A Big Breakthrough for the Tiniest Patients

A new womb-like device may dramatically reduce the effects of prematurity.

Infants born near the limit of viability — at 22 to 26 weeks gestation, or about four months early — weigh as much as a bottle of water and are so small they fit in a mother’s hand.

Fewer than half survive. Of those who do, 90 percent suffer sickness and disability, such as lung disease, cerebral palsy, blindness and brain damage.

Surgeons and neonatologists at Children’s Hospital of Philadelphia witness the effects of prematurity every day. And now a team of them has innovated a system that could revolutionize care for these tiny and vulnerable babies.

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A team lead by Alan Flake, MD, (right) has created a device that could transform care for infants like Savion (left), who weighed less than a pound when he was born at 24 weeks gestation.

Premature babies are not ready to breathe. From birth, they are placed on mechanical ventilators. Necessary to save them, ventilators also hurt them, exposing the lungs to levels of oxygen that arrest normal development. This causes a cascade of severe health effects.

The system invented at CHOP represents a radically different approach. The device — which is in an experimental stage using animal models — replicates the womb. The fetuses remain immersed in fluid and their lungs are kept at rest.

Researchers have been attempting to build such a device for more than 60 years. Previously, success at sustaining life was measured in hours.

The new system is strikingly better: It has supported animal fetuses for as long as 28 days, and they grow normally, with no damage to lungs or brain.

The results, published in April in Nature Communications, show great promise. The research team, led by surgeon Alan Flake, MD, Director of the Center for Fetal Research at CHOP, is currently working to scale down the system for use in human infants, who are much smaller than infant lambs.

“If our system is as successful as we think it can be, ultimately the majority of pregnancies predicted at-risk for extreme prematurity would be delivered onto an system that keeps them immersed, rather than being delivered onto a ventilator,” says Flake. “With that we would have normal physiologic development and avoid essentially all of the major risks of prematurity — and that would translate into a huge impact on pediatric health.”

Many to Help

In the United States, 30,000 babies are born every year at 26 weeks gestation or less. This extreme prematurity is the nation’s leading cause of infant mortality (death) and morbidity (sickness). The annual cost of hospital care for these babies is estimated at more than $40 billion.

The new system is intended to be a bridge to carry babies to the equivalent of 28 weeks gestation, when morbidity and mortality rates improve. It is not intended to extend viability beyond its current limit.

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Emily Partridge, MD, PhD, (top) and Marcus Davey, PhD, helped lead the round-the-clock effort to create the device. Davey is shown at left in the laboratory, with research technician Grace Hwang, and above in his father-in-law’s garage, which he used as a workshop to build and modify the prototypes.

How It Works

When they started four years ago, the researchers pored through publications about previous attempts. They also consulted another source: nature.

“Every obstacle that we’ve encountered, we’ve been able to overcome by turning to Mother Nature’s normal physiology, and that’s the beauty of this system,” says Flake.

In the womb, the lungs rest and grow. The fetus gets oxygen from the mother’s blood, which travels through the umbilical cord into the fetus’ bloodstream.

The new system is built to replicate this. The fetus rests in a heavy bag filled with lab-made amniotic fluid. The bag has an opening for the umbilical cord, which is kept long during c-section delivery. Surgeons insert tubes called cannulas into the blood vessels at the cut end of the cord.

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Most previous attempts at creating a womb-like device used artificial pumps to drive the blood through the system, causing heart failure. In the system invented at CHOP, the fetal heart is the only pump.

It is different in other key ways. Use of the bag, rather than a more open container, nearly eliminated the infection issues that contributed to previous failures. And while previous attempts relied on blood vessels in the neck, the CHOP team figured out how to quickly and successfully insert tubes (cannulas) into the notoriously touchy umbilical vessels.

The circuit works like this: Blood flows out of the umbilical cord, through plastic tubes, to an oxygenator. This device (developed for heart bypass surgery) extracts carbon dioxide and adds oxygen. Then the blood flows back to the fetus. The fetus is fed fluid nutrition from an IV bag connected to the circuit.

Imagination and Team

The spark for this breakthrough invention came from Emily Partridge, MD, PhD, a surgeon who is a fellow in Flake’s research lab.

She was convinced building a womb-like device was possible and believed the key would be avoiding artificial pumps, which had been used in most previous attempts. In the new system, the fetal heart is the only pump.

At first, the team had difficulty finding funding, as the idea seemed far-fetched. So they improvised, building prototypes with parts and equipment from other uses.

“Thomas Edison said, ‘To be an inventor, all you need is imagination and a pile of junk,’ and essentially, that is the story of our system,” says Marcus Davey, PhD, a fetal physiologist who designed — and redesigned and redesigned — the device. “We had to be very resourceful.”

Four prototypes were developed, each more effective than the last. Funding increased. And a growing team at CHOP — neonatologists, experts in heart-lung bypass and others — helped, believing the research would someday help children.

“The dedication that it takes to pull off an effort like this is tremendous,” Partridge says. “It would be impossible to tally the hours. But it has been nothing but a privilege to do this work because of the potential it represents. These infants are desperate for solutions and for innovation.”

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Recreating the Womb: New Hope for Premature Babies

In this video, researchers from Children’s Hospital of Philadelphia talk about a device that recreates the womb and may transform care for extremely premature infants.

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