Artificial womb keeps premature lamb alive for 4 weeks: Giant leap towards developing artificial wombs for extreme preemies.

CHILDREN'S HOSPITAL OF PHILADELPHIA

A group of clinicians and researchers at Children's Hospital of Philadelphia in US has taken a giant leap toward developing an artificial womb for humans—by building and testing one designed to keep very premature lambs alive outside the bodies of their mothers.

Lambs born at the equivalent of 23 weeks of human pregnancy were kept alive and appeared to develop normally while floating inside the transparent, womb-like device for four weeks after birth.

This pioneering approach could radically improve outcome for babies born so early that they cannot breathe, feed or fight infection without medical help.

The study was published in Journal Natures Communications online 25 April 2017.

Extreme prematurity is leading cause of neonatal morbidity and mortality. Over one-third of all infant deaths and one-half of cerebral palsy attributed to prematurity.

Taking a cue from nature, Alan Flake, a researcher and neonatal surgeon at the Children's Hospital of Philadelphia along with Emily A. Partridge, and Marcus G. Davey created this new incubator after 5 years of research. It mimics the fluid-filled milieu  of the mother's womb while still maintaining a connection to the outside world.

He said, “the proposed system could act as an urgently needed bridge between the mother’s womb and the outside world for babies born at between 23 to 28 weeks’ gestation.”

 “If we can support growth and organ maturation for only a few weeks, we can dramatically improve outcomes for extremely premature babies,” he said.

This concept of extracorporeal support of the fetus is very appealing which maintains the intrauterine milieu by providing gas exchange by ‘artificial placenta’. The system consists of 3 main components namely:

1. a pumpless arteriovenous circuit,
2. a closed fluid environment with continuous fluid exchange
3. and a new technique of umbilical vascular access.  

The current device was created after identifying and rectifying many obstacles identified in series of pilot studies and years of tweaking.

A pumpless arteriovenous circuit

The blood flow is completely driven by pumping of the fetal heart  and is combined with a very low resistance oxygenator that most closely mimic the normal fetal/placental gas exchange interface.

A closed sterile fluid environment

The device uses a ‘Biobag’ design consisting of a single use completely closed system that houses and circulates fluid similar to amniotic fluid and that can closely replicate the size and shape of the uterus. The fluid's chemical composition is similar to amniotic fluid and contains electrolyte.

Umbilical vascular access

This closely approximate flow dynamics in utero because of double umbilical artery and single umbilical vein cannulation (abbreviated UA/UV) cannulation. The team devised adapters that helps to quickly cannulate the umbilical cord after birth, that is connected to external oxygenator, which serves the function of a lung. Umbilical cord spasm are avoided by adapting a number of techniques.

The study reported successful results with 8 lambs. They were in the ‘artificial womb’ for 1 month, with normal heart, lungs and brain development.

CHILDREN'S HOSPITAL OF PHILADELPHIA

Clinical application will require further evolution and modification of the design, safety and scientific evaluation of the entire system. But the target population for which the device is being developed is 23–25-week extreme premature infants.

The researchers do not aim to extend the current limit of viability, but to improve outcomes for those already treated in neonatal intensive care units (NICU).

Other therapeutics applications include treatment of  fetal growth retardation, salvage of preterm infants threatening to deliver after fetal intervention or fetal surgery.

This innovative technology could play a role to save  infants who have  congenital malformations of the heart, lung and diaphragm.

Numerous applications related to fetal pharmacologic, stem cell or gene therapy could be facilitated by removing the possibility for maternal exposure and enabling direct delivery of therapeutic agents to the isolated fetus.

The next steps for the Philadelphia team include one more animal study , as well as creating a device with medical-grade plastics for eventual use on humans.

Article source:  Partridge, E. A. et al. An extra-uterine system to physiologically support the extreme premature lamb. Nat. Commun. 8, 15112 doi: 10.1038/ncomms15112 (2017).

The full text of the Nature Communication article can be accessed here .