Infant diet and cardiometabolic risk among children born preterm

项目摘要/摘要 每年，超过6.3万名美国婴儿在怀孕32周之前早产。现在为90% 由于更好的产科和新生儿重症监护病房(NICU)管理， 目前的挑战是减少幸存者经历的短期和长期疾病，包括两名至 年轻人患肥胖症、糖尿病、高血压和代谢综合征的风险增加四倍 成人期。《健康与疾病的发展起源》(DOHAD)框架认为慢性 疾病是由易受伤害的发育阶段的不良暴露引起的，称为“危急”或 “敏感”时期。尤其重要的是生命的头1000天，当关键的发育过程 为终身健康做好准备。正如他们所需要的，早产儿是一个特别脆弱的群体。 NICU在出生后2-4个月提供支持，恰逢怀孕第三个月--这是一个确定的敏感期 肥胖和心脏代谢风险的规划。在这方面，最具可修改性和相关性的 在NICU住院期间，暴露是饮食，这可能有助于加速脂肪团的积累 相对于脱脂质量。住院的早产儿通常体重增加受损，发育迟缓 相对于典型的胎儿，直线生长和多余的脂肪堆积。为了抵消这些问题并支持大脑 在发展过程中，将母乳的膳食强化作为护理的标准。然而，后果是 饮食强化对心脏代谢健康在这一人群中的作用知之甚少。这项提议旨在 揭示基于饮食的干预措施在多大程度上促进了身体发育和大脑发育 在敏感时期也可能导致心脏代谢风险。我们将研究130名出生在24-31岁之间的婴儿 参与营养研究(R01HD097327l；PI：Belfort)的怀孕数周者，正在进行的 个体靶向母乳强化与标准母乳强化效果的随机对照试验 在NICU住院期间的护理。通过延长该队列的随访时间并增加心脏代谢药物 生物标记在2岁和5岁时，我们有一个独特的机会来研究大量营养素和能量是如何 在敏感时期分娩有助于或保护儿童时期的心脏代谢风险。我们 进一步准备解决有关NICU增长模式与#年心脏代谢健康有关的关键问题 这群人。这项工作的发现有很大的潜力影响临床护理，因为它通知饮食 在发展的敏感时期制定战略，以优化弱势群体的终身健康。

Project Summary / Abstract Each year, over 63,000 U.S. infants are born very preterm, prior to 32 weeks of gestation. With >90% now surviving to discharge due to better obstetrical and neonatal intensive care unit (NICU) management, the present challenge is to reduce short- and long-term morbidities experienced by survivors, including the two- to four-fold increased risk of obesity, diabetes, hypertension, and metabolic syndrome that manifest by young adulthood. The Developmental Origins of Health and Disease (DOHaD) framework posits that chronic conditions result from adverse exposures during vulnerable developmental stages known as “critical” or “sensitive” periods. Of particular importance is the first 1000 days of life, when key developmental processes set the stage for lifelong health. Very preterm infants are an especially vulnerable population, as they require NICU support for 2-4 months after birth, coinciding with the 3rd trimester – an established sensitive period for programming of obesity and cardiometabolic risk. In this context, the most highly modifiable and relevant exposure is diet during the NICU hospitalization, which may contribute to the accelerated accretion of fat mass relative to fat-free mass. Hospitalized very preterm infants typically experience impaired weight gain, stunted linear growth, and excess fat accretion relative to the typical fetus. To offset these issues and support brain development, dietary fortification of human milk is provided as standard of care. However, the consequences of dietary fortification for cardiometabolic health in this population are poorly understood. This proposal seeks to uncover the extent to which diet-based interventions that promote physical growth and brain development during a sensitive period may also contribute to cardiometabolic risk. We will study 130 infants born 24-31 weeks of gestation who are participating in the Nourish Study (R01HD097327l; PI: Belfort), an ongoing randomized controlled trial testing the effect of individually targeted human milk fortification vs. standard of care during the NICU hospitalization. By extending follow-up of this cohort and adding cardiometabolic biomarkers at 2 and 5 years of age, we have a unique opportunity to investigate how macronutrient and energy delivery during a sensitive period contributes to, or protects from, cardiometabolic risk during childhood. We are further poised to address key questions about NICU growth patterns in relation to cardiometabolic health in this population. Findings from this work have strong potential to impact clinical care by informing dietary strategies during a sensitive window in development to optimize lifelong health for a vulnerable population.