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

摘要 低收入和中等收入国家（LMIC）营养不良的妇女经历更大的胎儿生长限制 妊娠和较差的出生结果，包括早产和小于胎龄儿（SGA）。婴儿 早产儿和/或SGA更容易发育迟缓和神经认知发育不足， 持续影响到成年期。针对妊娠期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，专家们达成了共识， 低收入国家孕妇和哺乳期妇女强化BEP“即用型”食品补充剂的规格， 这需要在营养不良的环境中测试改善出生和生长结果的功效。 目前，没有建议为母乳喂养的妇女提供补充剂， 在低收入国家，婴儿的生长速度缓慢，产妇营养不良严重， 建议母乳喂养。我们的研究目的是：1）评估每日BEP++在妊娠中的作用 和/或哺乳对出生后前6个月婴儿生长结果的影响; 2）评价每日BEP++对 妊娠和/或哺乳对母体营养状况的影响，并探讨对婴儿营养状况的潜在调节途径。 生长结果; 3）在生物样本子研究中，探索母婴之间的关系 营养状况，炎症，母乳成分和肠道微生物组通过补充怀孕 和/或哺乳与不哺乳。我们提出了一个以社区为基础的随机对照试验，每日BEP++ 在尼泊尔农村地区，哺乳期间补充维生素C（拟议增加）。我们的研究人群有很高的 产妇营养不良、不良的出生结果和不良的婴儿生长，并代表农村环境 在南亚。为了进行这项试验，我们将利用我们基于社区的现场基础设施和 计划于2022年开始在孕妇中进行BEP++补充剂的随机试验（母试验）。的 母试验将招募妊娠期孕妇，随机分配至妊娠期补充或不补充 补充，并随访至出生，以评估SGA发生率。我们建议1）增加产后 补充试验后，补充怀孕，使用2x2析因设计，以评估 在哺乳期补充BEP++，并在6个月时测量婴儿的生长结果，2）将 入组的孕妇的总体样本量，以检测 产后补充，以及3）在试验中嵌套生物样本子研究，以探索产后补充的目的。 母婴营养状况与婴儿生长发育之间的因果关系。2000个样本 孕妇将生产1，600个活产婴儿和1，440个婴儿，随访至6个月（占怀孕 失访和失访）。这将使我们能够检测到我们的主要结果，平均长度的差异， 6个月时的年龄Z评分，在哺乳期补充剂与无补充剂之间，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.