Trajectories of Regional Cardiopulmonary Structure and Function in A Longitudinal Cohort of Extremely Preterm Infants

摘要 早产是新生儿重症监护病房入院的主要原因，并造成严重的 疾病和医疗保健成本，在美国每年接近134亿美元。新生儿研究进展 产前类固醇和表面活性物质等药物提高了存活率，特别是在出生时间极短的婴儿中。 早产(胎龄30周前)。因此，支气管肺发育不良(BPD)的发病率正在增加。 在流行方面。这通常会导致终生的心肺后遗症，并与慢性疾病重叠 如哮喘、慢性阻塞性肺疾病和肺动脉高压，增加早产的风险 死亡。不幸的是，极早产或出生后类固醇治疗对心肺的影响 在学龄早期(6-8岁)，结构和功能没有得到严格的评估 识别可以防止长期的不良后果。因此，重大变化可能会发生并保持不变 在这个肺快速生长和肺泡化的关键年龄未被发现，在此期间干预可以 成为最有优势的。为了解决这一未得到满足的需求，我们将利用已有的两项尚未解决的资源 辛辛那提儿童医院：1)尖端的质子和超极化气体磁共振成像 (MRI)可以准确地描述辛辛那提BPD中心的BPD表型，2)一口井- 美国国立卫生研究院资助的辛辛那提婴儿中早产儿的特征人群队列 神经发育早期预测研究(CINEPS)，将在此资助期间达到上学年龄。我们 将招募极早产儿的CINEPS亚组(140名患有BPD；68名没有BPD)和一个新的队列 并在6岁和8岁时用质子和超极化对他们进行纵向研究 GAS MRI、肺活量测定、体积描记术、弥散能力和父母问卷。这样做的主要目标是 建议对极早产儿的心肺结构和功能变化进行定义 在早年上学时。我们将进一步评估出生后激素治疗对肺结构的影响 与使用倾向分数加权匹配的未治疗婴儿进行功能比较。这项新颖的建议 代表了超极化气体磁共振在一组极早产儿中的第一次应用。此外，这一点 该方案代表了对极端早产儿对心肺的影响轨迹的最详细评估 结构和功能一直延续到学龄早期。这项高影响力的研究将定义肺部的进展， 心脏、肺血管疾病以及产后治疗的反应提供了独特的 早期识别与极早产有关的慢性变化的患者的机会 和BPD。

ABSTRACT Premature birth is the leading cause of neonatal intensive care unit admissions and exerts a high burden of disease and health care cost, approaching $13.4 billion annually in the United States. Advances in neonatal medicine such as antenatal steroids and surfactant have improved survival, particularly in infants born extremely premature (before 30 weeks’ gestational age). Consequently, bronchopulmonary dysplasia (BPD) is increasing in prevalence. This often results in lifelong cardiopulmonary sequelae that overlap with chronic diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary hypertension, increasing the risk of premature death. Unfortunately, the impact of extreme prematurity or postnatal steroid treatment on cardiopulmonary structure and function has not been rigorously evaluated during early school age (6-8 years), when early identification could prevent long-term adverse outcomes. Thus, significant changes can occur and remain undetected during this critical age of rapid lung growth and alveolarization, a time during which intervention could be the most advantageous. To address this unmet need, we will capitalize on two outstanding resources already in place at Cincinnati Children’s: 1) cutting-edge proton and hyperpolarized-gas magnetic resonance imaging (MRI) that can precisely characterize phenotypes of BPD in the Cincinnati BPD Center and 2) a well- characterized population-based cohort of preterm infants from the NIH-funded Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS) that will reach school age during this funding period. We will recruit the CINEPS subgroup of extremely preterm infants (140 with BPD; 68 without BPD) and a new cohort of 50 term-born controls and study them longitudinally at 6 and 8 years of age with proton and hyperpolarized gas MRI, spirometry, plethysmography, diffusion capacity, and a parent questionnaire. The primary goal of this proposal is to define changes in cardiopulmonary structure and function in extremely preterm infants during early school age. We will further evaluate the effects of postnatal steroids therapy on lung structure and function compared to untreated infants matched using propensity score weighting. This novel proposal represents the first application of hyperpolarized gas MRI in a cohort of extremely preterm children. Further, this proposal represents the most detailed evaluation of the trajectory of extreme prematurity on cardiopulmonary structure and function through early school age. This high-impact research will define the progression of lung, heart, and pulmonary vascular disease as well as response to postnatal therapies and provide a unique opportunity for early identification of patients who will develop chronic changes related to extremely preterm birth and BPD.