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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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2023.1219185/full |
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| author | Haruo Usuda Haruo Usuda Hideyuki Ikeda Hideyuki Ikeda Shimpei Watanabe Shinichi Sato Erin L. Fee Sean W. D. Carter Sean W. D. Carter Yusaku Kumagai Yuya Saito Tsukasa Takahashi Tsukasa Takahashi Yuki Takahashi Yuki Takahashi Shinichi Kawamura Takushi Hanita Masatoshi Saito Masatoshi Saito Atsuo Kikuchi Mahesh A. Choolani Nobuo Yaegashi Matthew W. Kemp Matthew W. Kemp Matthew W. Kemp Matthew W. Kemp |
| author_facet | Haruo Usuda Haruo Usuda Hideyuki Ikeda Hideyuki Ikeda Shimpei Watanabe Shinichi Sato Erin L. Fee Sean W. D. Carter Sean W. D. Carter Yusaku Kumagai Yuya Saito Tsukasa Takahashi Tsukasa Takahashi Yuki Takahashi Yuki Takahashi Shinichi Kawamura Takushi Hanita Masatoshi Saito Masatoshi Saito Atsuo Kikuchi Mahesh A. Choolani Nobuo Yaegashi Matthew W. Kemp Matthew W. Kemp Matthew W. Kemp Matthew W. Kemp |
| author_sort | Haruo Usuda |
| collection | DOAJ |
| 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 | doaj.art-ac6151b38f3a483ba49a0fd5ee68d77d2023-08-25T07:19:09ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2023-08-011410.3389/fphys.2023.12191851219185Artificial 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 growthHaruo Usuda0Haruo Usuda1Hideyuki Ikeda2Hideyuki Ikeda3Shimpei Watanabe4Shinichi Sato5Erin L. Fee6Sean W. D. Carter7Sean W. D. Carter8Yusaku Kumagai9Yuya Saito10Tsukasa Takahashi11Tsukasa Takahashi12Yuki Takahashi13Yuki Takahashi14Shinichi Kawamura15Takushi Hanita16Masatoshi Saito17Masatoshi Saito18Atsuo Kikuchi19Mahesh A. Choolani20Nobuo Yaegashi21Matthew W. Kemp22Matthew W. Kemp23Matthew W. Kemp24Matthew W. Kemp25Division of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA, AustraliaCenter for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, JapanDivision of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA, AustraliaCenter for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, JapanCenter for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, JapanCenter for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, JapanDivision of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA, AustraliaDivision of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA, AustraliaDepartment of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeCenter for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, JapanCenter for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, JapanDivision of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA, AustraliaCenter for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, JapanDivision of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA, AustraliaCenter for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, JapanNipro Corporation, Osaka, JapanCenter for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, JapanDivision of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA, AustraliaCenter for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, JapanCenter for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, JapanDepartment of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeCenter for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, JapanDivision of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA, AustraliaCenter for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, JapanDepartment of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeSchool of Veterinary and Life Sciences, Murdoch University, Perth, WA, AustraliaIntroduction: 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.https://www.frontiersin.org/articles/10.3389/fphys.2023.1219185/fullartificial placentaextremely preterm infantfetal growthextracorporeal membranous oxygenatorfetal circulationgrowth restriction |
| spellingShingle | Haruo Usuda Haruo Usuda Hideyuki Ikeda Hideyuki Ikeda Shimpei Watanabe Shinichi Sato Erin L. Fee Sean W. D. Carter Sean W. D. Carter Yusaku Kumagai Yuya Saito Tsukasa Takahashi Tsukasa Takahashi Yuki Takahashi Yuki Takahashi Shinichi Kawamura Takushi Hanita Masatoshi Saito Masatoshi Saito Atsuo Kikuchi Mahesh A. Choolani Nobuo Yaegashi Matthew W. Kemp Matthew W. Kemp Matthew W. Kemp Matthew W. Kemp 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 Frontiers in Physiology artificial placenta extremely preterm infant fetal growth extracorporeal membranous oxygenator fetal circulation growth restriction |
| 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 | artificial placenta extremely preterm infant fetal growth extracorporeal membranous oxygenator fetal circulation growth restriction |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2023.1219185/full |
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