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Background Artificial placenta therapy (APT) is an experimental care strategy for extremely preterm infants born at 21–24 weeks’ gestation. In our previous studies, blood taken from the maternal ewe was used as the basis of priming solutions for the artificial placenta circuit. However, the use of maternal blood as a priming solution is accompanied by several challenges. We explored the use of synthetic red cells (hemoglobin vesicles; HbV) as the basis of a priming solution for APT used to manage extremely early preterm ovine fetuses. Methods Six ewes with singleton pregnancies at 95 d gestation (term = 150 d) were adapted to APT and maintained with constant monitoring of key vital parameters. The target maintenance period was 72 h in duration. A synthetic red cell solution consisting of HbV, sheep albumin and electrolytes was used as priming solutions for the APT circuit. Fetuses were evaluated on gross appearance, physiological parameters and bleeding after euthanasia. Results Two out of six APT fetuses were successfully maintained for the targeted 72 h experimental period with controllable anemia (>10 g/dl) and methemoglobinemia (<10%) using an infusion of blood transfusion and nitroglycerin delivered >1 h after APT commencement, a sufficient period of time to cross-match blood products and screen for viral agents of concern. Conclusions Extremely preterm sheep fetuses were maintained for a period of up to 72 h using APT in combination with circuit priming using a synthetic red cell (HbV) preparation. Although significant further refinements are required, these findings demonstrated the potential clinical utility of synthetic blood products in the eventual clinical translation of artificial placenta technology to support extremely preterm infants.

[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

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