Effects of an artificial placenta on brain development and injury in premature lambs

Church, John; Werner, N.; Coughlin, Meghan A.; Menzel-Smith, Julia; Najjar, Mary; Carr, Benjamin; Parmar, Hemant; Neil, Jeff; Alexopoulos, Dimitrios; Pérez-Torres, Carlos J.; Ge, Xia; Beeman, Scott C.; Garbow, Joel R.; Mychaliska, George B.

doi:10.1016/j.jpedsurg.2018.02.091

Cited by 23 publications

(17 citation statements)

References 30 publications

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“…The AP did not encumber regional cerebral oxygenation, blood flow, and autoregulation in 2‐day long experiments 102 . Normal cerebral maturation and absence of white matter injury (WMI) and intracranial hemorrhage (ICH) was found in animals supported for 1 week 107 . Examination of the gastro‐intestinal tract showed mild small bowel epithelial injury despite preserved mucosal architecture.…”

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

confidence: 91%

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: 91%

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

et al. 2020

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“…[7][8][9][10] Other investigators have reported the successful application of artificial-placenta based therapies for up to h with similar concepts and extracorporeal gas exchange systems. [11][12][13][14] Accordingly, the feasibility of long survival with a pumpless extracorporeal system has been well documented in the experimental literature.…”

Section: A N U S C R I P Tmentioning

confidence: 99%

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

Usuda

Watanabe

Saito

et al. 2019

American Journal of Obstetrics and Gynecology

132

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“…The concept of an artificial placenta (AP), whereby gas exchange is achieved using an extracorporeal membrane oxygenator (ECMO) connected to the fetal circulation via the umbilical vessels has been investigated since the 1950s (Westin et al, 1958). Recent research has established the feasibility of AP support of preterm sheep for periods of up to a month using a pumpless ECMO circuit (Arens et al, 2011; Church, Coughlin, et al, 2018; Church, Perkins, et al, 2018; Church, Werner, et al, 2018; El‐Sabbagh et al, 2018; Gray et al, 2013; Hornick et al, 2018; Lawrence et al, 2018; Miura et al, 2012, 2015, 2016; Partridge, Davey, Hornick, McGovern, et al, 2017; Reoma et al, 2009; Rochow et al, 2013; Schoberer et al, 2014; Usuda et al, 2017, 2019; Westin et al, 1958; Zapol et al, 1969). Importantly, two groups have provided evidence of near‐normal fetal growth and development using this approach without any of the typical organ injury associated with preterm birth (Hornick et al, 2018; Partridge, Davey, Hornick, McGovern, et al, 2017; Usuda et al, 2017, 2019).…”

Section: Introductionmentioning

confidence: 99%

Achieving sustained extrauterine life: Challenges of an artificial placenta in fetal pigs as a model of the preterm human fetus

et al. 2021

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Artificial placenta (AP) technology aims to maintain fetal circulation, while promoting the physiologic development of organs. Recent reports of experiments performed in sheep indicate the intrauterine environment can be recreated through the cannulation of umbilical vessels, replacement of the placenta with a low‐resistance membrane oxygenator, and incubation of the fetus in fluid. However, it remains to be seen whether animal fetuses similar in size to the extremely preterm human infant that have been proposed as a potential target for this technology can be supported in this way. Preterm Yucatan miniature piglets are similar in size to extremely preterm human infants and share similar umbilical cord anatomy, raising the possibility to serve as a good model to investigate the AP. To characterize fetal cardiovascular physiology, the carotid artery (n = 24) was cannulated in utero and umbilical vein (UV) and umbilical artery were sampled. Fetal UV flow was measured by MRI (n = 16). Piglets were delivered at 98 ± 4 days gestation (term = 115 days), cannulated, and supported on the AP (n = 12) for 684 ± 228 min (range 195–3077 min). UV flow was subphysiologic (p = .002), while heart rate was elevated on the AP compared with in utero controls (p = .0007). We observed an inverse relationship between heart rate and UV flow (r2 = .4527; p < .001) with progressive right ventricular enlargement that was associated with reduced contractility and ultimately hydrops and circulatory collapse. We attribute this to excessive afterload imposed by supraphysiologic circuit resistance and augmented sympathetic activity. We conclude that short‐term support of the preterm piglet on the AP is feasible, although we have not been able to attain normal fetal physiology. In the future, we propose to investigate the feasibility of an AP circuit that incorporates a centrifugal pump in our miniature pig model.

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Effects of an artificial placenta on brain development and injury in premature lambs

Abstract: Research study.

Cited by 23 publications

References 30 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

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

Achieving sustained extrauterine life: Challenges of an artificial placenta in fetal pigs as a model of the preterm human fetus

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