Key messages
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Iron supplements do not increase the risk of malaria in children when malaria prevention and management services are available.
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Iron supplements may slightly increase the risk of malaria in areas without malaria prevention and management services, but the increased risk is small.
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Future studies are needed to better understand which groups of children benefit most, whether folic acid changes the effects of iron, and how to safely deliver iron in settings with limited malaria services.
What are anaemia and malaria?
Anaemia is a condition where the body does not have enough healthy red blood cells to carry oxygen to its tissues. It is often caused by a lack of iron in the diet, leading to symptoms like tiredness, weakness, and poor growth and development in children.
Malaria is a serious disease caused by parasites transmitted to people through the bites of infected mosquitoes. It is common in many tropical and subtropical regions. Symptoms include fever, chills, and flu-like illness, and it can be life-threatening if not treated promptly.
In areas where malaria is endemic, meaning it is constantly present and occurs at a relatively stable and predictable rate throughout the year, there has been concern that giving iron supplements to children might increase their risk of getting malaria. This is because the malaria parasite needs iron to grow, so higher iron levels in the blood could potentially help the parasite. However, anaemia can weaken the immune system, making children more susceptible to infections, including malaria.
What did we want to find out?
We wanted to find out whether giving iron supplements to children living in malaria-endemic areas is safe and effective. Specifically, we aimed to determine whether providing iron supplements to children in malaria-endemic areas affects the risk of:
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clinical malaria (defined as fever and malaria parasites in the blood);
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severe malaria (a more dangerous form of the disease that may cause coma, severe anaemia, or organ failure);
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death; and
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hospitalisations or clinic visits.
What did we do?
We searched for studies that looked at giving iron supplements (with or without folic acid) to children under 18 years old living in areas with high malaria transmission. This included all studies from the 2016 version of the review as well as newly identified studies. We included studies that compared iron supplements to a placebo (dummy pill) or no treatment. We also included studies looking at giving iron along with antimalarial treatment.
We found 40 studies involving 33,785 children. We compared and summarised the results of the studies and rated our confidence in the evidence based on study methods and sizes.
What did we find?
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Iron treatment results in little to no difference in clinical malaria; slightly reduces the risk of severe malaria; and may result in little to no difference in death or hospitalisations and clinic visits.
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Iron with folic acid may result in little to no difference in severe malaria, death, and hospitalisations.
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In areas with good malaria prevention and management that includes mosquito nets, spraying to reduce mosquito populations, and access to testing and treatment, iron may reduce the risk of clinical malaria. In areas where such resources are not available, iron may increase the risk of clinical malaria.
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Iron combined with malaria prophylaxis greatly reduces clinical malaria; may not reduce the risk of death; and probably reduces hospitalisations and clinic visits.
What are the limitations of the evidence?
Our confidence in the evidence varied. We are confident that oral iron supplements do not increase the risk of clinical or severe malaria. In cases where our confidence was limited, studies did not provide detailed information about how they were conducted, making it hard to know if their findings are reliable. In areas without malaria prevention and management services, the evidence is less certain because it is based mainly on a single large study. Finally, we have limited information about the effects of combining iron with folic acid.
How up-to-date is the evidence?
The evidence is current to 20 May 2025.
阅读完整摘要
Iron-deficiency anaemia is common during childhood. Iron administration has been claimed to increase the risk of malaria.
研究目的
To evaluate the effects and safety of iron supplementation, with or without folic acid, in children living in areas with hyperendemic or holoendemic malaria transmission, where malaria is intense and occurs year-round.
检索策略
We searched CENTRAL (Wiley), MEDLINE (Ovid), Embase (Ovid), and Global Index Medicus (WHO) up to 30 April 2024. We also searched two trial registries, ClinicalTrials.gov and WHO ICTRP, to 30 April 2024. We conducted a top-up search on 20 May 2025. We contacted trial investigators and scanned references of included trials and reviews for relevant studies.
纳入排除标准
We included individually randomized controlled trials (RCTs) and cluster RCTs conducted in hyperendemic and holoendemic malaria regions or that reported on any malaria-related outcomes that included children younger than 18 years of age. We included trials that compared orally administered iron, iron with folic acid, and iron with antimalarial treatment versus placebo or no treatment. We included trials of iron supplementation or fortification interventions if they provided at least 80% of the Recommended Dietary Allowance (RDA) for prevention of anaemia by age. Antihelminthics could be administered to either group, and micronutrients had to be administered equally to both groups.
资料收集与分析
The primary outcomes were clinical malaria, severe malaria, and death from any cause. We assessed the risk of bias in included trials with domain-based evaluation and assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We performed a fixed-effect meta-analysis for all outcomes and random-effects meta-analysis for hematological outcomes, and adjusted analyses for cluster RCTs. We based the subgroup analyses for anaemia at baseline, age, and malaria prevention or management services on trial-level data.
主要结果
Thirty-five trials (31,955 children) met the inclusion criteria. Overall, iron does not cause an excess of clinical malaria (risk ratio (RR) 0.93, 95% confidence intervals (CI) 0.87 to 1.00; 14 trials, 7168 children, high quality evidence). Iron probably does not cause an excess of clinical malaria in both populations where anaemia is common and those in which anaemia is uncommon. In areas where there are prevention and management services for malaria, iron (with or without folic acid) may reduce clinical malaria (RR 0.91, 95% CI 0.84 to 0.97; seven trials, 5586 participants, low quality evidence), while in areas where such services are unavailable, iron (with or without folic acid) may increase the incidence of malaria, although the lower CIs indicate no difference (RR 1.16, 95% CI 1.02 to 1.31; nine trials, 19,086 participants, low quality evidence). Iron supplementation does not cause an excess of severe malaria (RR 0.90, 95% CI 0.81 to 0.98; 6 trials, 3421 children, high quality evidence). We did not observe any differences for deaths (control event rate 1%, low quality evidence). Iron and antimalarial treatment reduced clinical malaria (RR 0.54, 95% CI 0.43 to 0.67; three trials, 728 children, high quality evidence). Overall, iron resulted in fewer anaemic children at follow up, and the end average change in haemoglobin from base line was higher with iron.
作者结论
Iron treatment results in little to no difference in the risk of clinical malaria (high-certainty evidence). Where resources are limited, iron can be administered without screening for anaemia or iron deficiency, as long as malaria prevention or management services are provided efficiently. Where resources for the prevention and treatment of malaria are limited, iron may increase the risk of clinical malaria (low-certainty evidence). These conclusions are consistent with those reported in the previous version of this review (2016).
资助
The editorial base for the Cochrane Infectious Diseases Group (CIDG) is funded by the UK Department for International Development for the benefit of developing countries. Dafna Yahav (DY) received a grant from the Research Programme Consortium funded by the UK Department for International Development to complete the 2014 update. Ami Neuberger (AN) received funding from the Department of Nutrition for Health and Development, World Health Organization, for the 2016 update.
注册
Protocol (2007) DOI: 10.1002/14651858.CD006589
Original review (2009) DOI: 10.1002/14651858.CD006589.pub2
Review update (2011) DOI: https://doi.org/10.1002/14651858.CD006589.pub3
Review update (2016) DOI: 10.1002/14651858.CD006589.pub4
