Successful use of an artificial placenta to support extremely preterm ovine fetuses at the border of viability

Background Ex-vivo uterine environment (EVE) therapy is an experimental life support platform designed to reduce the risk of morbidity and mortality for extremely preterm infants born at the border of viability (21-24 weeks gestation). To spare the functionally immature lung, this platform performs gas exchange via a membranous oxygenator connected to the umbilical vessels, and the fetus is submerged in a protective bath of artificial amniotic fluid. We and others have demonstrated the feasibility of extended survival with EVE therapy in late preterm fetuses; however, there is presently no evidence to show that the use of such a platform can support extremely preterm fetuses, the eventual translational target for therapy of this nature. Objectives To use our EVE therapy platform to support the healthy maintenance of 600-700 g / 95 d gestational age (equivalent to 24 weeks of human gestation) sheep fetuses. Primary outcome measures were: i) maintenance of key physiological variables; ii) absence of infection; iii) absence of brain injury; and iv) growth and cardiovascular function patterns matching that of non-instrumented, age-matched in utero controls. Study Design Singleton fetuses from eight ewes underwent surgical delivery at 95 d gestation (term=150 d). Fetuses were adapted to EVE therapy and maintained for 120 h with real-time monitoring of key physiological variables. Umbilical artery blood samples were regularly collected to assess blood gas data, differential counts, inflammation and microbial load to exclude infection. Brain injury was evaluated by gross anatomical and histopathological approaches after euthanasia. Nine pregnant control animals were euthanised at 100 d gestation to allow comparative post-mortem analyses. Data were tested for mean differences with ANOVA. Results Seven of eight EVE group fetuses (87.5%) completed 120 h of therapy with key parameters maintained in a normal physiological range. There were no significant inter-group differences