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. 2021 Sep 26;2021(9):CD013092. doi: 10.1002/14651858.CD013092.pub2

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.