Antenatal and preschool iron and zinc use and cognition

说明(申请人提供)：基本微量营养素的慢性缺乏是发展中国家最常见的、可预防的营养不良形式，影响到数百万婴儿、幼儿和孕妇。人们越来越有兴趣了解生命早期特定的微量营养素缺乏对儿童发育的影响，特别是铁和锌。充足的铁和锌营养对于大脑的最佳发育和功能是必要的。胎儿或出生后早期缺乏营养可能会导致不可逆转的神经认知功能障碍，并损害运动或行为发育。然而，缺乏实验数据来揭示营养不良人群中缺乏铁或锌的原因，或者补充铁或锌对发育的好处。尼泊尔农村有一个独特的机会，可以研究在(1)怀孕(宫内)、(2)幼儿和(3)两个时期对1750名6-7岁儿童的神经认知功能的影响，无论是否添加锌。招募的儿童将参加之前的两项随机对照补充试验：一项是他们的母亲从怀孕的第一个月到产后6周每天服用安慰剂或铁(+叶酸)，或不加锌；第二项是孩子们自己在12到35个月时以2x2析因设计每天服用安慰剂、铁和/或锌。-因此，通过保留每个原始设计，拟议的研究将保留两阶段随机试验的推论强度。在18个月后，儿童将在家中和诊所通过标准的智力、运动功能、情感和行为测试进行评估。我们将评估任何补充组的儿童是否表现出更快的信息处理速度和更强的抑制性控制，这些认知功能依赖于多巴胺能通路，而多巴胺能通路反过来对缺铁敏感。然而，补充的累积效应也有可能对智力功能产生更普遍的影响，这是我们独立评估的。还将评估社会经济状况、家庭环境以及营养和炉灶状况。分析将通过原始的Matemo-Child补充剂暴露来评估儿童结果。这项研究将填补知识的重大空白，并向政策提供关于选择性微量营养素干预在怀孕和儿童早期改善学龄儿童认知能力的有效性的信息。

DESCRIPTION (provided by applicant): Chronic deficiency of essential micronutrients is the most common, preventable form of malnutrition in the developing world, affecting millions of infants, young children and pregnant women. Interest is growing in understanding effects of specific micronutrient deficiencies early in life, particularly iron and zinc, on child development. Adequate nutriture of both iron and zinc is necessary for optimal brain development and functioning. Deficiencies of either nutrient in fetal or early postnatal life may lead to irreversible neurocognitive dysfunction and impaired motor or behavioral development. Yet, experimental data are lacking to reveal either deficiency as a cause, or the developmental benefits of iron or zinc supplementation in undernourished populations. A unique opportunity exists in rural Nepal to examine effects of iron supplementation, with or without added zinc, during (i) pregnancy (in utero), (ii) early childhood and (iii) both periods on neurocognitive function in a cohort of 1750 children at 6-7 yr of age, the usual age at school entry. Recruited children will have participated in two, previous randomized controlled supplementation trials: one in which their mothers received either placebo or iron (+folic acid), with or without zinc daily from 1st trimester to 6 weeks post partum, and the second in which the children themselves were dosed daily with placebo, iron and/or zinc, in a 2x2 factorial design, when they were 12 to 35 months of age. -Thus, by preserving each original design, the proposed study will retain inferential strength of a 2-stage randomized trial. Over 18 months, children will be evaluated at home and in a clinic by standard tests of intelligence, motor function, affect and behavior. We will assess whether children in any of our supplementation groups show faster processing of information and greater inhibitory control, cognitive functions that rely on dopaminergic pathways, which in turn are sensitive to iron deficiency. However, it is also possible that the cumulative effect of supplementation could have a more general effect on intellectual functioning, which we assess independently. Socioeconomic status, home environment, and nutrition and hearth status will also be assessed. Analyses will evaluate child outcomes by original matemo-child supplement exposures. The study will fill critical gaps in knowledge and inform policy on the efficacy of selective micronutrient interventions in pregnancy and early childhood to improve school-aged cognition.