Across the world, preterm birth is the leading cause of death and disability in babies under five. Today, treatment for these babies consists primarily of supplements and support to aid in the newborn’s physiological health. While the survival rate of these newborns increases every year, there has been little progress in raising survival rates to those of full-term newborns, who are physically healthier, physiologically independent, and more likely to develop normally mentally.
For over 60 years, the idea of artificial womb technology has lingered as a brighter hope for the treatment of preterm births. Over the course of the last six years, proof-of-principle artificial womb technology has been established, meaning the methods to prove the viability of the idea have been realized. This makes it finally possible to bring the concept to testing and clinical trials.
“Over the course of the last six years, proof-of-principle artificial womb technology has been established. This makes it finally possible to bring the concept to testing and clinical trials.”
One team at the University of Western Australia and one at the University of Pennsylvania have created the EVE platform and EXTrauterine Environment for Newborn Development (respectively), which are similar designs that seal the fetus in a sterile plastic bag filled with warm, synthetic amniotic fluid. Catheters are used to deliver water and nutrients and to remove waste. The synthetic amniotic fluid carries these nutrients and prevents infection, and an oxygenator provides oxygen while allowing the subject’s heartbeat to control circulation. This design intends to allow preterm babies to continue to grow their organs until they reach full development and can support their physiological functions on their own.
The EVE design was tested with lamb fetuses, which are developmentally similar to humans. They found high incidences of morbidity and mortality, so the EVE platform has been subject to redesign. However, the EXTEND, also called the “biobag,” delivered all the animal trial test subjects with a 100% survival rate and full development, leading the team to conclude that the device may be ready for human testing.
On Sept. 19 and 20, the FDA reviewed the findings of the team at the University of Pennsylvania and the EXTEND, deciding if the research should be continued to the third phase, which would include testing with human fetuses. The two-day meeting was conducted with an FDA Pediatric Advisory Committee, which discussed the ethical implications of such a study, the safeguards that would have to be put in place to protect the children, and ultimately, whether or not the biobag is actually an advance in care over the currently used Neonatal Intensive Care Unit (NICU).
The advisory committee panel began the meeting with a discussion about the validity of the animal trials that had been conducted up to date. It was agreed that the duration of the tests would need to be longer, and the variety of animals tested would need to be greater before it could be determined conclusively that human trials would be safe and ethical. The panelists also determined that one of the primary ethical considerations was the danger associated with cesarean section deliveries, which is a requirement for the fetuses’ transitions to the biobag. As such, participation in the study would require babies to be delivered by this method despite potentially being able to be delivered vaginally, increasing risk for the mother and any of the mother’s future pregnancies. This factor introduced some doubt about the feasibility of any potential human trials and would need to be discussed at greater length by the FDA.
It was also decided that only one patient could be enrolled in the study at a time should the human trials proceed, in order to avoid any unforeseen complications in multiple patients. However, the long-term neurocognitive development of the fetuses delivered with the biobag should not be considered when enrolling future patients in human trials.
The limitations of EXTEND also arose in discussion. Premature babies are born with thick-walled and underdeveloped lungs, with insufficient alveoli to oxygenate properly. Oxygenation must be done carefully to prevent a lack of oxygen to the brain, which, if done incorrectly, would slow brain development. This delivery may prove to be a challenge in some cases. Secondly, to prevent clots from forming where the oxygen tube enters the babies’ bodies, they would need to be put on blood thinners. However, because the newborns’ brains are still underdeveloped, this would put them at greater risk of brain bleeds.
The question remains to be answered: How can the ethical concerns be navigated to ensure safe advancements in reproductive technology? The FDA does not have to follow the recommendation of the advisory committee, which concluded that the data available right now is not enough to move forward with testing in humans; however, the scientists behind EXTEND are adamant that human trials are still nearing.
