Preterm human milk composition in conditions of maternal overweight and obesity and effects of milk constituents on preterm infant body composition

考虑到孕妇超重和肥胖（OW/OB）在妊娠期和哺乳期的比例不断增加，关于孕妇代谢通过改变早产儿母乳成分对早产儿健康的影响存在知识缺口。有一个关键的需要，以确定纵向变化的早产母乳成分所造成的母亲OW/OB，特别是在早产儿的健康结果。我们的长期目标是优化早产条件下母乳营养质量的知识，同时考虑到妊娠和哺乳期孕产妇健康的流行病学变化。总体目标是记录早产母乳成分的纵向变化，特别是与母亲OW/OB相关的母乳脂肪酸（FA）和激素，并测量母乳成分对婴儿身体成分的调节作用。我们的中心假设是，OW/OB妇女产生的早产儿乳汁与正常体重妇女的乳汁成分不同，早产儿肥胖易受母体代谢状态和饮食的影响，通过改变乳汁成分。这项拟议研究的基本原理是推进和定制早产儿营养的建议，确保指南考虑到婴儿和母亲的新陈代谢。为了实现这些目标并检验假设，目标1将记录早产乳FA和与婴儿身体成分调节相关的激素的纵向变化，测量母体OW/OB引起的变异性。这将在一项母亲-早产儿配对的前瞻性队列研究中完成，其中招募了两组（共144名参与者）：1.主要：妊娠280/7-316/7周分娩的女性及其婴儿（n=42名女性，n=42名婴儿）和2.参考：比较妊娠340/7-366/7周分娩的女性及其婴儿（n=30名女性，n=30名婴儿）。筛选和入组将计入孕前体重指数（BMI），以在两组的正常、超重和肥胖BMI（各占三分之一）中平均分布。将在哺乳期第5周内采集系列早产儿乳汁样本。将对妇女和婴儿进行严格的临床表型分析，并获得妇女在哺乳期的饮食摄入量。目的2将评估牛奶FA和激素摄入量与早产儿身体成分的关系。空气置换体积描记法以及皮肤褶皱厚度将测量婴儿身体成分。通过记录每日营养摄入量来估计婴儿的母乳FA和激素摄入量，然后根据婴儿身体成分进行评价。拟议的贡献是重要的，因为它们将确定孕产妇和早产儿营养的方面，这些方面是可以干预的，并且最有可能解决母乳变异性和尚未纳入婴儿喂养标准的早产儿代谢能力。计划中的研究具有创新性，建议推进科学，以确定早产儿的营养状况和需求，使用增强的风险分层，部分基于怀孕和哺乳期间的孕产妇代谢和健康指标。

Considering the increasing rates of maternal overweight and obesity (OW/OB) in pregnancy and lactation, a knowledge gap exists regarding influences of the maternal metabolism on preterm infant health through alterations in preterm human milk composition. There is a critical need to define longitudinal changes in preterm milk composition resulting from maternal OW/OB especially in conjunction with preterm infant health outcomes. Our long-term goal is to optimize knowledge of human milk nutrient quality in conditions of preterm birth while ac- counting for the changing epidemiology of maternal health in pregnancy and lactation. The overall objective is to document longitudinal changes in preterm human milk composition, specifically milk fatty acids (FA) and hormones, associated with maternal OW/OB and measure regulatory effects of milk components on infant body composition. Our central hypothesis is that women with OW/OB produce preterm milk that is compositionally different from women with normal weight and that preterm infant adiposity is susceptible to maternal metabolic status and diet via altered milk composition. The rationale for this proposed research is to advance and tailor recommendations for preterm infant nutrition, assuring guidelines account for infant and maternal metabolism. To fulfill these objectives and test the hypotheses, Aim 1 will document longitudinal changes in preterm milk FA and hormones associated with regulation of infant body composition, measuring variability resulting from maternal OW/OB. This will be accomplished in a prospective cohort study of mother-preterm infant dyads with two groups enrolled (n=144 total participants): 1. Primary: women who deliver at 280/7-316/7 weeks of gestation and their infants (n=42 women, n=42 infants) and 2. Reference: comparison women who deliver at 340/7-366/7 weeks of gestation and their infants (n=30 women, n=30 infants). Screening and enrollment will ac- count for pre-pregnancy body mass index (BMI) to accrue an even distribution across normal, overweight and obese BMIs (one-third in each) for both groups. Serial preterm milk samples will be obtained through week 5 of lactation. Rigorous clinical phenotyping of women and infants will occur as well as obtaining women’s dietary intake during lactation. Aim 2 will assess the association of milk FA and hormone intake with preterm infant body composition. Air displacement plethysmography as well as skin folds thickness will measure infant body composition. Infant intake of milk FA and hormones will be estimated by documenting daily nutritional intake and then evaluated in relation to infant body composition. The proposed contributions are significant because they will identify aspects of both maternal and preterm infant nutrition that are amenable to intervention and which hold greatest potential to address human milk variability and the metabolic susceptibilities of the preterm infant not as yet incorporated within infant feeding standards. The planned research is innovative in proposing to advance the science towards defining preterm infant nutritional status and requirements using enhanced risk stratification, based in part on indicators of maternal metabolism and health during pregnancy and lactation.