abruptly halted. Nearly 48% of the babies who had the fetoscopic laser procedure were alive and neurologically sound at six months compared with only 26% of those who had had amnioreduction.

“It was the first randomized controlled trial that showed any benefit for a fetal intervention, which was fantastic,” says Nick Fisk, a fetal-medicine specialist and director of the University of Queensland Centre for Clinical Research in Brisbane, Australia. “And initially, laser ablation appeared also to significantly reduce neurological injury in neonates. But there was no long-term reduction of cerebral palsy rates.”