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的、可预防的营养不良形式，影响着数百万婴儿、幼儿和孕妇。人们越来越有兴趣了解生命早期缺乏特定微量营养素，特别是缺乏铁和锌对儿童发育的影响。充足的铁和锌的营养对于大脑的最佳发育和功能是必要的。胎儿期或产后早期营养缺乏可能导致不可逆转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缺铁是导致营养不良的原因，或者在营养不良人群中补充铁或锌对发育有益。在尼泊尔农村地区，有一个独特的机会来研究在(i)怀孕（子宫内）、（ii）幼儿期和（iii）这两个时期补铁对1750名6-7岁儿童（通常入学年龄）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：一项试验中，他们的母亲从妊娠早期到产后6周每天服用安慰剂或铁（+叶酸），每天服用或不服用锌；另一项试验中，孩子们自己每天服用安慰剂、铁和/或锌，采用2x2因子设计，时间为12至35个月。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断强度。在18个月以上的时间里，孩子们将在家里和诊所接受智力、运动功能、情感和行为的标准测试。我们将评估补充组的儿童是否表现出更快的信息处理和更强的抑制性控制，以及依赖多巴胺能途径的认知功能，而多巴胺能途径反过来对缺铁敏感。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。社会经济地位、家庭环境、营养和健康状况也将被评估。分析将评估原始母子补充剂暴露的儿童结果。这项研究将填补知识方面的关键空白，并为有关孕期和幼儿期选择性微量营养素干预改善学龄认知效果的政策提供信息。

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.