Early iron supplementation of exclusively breastfed African infants: a proof-of-principle, placebo-controlled, randomised, double-blinded efficacy trial
Early iron supplementation of exclusively breastfed African infants: a proof-of-principle, placebo-controlled, randomised, double-blinded efficacy trial
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纯母乳喂养的非洲婴儿早期补铁：一项原理验证、安慰剂对照、随机、双盲疗效试验
DOI：
10.1101/2023.01.12.22284059
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Bah M
中科院分区：
文献类型：
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作者：
Bah M
我们以前已经表明，母乳喂养的冈比亚儿童在6个月前就耗尽了他们的新生儿铁营养。我们测量了14周的每日补铁对血清铁浓度和其他铁标志物母乳喂养的冈比亚infants.MethodIn一项双盲试验，健康的纯母乳喂养的农村冈比亚6至10周的婴儿从疫苗接种诊所和当地社区。符合条件的儿童（n=101）被单独随机分配至14周的每日补充铁（7.5mg硫酸亚铁的山梨醇溶液）或安慰剂（山梨醇溶液）。主要结果是补充99天后的血清铁浓度（98天干预加1天洗脱）。我们使用意向治疗分析和多重插补来替换缺失值。该试验在clinicaltrials.gov注册（NCT 04751994）。结果铁给药增加血清铁浓度（平均值的粗差：2.5 μmol/L; 95%CI：0.6至4.3 μmol/L，p=0.0091），并有意义地改善了铁和血液学状态的其他标志物。有10起严重不良事件（5铁/5安慰剂）和106起非严重不良事件（54铁/52安慰剂），无死亡。在母亲报告的腹泻、发热、咳嗽、皮肤感染、眼睛感染和鼻涕的发作方面没有明显的组间差异。解释在纯母乳喂养的婴儿中，早期引入铁补充剂可以提高铁供应到婴儿早期快速发育的组织中，并且需要在大规模试验中进行进一步的调查，并对功能结果和安全性进行额外的测量。英国医学研究理事会，国家健康研究和护理研究所，惠康信托基金。研究前的背景证据世界卫生组织（世卫组织）建议婴儿应完全母乳喂养6个月。人乳中的铁含量非常低，因此纯母乳喂养的婴儿被迫利用其肝脏铁蛋白和胎儿血红蛋白的出生禀赋来满足生长和组织发育的需要。在低收入国家，许多婴儿早产、出生体重低或母亲缺铁。这些婴儿出生时铁储备量低，因此在6个月大时经常严重缺铁。在许多高收入国家，建议这些婴儿在出生后不久就应接受铁补充剂。虽然世界卫生组织关于纯母乳喂养的建议没有特别排除，但人们普遍认为补充剂的提供是不必要的，并破坏了该建议的精神。本研究的附加值在这项原理验证试验中，我们证明了从6周龄起每天为纯母乳喂养的冈比亚婴儿提供7.5mg铁，可显著改善6个月龄时铁状况的所有标志物。有没有对生长或对infection.Implications的不利影响的信号所有现有的evidenceforth严重缺铁在许多纯母乳喂养的婴儿在低收入国家损害铁供应迅速发展的组织，包括免疫和神经细胞和扩大红细胞池。早期引入铁补充剂可以扭转这种缺陷，并保证在大规模试验中进行进一步测试，并对功能结局和安全性进行额外测量。
SummaryBackgroundWe have previously shown that breastfed Gambian children have depleted their neonatal iron endowment before 6 months. We measured the effect of daily iron supplementation for 14 weeks on serum iron concentration and other iron markers among breastfed Gambian infants.MethodIn a double-blind trial, healthy exclusively breastfed rural Gambian infants aged 6 to 10 weeks were identified from vaccination clinics and local communities. Eligible children (n=101) were individually randomised to 14 weeks of daily supplementation with either iron (7·5mg as ferrous sulphate in sorbitol solution) or placebo (sorbitol solution). The primary outcome was serum iron concentration after 99 days of supplementation (98 days intervention plus 1-day washout). We used intention-to-treat analysis with multiple imputation to replace missing values. This trial was registered with clinicaltrials.gov (NCT04751994).FindingsIron administration increased serum iron concentration (crude difference in means: 2.5 μmol/L; 95%CI: 0·6 to 4·3μmol/L, p=0.0091) and meaningfully improved additional markers of iron and haematological status. There were 10 serious adverse events (5 iron/5 placebo) and 106 non-serious adverse events (54 iron/52 placebo) with no deaths. There were no marked group differences in maternally-reported episodes of diarrhoea, fever, cough, skin infection, eye infection and nasal discharge.InterpretationIn exclusively breastfed infants, early introduction of iron supplements can enhance iron supply to rapidly developing tissues in early infancy and warrants further investigation in large-scale trials with additional measurements of functional outcomes and safety.FundingUK Department for International Development, Medical Research Council UK, National Institute for Health Research and Care Research, Wellcome Trust.Research in contextEvidence before the studyThe World Health Organisation (WHO) recommends that infants should be exclusively breastfed for 6 months. Human milk contains very little iron so exclusively breastfed infants are forced to utilise their birth endowment of liver ferritin and fetal haemoglobin to meet the needs of growth and tissue development. In low-income countries many infants are born prematurely, at low birthweight or to iron deficient mothers. These infants start life with low iron reserves and hence frequently become very iron deficient by 6 months of age. In many high-income countries it is recommended that such infants should receive iron supplements from soon after birth. Although not specifically precluded by WHO’s recommendation on exclusive breastfeeding, the provision of supplements is widely viewed as being unnecessary and as undermining the ethos of the recommendation.Added value of this studyIn this proof-of-principle trial we demonstrated that providing 7·5mg iron per day to exclusively breastfed Gambian infants from 6 weeks of age substantially improved all markers of iron status at 6 months of age. There were no signals of adverse effects on growth or on infections.Implications of all the available evidenceSerious iron deficiency in many exclusively breastfed infants in low-income countries impairs iron supply to rapidly developing tissues including immune and neural cells and the expanding erythroid pool. Early introduction of iron supplements can reverse this deficiency and warrants further testing in large-scale trials with additional measurements of functional outcomes and safety.
在中国农村进行的一项随机临床试验中，婴儿期低剂量铁补充剂可适度提高婴儿 9 个月时的铁状况，而不会降低生长或增加疾病。
DOI：
10.3945/jn.115.223917
发表时间：
2016
期刊：
The Journal of nutrition
影响因子：
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作者：
Lozoff,Betsy;Jiang,Yaping;Li,Xing;Zhou,Min;Richards,Blair;Xu,Guobin;Clark,KatyM;Liang,Furong;Kaciroti,Niko;Zhao,Gengli;Santos,DeniseCc;Zhang,Zhixiang;Tardif,Twila;Li,Ming
通讯作者：
Li,Ming