Verhoef Hans, West Clive E, Nzyuko Silas M, de Vogel Stefan, van der Valk Rikkert, Wanga Mike A, Kuijsten Anneleen, Veenemans Jacobien, Kok Frans J
Division of Human Nutrition and Epidemiology, Wageningen University, Wageningen, Netherlands.
Lancet. 2002 Sep 21;360(9337):908-14. doi: 10.1016/S0140-6736(02)11027-0.
Iron supplementation is recommended for children at high risk of anaemia, but its benefits may not outweigh the associated risk of malaria in areas of seasonal transmission. We investigated the effect on haemoglobin concentrations of intermittent administration of iron supplements and sulfadoxine-pyrimethamine in symptom-free children under intense health surveillance.
In a trial of two by two factorial design, 328 anaemic Kenyan children were randomly assigned either iron or placebo and sulfadoxine-pyrimethamine or placebo (82 to each group). Primary outcomes were haemological indicators of iron status and inflammation at the end of the follow-up, and occurrence of malaria attacks. Morbidity surveillance consisted of medical examinations every 4 weeks, continuous passive case detection, and visits twice a week to community health-workers. Analyses were by intention to treat.
After 12 weeks, the groups assigned iron plus sulfadoxine-pyrimethamine, iron alone, or sulfadoxine-pyrimethamine alone had higher haemoglobin concentrations than the group assigned placebo (treatment effect adjusted for prognostic factors at baseline: 11.1 g/L [95% CI 7.5 to 14.7]; 10.7 g/L [7.1 to 14.3]; and 3.1 g/L [-0.5 to 6.7]). Administration of iron plus sulfadoxine-pyrimethamine also lowered the proportion with anaemia from 100% at baseline to 36% at 12 weeks, and of iron deficiency from 66% at baseline to 8% at 12 weeks. Survival analysis showed no evidence of substantially increased risk of malaria after iron supplementation.
Iron supplementation gives substantial health benefits, which may outweigh possible inherent risks caused by malaria. A larger study than ours is needed to assess benefits and risks of intermittent administration of sulfadoxine-pyrimethamine in reducing the incidence of malaria attacks in areas of seasonal malaria transmission.
对于有贫血高风险的儿童，建议补充铁剂，但在季节性传播地区，其益处可能无法超过疟疾相关风险。我们在严格的健康监测下，研究了对无症状儿童间歇性补充铁剂和磺胺多辛 - 乙胺嘧啶对血红蛋白浓度的影响。
在一项二乘二析因设计试验中，328名贫血的肯尼亚儿童被随机分配接受铁剂或安慰剂以及磺胺多辛 - 乙胺嘧啶或安慰剂（每组82名）。主要结局是随访结束时铁状态和炎症的血液学指标，以及疟疾发作情况。发病率监测包括每4周进行一次医学检查、持续被动病例检测以及每周两次走访社区卫生工作者。分析采用意向性分析。
12周后，接受铁剂加磺胺多辛 - 乙胺嘧啶、单独铁剂或单独磺胺多辛 - 乙胺嘧啶治疗的组，其血红蛋白浓度高于接受安慰剂治疗的组（根据基线预后因素调整后的治疗效果：11.1 g/L [95%CI 7.5至14.7]；10.7 g/L [7.1至14.3]；以及3.1 g/L [-0.5至6.7]）。铁剂加磺胺多辛 - 乙胺嘧啶治疗还使贫血比例从基线时的100%降至12周时的36%，缺铁比例从基线时的66%降至12周时的8%。生存分析表明，补充铁剂后没有证据显示疟疾风险大幅增加。
补充铁剂带来显著的健康益处，这可能超过疟疾可能带来的固有风险。需要开展一项比我们的研究规模更大的研究，以评估间歇性给予磺胺多辛 - 乙胺嘧啶在季节性疟疾传播地区降低疟疾发作发病率方面的益处和风险。
