The association between preterm milk immunobiology and infant health

描述（由申请人提供）：拟议的研究将调查乳汁免疫生物学和体积是否与极早产儿（750至1500克）的肠内健康、皮肤免疫和临床结果相关。母乳可能在这些脆弱的婴儿面临的多重风险中发挥调节作用，但早产儿接受的母乳总量是极不稳定的。在新生儿重症监护病房（NICU），研究将进行，只有40%的婴儿出院时接受任何母乳，这并不罕见。人们对早产母乳的基本成分知之甚少，也不知道是否有一些成分对婴儿的最佳结局至关重要。将招募100名母婴，预计至少有75名将继续进行研究，并在新生儿重症监护病房进行为期6周的研究。每次喂食时，将从母亲提供的乳汁中提取非常小的样本，然后将其与配方奶粉和补充剂混合。这些等量将被汇总并每周用细胞因子、趋化因子和生长因子的多重面板进行分析。分泌性免疫球蛋白A浓度也将被检测。每次喂养的准确记录，包括量、人乳量、配方奶和强化剂的量。此外，每周将从尿布中收集粪便样本，每周分析粪便钙保护蛋白，这是肠内病理生理的早期标志。皮肤免疫将被评估为免疫能力的潜在生物标志物，方法是使用贴在额头上的小胶带，然后通过多重试验去除并分析一组皮肤免疫成分和细胞因子。其他临床结果包括口服喂养时间、体重增加、出院时间和任何显著的不良健康结果，如感染或坏死性小肠结肠炎。这将是第一次仔细的研究，将提供计算在新生儿重症监护室期间的母乳因素和体积，并测量与婴儿健康，生物标志物和临床结果的关系。它将为我们目前所知甚少的重要关系提供效应量。

DESCRIPTION (provided by applicant): The proposed study will investigate if milk immunobiology and volume are associated with enteral health, skin immunity and clinical outcomes in very preterm infants (750 to 1500 gm). Human milk may play a moderating role in the multiple risks these vulnerable infants face, yet the total volume of human milk preterm infants receive is extremely variable. In the Neonatal Intensive Care Unit (NICU) where the study will be performed, only 40% of infants are discharged receiving any human milk at all, and this is not atypical. Little is known about the essential components of preterm mother's milk and whether there may be some components that are critically involved in the most optimal infant outcomes. One hundred maternal-infant dyads will be recruited, with the expectation that at least 75 will continue through the study, and studied for 6-weeks of their stay in the NICU. At each feeding a very small sample will be aliquoted from the milk mothers provide before it is mixed with formula and supplement. These aliquots will be pooled and analyzed weekly with a multiplex panel for cytokines, chemokines and growth factors. Secretory Immunoglobulin A concentration will also be assayed. Exact recordings of each feeding, in terms of volume, volume of human milk, and volume of formula and fortifiers will be done. In addition, weekly stool samples will be collected from diapers for a weekly analysis of fecal calprotectin, known to be an early marker of enteral pathophysiology. Skin immunity will be assessed as a potential biomarker of immunocompetency through the use of a small tape applied to the forehead, then removed and assayed for a panel of skin immune components and cytokines by multiplex assay. Other clinical outcomes will include time to oral feeding, weight gain, time to discharge, and any significant adverse health outcomes such as infections or necrotizing enterocolitis. This will be the first careful study that will provide a computation of human milk factors and volumes across a NICU stay and a measurement of relationships to infant health, biomarkers and clinical outcomes. It will provide effect sizes for important relationships about which we currently know so little. PUBLIC HEALTH RELEVANCE: This project will study the relationships between human milk immunity and milk volume with clinical outcomes and immune and enteral biomarkers in preterm infants while hospitalized in the neonatal intensive care unit.