Antenatal and preschool iron and zinc use and cognition

描述（由申请人提供）：慢性必需微量营养素缺乏是发展中国家最常见、最可预防的营养不良形式，影响着数百万婴儿、幼儿和孕妇。人们越来越关注了解生命早期特定微量营养素缺乏，特别是铁和锌缺乏对儿童发育的影响。充足的铁和锌营养对大脑的最佳发育和功能是必要的。胎儿或出生后早期营养素缺乏可能导致不可逆的神经认知功能障碍和运动或行为发育受损。然而，缺乏实验数据来揭示营养不良人群中铁或锌补充剂的缺乏原因或发育益处。在尼泊尔农村地区，有一个独特的机会，可以在（一）怀孕（子宫内），（二）幼儿期和（三）这两个时期对1 750名6-7岁儿童（通常入学年龄）的神经认知功能进行铁补充剂（有或没有添加锌）的影响。招募的儿童将参加两个先前的随机对照补充试验：一个是他们的母亲从妊娠早期到产后6周每天接受安慰剂或铁（+叶酸），有或没有锌，第二个是儿童自己每天服用安慰剂，铁和/或锌，采用2x2析因设计，当他们12到35个月大时。因此，通过保留每个原始设计，拟议的研究将保留2阶段随机试验的推理强度。超过18个月，儿童将在家中和诊所通过智力，运动功能，情感和行为的标准测试进行评估。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和更强的抑制控制，以及依赖多巴胺能通路的认知功能，而多巴胺能通路又对缺铁敏感。然而，补充剂的累积效应也可能对智力功能产生更普遍的影响，我们对此进行了独立评估。还将评估社会经济状况、家庭环境、营养和壁炉状况。分析将通过最初的母婴补充剂暴露来评估儿童结局。这项研究将填补知识方面的重大空白，并为政策提供信息，说明在怀孕和幼儿期采取选择性微量营养素干预措施的功效，以提高学龄儿童的认知能力。

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.