Building an artificial womb

Artificial wombs spur futurists’ dreams about reproduction. One researcher is working to make them a reality.

birdArtificial wombs and placentas could mean the difference between life and death for babies born at the border of viability. These systems may eventually even be used for the entire fetal period, revolutionizing the reproductive options of women for whom pregnancy is risky. But the medical complexity of the natural womb makes it difficult to replicate. Stephen Bird is up for the challenge and is working to make LifePod, an artificial womb and placenta, a reality. We speak with him about the technology and its ethical implications.

ResearchGate: In what instances would LifePod be used?

Stephen Bird: Infants born extremely preterm—say at 22 weeks—with no treatment option other than making them comfortable, would be treated using LifePod. Ideally, parents at risk of preterm delivery would be identified and enrolled early. Supporting micropreemies to the point that they are healthy enough to advance onto conventional treatments would be a major milestone and enable entry to further clinical studies. This would pave the way for treating 24.9 week or earlier preemies and beyond.

RG: Can you tell us more about the babies that would go into the artificial wombs? What are extreme preterm births and what do they mean for the child?

Bird: Babies born around 6 months (22-28 weeks) are extremely preterm and the lower end of this range (22-25 weeks) is defined as the “border of viability.” Owing to low birth weights as small as 300g, micropreemies often die because their hearts, kidneys and lungs are too immature to support them outside the womb and therapies that involve ventilation teeter on the fringe of efficacy. Infants born at 22 weeks have less than 10% survival and receive no treatment, while infants at 25 weeks receive unconditional offers of support. Micropreemies spend months in the neonatal intensive care unit as they continue to develop outside the womb. Life threatening complications often occur including brain haemorrhage, damage to delicate lungs and severe infections.

Micropreemies often forget to breathe and become deprived of oxygen, causing damage to their developing brains and hearts. Multiple injection sites for medicines and fluids are vulnerable to infection. The infants require a feeding tube, because they have not learned to swallow, and need supplemental nutrition. The skin is thin and weepy and does not provide an adequate barrier to infections. Longer term complications can be severe including, chronic lung disease, developmental delay, and brain injury. Research evidence shows that low birth weight in term infants predisposes them to poor health as adults. This backdrop of disease etiology due to low birth weight adds to their prematurity related morbidities.

RG: How widespread is this problem?

Bird: Estimates from reliable published data in wealthy countries indicate that 0.3% of all births fall within the “gray zone” (24.9 weeks or earlier). This equates to approximately 270,000 infants across the developed world annually, and 70% of these infants will die within the first few hours of life. These estimates do not account for the numbers of deaths in poor countries, because reliable data is scarce.

RG: How would LifePod work?

Bird: At birth, the first breath inflates the fetal lungs and establishes a rapid and irreversible cascade of events which alters the flow of blood from the placenta to the lungs. Prevention of this perinatal transition is critical to keep the baby in a fetal-like state. Effectively, LifePod will artificially prevent an infant from being born. An infant would be transferred from its mother’s womb into an artificial womb and placed in a synthetic amniotic fluid. The infant would be connected to the artificial placenta via the umbilical cord blood vessels, and this would take on the role of supplying oxygen and nutrients while also removing the waste carbon dioxide and nitrogenous products usually removed by the kidneys. Constant fetal monitoring would occur automatically and sense changes in vital functions. Sophisticated software would analyze and adjust LifePod function to restore anomalies back to normal.

RG: What would “birth” from the LifePod be like?

Bird: Ideally, once the infant achieved "full term" developmental milestones equivalent to a 9-month pregnancy, the medical team would assess and decide whether the infant could "be born." Transfer from the artificial womb will occur as with natural birth ensuring the infant's lungs are working to full capacity.

RG: What are the most significant medical challenges to a functioning artificial womb and placenta?

Bird: Prevention of the perinatal transition, in addition to adequate control of blood flow in the circulatory system and infant’s tissue, are major challenges for developers of artificial placentae. Clotting can occur when blood is passed through medical devices. To mitigate this, anticlotting drugs are used to keep blood flowing freely. The down side of reduced clotting ability in these tiny infants is the risk of vascular accident in the brain. Innovations that address issues with blood carriage would reduce or eliminate the need for anticoagulant drugs in these devices.

RG: What have previous attempts to create an artificial womb been like? How do you hope to improve on these?

Bird: Research over 60 years using animal models has provided important lessons and milestones on adapting extracorporeal membrane oxygenation (ECMO) for extreme preterm birth. ECMO involves directing fetal blood through a vein or artery into a specialized membrane. Blended oxygen enriched gases are passes across the membrane to reach fetal red blood cells, displacing waste carbon dioxide. The refreshed oxygenated blood flows back to the body and is available to organs and tissues. A Japanese research group successfully maintained a goat fetus for three weeks using an ECMO based artificial placenta and womb. Currently, at least four groups in Canada, Japan, Germany and USA are researching improved methods of ECMO for artificial placentation. Others are experimenting with tissue engineering approaches to create biological artificial placentae.

LifePod adds to these contributions by replicating more of the functions of the natural womb in order to help maintain the infant’s stability. The reasoning is that disruption of one or more physiological parameter initiates a perilous cascade of events that sets the infant on a path of no return. LifePod will therefore provide improved stability around renal support, nutrients and waste removal, to name a few.

RG: How far has the project progressed at this point?

Bird: The project is currently seeking early stage research funding and product development funding from philanthropy.

RG: Do you think we’ll ever use artificial womb as a complete replacement for human wombs?

Bird: The first clinical LifePod will fill a need for emergency care. There is no doubt that spending more time in the womb would lead to better outcomes for micropreemies. Whether spending time in an artificial womb with placenta would provide similar benefit in other instances requires evidence from robust research. For now, the target group will be previable infants born between 22-25 weeks. Iterative improvements and refinement to the technology will produce versions that better mimic the natural placenta and womb. The natural consequence is that future artificial systems will eventually be able to provide complete support during the entire fetal period (weeks 8 to 40). In the future it is reasonable to expect that artificial placentation will be used by couples unable to maintain pregnancy. Artificial placentation will be a game changer for mothers at high risk of pregnancy loss and perhaps still birth. This need will create demand in the same way that IVF has transformed infertility. Other applications will include intensive care for children and adults with heart and lung disease unable to receive ventilation therapies.

RG: What are the ethical considerations for future applications of this technology?

Bird: The main ethical concern is that any new technology must not trade mortality for suffering. In other words, does the end justify the means? As harsh as this sound, parents along with their medical team must make the agonizing decision whether to initiate life support treatments for their extremely preterm infant, given low prospects for survival and high prospect of severe ill health. Care to ensure comfort is considered a more humane option than an infant suffering. Committed determination to pioneer a new way forward for these infants could potentially eliminate this tragic dilemma.

Any artificial womb and placenta system must demonstrate that it is not trading death for extreme suffering. In my view any artificial womb must achieve two pivotal objectives: It must eliminate pain and suffering during treatment. It also needs to reduce or eliminate morbidity and allow an infant to thrive.

The early versions of LifePod must transition an infant from previable to viable so that outcomes are equivalent or better than infants beyond the gray zone.This is an extremely exciting societal and technological challenge. The scope of the project has the potential not only to save millions of lives and offer a backup “safety net” to pregnancy loss, but to provide new insights into the fetal period and inform safer pregnancy outcomes.

Featured image courtesy of Seán Ó Domhnaill.