4. Characteristics of included systematic reviews: preschool and school‐aged children (aged 2 to 10 years).
Review | Date of search | Number of included trials (number of participants included) | Review question/objective | Trial designs included | Participants | Setting, anaemia and malaria prevalence | Intervention and comparison | Relevant outcomes (definition used in the review, adjusted for smoking and altitude) |
GRADE assessment of relevant outcomes Method used to assess risk of bias and summary |
Supplementation | |||||||||
Low 2013 Effects of daily iron supplementation in primary‐school‐aged children: systematic review and meta‐analysis of randomized controlled trials |
July 2013 | 32 trials (7089 children) | To review of the effects of daily iron supplementation, a commonly used strategy to combat anaemia | RCTs Cluster‐RCTs |
Primary school–aged children (5–12 years) | Low or middle‐income countries, except for 1 trial Malaria: 9 trials conducted in endemic areas Anaemia prevalence: not reported |
Intervention: daily iron supplementation Comparison: placebo or control |
Hb (g/L) Anaemia (Hb < 120 g/L or as defined by trial authors) IDA ID Adverse effects (gastrointestinal upset, constipation, vomiting) Adjustments: not reported |
GRADE: not assessed Cochrane RoB 1 tool. Only 4 trials were considered at low overall risk of bias. Many trials did not report the randomisation method (20 trials), allocation concealment (25 trials) or blinding (18 trials). |
De‐Regil 2011 Intermittent iron supplementation for improving nutrition and development in children under 12 years of age |
May 2011 | 33 trials (13,114 children) | To assess the effects of intermittent iron supplementation, alone or in combination with other vitamins and minerals, on nutritional and developmental outcomes in children from birth to 12 years of age compared with a placebo, no intervention or daily supplementation | RCTs Cluster‐RCTs Quasi‐RCTs |
Children under 12 years of age | Low and middle‐income countries in Asia, Africa and Latin America Malaria: 6 trials conducted in endemic areas, most trials did not report on malaria Anaemia prevalence: not reported |
Intervention: intermittent supplementation with iron alone or with other nutrients Comparison: placebo or no intervention or daily supplementation |
Hb (g/L) Anaemia (Hb below a cut‐off defined by trialists, taking into account the age and altitude) IDA (defined by the presence of anaemia plus ID, diagnosed with an indicator of iron status selected by trialists) ID (as measured by trialists by using indicators of iron status, such as ferritin or transferrin) Diarrhoea Any other adverse side effects (as measured by trialists, such as stained teeth, headache, stomach ache, discomfort, constipation) Adjustments: not reported |
GRADE: intermittent iron supplementation versus placebo or no intervention: Hb = low, anaemia = moderate, IDA = no data, ID = very low; intermittent iron supplementation versus daily iron supplementation: Hb = low, anaemia = low, IDA = no data, ID = very low, other outcomes = not assessed Cochrane RoB 1 tool. Many trials were rated at unclear risk of bias for, random sequence generation, allocation concealment and attrition rates. In half of the trials, blinding of participants and personnel was rated at high risk of bias. Overall, less than one‐third of the trials were rated at low risk of bias. |
Mayo‐Wilson 2014a Zinc supplementation for preventing mortality, morbidity, and growth failure in children aged 6 months to 12 years of age |
January 2013 | 80 trials (205,401 participants) | To assess the effects of zinc supplementation for preventing mortality and morbidity, and for promoting growth, in children aged 6 months to 12 years of age | RCTs Cluster‐RCTs Cross‐over RCTs |
Children aged 6 months to 12 years of age (mean age = 28 months) | 73 trials (91%) were conducted in
low‐ or middle‐income countries: Asia (37 trials), Latin America and the Caribbean (26 trials) and sub‐Saharan Africa (10 trials); 7 conducted in North America or Europe Anaemia and malaria prevalence: measured in some trials, but not specified |
Intervention: zinc supplementation Comparison: placebo, no intervention |
Blood Hb concentration Prevalence of anaemia Prevalence of ID Side effects (participants with ≥ 1 side effect, vomiting episodes, participants with ≥ 1 vomiting episode) Adjustments: not reported |
GRADE: side effect participants with ≥ 1 vomiting episode = high, other outcomes = not assessed Cochrane RoB 1 tool. One‐third of the trials were at low risk of bias for random sequence generation and allocation concealment. The remaining trials were at unclear risk of bias. 80% of the trials were at low risk of bias for blinding. Selective reporting was unclear in 50% of the trials and high risk in 40%. |
Thompson 2013 Effects of daily iron supplementation in 2‐ to 5‐year‐old children: systematic review and meta‐analysis |
April 2012 | 15 trials | To summarise the evidence for effects of daily iron supplementation administered to children 2 to 5 years of age | RCTs Cluster‐RCTs |
Children from 2 to 5 years of age | Mainly low‐middle‐income countries Anaemia and malaria prevalence: 4 trials in malaria endemic areas |
Intervention: oral iron supplement Comparison: placebo or other supplementations |
Hb (g/L) Anemia (defined by authors) Adjustments: not reported |
GRADE: Hb = high, anaemia = very low Cochrane RoB 1 tool. 13 trials at unclear risk of bias for random sequence generation and allocation concealment. Blinding was adequate in 11 trials. |
Fortification | |||||||||
Aaron 2015 Multiple‐micronutrient fortified non‐dairy beverage interventions reduce the risk of anemia and iron deficiency in school‐aged children in low‐middle income countries: a systematic review and meta‐analysis |
February 2015 | 10 trials (4645 participants) | To evaluate the nutritional impacts of MMN‐fortified beverages in the context of low‐middle‐income countries | RCTs | Apparently healthy (school‐aged) children and women of reproductive age | School setting in low‐middle‐income countries: Bangladesh, Botswana, India, Nigeria, the Philippines, South Africa, and Tanzania Anaemia and malaria prevalence: not reported |
Intervention: non‐dairy MMN‐fortified beverages Comparison: iso‐caloric non‐fortified, non‐intervention controls, MMN‐fortified non‐caloric beverage or unfortified non‐caloric control |
Hb (g/L) Anaemia (Hb < 110 to 120 g/L) ID (ferritin < 27 to 45 pmol/L) IDA (Hb < 110 to 120 g/L and ferritin < 27 to 45 pmol/L) Adjustments: not reported |
GRADE: Hb = moderate, anaemia = moderate, ID = moderate, IDA = low Risk of bias tool not stated, but trial bias was assessed by publication bias, randomisation methods, type of blinding (single or double), the percentage of loss to follow‐up (low versus high) and subgroup analyses. Methodological quality was high in 2 trials, moderate in 7 and low in 1 |
Das 2013a Systematic review of zinc fortification trials |
October 2012 | 11 trials (771 women and children) | To assess impact of food fortification with zinc on the health and nutrition of women and children | RCTs Quasi‐RCTs |
Woman and children (newborn, infants and school‐aged children) Hb data only available for school‐aged children |
4 trials were conducted in low‐income countries, while the rest were from high‐income countries. Anaemia and malaria prevalence: not reported |
Intervention: fortified food with zinc as the only micronutrient Comparison: no intervention group, with a regular diet or unfortified foods |
Serum haemoglobin Adjustments: not reported |
GRADE = not assessed Risk of bias tool not stated, but risk of bias was assessed for the following domains: sequence allocation, allocation concealment, blinding, incomplete outcome data addressed, selective reporting. In 2 trials, risk of bias was low; most trials were at unclear or high risk of bias |
De‐Regil 2017 Point‐of‐use fortification of foods with micronutrient powders containing iron in children of preschool and school age |
December 2016 and April 2017 | 13 trials (5810 participants) | To assess the effects of point‐of‐use fortification of foods with iron‐containing MNP alone, or in combination with other vitamins and minerals on nutrition, health and development among children at preschool (24 to 59 months) and school (5 to 12 years) age | RCTs Quasi‐RCTs Cluster‐RCTs |
Children aged 24 months (2 years) to 59 months (< 5 years of age) and 5 to 12 years of age at the time of receiving the intervention with MNP | Low‐ and middle‐income populations, with the authors of 7 trials reporting that participants were of low socioeconomic status 3 trials conducted in malaria‐endemic areas Anaemia prevalence: range = 7.3% to 92% among the 9 trials reporting these data that did not exclude participants with anaemia |
Intervention: provision of MNP for point‐of‐use fortification given at any dose, frequency and duration Comparison: no intervention, placebo or usual supplementation |
Hb (g/L) Anaemia (defined as Hb < 110 g/L for children aged 24 to 59 months and < 115 g/L for children aged 5 to 11.9 years, adjusted by altitude where appropriate) IDA (defined by the presence of anaemia plus ID, diagnosed with an indicator of iron status as selected by trialists) ID (defined by using ferritin concentrations < 15 μg/L) Adverse effects (any, as defined by trialists) Diarrhoea (3 liquid stools or more per day) Adjustments: not reported |
GRADE: Hb = low, anaemia = moderate, ID = moderate, adverse effects = moderate, diarrhoea = low Cochrane RoB 1 tool. 9 of the 13 trials were considered at low risk of bias. In most trials, the main limitation was the lack of blinding at all levels. |
Eichler 2019 Health effects of micronutrient fortified dairy products and cereal food for children and adolescents: A systematic review |
January 2018 | 24 studies (9367 children and adolescents) | To assess the impact of MN fortified dairy products and cereal food on the health of children and adolescents (aged 5 to 15 years) compared with non‐fortified food | RCTs Cluster‐RCTs |
Children (aged 5 to 12 years) and adolescents (aged 12 to 15 years) of both sexes and from all risk groups. Studies with mixed population groups were included only if the majority of participants were within the age range of 5 to 15 years | Low‐ and middle‐income countries Anaemia and malaria prevalence: not reported |
Intervention: centrally‐processed fortified dairy products and fortified cereals, using any fortification strategy Comparison: non‐fortified food |
Hb (g/dL; conversion to g/L with factor 10) Anaemia rate (< 11.5 g/dL (5 to 11 years of age)); < 12.0 g/dL (12 to 15 years of age)) IDA ID (ferritin level) Adverse events Adjustments: not reported |
GRADE: Hb = very low, anaemia = very low, IDA = very low, ID = very low, adverse events = low Cochrane RoB 1 tool for RCTs. Only 4 of 24 studies were judged as having a low risk of bias in at least 5 of 6 assessed domains. |
Fe: ferrum (iron); Hb: haemoglobin; ID: iron deficiency; IDA: iron deficiency anaemia; MMN: multiple micronutrient; MN: micronutrient; MNP: micronutrient powders; RCT: randomised controlled trial; WHO: World Health Organization.