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， 疾病和医疗保健费用，在美国每年接近134亿美元。新生儿医学研究进展 产前类固醇和表面活性剂等药物提高了存活率，特别是在出生于极低年龄段的婴儿中， 早产（胎龄30周之前）。因此，支气管肺发育不良（BPD）正在增加 in prevalence流行.这通常会导致终身心肺后遗症，与慢性疾病重叠， 如哮喘、慢性阻塞性肺疾病和肺动脉高压， 死亡不幸的是，极端早产或出生后类固醇治疗对心肺功能的影响 结构和功能在学龄早期（6-8岁）没有得到严格的评估， 识别可以防止长期不良后果。因此，重大变化可能会发生， 在这个肺快速生长和肺泡形成的关键年龄，在此期间，干预可以 是最有利的。为了满足这一未得到满足的需求，我们将利用两项尚未得到满足的资源， 在辛辛那提儿童医院：1）尖端质子和超极化气体磁共振成像 (MRI)可以精确表征辛辛那提BPD中心的BPD表型，2）良好的- 来自NIH资助的辛辛那提婴儿中心的早产儿特征性人群队列 神经发育早期预测研究（CINEPS）将在此资助期间达到学龄。我们 将招募CINEPS极早产儿亚组（140例BPD; 68例无BPD）和一个新的队列 的50名足月出生的对照，并在6岁和8岁时用质子和超极化纵向研究他们。 气体核磁共振，肺量测定，体积描记，弥散能力，和父母问卷。这个的主要目标 一项建议是定义极早产儿心肺结构和功能的变化 在学龄早期。我们将进一步评估出生后类固醇治疗对肺结构的影响 和使用倾向评分加权匹配的未治疗婴儿相比的功能。这个新颖的提议 代表了超极化气体MRI在极早产儿队列中的首次应用。此外，这 该提案代表了对极早产儿心肺功能轨迹的最详细评估， 结构和功能通过早期学龄。这项高影响力的研究将定义肺的进展， 心脏和肺血管疾病以及对产后治疗的反应，并提供了一个独特的 有机会早期识别将发生与极早产相关的慢性变化的患者 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.