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Artificial placenta support of extremely preterm ovine fetuses at the border of viability for up to 336 hours with maintenance of systemic circulation but reduced somatic and organ growth

Introduction: Artificial placenta therapy (APT) is an experimental life support system to improve outcomes for extremely preterm infants (EPI) less than 1,000 g by obviating the need for pulmonary gas exchange. There are presently no long-term survival data for EPI supported with APT. To address thi...

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Autores principales: Usuda, Haruo, Ikeda, Hideyuki, Watanabe, Shimpei, Sato, Shinichi, Fee, Erin L., Carter, Sean W. D., Kumagai, Yusaku, Saito, Yuya, Takahashi, Tsukasa, Takahashi, Yuki, Kawamura, Shinichi, Hanita, Takushi, Saito, Masatoshi, Kikuchi, Atsuo, Choolani, Mahesh A., Yaegashi, Nobuo, Kemp, Matthew W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484719/
https://www.ncbi.nlm.nih.gov/pubmed/37692998
http://dx.doi.org/10.3389/fphys.2023.1219185
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author Usuda, Haruo
Ikeda, Hideyuki
Watanabe, Shimpei
Sato, Shinichi
Fee, Erin L.
Carter, Sean W. D.
Kumagai, Yusaku
Saito, Yuya
Takahashi, Tsukasa
Takahashi, Yuki
Kawamura, Shinichi
Hanita, Takushi
Saito, Masatoshi
Kikuchi, Atsuo
Choolani, Mahesh A.
Yaegashi, Nobuo
Kemp, Matthew W.
author_facet Usuda, Haruo
Ikeda, Hideyuki
Watanabe, Shimpei
Sato, Shinichi
Fee, Erin L.
Carter, Sean W. D.
Kumagai, Yusaku
Saito, Yuya
Takahashi, Tsukasa
Takahashi, Yuki
Kawamura, Shinichi
Hanita, Takushi
Saito, Masatoshi
Kikuchi, Atsuo
Choolani, Mahesh A.
Yaegashi, Nobuo
Kemp, Matthew W.
author_sort Usuda, Haruo
collection PubMed
description Introduction: Artificial placenta therapy (APT) is an experimental life support system to improve outcomes for extremely preterm infants (EPI) less than 1,000 g by obviating the need for pulmonary gas exchange. There are presently no long-term survival data for EPI supported with APT. To address this, we aimed to maintain 95d-GA (GA; term-150d) sheep fetuses for up to 2 weeks using our APT system. Methods: Pregnant ewes (n = 6) carrying singleton fetuses underwent surgical delivery at 95d GA. Fetuses were adapted to APT and maintained for up to 2 weeks with constant monitoring of key physiological parameters and extensive time-course blood and urine sampling, and ultrasound assessments. Six age-matched in-utero fetuses served as controls. Data were tested for group differences with ANOVA. Results: Six APT Group fetuses (100%) were adapted to APT successfully. The mean BW at the initiation of APT was 656 ± 42 g. Mean survival was 250 ± 72 h (Max 336 h) with systemic circulation and key physiological parameters maintained mostly within normal ranges. APT fetuses had active movements and urine output constantly exceeded infusion volume over the experiment. At delivery, there were no differences in BW (with edema in three APT group animals), brain weight, or femur length between APT and in-utero Control animals. Organ weights and humerus lengths were significantly reduced in the APT group (p < 0.05). Albumin, IGF-1, and phosphorus were significantly decreased in the APT group (p < 0.05). No cases of positive blood culture were detected. Conclusion: We report the longest use of APT to maintain extremely preterm fetuses to date. Fetal systemic circulation was maintained without infection, but growth was abnormal. This achievement suggests a need to focus not only on cardiovascular stability and health but also on the optimization of fetal growth and organ development. This new challenge will need to be overcome prior to the clinical translation of this technology.
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spelling pubmed-104847192023-09-08 Artificial placenta support of extremely preterm ovine fetuses at the border of viability for up to 336 hours with maintenance of systemic circulation but reduced somatic and organ growth Usuda, Haruo Ikeda, Hideyuki Watanabe, Shimpei Sato, Shinichi Fee, Erin L. Carter, Sean W. D. Kumagai, Yusaku Saito, Yuya Takahashi, Tsukasa Takahashi, Yuki Kawamura, Shinichi Hanita, Takushi Saito, Masatoshi Kikuchi, Atsuo Choolani, Mahesh A. Yaegashi, Nobuo Kemp, Matthew W. Front Physiol Physiology Introduction: Artificial placenta therapy (APT) is an experimental life support system to improve outcomes for extremely preterm infants (EPI) less than 1,000 g by obviating the need for pulmonary gas exchange. There are presently no long-term survival data for EPI supported with APT. To address this, we aimed to maintain 95d-GA (GA; term-150d) sheep fetuses for up to 2 weeks using our APT system. Methods: Pregnant ewes (n = 6) carrying singleton fetuses underwent surgical delivery at 95d GA. Fetuses were adapted to APT and maintained for up to 2 weeks with constant monitoring of key physiological parameters and extensive time-course blood and urine sampling, and ultrasound assessments. Six age-matched in-utero fetuses served as controls. Data were tested for group differences with ANOVA. Results: Six APT Group fetuses (100%) were adapted to APT successfully. The mean BW at the initiation of APT was 656 ± 42 g. Mean survival was 250 ± 72 h (Max 336 h) with systemic circulation and key physiological parameters maintained mostly within normal ranges. APT fetuses had active movements and urine output constantly exceeded infusion volume over the experiment. At delivery, there were no differences in BW (with edema in three APT group animals), brain weight, or femur length between APT and in-utero Control animals. Organ weights and humerus lengths were significantly reduced in the APT group (p < 0.05). Albumin, IGF-1, and phosphorus were significantly decreased in the APT group (p < 0.05). No cases of positive blood culture were detected. Conclusion: We report the longest use of APT to maintain extremely preterm fetuses to date. Fetal systemic circulation was maintained without infection, but growth was abnormal. This achievement suggests a need to focus not only on cardiovascular stability and health but also on the optimization of fetal growth and organ development. This new challenge will need to be overcome prior to the clinical translation of this technology. Frontiers Media S.A. 2023-08-24 /pmc/articles/PMC10484719/ /pubmed/37692998 http://dx.doi.org/10.3389/fphys.2023.1219185 Text en Copyright © 2023 Usuda, Ikeda, Watanabe, Sato, Fee, Carter, Kumagai, Saito, Takahashi, Takahashi, Kawamura, Hanita, Saito, Kikuchi, Choolani, Yaegashi and Kemp. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Usuda, Haruo
Ikeda, Hideyuki
Watanabe, Shimpei
Sato, Shinichi
Fee, Erin L.
Carter, Sean W. D.
Kumagai, Yusaku
Saito, Yuya
Takahashi, Tsukasa
Takahashi, Yuki
Kawamura, Shinichi
Hanita, Takushi
Saito, Masatoshi
Kikuchi, Atsuo
Choolani, Mahesh A.
Yaegashi, Nobuo
Kemp, Matthew W.
Artificial placenta support of extremely preterm ovine fetuses at the border of viability for up to 336 hours with maintenance of systemic circulation but reduced somatic and organ growth
title Artificial placenta support of extremely preterm ovine fetuses at the border of viability for up to 336 hours with maintenance of systemic circulation but reduced somatic and organ growth
title_full Artificial placenta support of extremely preterm ovine fetuses at the border of viability for up to 336 hours with maintenance of systemic circulation but reduced somatic and organ growth
title_fullStr Artificial placenta support of extremely preterm ovine fetuses at the border of viability for up to 336 hours with maintenance of systemic circulation but reduced somatic and organ growth
title_full_unstemmed Artificial placenta support of extremely preterm ovine fetuses at the border of viability for up to 336 hours with maintenance of systemic circulation but reduced somatic and organ growth
title_short Artificial placenta support of extremely preterm ovine fetuses at the border of viability for up to 336 hours with maintenance of systemic circulation but reduced somatic and organ growth
title_sort artificial placenta support of extremely preterm ovine fetuses at the border of viability for up to 336 hours with maintenance of systemic circulation but reduced somatic and organ growth
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484719/
https://www.ncbi.nlm.nih.gov/pubmed/37692998
http://dx.doi.org/10.3389/fphys.2023.1219185
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