关键词: artificial placenta extracorporeal membranous oxygenator extremely preterm infant fetal circulation fetal growth growth restriction preterm birth sheep model

来  源:   DOI:10.3389/fphys.2023.1219185   PDF(Pubmed)

Abstract:
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.
摘要:
简介:人工胎盘疗法(APT)是一种实验性生命支持系统,可通过消除对肺气体交换的需求来改善小于1,000g的极度早产儿(EPI)的结局。目前没有APT支持的EPI的长期生存数据。为了解决这个问题,我们的目标是使用我们的APT系统维持95d-GA(GA;term-150d)绵羊胎儿长达2周.方法:携带单胎胎儿的怀孕母羊(n=6)在95dGA进行手术分娩。胎儿适应APT并维持2周,持续监测关键生理参数和大量时程血液和尿液采样。和超声评估。六个年龄匹配的子宫内胎儿作为对照。用ANOVA检验数据的组差异。结果:6例APT组胎儿(100%)成功适应APT。APT开始时的平均BW为656±42g。平均生存期为250±72h(最大336h),全身循环和关键生理参数大部分保持在正常范围内。在实验中,APT胎儿的运动活跃,尿量不断超过输液量。交货时,BW没有差异(在三个APT组动物中有水肿),大脑重量,或APT和子宫内对照动物之间的股骨长度。APT组的器官重量和肱骨长度显著降低(p<0.05)。白蛋白,APT组IGF-1和磷显著降低(p<0.05)。未检出血培养阳性病例。结论:我们报告了迄今为止使用APT维持极早产胎儿的最长时间。胎儿体循环维持,无感染,但是增长是不正常的。这一成就表明,不仅需要关注心血管稳定性和健康,还需要关注胎儿生长和器官发育的优化。在这项技术的临床转化之前,需要克服这一新的挑战。
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