Usuda Haruo, Watanabe Shimpei, Miura Yuichiro, Saito Masatoshi, Musk Gabrielle C, Rittenschober-Böhm Judith, Ikeda Hideyuki, Sato Shinichi, Hanita Takushi, Matsuda Tadashi, Jobe Alan H, Newnham John P, Stock Sarah J, Kemp Matthew W
Division of Obstetrics and Gynecology, University of Western Australia, Crawley, Australia; Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan.
Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan.
Am J Obstet Gynecol. 2017 Oct;217(4):457.e1-457.e13. doi: 10.1016/j.ajog.2017.05.046. Epub 2017 Jun 21.
Extremely preterm infants born at the border of viability (22-24 weeks' gestation) have high rates of death and lasting disability. Ex vivo uterine environment therapy is an experimental neonatal intensive care strategy that provides gas exchange using parallel membranous oxygenators connected to the umbilical vessels, sparing the extremely preterm cardiopulmonary system from ventilation-derived injury.
In this study, we aimed to refine our ex vivo uterine environment therapy platform to eliminate fetal infection and inflammation, while simultaneously extending the duration of hemodynamically stable ex vivo uterine environment therapy to 1 week.
Merino-cross ewes with timed, singleton pregnancies were surgically delivered at 112-115 days of gestation (term is ∼150 days) and adapted to ex vivo uterine environment therapy (treatment group; n = 6). Physiological variables were continuously monitored; humerus and femur length, ductus arteriosus directional flow, and patency were estimated with ultrasound; serial blood samples were collected for hematology and microbiology studies; weight was recorded at the end of the experiment. Control group animals (n = 7) were euthanized at 122 days of gestation and analyzed accordingly. Bacteremia was defined by positive blood culture. Infection and fetal inflammation was assessed with white blood cell counts (including differential leukocyte counts), plasma and lung proinflammatory cytokine measurements, and lung histopathology.
Five of 6 fetuses in the treatment group completed the 1-week study period with key physiological parameters, blood counts remaining within normal ranges, and no bacteremia detected. There were no significant differences (P > .05) in arterial blood oxygen content or lactate levels between ex vivo uterine environment therapy and control groups at delivery. There was no significant difference (P > .05) in birthweight between control and ex vivo uterine environment groups. In the ex vivo uterine environment group, we observed growth of fetal humerus (P < .05) and femur (P < .001) over the course of the 7-day experimental period. There was no difference in airway or airspace morphology or consolidation between control and ex vivo uterine environment animals, and there was no increase in the number of lung cells staining positive for T-cell marker CD3.
Five preterm lambs were maintained in a physiologically stable condition for 1 week with significant growth and without clinically significant bacteremia or systemic inflammation. Although substantial further refinement is required, a life support platform based around ex vivo uterine environment therapy may provide an avenue to improve outcomes for extremely preterm infants.
在可存活边缘（妊娠22 - 24周）出生的极早产儿死亡率和长期残疾率很高。体外子宫环境疗法是一种实验性的新生儿重症监护策略，它通过连接到脐血管的平行膜式氧合器进行气体交换，使极早产儿的心肺系统免受通气相关损伤。
在本研究中，我们旨在优化我们的体外子宫环境疗法平台，以消除胎儿感染和炎症，同时将血流动力学稳定的体外子宫环境疗法持续时间延长至1周。
对妊娠112 - 115天（足月约150天）的美利奴杂交母羊进行手术分娩，并使其适应体外子宫环境疗法（治疗组；n = 6）。持续监测生理变量；用超声估计肱骨和股骨长度、动脉导管方向血流和通畅情况；采集系列血样进行血液学和微生物学研究；在实验结束时记录体重。对照组动物（n = 7）在妊娠122天时实施安乐死并进行相应分析。菌血症通过血培养阳性来定义。通过白细胞计数（包括白细胞分类计数）、血浆和肺促炎细胞因子测量以及肺组织病理学评估感染和胎儿炎症。
治疗组6只胎儿中有5只完成了为期1周的研究期，关键生理参数、血细胞计数保持在正常范围内，未检测到菌血症。分娩时，体外子宫环境疗法组与对照组之间动脉血氧含量或乳酸水平无显著差异（P > 0.05）。对照组与体外子宫环境组出生体重无显著差异（P > 0.05）。在体外子宫环境组中，我们观察到在7天的实验期内胎儿肱骨（P < 0.05）和股骨（P < 0.001）生长。对照组与体外子宫环境组动物在气道或气腔形态或实变方面无差异，并且肺细胞中T细胞标志物CD3染色阳性数量没有增加。
五只早产羔羊在生理稳定状态下维持了1周，有显著生长，且无临床显著的菌血症或全身炎症。尽管需要大量进一步优化，但基于体外子宫环境疗法的生命支持平台可能为改善极早产儿的预后提供一条途径。
