An extra-uterine system to physiologically support the extreme premature lamb

Abstract

In the developed world, extreme prematurity is the leading cause of neonatal mortality and morbidity due to a combination of organ immaturity and iatrogenic injury. Until now, efforts to extend gestation using extracorporeal systems have achieved limited success. Here we report the development of a system that incorporates a pumpless oxygenator circuit connected to the fetus of a lamb via an umbilical cord interface that is maintained within a closed ‘amniotic fluid' circuit that closely reproduces the environment of the womb. We show that fetal lambs that are developmentally equivalent to the extreme premature human infant can be physiologically supported in this extra-uterine device for up to 4 weeks. Lambs on support maintain stable haemodynamics, have normal blood gas and oxygenation parameters and maintain patency of the fetal circulation. With appropriate nutritional support, lambs on the system demonstrate normal somatic growth, lung maturation and brain growth and myelination.

Chronically Hypoxic Fetal Lambs Supported by an Extra-Uterine Device Exhibit Mitochondrial Dysfunction and Elevations of Hypoxia Inducible Factor 1-Alpha

“…We have previously demonstrated physiologic fetal oxygen delivery in premature lambs supported by EXTEND [4], and we continue to do so in this study. Appropriate oxygen utilization, however, is not guaranteed simply by the presence of normal oxygen availability.…”

“…All aspects of the cannulation procedure as well as the care of lambs on EXTEND have been previously described in detail [4]. All procedures were approved by the Institutional Animal Care and Use Committee (IA-CUC) of The Children's Hospital of Philadelphia.…”

“…We have recently developed an extra-uterine environment for neonatal development (EXTEND) capable of physiologically supporting extremely premature lambs for up to 4 weeks [4]. Using this unique experimental model, we have the ability to replicate hypoxic in utero conditions by controlling oxygen delivery to the fetus.…”

Early-Stage Translational Research in Perinatal Medicine

“…To improve the survival of babies born extremely preterm, researchers in Philadelphia are developing an artificial womb, in which extremely preterm lambs receive oxygenation and nutrition via the umbilical vessels while the lambs are submerged in sterile, artificial, amniotic fluid [22]. The initial pilot studies in preterm lambs had a high mortality rate as the technology was developed.…”

Achievements in 2017, Promises of 2018

“…Fetal lambs that are developmentally equivalent to the extreme premature human infant were physiologically supported in this extra-uterine device for up to 4 weeks. By creating an artificial placenta that kept premature lamb babies alive for 1 month, the authors have raised the hope that we may have a solution for prematurity in the near future [2].…”