Enhancing brain development by early iron supplementation of African infants: An enabling pilot study

铁对大脑发育至关重要，婴儿期早期缺铁会造成无法弥补的损害。最新的全球疾病负担分析数据估计，缺铁比所有其他微量营养素缺乏症的总和还要常见。这一负担主要集中在撒哈拉以南非洲和南亚。母乳中含有很少的铁，所以婴儿在胎儿后期会利用肝脏中储存的铁。然而，缺铁母亲的婴儿出生时铁禀性有限，可能会迅速发展为缺铁。我们最近的研究表明，在5个月大的时候，几乎95%的冈比亚农村婴儿的循环铁水平低于美国参考范围的下限。这表明这些婴儿严重缺铁。美国儿科学会（AAP）建议纯母乳喂养的婴儿从4个月大开始补充铁。美国儿科学会还建议早产婴儿在两周内开始补充维生素d。然而，在低收入环境中进行的先前和正在进行的补铁试验开始的时间要晚得多（例如，在孟加拉国进行的一项正在进行的大型试验中，补铁时间为800万至900万美元）。我们的数据表明，要防止早期缺铁损害大脑发育，这已经太晚了。因此，我们建议从6周龄开始进行早期补铁的大型随机对照试验。为了准备这样的试验，我们需要对以下问题进行初步研究：我们能否通过每天给铁滴剂有效地提高婴儿早期的循环铁水平？我们能否在不影响纯母乳喂养持续时间的情况下实现这一目标？铁是否会改变婴儿肠道菌群的平衡，从而导致腹泻？铁补充剂是否会影响锌和铜的吸收，因此需要三重补充？这些问题将在一项小型研究中进行测试，该研究将为预期的全面试验的设计提供信息。

Iron is crucial for brain development and early deficiencies during infancy can cause irreparable damage. Figures from the latest Global Burden of Disease analysis estimate that iron deficiency is more common than all other micronutrient deficiencies combined. This burden is concentrated in sub-Saharan Africa and South Asia. Breast milk contains very little iron, so babies draw upon iron stores laid down in their liver during late foetal life. However, the babies of iron deficient mothers are born with a limited endowment of iron and can rapidly develop iron deficiency. We have recently shown that, by 5 months of age, almost 95% of rural Gambian infants have circulating iron levels below the lower limit of the US reference range. This indicates that these babies are profoundly iron deficienct. The American Academy of Pediatrics (AAP) recommends iron supplementation in exclusively breastfed infants beginning at 4 months of age. AAP also recommends that babies born prematurely start supplementation at 2 weeks. Yet prior and on-going trials of iron supplementation in low-income settings have commenced supplementation much later (eg 8-9m in a large on-going trial in Bangladesh). Our data suggest that this will be too late to prevent early iron deficiency from impairing brain development. We therefore propose a large randomised controlled trial of early iron supplementation starting at 6wks of age. In preparation for such a trial we need to conduct preliminary studies addressing the following questions: Can we effectively enhance circulating iron levels in early infancy by giving daily iron drops? Can we achieve this without undermining duration of exclusive breast feeding? Might the iron alter the balance of the babies' gut microbial flora and thereby cause diarrhoea? Might iron supplementation impair the absorption of zinc and copper and hence require a triple supplement?These questions will be tested in a small enabling study that will inform the design of the intended full trial.