One out of every three infant deaths in the United States can be attributed to preterm birth. Researchers have recently reported the development of an external womb, which could give premature babies a more natural, uterus-like environment to aid in continued development. Preliminary results from lambs are very promising, and we may see human trials as early as 2020.

Extreme Premature Births and Infant Mortality

Extreme prematurity is the leading cause of infant mortality and morbidity in the developed world. In the United States, 1 out of every ten babies is born prematurely. Over one-third of all neonatal deaths and half of the new cases of cerebral palsy can be attributed to preterm births. We need new approaches to support the care and development of extremely premature infants.

While advances in neonatal intensive care have improved the chances of survival, complications arising from organ immaturity, such as chronic lung disease, remain a primary concern. Since the 1950s, researchers have attempted to create a viable artificial placenta to maintain an extracorporeal gas exchange. This concept is appealing because of the analogy to the innate fetal physiology, in which the placenta maintains this gas exchange. However, most efforts have been met with very limited success.

The Design of a Novel External Womb

Researchers from the Children’s Hospital of Philadelphia have recently reported a novel system, called the Biobag, that promises to overcome the barriers faced by previous efforts. Their system consists of three main components: a pumpless oxygenator circuit, an umbilical cord interface, and a closed fluid circuit.

The pumpless oxygenator circuit circulates blood to allow for an exchange of oxygen for carbon dioxide. External pumps can damage a fetus’ developing heart, so the researchers created a system that allows for flow so smooth that it can be powered by the fetus’s heart alone. This circuit was then connected to the lamb fetus via an umbilical cord interface, which was designed to more closely approximate flow dynamics found in the uterus.

The researchers also created a sterile, safe environment to maintain the fetus by designing a closed amniotic fluid circuit that mimics the mother’s womb. It contains an electrolyte solution that functions similarly to amniotic fluid, and which is enclosed in a plastic bag. This design allows for fluid flow to remove waste, deliver nutrients, and protect the fetus from infection. It also allows the developing lungs to remain filled with fluid—essential for their proper development.

Promising Results in Fetal Lambs

Using this extra-uterine device, the researchers demonstrated the ability to support extreme premature fetal lambs for up to 4 weeks without observed negative consequences (such as organ failure). They continue to monitor the lambs that were taken off the ventilator for long-term problems, but so far all indicators remain positive.

Of course, clinical applications will require further scientific and safety validation, and refinements to the design of the Biobag. These fetal lambs are developmentally equivalent to extreme premature human infants but are much larger. However, in pilot studies on far less mature lambs (that would be equivalent in size to the target preterm human fetuses), the researchers found the technical feasibility of using their apparatus at this magnitude.

Human Trials as Early as 2020

According to lead author Alan Flake, “It’s realistic to think about three years for first-in-human trials.” The initial clinical target population will probably be extreme premature infants at 23–25 weeks old. These infants are being routinely resuscitated and cared for in neonatal intensive care units, but still face high rates of morbidity and mortality.

While some commentators have looked at this device as the precursor to a self-sufficient artificial womb, Flake cautions again making that leap. “It’s complete science fiction to think that you can take an embryo and get it through the early developmental process and put it on our machine without the mother being the critical element there.”

There are, however, numerous potential other uses to be explored in the future, including treatment of fetal growth retardation due to placental insufficiency, saving of preterm infants threatening to deliver after fetal surgery, and the ability to deliver infants affected by congenital malformations for early therapy. Also, the Biobag would allow physicians to directly deliver therapeutics (such as stem cell or gene therapy) without risk of exposure to the mother.

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