SECONDARY ANALYSES OF RCT DATA ON SENSITIVE PERIODS IN FLAVOR LEARNING AND DIET AMONG BREASTFEEDING DYADS

摘要 Precis：我们的目标是评估产后饮食的直接和间接影响。 母乳喂养的母婴双胞胎。除了实现随机对照的主要目标外， 试验(RCT)旨在表征母乳中饮食传递的蔬菜口味在母乳中的影响 在味觉学习的敏感期，我们拥有一套全面的重复和多样的母体和 在随机对照试验过程中收集的婴儿表型。试验从产后2周一直持续到 婴儿断奶后食用固体食物，干预后分别在10.5个月和1岁时进行随访。因此，我们有 一个独特的机会，超越了最初关于高度普遍现象的RCT的目标 母乳喂养和营养规划。 在整个干预期间和干预后收集的次要结果表型(10.5 MOS，1年)包括人体测量(我们根据测量结果确定体重增加轨迹[g/d]，这是一种风险 后来肥胖的因素)和两个二分体成员的饮食摄入量；婴儿发育里程碑；脂肪 和母乳的卡路里含量；以及母亲的喂养方式和目标。我们提出的二次分析 这里将测试几个假设，以比较基于实验室的次要结果和主要结果 衡量婴儿对蔬菜的接受程度、母亲对蔬菜的品尝等级和品尝类型。母乳喂养 (BF)对于我们的随机对照试验队列来说是健壮和持久的，对81%的婴儿持续10.5个月或更长时间，以及 只有三分之一的人喂过婴儿配方奶粉。因此，对于两个目标(目标1、2)，我们还将比较从 这一具有良好特征的BF队列使用相同的方法在纵向队列中收集数据 完全由配方奶粉喂养的婴儿和母亲。提案的核心是四个目标，这四个目标 完成后将产生至少六份出版物。 目标1将使用母亲喂养习惯和母乳成分的重复测量数据来测试 母乳脂肪含量和母体反应性喂养对婴儿有贡献的初步假设 随着时间的推移体重增加的轨迹。因为母乳喂养在1岁时可以预防肥胖。 队列，我们还将确定BF组和FF组在母亲喂养方面是否存在差异 随时间推移的饮食风格和他们喂养婴儿的补充饮食的类型。目标2将确定多早的风险 因素-快速体重增加轨迹和母乳成分-共同作用或独立作用 影响乳牙萌出，一个假想的未来肥胖风险的生物标记物。《目标3》将描述 随着时间的推移，母亲的饮食中的营养和能量含量与她们孩子的饮食相一致。而当 遗传变异对最初的蔬菜接受度没有贡献，AIM 4将检验TAS2R38的假设 基因型解释了干预后饮食措施的差异，因此那些携带不敏感等位基因的人将表现出 比那些苦味敏感等位基因纯合子的蔬菜摄入量更大。 从这些二次分析中获得的知识可以转化为行为干预 促进健康的母亲饮食和喂养做法，从而支持婴儿的健康体重增加和饮食。

ABSTRACT Précis: Our goal is to assess both the direct and indirect effects of diet during the postpartum period in breastfeeding mother-infant dyads. In addition to accomplishing the primary aims of a randomized controlled trial (RCT) designed to characterize the effects of diet-transmitted vegetable flavors in mother’s milk during sensitive period in flavor learning, we have a comprehensive data set of repeated and diverse maternal and infant phenotypes collected during the course of the RCT. The trial lasted from 2 weeks postpartum until the infants were weaned to solid foods, with post-intervention visits at 10.5 months and 1 year. Therefore, we have a unique opportunity that goes beyond the goals of the original RCT on the highly pervasive phenomenon of breastfeeding and nutritional programming. The secondary outcome phenotypes collected throughout the intervention and post-intervention periods (10.5 mos, 1 y) included measures of anthropometry (from which we determined weight gain trajectories [g/d], a risk factor for later obesity) and dietary intake of both members of the dyad; infant developmental milestones; fat and caloric content of breast milk; and maternal feeding styles and goals. The secondary analyses we propose here will test several hypotheses to compare the secondary outcomes with primary outcomes of lab-based measures of infant vegetable acceptance, maternal vegetable taste ratings, and taste genotype. Breastfeeding (BF) was robust and persistent for our RCT cohort, lasting for 10.5 mos or longer for 81% of the infants, and only one-third ever fed infant formula. Thus, for two aims (AIMS 1, 2) we will also compare data collected from this well-characterized BF cohort with data collected using identical methods on a longitudinal cohort of exclusively formula-fed (FF) infants and mothers. At the heart of the proposal are four aims, which upon completion will yield at least six publications. AIM 1 will use data from repeated measures of maternal feeding practices and breast milk composition to test the primary hypothesis that the fat content of breast milk and maternal responsive feeding contributes to infant weight gain trajectories over time. Because breastfeeding protected against obesity at 1 y compared to the FF cohort, we will also determine whether there are differences between BF and FF groups in maternal feeding styles over time and the type of complementary diet they feed their infants. AIM 2 will determine how early risk factors—rapid weight gain trajectories and breast milk composition,—interact together or act independently to influence primary tooth eruption, a hypothesized biomarker for later obesity risk. AIM 3 will characterize nutrient and energy content of the diets of mothers over time and concordance with their children’s diets. While genetic variation did not contribute to initial vegetable acceptance, AIM 4 will test the hypothesis that TAS2R38 genotype explains variation in post-intervention diet measures such that those with insensitive alleles will show greater vegetable intakes than those homozygous for the bitter-sensitive allele. The knowledge gained from these secondary analyses could be translated to behavioral interventions to promote healthy maternal diet and feeding practices that in turn support healthy weight gain and diet in infants.