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Scientists Create 'Revolutionary' Artificial Womb

The researchers successfully tested the system on fetal lambs, but they hope that the technology can one day be applied to helping save the lives of critically preterm infants.

Published April 26, 2017

 (Children's Hospital of Philadelphia / Nature Communications)
Image Via Children's Hospital of Philadelphia / Nature Communications

On 25 April 2017, Nature Communications published a study headed by Alan Flake, Director of the Center for Fetal Research at the Center for Fetal Diagnosis and Treatment at Children’s Hospital of Philadelphia, that provided the most successful demonstration yet of what is being described as an "artificial womb".

The study describes a new system that allows fetal lambs at a similar stage of development as critically pre-term human infants (defined as births earlier than 24 weeks) to survive outside of the mother’s womb for up to four weeks. In the study, the researchers argue that this is a crucial challenge that needs to be met, because while new technology has allowed for the viability of earlier births, those births are often associated with chronic conditions:

In the United States, extreme prematurity is the leading cause of infant morbidity and mortality, with over one-third of all infant deaths and one-half of cerebral palsy attributed to prematurity. Advances in neonatal intensive care have improved survival and pushed the limits of viability to 22 to 23 weeks of gestation.

However, survival has been achieved with high associated rates of chronic lung disease and other complications of organ immaturity, particularly in infants born before 28 weeks. In fact, with earlier limits of viability, there are actually more total patients with severe complications of prematurity than there were a decade ago.

As discussed in a feature in The Atlantic, one of the most pressing concerns in premature infants is the development of the lungs, which can be halted if the fetus’s respiratory system is exposed to gaseous oxygen too soon in a condition termed bronchopulmonary dysplasia:

One reason preterm birth is so dangerous is that, for an underweight baby, the first few breaths of air halt the development of the lungs. “Infants that are currently born and supported in a neonatal intensive care unit with gas-based ventilation demonstrate an arrest of lung development,” [lead author Emily] Partridge says, “which manifests in a long-term, severe restriction of lung function.”

Another factor limiting the success of earlier attempts (which have been investigated numerous times since the first study published in 1964) is the development of circulatory problems caused by an overworked fetal heart, either by a system that adds resistance to blood flow or a system that imposes stress through the addition of an external pump. As discussed in a Children’s Hospital of Philadelphia press release, the new system aims to minimize both complications:

The current system mimics life in the uterus as closely as possible, building on knowledge from previous neonatal research. There is no external pump to drive circulation, because even gentle artificial pressure can fatally overload an underdeveloped heart, and there is no ventilator, because the immature lungs are not yet ready to do their work of breathing in atmospheric oxygen. Instead, the baby’s heart pumps blood via the umbilical cord into the system’s low-resistance external oxygenator that substitutes for the mother’s placenta in exchanging oxygen and carbon dioxide.

An additional innovation comes in something researchers are calling a BioBag, a sterile, single-use bag that circulates a substitute for amniotic fluid, designed to mimic the sterile conditions and actual environment to which a fetus would be exposed:

To further address issues of sterility, size adaptability and efficiencies of space and fluid volume, a ‘Biobag’ design was developed — a single-use, completely closed system that minimizes amniotic fluid volumes and can be customized to more closely replicate the size and shape of the uterus.

The results were promising, as reported by New Scientist:

In their experiments, the team used lambs that were 15 and 17 weeks into the full 21-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.

Previous attempts to design a pumpless artificial womb have been hampered by acidosis of the blood and early signs of brain damage in fetal lambs, and previously, the longest experiment had a predetermined limit of 60 hours, the team reported. Other pump-aided systems have had longer periods of operation, with the longest survival being 538 hours. This new study, the researchers argue, is an improvement in terms of both survivability (the team successfully operated their model for up to 670 hours) in the artificial womb, and outlook after birth.

While most of the lambs were euthanized, some of them were successfully "born", and the oldest is currently more than a year old and good condition. “These animals are, by any parameter we’ve measured, normal,” Flake told New Scientist. The researchers are optimistic about the future of the technology and are looking toward conducting clinical trials, reported Science magazine:

Flake is working with U.S. Food and Drug Administration to design an animal trial in accordance with the agency’s standards; he estimates that human testing is at least 3 years off.

Some have expressed concern that this technology could be used to argue for increased restrictions on abortion by extending the viability of a fetus to an earlier threshold, as discussed in The Atlantic:

If they ever materialize, artificial wombs may stir concerns among pro-choice advocates, since the devices could push the point of viability for human fetuses even lower. That might encourage even more states to curtail abortions after, say, 20 weeks’ gestation.

The researchers stress, however, that their goal is not to extend fetal viability, but instead to offer improved treatment to those infants already in neonatal intensive care:

Flake stresses that the team does not aim to extend viability to an earlier period than the current mark of 23 weeks. Before that point, limitations of physical size and physiologic functioning would impose unacceptably high risks.

The idea that this technology could be ready for clinical trials in such a short time period may be a bit optimistic, some argue, but overall researchers have hailed this study as a milestone. Tippi Mackenzie, a fetal and pediatric surgeon at the University of California, San Francisco, told Science that she imagines this technology will revolutionize neonatal care.

“I don’t think that’s too much to say,” she added.

Sources

Partridge, Emily A., et al.   "An Extra-uterine System to Physiologically Support the Extreme Premature Lamb."     Nature Communications.   25 April 2017.

Khazan, Olga.   “Babies Floating in Fluid-Filled Bags."     The Atlantic.   25 April 2017.

Callaghan, J.C., et al.   "Studies of the First Successful Delivery of an Unborn Lamb After 40 Minutes in the Artificial Placenta."     Canadian Journal of Surgery.   April 1963.

Children’s Hospital of Philadelphia.   "A Unique Womb-Like Device Could Reduce Mortality and Disability for Extremely Premature Babies."     25 April 2017.

Hamzelou, Jessica.   “Artificial Womb Helps Premature Lamb Fetuses Grow for 4 Weeks."     New Scientist.   25 April 2017.

Miura, Yuichiro, et al.   "A Parallelized Pumpless Artificial Placenta System Significantly Prolonged Survival Time in a Preterm Lamb Model."     Artificial Organs.   8 December 2015.

Unno, Nobuya, et al.   "Development of an Artificial Placenta: Survival of Isolated Goat Fetuses for Three Weeks with Umbilical Arteriovenous Extracorporeal Membrane Oxygenation."     Artificial Organs.   December 1993.

Couzin-Frankel, Jennifer.   “Fluid-filled ‘Biobag’ Allows Premature Lambs to Develop Outside the Womb."     Science.   25 April 2017.

Alex Kasprak is an investigative journalist and science writer reporting on scientific misinformation, online fraud, and financial crime.

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