Lamb in a bag: artificial uterus could offer hope for human babies

Extremely premature lambs have been kept alive in an artificial uterus for four weeks (New Scientist, 2017). The system uses a fluid-filled plastic bag and could be used for premature babies within the next three years.

“We’ve developed a system that, as closely as possible, reproduces the environment of the womb and replace the function of the placenta” said Alan Flake at the Children’s Hospital of Philadelphia in Pennsylvania, who led the study.

“It is fascinating” said Neil Marlow, at University College London. “People have been trying to do this for ages.” But he said the system will have to undergo years of testing to be sure it is safe for babies.

Alan Flake and his colleagues developed their system with babies in mind. Being born extremely prematurely is the most common cause of death in babies. Infants born at twenty two to twenty four weeks, instead of the full forty weeks, have only a 10% chance of survival. Those that do survive are vulnerable to a host of disorders, and can develop lasting disabilities, such as poor vision or hearing or cerebral palsy. Alan Flake said “They have very immature organs. They’re simply not ready to be born yet.”

Babies supported in incubators are prone to infections, and the gas ventilation that is needed to help babies breathe can leave them with lung damage. But the plastic bag system provides a sealed environment that should protect a foetus from infections. To mimic the environment of the uterus, the team filled their bags with fluid comprising water and salts. In place of a placenta, which supplies a healthy foetus with oxygen and other substances, the team connected oxygenator devices to the umbilical cords of the developing lambs.

Instead of pumping oxygen into the lambs, the team developed a technique that uses the animals’ own heartbeats to drive the collection of oxygen from the device. They hope that providing oxygen in this way would be better than the ventilators currently used for premature babies, which can damage their lungs.

In their experiments, the team used lambs that were fifteen and seventeen weeks into the full twenty one week gestational period for sheep. These were removed by Caesarean section, carefully placed into the bags, connected to the oxygenators, and then closely monitored.

The lambs were kept in the bags for up to four weeks. Most of them were then euthanised and examined. All of the lambs appeared to show healthy development, and the team found no abnormalities in the lambs’ brains and lungs. Alan Flake said “These animals are, by any parameter we’ve measured, normal.”

Some of the lambs were “born” by being removed from the bags and bottle-weaned. The team said the oldest is now a year old and is doing well.

The team is now working with the US Food and Drug Administration to develop a version of the device for extremely premature human infants. Their plan is to support babies born at around twenty four weeks, until they reach around twenty eight weeks. By this point, their odds of survival are much higher. This is a “very reasonable” plan, said Mark Turner at the University of Liverpool.

However, Mark Turner is cautious of the team’s aim to trial the device on babies within three to five years. He said “I have concerns about getting the details just right.” Some treatments for premature babies have previously been rushed through, only for it to be discovered later that they are harmful. In the sixties babies were often given too much oxygen. This disrupted the formation of blood vessels, in some cases causing the retina to be separated from the back of the eye. Mark Turner said “Several thousand children went blind because of that, including Stevie Wonder.”

If the team can get the system working for human infants, it would be useful for only about half of the babies that are born extremely prematurely, those that can be delivered by C-section.

For their human device, Alan Flake’s team hope to improve the fluid that the babies will be bathed in. Amniotic fluid contains nutrients and growth factors, as well as foetal urine. The team plan on adding substances that are known to aid the development of the gut, for example.

The human device will look different, too. Alan Flake said “I don’t want this to be visualised as fetuses hanging on the wall in bags.” He said the device will eventually look like an incubator, with a cover and a dark interior. He also plans to make the device “parent-friendly” so that parents can communicate sounds to the baby and see it with a camera. Neil Marlow said this is an important consideration, as having a premature infant can be extremely distressing for parents.

On the whole, Neil Marlow is optimistic about the device, but shares similar concerns to Mark Turner. “Anything that is more gentle, and interferes in normal development as little as possible, is to be welcomed” said Neil Marlow “But we need to keep an eye on the risks.”

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