https://www.thelancet.com/pdfs/journals/langlo/PIIS2214-109X(13)70001-9.pdf

Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995–2011: a systematic analysis of population-representative data

The continuing unresolved debate over the interaction of iron and infection indicates a need for quantitative review of clinical morbidity outcomes. Iron deficiency is associated with reversible abnormalities of immune function, but it is difficult to demonstrate the severity and relevance of these in observational studies. Iron treatment has been associated with acute exacerbations of infection, in particular, malaria. Oral iron has been associated with increased rates of clinical malaria (5 of 9 studies) and increased morbidity from other infectious disease (4 of 8 studies). In most instances, therapeutic doses of oral iron were used. No studies in malarial regions showed benefits. Knowledge of local prevalence of causes of anemia including iron deficiency, seasonal malarial endemicity, protective hemoglobinopathies and age-specific immunity is essential in planning interventions. A balance must be struck in dose of oral iron and the timing of intervention with respect to age and malaria transmission. Antimalarial intervention is important. No studies of oral iron supplementation clearly show deleterious effects in nonmalarious areas. Milk fortification reduced morbidity due to respiratory disease in two very early studies in nonmalarious regions, but this was not confirmed in three later fortification studies, and better morbidity rates could be achieved by breast-feeding alone. One study in a nonmalarious area of Indonesia showed reduced infectious outcome after oral iron supplementation of anemic schoolchildren. No systematic studies report oral iron supplementation and infectious morbidity in breast-fed infants in nonmalarious regions.

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Iron and Its Relation to Immunity and Infectious Disease

Objectives To summarise evidence on the associations of maternal anaemia and prenatal iron use with maternal haematological and adverse pregnancy outcomes; and to evaluate potential exposure-response relations of dose of iron, duration of use, and haemoglobin concentration in prenatal period with pregnancy outcomes. Design Systematic review and meta-analysis Data sources Searches of PubMed and Embase for studies published up to May 2012 and references of review articles. Study selection criteria Randomised trials of prenatal iron use and prospective cohort studies of prenatal anaemia; cross sectional and case-control studies were excluded. Results 48 randomised trials (17 793 women) and 44 cohort studies (1 851 682 women) were included. Iron use increased maternal mean haemoglobin concentration by 4.59 (95% confidence interval 3.72 to 5.46) g/L compared with controls and significantly reduced the risk of anaemia (relative risk 0.50, 0.42 to 0.59), iron deficiency (0.59, 0.46 to 0.79), iron deficiency anaemia (0.40, 0.26 to 0.60), and low birth weight (0.81, 0.71 to 0.93). The effect of iron on preterm birth was not significant (relative risk 0.84, 0.68 to 1.03). Analysis of cohort studies showed a significantly higher risk of low birth weight (adjusted odds ratio 1.29, 1.09 to 1.53) and preterm birth (1.21, 1.13 to 1.30) with anaemia in the first or second trimester. Exposure-response analysis indicated that for every 10 mg increase in iron dose/day, up to 66 mg/day, the relative risk of maternal anaemia was 0.88 (0.84 to 0.92) (P for linear trend Conclusions Daily prenatal use of iron substantially improved birth weight in a linear dose-response fashion, probably leading to a reduction in risk of low birth weight. An improvement in prenatal mean haemoglobin concentration linearly increased birth weight.

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Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis

https://zenodo.org/record/979191/files/article.pdf

Iron availability and infection

Anemia is an important cause of health loss. We estimated levels and trends of nonfatal anemia burden for 23 distinct etiologies in 188 countries, 20 age groups, and both sexes from 1990 to 2013. All available population-level anemia data were collected and standardized. We estimated mean hemoglobin, prevalence of anemia by severity, quantitative disability owing to anemia, and underlying etiology for each population using the approach of the Global Burden of Disease, Injuries and Risk Factors 2013 Study. Anemia burden is high. Developing countries account for 89% of all anemia-related disability. Iron-deficiency anemia remains the dominant cause of anemia.

The Global Burden of Anemia

A placebo-controlled trial of intramuscular iron dextran prophylaxis for two-month-old infants was carried out on the north coast of Papua New Guinea where there is high transmission of malaria. The results indicate that the placebo group became relatively iron deficient whereas the iron dextran group had adequate iron stores and, in the absence of malaria, a higher mean haemoglobin. However in the iron dextran group there was a higher prevalence of malaria, as judged by parasite and spleen rates at 6- and 12-month follow-up; a lower haemoglobin associated with malaria when compared with the placebo group and a greater reticulocytosis in response to malaria infection. Within the placebo group it was noticed that the malaria rates were lower at follow-up in those infants who had had a low birth haemoglobin. In neither group was there apparent suppression of marrow activity in the presence of malaria. Malaria infection in both groups was associated with a significantly raised serum ferritin level and transferrin saturation. Over-all these data give evidence for a protective role of iron deficiency against malaria and would argue against the injudicious use of iron replacement in areas where malaria is endemic.

Cathy Harrison

Papers

Iron supplementation increases prevalence and effects of malaria: report on clinical studies in Papua New Guinea