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

Usuda, Haruo; Watanabe, Shimpei; Saito, Masatoshi; Ikeda, Hideyuki; Koshinami, Shota; Sato, Shinichi; Musk, Gabrielle C.; Fee, Erin L.; Carter, Sean; Kumagai, Yusaku; Takahashi, Tsukasa; Takahashi, Yuki; Kawamura, Shinichi; Hanita, Takushi; Kure, Shigeo; Yaegashi, Nobuo; Newnham, John P.; Kemp, Matthew W.

doi:10.1016/j.ajog.2020.04.036

Cited by 24 publications

(27 citation statements)

References 101 publications

(142 reference statements)

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“…Most recently, the group also investigated the EVE's ability to support 95‐day fetal lambs compromised by lipopolysaccharide‐induced intrauterine inflammation 112 . From the 8 out of 10 animals that survived 5 days on EVE, three had evidence of WMI on histology and six required dexamethasone to manage refractory hypotension.…”

Section: Current Successful Ap and Aw Models: Design And Outcomesmentioning

confidence: 99%

Artificial placenta and womb technology: Past, current, and future challenges towards clinical translation

et al. 2020

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Extreme prematurity remains a major cause of neonatal mortality and severe long‐term morbidity. Current neonatal care is associated with significant morbidity due to iatrogenic injury and developmental immaturity of extreme premature infants. A more physiologic approach, replacing placental function and providing a womb‐like environment, is the foundational principle of artificial placenta (AP) and womb (AW) technology. The concept has been studied during the past 60 years with limited success. However, recent technological advancements and a greater emphasis on mimicking utero‐placental physiology have improved the success of experimental models, bringing the technology closer to clinical translation. Here, we review the rationale for and history of AP and AW technology, discuss the challenges that needed to be overcome, and compare recent successful models. We conclude by outlining some remaining challenges to be addressed on the path towards clinical translation and opportunities for future research.

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Section: Current Successful Ap and Aw Models: Design And Outcomesmentioning

confidence: 99%

Artificial placenta and womb technology: Past, current, and future challenges towards clinical translation

et al. 2020

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“…Midazolam was continuously administered for the first 6 h (0.15 mg/kg/hour) 5 . Oxygen supply to the membranous oxygenators was adjusted to maintain fetal PaO 2 within a normal range between 15 and 30 mm Hg 5,6 . All fetuses were scheduled for a 72 h maintenance on artificial placenta therapy, followed by euthanasia with intravenous pentobarbitone (160 mg/kg/dose) for necropsy.…”

Section: Methodsmentioning

confidence: 99%

“…5 Oxygen supply to the membranous oxygenators was adjusted to maintain fetal PaO 2 within a normal range between 15 and 30 mm Hg. 5,6 All fetuses were scheduled for a 72 h maintenance on artificial placenta therapy, followed by euthanasia with intravenous pentobarbitone (160 mg/kg/dose) for necropsy. Antibiotic therapy and parental nutrition were as described previously.…”

Section: Maintenance After Deliverymentioning

confidence: 99%

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Assessment of synthetic red cell therapy for extremely preterm ovine fetuses maintained on an artificial placenta life‐support platform

et al. 2021

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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 crossmatch blood products and screen for viral agents of concern.

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“…Recently, H. Usuda et al investigated the EVE's ability to support 95-day fetal lambs compromised by lipopolysaccharide-induced intrauterine inflammation, with this study noting that eight out of ten lambs survived five days on EVE. Three of the lambs had evidence of WMI on histology and six required dexamethasone to manage refractory hypotension (H. Usuda et al, 2020).…”

Section: Ex Vivo Uterine Environment (Eve)mentioning

confidence: 99%

Nursing profoundly premature newborns with artificial placentae: a review

Oyedele

Murashko

2021

V.F.Snegirev Archives of Obstetrics and Gynecology

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Neonatal mortality and morbidity are substantial issues affecting the maternal healthcare sector. Extremely premature infants, notably those born before the 28-week mark, experience significant morbidity and mortality rates during neonatal care. This is a result of developmental immaturity and iatrogenic injury. Several attempts have been made to develop a womb-like environment to mimic uteroplacental physiology, but limited success has been noted over the last decade. This review aims to summarize the current literature on improved techniques implemented in creating an artificial placenta, the principles of these procedures, and their limitations. Our findings indicate that implementing techniques that closely mimic uteroplacental pathophysiology is crucial in decreasing the excessive neonatal mortality and morbidity rates seen in extremely premature infants.

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

Cited by 24 publications

References 101 publications

Artificial placenta and womb technology: Past, current, and future challenges towards clinical translation

Artificial placenta and womb technology: Past, current, and future challenges towards clinical translation

Assessment of synthetic red cell therapy for extremely preterm ovine fetuses maintained on an artificial placenta life‐support platform

Nursing profoundly premature newborns with artificial placentae: a review

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