Successful use of an artificial placenta-based life support system to treat extremely preterm ovine fetuses compromised by intrauterine inflammation

[Introduction] Ex-vivo uterine environment (EVE) therapy is an experimental intensive care strategy for extremely preterm infants born between 21 and 24 weeks of gestation. Gas exchange is performed by membranous oxygenators connected by catheters to the umbilical vessels. The fetus is submerged in a bath of synthetic amniotic fluid. The lungs remain fluid-filled and pulmonary respiration does not occur. Intrauterine inflammation is strongly associated with extremely early preterm birth and fetal injury. Presently, there are no data of which we are aware to show that artificial placenta-based systems can be used to support extremely preterm fetuses compromised by exposure to intrauterine inflammation. [Objectives] To evaluate the ability of our EVE therapy platform to support extremely preterm ovine fetuses (95 d gestational age; approximately equivalent to 24 weeks of human gestation) exposed to intrauterine inflammation for a period of 120 hours, the following primary endpoints were chosen: i) maintenance of key physiological variables within normal ranges; ii) absence of infection and inflammation; iii) absence of brain injury; and iv) gross fetal growth and cardiovascular function matching that of age-matched in utero controls. [Study Design] Ten ewes with singleton pregnancies were each given a single intraamniotic injection of 10 mg E.coli lipopolysaccharides (LPS) under ultrasound guidance 48h before undergoing surgical delivery for adaptation to EVE therapy at 95d gestation (term=150d). Fetuses were adapted to EVE therapy and maintained for 120h with constant monitoring of key vital parameters (EVE Group) before being euthanised at 100d equivalent gestational age. Umbilical artery blood samples were regularly collected to assess blood gas data, differential counts, biochemical parameters, inflammatory markers and microbial load to exclude infection. Ultrasound was conducted at 48 h after intraamniotic LPS (before surgery) to confirm fetal viability and at th