Researchers are making progress on new artificial womb technology to care for extremely premature infants, but numerous scientific, logistical and ethical considerations remain.
The Food and Drug Administration’s (FDA’s) Pediatric Advisory Committee mulled these issues during an all-day meeting Tuesday intended to help guide additional research and future human trials.
“This is new frontier. We are developing a technology that literally will have a big impact on society,” said the panel’s consumer representative Randi Oster, M.B.A., co-founder and CEO of Help Me Health.
About 0.6% of all live births in the U.S. each year are extremely preterm at less than 28 weeks’ gestation. When actively treated, about 70% of infants born at 24 weeks’ gestation, 56% of those born at 23 weeks’ gestation and 30% of those born at 22 weeks’ gestation survive to discharge or 1 year, according to estimates from the National Institute for Child Health and Human Development. Those who survive have high rates of health and developmental issues.
Hospital neonatal intensive care units have advanced technology to care for extremely preterm infants, but infants still may experience complications including bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, sepsis, neurodevelopmental impairment and death.
Artificial womb technology devices are designed to treat extremely premature infants after 22 weeks’ gestation. Researchers believe they can improve the health of these infants by providing an environment to promote organ development, stable gas exchange and hemodynamics, and avoidance of potentially harmful mechanical ventilation, according to the FDA. Several systems are in development, and features may include a system for submersing the infant in sterile fluid, an oxygenator, umbilical cannulas and monitoring systems.
The FDA noted there still could be potential complications related to the cannulation procedure, thrombosis/bleeding, circuit resistance/cardiac afterload, artificial fluid, concomitant medications and prolonged total parenteral nutrition.
Several institutions have been studying various models for this technology using animals. Artificial womb technology is being studied using lambs at the Children’s Hospital of Philadelphia, Tohoku University in Japan and the University of Western Australia and in pigs at the University of Toronto. The University of Michigan is studying artificial placenta with lambs.
FDA advisers expressed some concerns about the differences between these animals and human infants, citing differences in size, physiology and development rate as well as challenges of following the long-term consequences of using the technology. They said more data will be needed to assess the risks and benefits.
Researchers seeking to conduct trials of the artificial womb technology in humans will have to follow FDA regulations and show there is direct clinical benefit, the risks are justified based on that benefit and the benefit/risk consideration is at least as favorable as routine clinical care.
Human trials likely would start with a single infant, but when and how to proceed with more children raise difficult questions about what adverse events would necessitate stopping the trial, how to distinguish adverse events related to prematurity versus the device and how long the child would be followed since neurodevelopmental issues may not be apparent until years later.
Panelist Sarah Hoehn, M.D., M.Be, chief medical officer at La Rabida Children’s Hospital, suggested looking at short-term issues like mortality, bleeding, clots, infection and growth. Committee member Jonathan Davis, M.D., chief of newborn medicine at Tufts Medical Center, said sorting out adverse events with a small number of trial participants will be difficult and suggested focusing on whether the equipment functioned properly, whether there was cardiovascular instability and whether the patients can easily get cannulated. Difficulty for one infant doesn’t necessarily need to mean stopping the trial for others, he said.
The group also discussed ethical considerations. Mark Mercurio, M.D., M.A., FAAP, professor of pediatrics and the director of the Program for Biomedical Ethics at the Yale School of Medicine, laid out many of these including the vulnerability of extremely preterm infants, the success rate with the current standard of care, potential for cesarean delivery when it otherwise would not have been indicated, getting consent from parents or guardians who are fully informed and considering outcomes like disabilities in addition to survival.
“I think this is a very promising technology and while I think we have to approach it with caution, with eyes wide open and with open … discussion of the ethical issues, I think we should move forward with discussions,” Dr. Mercurio said.
The group took a closer look at the issue of obtaining parent/guardian permission, which can be difficult given the complexity of the technology, emotional circumstances, parents potentially feeling pressured and the mother being a potential research subject.
The committee’s patient-family representative, Gianna McMillan, D.Be, associate director of the Bioethics Institute at Loyola Marymount University, said she personally was asked to consent for a procedure for her child. She found it important to have complete information, understandable language with visuals, multiple opportunities to ask questions, access to an objective third party and ongoing emotional support. Other committee members echoed these principles and pushed for educating people with high-risk pregnancies as early as possible and using patient advocates. Oster also stressed the need for providing information on liability for adverse events.
The FDA committee planned to hold additional private conversations Wednesday to discuss confidential commercial information around the technology. The FDA will take the group’s input into consideration when determining whether and how to proceed with trials.
Resource
View the slides from the meeting.
