Teshome Emily M, Andang'o Pauline E A, Osoti Victor, Terwel Sofie R, Otieno Walter, Demir Ayşe Y, Prentice Andrew M, Verhoef Hans
MRCG Keneba at MRC Unit, Banjul, The Gambia.
MRC International Nutrition Group, Faculty of Epidemiology and Population Heath, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, England, UK.
BMC Med. 2017 Apr 28;15(1):89. doi: 10.1186/s12916-017-0839-z.
We aimed to show the non-inferiority of home fortification with a daily dose of 3 mg iron in the form of iron as ferric sodium ethylenediaminetetraacetate (NaFeEDTA) compared with 12.5 mg iron as encapsulated ferrous fumarate in Kenyan children aged 12-36 months. In addition, we updated a recent meta-analysis to assess the efficacy of home fortification with iron-containing powders, with a view to examining diversity in trial results.
We gave chemoprevention by dihydroartemisinin-piperaquine, albendazole and praziquantel to 338 afebrile children with haemoglobin concentration ≥70 g/L. We randomly allocated them to daily home fortification for 30 days with either placebo, 3 mg iron as NaFeEDTA or 12.5 mg iron as encapsulated ferrous fumarate. We assessed haemoglobin concentration (primary outcome), plasma iron markers, plasma inflammation markers and Plasmodium infection in samples collected at baseline and after 30 days of intervention. We conducted a meta-analysis of randomised controlled trials in pre-school children to assess the effect of home fortification with iron-containing powders on anaemia and haemoglobin concentration at end of intervention.
A total of 315 children completed the 30-day intervention period. At baseline, 66.9% of children had inflammation (plasma C-reactive protein concentration >5 mg/L or plasma α -acid glycoprotein concentration >1.0 g/L); in those without inflammation, 42.5% were iron deficient. There was no evidence, either in per protocol analysis or intention-to-treat analysis, that home fortification with either of the iron interventions improved haemoglobin concentration, plasma ferritin concentration, plasma transferrin receptor concentration or erythrocyte zinc protoporphyrin-haem ratio. We also found no evidence of effect modification by iron status, anaemia status and inflammation status at baseline. In the meta-analysis, the effect on haemoglobin concentration was highly heterogeneous between trials (I : 84.1%; p value for test of heterogeneity: <0.0001).
In this population, home fortification with either 3 mg iron as NaFeEDTA or 12.5 mg iron as encapsulated ferrous fumarate was insufficiently efficacious to assess non-inferiority of 3 mg iron as NaFeEDTA compared to 12.5 mg iron as encapsulated ferrous fumarate. Our finding of heterogeneity between trial results should stimulate subgroup analysis or meta-regression to identify population-specific factors that determine efficacy.
The trial was registered with ClinicalTrials.gov ( NCT02073149 ) on 25 February 2014.
我们旨在证明，对于肯尼亚12至36个月大的儿童，每日服用3毫克乙二胺四乙酸铁钠（NaFeEDTA）形式的铁进行家庭强化补铁，与每日服用12.5毫克微囊富马酸亚铁相比，不存在非劣效性。此外，我们更新了近期的一项荟萃分析，以评估含铁粉进行家庭强化补铁的疗效，旨在研究试验结果的多样性。
我们对338名血红蛋白浓度≥70g/L的无发热儿童给予双氢青蒿素哌喹、阿苯达唑和吡喹酮进行化学预防。我们将他们随机分配，让其在家中每日服用安慰剂、3毫克NaFeEDTA形式的铁或12.5毫克微囊富马酸亚铁进行30天的强化补铁。我们在基线期和干预30天后采集的样本中评估血红蛋白浓度（主要结局）、血浆铁标志物、血浆炎症标志物和疟原虫感染情况。我们对学龄前儿童的随机对照试验进行了荟萃分析，以评估含铁粉进行家庭强化补铁对干预结束时贫血和血红蛋白浓度的影响。
共有315名儿童完成了30天的干预期。在基线期，66.9%的儿童存在炎症（血浆C反应蛋白浓度>5mg/L或血浆α-酸性糖蛋白浓度>1.0g/L）；在无炎症的儿童中，42.5%存在缺铁。在符合方案分析或意向性分析中，均没有证据表明任何一种铁干预措施进行家庭强化补铁能改善血红蛋白浓度、血浆铁蛋白浓度、血浆转铁蛋白受体浓度或红细胞锌原卟啉-血红素比值。我们也没有发现基线期的铁状态、贫血状态和炎症状态对干预效果产生影响的证据。在荟萃分析中，各试验之间对血红蛋白浓度的影响存在高度异质性（I²：84.1%；异质性检验的p值：<0.0001）。
在该人群中，每日服用3毫克NaFeEDTA形式的铁或12.5毫克微囊富马酸亚铁进行家庭强化补铁的疗效不足，无法评估3毫克NaFeEDTA形式的铁相对于12.5毫克微囊富马酸亚铁的非劣效性。我们发现试验结果之间存在异质性这一情况，应促使进行亚组分析或Meta回归分析，以确定决定疗效的人群特异性因素。
该试验于2014年2月25日在ClinicalTrials.gov（NCT02073149）注册。
