Balanced Energy Protein Supplement in Early Lactation on Infant Growth in Southern Nepal

摘要 中低收入国家(LMIC)营养不良的妇女面临更大的胎儿生长限制 妊娠和较差的分娩结局，包括早产和小于胎龄(SGA)。婴儿 出生的早产儿和/或SGA更容易受到发育迟缓和神经认知发育不足的影响， 对成年有持久的影响。针对妊娠和哺乳期的营养干预措施 有可能打破营养不良的代际循环。最近，一项专家共识形成了 LMICs中孕妇和哺乳期妇女强化BEP“即用”食品补充剂规范， 这需要在营养不良的环境中测试改善出生和生长结果的有效性。 目前，没有建议母乳喂养的妇女服用补充剂，尽管母乳喂养的妇女 LMICs的早期生长速度步履蹒跚，那里的母亲营养不良很严重，而且是唯一的 建议母乳喂养。我们的研究目的是：1)评估孕期每日服用BEP++的效果 和/或哺乳对出生前6个月婴儿生长发育的影响；2)评估每日BEP++对婴儿生长发育的影响 妊娠和/或哺乳对母亲营养状况的影响并探索对婴儿的潜在调节途径 生长结果；以及3)在生物质子组研究中，探索母婴之间的关系 孕期补充营养状态、炎症、母乳成分和肠道微生物群 和/或哺乳期与非哺乳期。我们提出了一项基于社区的、随机对照的每日BEP++试验 尼泊尔农村地区哺乳期间的补充(建议增加)。我们的研究人群中有很高的 产妇营养不良、不良出生结局和婴儿生长不良，是农村环境的代表 在南亚。为了进行这次试验，我们将利用我们基于社区的现场站点的基础设施和 计划于2022年开始的孕妇BEP++补充剂的随机试验(父母试验)。这个 父母试验将招募怀孕妇女，随机选择她们在怀孕期间或不补充 补充，并跟踪到出生，以评估SGA的发生率。我们建议1)产后再加一个 妊娠期补充试验，采用2x2析因设计，评价 在哺乳期补充BEP++，并在6个月大时测量婴儿的生长发育结果，2)增加一倍 登记的孕妇的总体样本量，以便检测有意义的差异 产后补充，以及3)在试验中嵌套一项生物素亚组研究，以探索 母婴营养状况与婴儿生长发育的因果关系。2,000份样本 孕妇将生产1,600个活产，1,440个婴儿随访至6个月(占怀孕 损失和后续行动的损失)。这将使我们能够检测主要结果的差异，平均长度为- 6个月时，在哺乳期补充与不补充之间的年龄Z评分为0.16。

ABSTRACT Undernourished women in low-and-middle income countries (LMICs) experience greater fetal growth restriction in pregnancy and poorer birth outcomes, including preterm birth and small-for-gestational age (SGA). Infants born preterm and/or SGA are more vulnerable to stunting and inadequate neurocognitive development, with lasting effects through adulthood. Nutritional interventions targeted in pregnancy and lactation have the potential to break the intergenerational cycle of malnutrition. Recently, an expert consensus developed specifications for a fortified BEP “ready-to-use” food supplement for pregnant and lactating women in LMICs, which requires testing in undernourished settings for efficacy in improving birth and growth outcomes. Currently, there is no recommendation for supplementation for women who are breastfeeding, despite high rates of growth faltering in early life in LMICs, where maternal undernutrition is high and exclusive breastfeeding is recommended. Our research aims to 1) Evaluate the effect of daily BEP++ in pregnancy and/or lactation on infant growth outcomes in the first 6 months of life; 2) Evaluate the effect of daily BEP++ in pregnancy and/or lactation on maternal nutritional status and explore potential mediation pathways on infant growth outcomes; and 3) In a biospecimen sub-study, explore relationships between maternal and infant nutrient status, inflammation, human milk composition, and gut microbiome by supplementation in pregnancy and/or lactation vs. not. We propose a community-based, randomized controlled trial of daily BEP++ supplementation during lactation in rural Nepal (proposed addition). Our study population has high rates of maternal undernutrition, adverse birth outcomes, and poor infant growth, and is representative of rural settings in South Asia. To conduct this trial, we will leverage the infrastructure of our community-based field site and a randomized trial of a BEP++ supplement in pregnant women scheduled to begin in 2022 (parent trial). The parent trial will recruit pregnant women in pregnancy, randomize them to supplement in pregnancy or no supplement, and follow-up until birth to assess SGA incidence. We propose to 1) add a postpartum supplementation trial following supplementation in pregnancy, using a 2x2 factorial design, to evaluate the BEP++ supplement during lactation and measure infant growth outcomes at 6 months of life, 2) double the overall sample size of pregnant women enrolled to allow for detection of meaningful differences between postpartum supplementation, and 3) nest a biospecimen sub-study within the trial to explore aims on the causal relationships between maternal and infant nutritional status and infant growth. A sample of 2,000 pregnant women will yield 1,600 live births and 1,440 infants followed until 6 months (accounting for pregnancy loss and loss to follow-up). This will allow us to detect a difference for our primary outcome, mean length-for- age Z score at 6 months, between supplement in lactation vs. no supplement, of 0.16 Z scores.