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Intermittent iron supplementation for improving nutrition and development in children under 12 years of age

  1. Luz Maria De-Regil1,*,
  2. Maria Elena D Jefferds2,
  3. Allison C Sylvetsky3,
  4. Therese Dowswell4

Editorial Group: Cochrane Developmental, Psychosocial and Learning Problems Group

Published Online: 7 DEC 2011

Assessed as up-to-date: 23 OCT 2011

DOI: 10.1002/14651858.CD009085.pub2


How to Cite

De-Regil LM, Jefferds MED, Sylvetsky AC, Dowswell T. Intermittent iron supplementation for improving nutrition and development in children under 12 years of age. Cochrane Database of Systematic Reviews 2011, Issue 12. Art. No.: CD009085. DOI: 10.1002/14651858.CD009085.pub2.

Author Information

  1. 1

    Micronutrient Initiative, Ottawa, ON, Canada

  2. 2

    Centers for Disease Control and Prevention, International Micronutrient Malnutrition Prevention and Control Program, Nutrition Branch, Division of Nutrition, Physical Activity and Obesity, Atlanta, Georgia, USA

  3. 3

    Emory University, Graduate Division of Biological and Biomedical Sciences, Atlanta, Georgia, USA

  4. 4

    The University of Liverpool, Cochrane Pregnancy and Childbirth Group, Department of Women's and Children's Health, Liverpool, UK

*Luz Maria De-Regil, Micronutrient Initiative, 180 Elgin Street, Suite 1000, Ottawa, ON, K2P 2K3, Canada. lderegil@micronutrient.org.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 7 DEC 2011

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Characteristics of included studies [ordered by study ID]
Aguayo 2000

MethodsRandomised double-blind placebo-controlled trial. 2-arm design with individual randomisation.


Participants73 children (64 children followed up), both sexes (30 females (47%)), aged 6–11.9 years (9 years in average), from outskirts of La Paz, Bolivia (4000 m above sea level). Inclusion criterion: non-anaemic. Socioeconomic status not reported.


InterventionsParticipants were allocated to one of the following groups:

Group 1 (n = 37): children received weekly tablets containing iron. The iron dose was calculated to provide children with 3 mg of elemental iron per kg of body weight (approximately 85 mg of iron per week). The supplement consisted of two types of tablets containing either 20 mg or 36 mg of elemental iron (as ferrous sulphate). These tablets were used in combination to adjust the dose to the child’s weight;

Group 2 (n = 36): children received a placebo similar in colour and appearance to the iron supplement.

Length of the intervention: 18 weeks


OutcomesHaemoglobin, mean haemoglobin change, anaemia, anthropometric measurements (weight for age Z-score, height for age Z-score and mid-upper arm circumference), and side effects.


NotesA teacher trained by the principal investigator was responsible for delivering the iron tablets in the classrooms. All children completed at least 17 doses. Pills were administered on Wednesday and students who were not in school on Wednesday were administered the supplements on Thursday.

Z-scores used the National Center for Health Statistics data as a reference.

Non-malaria area.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskChildren were randomly assigned to the treatment or the control group using a table with randomly assorted digits.

Allocation concealment (selection bias)Low riskA teacher trained by the principal investigator was responsible for the delivery of the iron tablets in the classrooms. The teacher was provided with a list of the names of the children and the number and kind of pills (colour coded) each child should take every week. Neither the teacher nor the assistant were aware of the composition of the tablets delivered to the children and tablets were similar in appearance.

Blinding (performance bias and detection bias)
All outcomes
Low riskTablets were similar in appearance.

Participants:Children were not aware of the treatment.

Personnel: Neither the teacher nor his assistant were aware of the composition of the tablets delivered to the children

Outcome assessors: not described.

Incomplete outcome data (attrition bias)
All outcomes
Low riskA complete set of data was obtained for 33 children in the treatment group (89.2 %) and for 31 children (86.1 %) in the control group

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasLow riskNo significant differences at baseline in the variables studied,and females/males ratio. No differences at baseline between those that completed the study and those who dropped out.

Arcanjo 2011 (C)

MethodsCluster-randomised, placebo-controlled double-blind trial. 2 arm design with randomisation at classroom level.


Participants106 preschool children, both sexes (56 females (52.8%), aged 5 years. The study was conducted in a public school located in the City of Sobral, in the northeast of Brazil between September and December 2009. Exclusion criteria: current supplement intake. Baseline prevalence of anaemia: 58.5%. Forty per cent of the families had an income <300 USD.


InterventionsClassrooms were allocated to one of the following groups:

Group 1 (3 classrooms, 52 children): children received once a week 50 mg of elemental iron (as ferrous sulphate heptahydrate) once a week;

Group 2 (3 classrooms, 54 children): children received once a week a placebo (on Wednesdays). The placebo contained 2 ml of natural colour additive, annatto, which is odourless and tasteless, providing a yellow–orange colour similar to that of the elemental iron used in the study.

Length of the intervention: 14 weeks.


OutcomesHaemoglobin, hematocrit and anaemia (Hb less than 115 g/L)


NotesThe supplements were administered on Wednesdays. The supplement was administered by a teacher using a plastic medical syringe with scale to squirt the composition into the child’s mouth. The syringes were prepared on an individual basis by medical staff.

We adjusted the results of this study to account for the effect of clustering in data; the estimated effective sample size was used in the analyses. 

Malaria endemicity not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskAn allocation code was generated with a table of random numbers for randomizations of schools and classes.

Allocation concealment (selection bias)Low riskThe study used a placebo. Since randomisation occurred at classroom level, it is unlikely a selection bias at individual level.

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants: were not aware of different interventions.

Personnel: the teacher was not aware of the treatment nor involved in data collection.

Ouctome assessors: the staff involved in data collection was blinded with regard to the intervention and placebo groups.

Incomplete outcome data (attrition bias)
All outcomes
Low riskDuring the study, there were 2 (3.8%) dropouts in group 1, and 5 (9.2%) dropouts in group 2. Intention to treat analysis.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasUnclear riskThe data was not adjusted by the effect of clustering.

Anaemia prevalence at baseline was not balanced between groups: 48% in group 1 and 69% in group 2 (but similar concentrations of haemoglobin).

Awasthi 2005 (C)

MethodsCluster-randomised community effectiveness trial. 2 arm design with randomisation at subcentre level.


Participants803 children, both sexes (730 females (45.4%)), aged 3-6 years, living in sub centres of Shahpur Baxolia and Sipa Hidayatpur from Nindura Block, Barabanki district, North India. Exclusion criteria: those without written informed consent, or those likely to move within the next three months. Children identified as severely anaemic were given iron and folic acid in therapeutic doses under close supervision (but does not say they were excluded). Baseline prevalence of anaemia in children was 53.79 %. Socioeconomic status not reported.


InterventionsSub centres were allocated to one of the following groups:

Group 1 (n = 403): children in Shahpur Baxolia sub centre received tablets containing 20 mg elemental iron (presumably in form of ferrous sulphate) iron and 100 μg (0.1 mg) folic acid twice a week, on fixed days (Wednesday and Saturday);

Group 2 (n = 400): children in Sipa Hidayatpur sub centre received one tablet daily.

Length of the intervention: one year.


OutcomesHaemoglobin, haemoglobin mean change, anaemia, and adherence.


NotesIron and folic acid was given to the children either by the Anganwadi worker, if they were registered and used the informal education services of the Integrated Child Health Development Services, or by the mother for non-registered children. Mothers could pick up monthly supplies for their children one day a month from an Anganwadi centre.

A monitoring in-charge was responsible for each intervention type. He visited each Anganwadi centre every 15 days to take an account of the IFA distributed to registered children. The monitor in-charge also visited 20 randomly selected houses of non-registered children and collected information about the IFA tablet intake, including the number of pills consumed.

Sample size was calculated taking into consideration a design effect of 2. We adjusted the results of this study to account for the effect of clustering in data; the estimated effective sample size was used in the analyses. 

Malaria endemicity not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskFor this study all sub centres were listed alphabetically, serially numbered, and two were selected by random for assessment of the interventional strategies, one per sub-centre. It is unclear whether the allocation to the treatment was at random.

Allocation concealment (selection bias)Low riskSince the intervention was allocated at sub-centre level, it is unlikely there was a selection bias at the individual level.

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants: Not reported.

Personnel: Not reported.

Outcome assessors: Not reported.

Incomplete outcome data (attrition bias)
All outcomes
Low riskLoss to follow up 8.34% at one year with no difference between groups (biweekly 8.1% versus daily 8.5%).

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasHigh riskSome children had directly observed intake and others were given the pills by the mother. About 1/3 of the children are registered to obtain services of the Anganwadi centre (under the ICDS services) and this had a differential effect on supplementation (favouring registered children).

Results did not account for the cluster effect.

Baqui 2003

MethodsRandomised, double-blinded community-based trial. 5-arm design with individual randomisation.


Participants799 Bangladeshi children, both sexes (406 females (50.8%)), enrolled at 5-6 months of age for a 6 month study (12 mo old when completed). Potential families were identified through ongoing health and demographic surveillance system. Participants were eligible if did not receive infant formula, were not severely malnourished (mid-upper arm circumference >110mm), not severely anaemic (haemoglobin >90 g/L), with no obvious neurologic disorders, physical disabilities, or chronic illnesses that might affect feeding, activity, and cognitive development. There were no differences in monthly income, household size or father's education across the arms. Approximately two-thirds of the children were mildly anaemic at recruitment.


InterventionsInfants were randomly allocated to one of the following groups:

Group 1 (n = 154): Infants received once a week multiple micronutrients in a dose that doubled the recommended dietary allowance (WHO standards) of thiamine, niacin, folic acid, pantothenic acid, iodine, copper, manganese, selenium, and vitamins C, D, E, B6 and B12. It contained 20 mg elemental iron (as ferrous sulphate), 20 mg elemental zinc (as zinc acetate), and 1 mg riboflavin.

Group 2 (n = 161): Infants received once a week 20 mg elemental iron and 1 mg riboflavin.

Group 3 (n = 161): Infants received once a week 20 mg of elemental zinc and 1 mg riboflavin.

Group 4 (n = 162): Infants received once a week 20 mg of elemental zinc, 20 mg elemental iron and 1 mg riboflavin.

Group 5 (n = 157): Infants received riboflavin (control).

For the purpose of this review, groups 1, 2 & 4 were merged and compared with group 5.

Length of the intervention: 6 months.


OutcomesFerritin, diarrhoea, ALRI, physical growth, mental, motor, behavioral development from 6 to 12 month (measured using Bayley II scales of infant development), adherence. Data on diarrhoea and ALRI was not combined as it is reported in incidence rate/(child-y)


NotesSupplements were prepared as capsules, which were mixed with flavoured syrup and fed to infants by community health workers.

All supplements had similar taste and appearance and all groups also received 100,000 IU of vitamin A at the beginning of the study, in line with national policy in Bangladesh.

Trial with sub-studies with different sample sizes.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskParticipants were randomly allocated to the study groups. Method of sequence generation not described.

Allocation concealment (selection bias)Low riskEach study infant received the assigned supplement in the same type of capsules and labelled in such a way that the various types of supplements could not be differentiated.

Blinding (performance bias and detection bias)
All outcomes
Low riskDescribed as doubled-blinded clinical trial. Each study infant received the assigned supplement in the same type of capsules and labelled in such a way that the various types of supplements could not be differentiated

Incomplete outcome data (attrition bias)
All outcomes
High riskDrop out rate much higher (41%) in the MM group than in other groups (8-19%). Motor/Cognitive outcomes: 125 kids (36%) did not complete 12 mo-assessment, leaving 221 children in final sample. There were no differences among arms or major sociodemographic variables for dropouts. 16.3% did not undergo evaluation with HOME scale.

5% did not have haemoglobin data at 12 mo, 1.8% did not have anthropometric data at 12 mo but did for other measures.

Selective reporting (reporting bias)High riskTrial with sub studies with different sample sizes.

Other biasUnclear riskNo discussion of adjustment or exclusion for inflammation for iron status analysis.

Berger 1997

MethodsDouble-blind randomised controlled trial. 3-arm design with individual randomisation.


Participants176 children, both sexes (91 females (52%)), aged 3.3-8.3 years (69 months old in average), attending the schools administered by the non-governmental organization "Fe y Alegria" located in a socio-economically disadvantaged district of La Paz, Bolivia (altitude of 4000 m above sea level). Inclusion criterion: anaemia (haemoglobin concentration equal to or lower than 144 g/L). No additional exclusion criteria listed. Socioeconomic status not reported.


InterventionsParticipants were allocated to one of the following groups:

Group 1 (n = 59): children received every Tuesday 3-4 mg of iron per kg of body weight (approximately 60-80 mg per week);

Group 2 (n = 59): children received a daily dose of 3-4 mg of iron per kg of body weight, 5 days per week, Monday to Fri. Daily group received 5 times as much iron as weekly;

Group 3 (n = 58): children received a placebo, once a week, every Tuesday. Placebo consisted of same tablets without iron.

Supplements given to groups 1 and 2 consisted of two types of tablets containing either 20 mg or 36 mg of elemental iron in form of ferrous sulphate. These tablets were used in combination to adjust the dose to the child’s weight

Length of the intervention: 16 weeks


OutcomesHaemoglobin, change in haemoglobin, anaemia, zinc erythrocyte protoporphyrin, adherence.


NotesTablets were given to children at school, with clean, boiled water, at mid morning, by trained school assistants, under the supervision of a member of the research team. Same tablets were used for weekly, daily, and same tablets without iron were used for placebo.

Non malaria area.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskChildren were randomly assigned to one of three groups. Method of sequence generation not described.

Allocation concealment (selection bias)Low riskMethod of concealment not described, but the study reported as double blind.

Blinding (performance bias and detection bias)
All outcomes
Low riskDescribed as double-blind trial. Same tablets were used for weekly, daily, and same tablets without iron were used for placebo.

Participants: children were not aware of the treatment

Personnel: personnel were not aware of the treatment

Outcome assessors: not described.

Incomplete outcome data (attrition bias)
All outcomes
Low riskOnly one person lost to follow-up in each group, 3 people total. Dropouts were due to migration of the family out of the area of study

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasLow riskThe study appears to be free of other sources of bias.

Da Silva 2008

MethodsRandomised controlled trial. 3-arm design with randomisation at individual level.


Participants135 children (114 followed up, 54 female (47%)), both sexes, aged 5 to 6.9 months, from Vicosa, the Southeast of Brazil. Children were identified from live birth forms and parents were interviewed; parents who were interested in participating were recruited (213 children were screened, 78 infants with anaemia were excluded and treated). Inclusion criteria: non-anaemic infants (Hb equal to or greater than 110 g/L), living in urban area; full term, singleton births; birth weight > 2500 g; mother aged > 19 years old; no neonatal abnormalities or chronic disease; no previous iron supplements; non-exclusive breastfeeding. Maternal years of education ranged between 4 and 11 years (mean approximately 8 years).


InterventionsParticipants were allocated to one of the following groups:

Group 1 (n = 51): infants received 1 mg of elemental iron/kg/day (as liquid ferrous sulphate);

Group 2 (n = 42): infants received 2 mg of elemental iron/kg/day (as liquid ferrous sulphate);

Group 3 (n = 42): infants received 25 mg elemental iron once a week (as liquid ferrous sulphate).

Length of the intervention: 16 weeks

For the purpose of this review only groups 2 and 3 were compared as the overall dose of iron given to the children was similar between them.


OutcomesHeight, weight and change scores for height and weight (with Z-scores), morbidity (diarrhoea, fever, cough, nasal congestion, wheezing).


NotesSupplements were provided free to all groups and participants were advised to take 1 hour before meals.

Z scores used the World Health Organization data as a reference.

Malaria endemicity not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskA computer-generated random number list (method communicated by the author).

Allocation concealment (selection bias)High riskOpen random allocation schedule. Children were enrolled to the study in a row; there was a list showing the sequence in which children would be allocated to the groups (method communicated by the author).

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants: Not reported.

Personnel: Not reported.

Outcome assessors: Not reported.

Incomplete outcome data (attrition bias)
All outcomes
High risk135 children were randomised. 114 completed the intervention (84%). Loss was not balanced across groups: 12/51 lost from group 1, 6/42 from group 2, 3/42 from group 3.

Reasons for loss included patient withdrawal (7) supplement intolerance (6) anaemia (2) and other reasons. It was not clear how many withdrew from each group for these reasons.

It was stated that analysis was based on an intention to treat principle, irrespective of adherence, but those lost to follow up did not appear to be included in the analysis, although denominators were not clear in the data tables.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasLow riskThe study appears to be free of other sources of bias.

Desai 2004 (C)

MethodsCluster-randomised trial. 2x2 factorial design in which housing compounds were the unit of randomisation.


Participants1049 children, both sexes (519 females (49.5%)), aged 2-59 months (27 months in average), living in 14 villages in Asembo, Bondo district, Nyanza Province, western Kenya. Inclusion criteria: haemoglobin 50-109 g/L (anaemic); asexual parasite count <20,000/mm; no history of intake of iron, sulphadoxine-pyrimethamine or amodiaquine use, or blood transfusion within the last 2 weeks, no known sickle cell disease

Baseline prevalence of anaemia in children was 74%. Caretakers had a median of 6 or more years of education across all arms and 48.6% of households had a wealth score above the median.


InterventionsCompounds were allocated to one of the following groups at baseline:

Group 1 (n = 266): children received two doses of 3-6 mg/kg each, separated by 3-4 days (total dose per week: 6-12 mg/kg; approximately 36-72 mg of iron per week). Supervised;

Group 2 (n = 271): children received two doses of 3-6 mg/kg each, separated by 3-4 days (total dose per week: 6-12 mg/kg). Unsupervised;

Group 3 (n = 261): children received one daily dose of 3-6 mg/(kg per day). Supervised;

Group 4 (n = 251): children received one daily dose of 3-6 mg/(kg per day). Unsupervised

Target iron dose was ferrous sulphate syrup 40 g/L, 27.5% elemental iron. Iron doses were based on body weight (<5 kg: 1.25 mL/d, 5-10 kg: 2.5 mL/d, >10 kg: 5.0 mL/d). No folic acid was given.

Supervised arms (Groups 1 and 3) were used to assess the haematological response while unsupervised groups (2 and 4) provided data on adherence and side effects.

Length of the intervention: 6 weeks.


OutcomesHaemoglobin, haemoglobin mean change, hematological recovery, microcytosis, all-cause morbidity, clinical malaria, malaria parasitaemia, adherence.


NotesAll parents received the 6-week supply of oral iron and received identical instructions in the local language about use, expected side effects, safety and correct dose of iron supplementation.

To determine differences in the duration of any treatment effect on Hb levels, children were seen again at 12 wk (1 d)

The mean cluster size was 1.5 children per compound, and the reported design effect was 1.035. Standard errors were adjusted for clustering at the compound level.

Malaria-endemic area.

All arms were given single treatment dose of sulfadoxine-pyrimethamine (SP).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskA computer-generated random number listing was used to sequentially assign eligible children to 1 of 4 treatment groups, using the housing compound as the randomisation unit.

Allocation concealment (selection bias)Low riskPlastic screw top bottles used, labelled with personal identifiers and dosing instructions. Since the intervention was allocated at compounds level, it is unlikely there was a selection bias at the individual level.

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants:were aware of the treatment assigned.

Personnel: no blinding

Outcome assessors: no blinding

Incomplete outcome data (attrition bias)
All outcomes
Low risk8.9% (n = 93) and equally divided among the four arms.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasUnclear riskChildren lost to follow up had lower (P=0.01) haemoglobin concentrations at enrolment than those successfully followed for 6 wk, but were not different for other characteristics. None of the characteristics differed among the groups after excluding children lost to follow up. 6 children (4 compounds) excluded from analyses at 6 wk follow up due to missing haemoglobin values. No discussion on adjustment/exclusion for inflammation.

Ekvall 2000

MethodsRandomised trial. 2-arm design with individual randomisation.


Participants207 children, both sexes (sex distribution unknown), 5 months-3 years of age, living in Fukayosi village, Bagamoyo district of coastal Tanzania, from June to November 1995, during the seasonal peak of perennial malaria transmission. Exclusion criteria: migration plans, the presence of congenital malformations and Hb concentration, 50 g/L at baseline, requiring immediate treatment. Baseline prevalence of anaemia in children was 89% (Hb lower than 110 g/L). Socioeconomic status not reported.


InterventionsParticipants were allocated to one of the following groups:

Group 1 (n = 104): children received three times a week 1 mL of a micronutrient preparation containing 10 mg iron (as ferrous sulphate), 1500 IU vitamin A, 400 IU vitamin D, 5 IU vitamin E, 35 mg vitamin C, 0.5 mg vitamin B1, 0.6 mg vitamin B2, 8 mg niacin and 0.4 mg vitamin B6;

Group 2 (n = 103): children received three times a week 1 mL of a placebo (1 mg of promethazine hydrochloride).

Iron compound and weekly dose: 30 mg of elemental iron (as ferrous sulphate) per week.

Length of the intervention: 5 months.


OutcomesHaemoglobin, mean cell volume as an indicator of iron status, clinical malaria, fever, adherence.


NotesAll children were to receive a total of 56 doses over 5 months administered during home visits by six research assistants who were assigned 30–35 children each.

Malaria holoendemic area. For active case detection of clinical malaria episodes, all children were seen fortnightly by the research team at the village dispensary for axillary temperature measurement. Children with malaria received chloroquine syrup (25 mg/kg over three days), and additional treatment with sulphadoxine pyrimethamine (SP) was given if a child showed clinical signs of treatment failure.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskThe children were randomly allocated to the supplement group or the placebo group by a computer-generated number table.

Allocation concealment (selection bias)Low riskThe supplement and placebo had different colours to facilitate correct administration. However, neither the research assistants involved in the project nor the mothers of
the children knew the treatment code.

Blinding (performance bias and detection bias)
All outcomes
Low riskThe supplement and placebo had different colours to facilitate correct administration.

Participants: mothers did not know the treatment code

Personnel: research assistants did not know the treatment code

Ouctome assessors: not described

Incomplete outcome data (attrition bias)
All outcomes
Low risk6 children were lost to follow up in each group (6%).

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasLow riskThe study appears to be free of other sources of bias.

Engstrom 2008 (C)

MethodsCluster-randomised trial. 3 arm design in which health facilities were the unit of randomisation.


Participants391 children, both sexes (184 females (47%)), 6 months old. Study carried out through primary healthcare units in Rio de Janeiro, Brazil. 15 health care centres (6 intervention, 9 control). Inclusion criteria: absence of iron supplementation in the month preceding recruitment and negative for sickle cell anaemia.

Baseline prevalence of anaemia (taken from the control group): 60.4%. Socioeconomic status:approximately 30% of the mothers worked outside the home; most families (> 90%) had access to radio and television, but < 20% had access to a car.


InterventionsHealth facilities were allocated to one of the following groups:

Group 1 (n = 188): children received weekly supplementation with 25 mg of elemental iron (as oral ferrous sulphate) per week in syrup and education on anaemia and diet;

Group 2 (n = 188): children received daily supplements containing 12.5 mg elemental iron dailyand education on anaemia and diet;

Group 3 (n = 94): children received received no intervention and was recruited retrospectively.

Length of the intervention: 24 weeks.

For the purposes of this review we only compared groups 1 and 2.


OutcomesHaemoglobin, anaemia (Hb <110 g/L) and adherence.


NotesAnalyses were performed taking into account cluster sampling.

Non-malaria area.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskHealthcare units were randomly selected. Method of sequence generation not described.

Allocation concealment (selection bias)Low riskNot reported. Since the intervention was allocated at health care unit level, it is unlikely there was a selection bias at the individual level.

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants: Mothers were aware of supplements

Personnel: Clinic staff were aware of supplements

Outcome assessors: Unlikely

Control group identified retrospectively so they were not aware of trial during treatment phase.

Incomplete outcome data (attrition bias)
All outcomes
High risk38/188 (20.2%) were lost to follow up the daily group and 41/188 (21.8%) in the weekly group.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasUnclear riskBaseline characteristics were similar for most variables. Regression analysis was carried out to identify possible confounders and where possible confounders accounted for at least 10% of variation they were entered into the final model. However for anaemia no confounders were maintained in the final regression analysis.

Ermis 2002

MethodsRandomised placebo-controlled trial. 4-arm design with individual randomisation.


Participants113 infants, both sexes (56 females (50%)), 5-month old, receiving routine paediatric care at the Research hospital of Karaelmas University in Zonguldak, Turkey. Inclusion criteria: no gestational problems (hypertension, preeclampsia, infection), no congenital anomalies, no neonatal complications, no emergency caesarian delivery, no jaundice requiring phototherapy, no hospitalisation, no chronic illness, no iron therapy, no formula feeding. Must have been exclusively breasted, birthweight > 3.0 kg and gestational age of > 37 weeks. Exclusion: Hb < 95 g/L, serum ferritin <12 ng/mL, MCV < 74 fl or infection during iron supplementation. Children were eliminated from the study if compliance was lower than 75%. 58.6%-74. Baseline prevalence of anaemia not reported. One percent of the mothers of participants included in the study graduated from high school or university.


InterventionsInfants were allocated to one of the following groups:

Group 1 (n = 30): infants were given a supplement containing 1 mg iron/kg (as ferrous sulphate) daily;

Group 2 (n = 30): infants were given a supplement of 2 mg iron/kg (as ferrous sulphate) daily;

Group 3 (n = 30): infants were given a supplement of 2 mg iron/kg (as ferrous sulphate)) every other day (approximately 42 mg of iron per week);

Group 4 (n = 23): infants received a placebo.

Length of the intervention: 4 months.

Groups 1 and 2 were combined and compared with group 3.


OutcomesHaemoglobin, MCV, ferritin, side effects.


NotesSupplements were given by mothers just before or just after breastfeeding and at least one hour before or after any other food intake.

Malaria endemicity not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskChildren were randomised to the different groups. Method of sequence generation not described.

Allocation concealment (selection bias)Unclear riskNot reported.

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants: Not reported.

Personnel: Not reported.

Outcome assessors: Not reported.

Incomplete outcome data (attrition bias)
All outcomes
Low riskTwo, three and one cases were eliminated because of low compliance(<75%), in group 1, 2 and 3, respectively. The causes of non-compliance were infection during iron usage, refusing iron droplets due to unpleasant taste, or mothers forgetting to use the iron drops.

Selective reporting (reporting bias)Unclear riskCases with less than 75% of adherence were excluded.

Other biasUnclear riskCases with less than 75% of adherence were excluded. It is unclear why the control group has 25% less participants.

Evangelista-Salazar 2004

MethodsRandomised controlled trial. 4-arm design with individual randomisation.


Participants100 newborns, both sexes (50 females), living in Urban areas in Colima, Mexico. Incluson criteria: healthy, term, single-born babies during their first year of life. Exclusion criteria: low birth weight, unknown date of last menses to calculate term pregnancy, twins, bleeding disorder or other medical conditions that may be associated with anaemia (i.e., malabsorption). Baseline prevalence of anaemia: unknown. Socioeconomic status not reported but children were born to parents that were receiving a salary.


InterventionsNeonates were randomly allocated at one of the following groups:

Group 1 (n = 25): infants were given weekly a supplement of 7.5 mg elemental iron (as ferrous sulphate), and 30 mg vitamin C;

Group 2 (n = 25): infants were given fortnightly a supplement of 7.5 mg elemental iron (as ferrous sulphate), and 30 mg vitamin C;

Group 3 (n = 25): infants were given monthly a supplement of 7.5 mg elemental iron (as ferrous sulphate) and 30 mg vitamin C;

Group 4 (n = 25): received no intervention.

Length of the intervention: 12 months. During the first 6 months children received 7.5 mg and after that the dose was double. We only included the first period of evaluation in our analysis.

For the purposes of this review we only compared groups 1 and 4.


OutcomesAnaemia, iron deficiency, haemoglobin, ferritin. Neurocognitive development (Brazelton score at birth, Bayley mental and motor assessment) and growth. The latter data were not extracted as no measures of dispersion are reported.


NotesTrained personnel visited families to assess illness incidence and adherence.

Ferritin data for the group receiving intermittent supplementation was 201.2 ± 51.08 and 120.0 ± 56.63 ng/mL (or μg/L). Although the results are consistent in terms of direction, these concentrations are much higher than those observed in the rest of the trials included in this review. The corresponding author was contacted to verify this information and we decided not include this information while we await for the response.

Malaria-free area. 


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskChildren randomly allocated to the study groups. Method of sequence generation not described.

Allocation concealment (selection bias)Unclear riskNot described.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskParticipants: unclear

Personnel: unclear

Outcome assessors: Not reported.

Trial reported as single blind but the use of placebos is not described, so it is not clear who was not aware of the intervention.

Incomplete outcome data (attrition bias)
All outcomes
Low riskApparently there were no losses to follow-up.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasLow riskThe study appears to be free of other sources of bias.

Faqih 2006

MethodsRandomised clinical effectiveness trial. 3-arm design with randomisation at individual level.


Participants134 children, both sexes (38.1% female at follow up), aged 2 to 6 years (in average 43 months), attending Prince Hashim Military Hospital of the Royal Medical Services in Zarqa, Jordan. This clinic is open to children from families affiliated with the army who are not medically insured and have generally low income. Inclusion criteria: Iron deficiency anaemia at baseline (Hb ≤ 105 g/L and mean corpuscular volume ≤ 75), born at full term with birthweight equal or higher than 2.5 kg and exhibited normal growth with no signs of thalassaemia, chronic illness, congential abnormalities, or chronic and repeated infections. Baseline prevalence of anaemia not reported. Socioeconomic status not reported.


InterventionsChildren were allocated to one of the following groups:

Group 1 (n = 45): children received a daily dose of 5 mg elemental iron per kilogram of body weight;

Group 2 (n = 45): children received once a week 5 mg of elemental iron per kg of body weight on Fridays (approximately 45 mg of iron per week);

Group 3 (n = 44): children received 5 mg of elemental iron per kilogram of body weight twice a week, Friday and Monday (approximately 90 mg of iron per week).

Parents were instructed to give the ferrous sulphate supplement in 2 portions between 30 to 60 minutes before breakfast and dinner. Parents were advised to mix the supplement with water, orange juice or lemonade if the child refused the supplement.

Length of the intervention: three months.

All the groups were analysed in this review. Groups 2 and 3 were combined and only reported separately for the subgroup analysis by regimen.


OutcomesWeight, height, haemoglobin, mean corpuscular value, hematocrit, ferritin.


NotesThe dose was administered by either of the parents who were advised to mix the supplement with water, orange juice,or lemonade if the child refused to take the supplement on an empty stomach. Families also counselled on nutritional causes of IDA, consequences if not treated, iron rich foods, enhancers and inhibitors. Families also received home check up visits every two weeks.

In Jordan, malaria, hookworm, and schistosoma do not constitute a problem.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskParticipants were allocated randomly to one of three groups according to a table of random digits.

Allocation concealment (selection bias)Unclear riskNot reported.

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants: Not reported

Personnel: Not reported

Outcome assessors: Not reported

Incomplete outcome data (attrition bias)
All outcomes
High risk71 of 134 children (53%) did not complete the study. Children lost because 1) refused to take the iron, 2) parents did not administer iron for 3 months, 3) parents did not return to clinic for follow up visits. Final number of participants did not differ across groups.

Selective reporting (reporting bias)High riskOnly 34 children had ferritin values.

Other biasHigh riskVery large age range and small sample size for the outcomes, age is important for risk of anaemia and iron deficiency. Baseline haemoglobin higher in group 2 than in group 1.

Hall 2002 (C)

MethodsCluster-randomised trial. 2-arm design with randomisation at school level (60 schools, 30 per arm).


ParticipantsChildren (1201 randomised, 1113 followed up), both sexes (613 female (51%)), aged 6-19 years (mean of 11.4 years), attending rural informal community schools in the Kolondieba district of Mali. Approximately 20 randomly children (10 boys and 10 females) attending 2nd or 4th grade were selected from each school. Any child with severe anaemia (Hb ≤80 g/L) were excluded. Baseline prevalence of anaemia: approximately 55%. Socioeconomic status not reported.


InterventionsSchools were allocated to one of the following groups:

Group 1 (n = 551 at follow up, number randomised not clear): children received 65 mg elemental iron (as 200 mg of ferrous sulphate) and 250 μg (0.25 mg) of folic acid once a week;

Group 2 (n = 562 at follow up, number randomised not clear): No intervention.

Length of the intervention: 10 weeks


OutcomesAnaemia, haemoglobin. Results by sex are included in the corresponding subgroup analysis.


NotesAll children in every school were treated for parasitic infections at baseline using albendazole, and vitamin A to treat night blindness. Supplements were given by the teachers and 83% of children were given all 10 tablets and 91% received at least nine tablets.

Malaria is endemic in Mali, although the study was done in the dry season when transmission is less intense than in the wet season.

Authors provided the ICC (0.0698) and design effect (2.22) to adjust data by the effect of clustering; the estimated effective sample size was used in the analyses. 


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk60 schools were randomly assigned to either a treatment or a comparison group by using a computer-generated random number list (information communicated by the author).

Allocation concealment (selection bias)Low riskNot reported. Since the intervention was allocated at health care unit level, it is unlikely there was a selection bias at the individual level.

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants: Not reported

Personnel: Not reported

Outcome assessors: Not reported

Incomplete outcome data (attrition bias)
All outcomes
Low risk1201 children at baseline, 1113 followed up at 14-16 weeks. (93% followed up). 88 children who did not provide second samples had similar Hb levels at baseline than as those children remaining in the study.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasLow riskThe study appears to be free of other bias.

Khademloo 2009

MethodsRandomised controlled trial. 2-arm design with individual randomisation


Participants100 Infants, both sexes (sex distribution not reported), aged 6-24 months referred to the public health care centre in Sari, Iran. Urban area. Inclusion and exclusion criteria were not adequately described. Baseline prevalence of anaemia not reported. Socioecomic status: although information on sex and mothers' educational level were collected this information was not reported.


InterventionsChildren were allocated to one of the following groups:

Group 1 (n = 50): infants received fifteen drops containing elemental iron (as ferrous sulphate) given daily.

Group 2 (n = 50): infants received thirty drops of iron once a week.

Length of the intervention: 12 weeks


OutcomesFerritin, haemoglobin.


NotesTrial not included in the subgroup analysis by dose

Malaria endemicity not reported.

The total dose of iron per week is unknown.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskBabies "randomly divided in two equal groups". Method of sequence generation not described.

Allocation concealment (selection bias)Unclear riskNot reported.

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants: Not reported

Personnel: Not reported

Outcome assessors: Not reported.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot described. Denominators not provided in the results tables.

Selective reporting (reporting bias)Unclear riskGroups were described as similar at baseline, but information on methods and results was scarce.

Other biasLow riskThe study appears to be free of other sources of bias.

Liu 1995 (C)

MethodsRandomised clinical trial. 3 arm design with randomisation at classroom level.


Participants246 healthy children, both sexes (131 females (57%)), aged 3 to 6 years, attending Kindergarten in Changxi, China, an autonomous region of China. Kindergarten has 9 large classrooms and two meals and two snacks are provided daily. Exclusion criteria were chronic infectious diseases, cardiopathies, or respiratory diseases, and intake during the previous month of supplements or drugs containing iron or specially prescribed iron-rich and absorption-promoting foods for the month prior to entering the study. Approximately 29 % of the children were anaemic at baseline. Socioeconomic status not reported.


InterventionsClassrooms were allocated to one of the following groups:

Group 1 (n = 89): children received 5-6 mg of elemental iron per kilogram (as ferrous sulphate) daily;

Group 2 (n = 74): children received 5-6 mg of elemental iron per kilogram (as ferrous sulphate) twice a week (approximately 170 -204 mg of iron per week);

Group 3 (n=83): children received 5-6 mg of elemental iron per kilogram (as ferrous sulphate) tablet once a week (approximately 75 -120 mg of iron per week);.

Iron tablets were administered by teachers under direct supervision 1 hour after breakfast, making sure that the child swallowed it.

Length of the intervention: 3 months

Group 2 and 3 were combined and compared with group 1; their individual results are presented in the subgroup analyses by regimen and by anaemia status.


OutcomesHaemoglobin and ferritin.


NotesWe adjusted the results of this study to account for the effect of clustering in data; the estimated effective sample size was used in the analyses. 

Malaria endemicity not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskChildren were randomly allocated to the classroom according to their age and then classrooms were randomised to each of the three intervention groups. Method of sequence generation not described.

Allocation concealment (selection bias)Low riskNot reported. Since randomisation occurred at classroom level, it is unlikely a selection bias at individual level.

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants: Not reported

Personnel: Not reported

Outcome assessors: Results were tabulated, without knowledge of the children's supplementation regimen, by two nurses in charge of the clinic at the kindergarten with the assistance of a nonparticipating physician.

Incomplete outcome data (attrition bias)
All outcomes
Low risk238 children completed the study. 5 left the kindergarten during the study and 3 children from daily group discontinued supplementation due to persistent nausea.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasHigh riskData not adjusted by the effect of clustering in data

Nguyen 2002

MethodsRandomised trial. 4 arm design with individual randomisation.


Participants280 children, both sexes (133 females (47.5%), aged 5 to 12 months, living in one of four communes in the rural district of Bac Ninh, Vietnam. Inclusion criteria: Hb< 70 g/L, no pathologies after a clinical examination and not receiving any iron supplements. Baseline prevalence of anaemia: ˜60%.Socioeconomic status: ˜95% dedicated to agriculture.


InterventionsTwo communes were allocated to one of the following groups:

Group 1 (n = 70): children received a placebo (2.5 ml of syrup without iron) every day;

Group 2 (n = 70): children received a daily dose of 15 mg elemental iron (2.0 ± 0.3 mg iron/day/kg body weight) (as ferrous sulphate).

Participants from other two communes were randomly allocated to one of the following groups:

Group 3 (n = 70): children received a daily dose of 15 mg elemental iron (2.0 ± 0.3 mg iron/day/kg body weight) (as ferrous sulphate);

Group 4 (n = 70): children received a weekly dose of 15 mg elemental iron (as ferrous sulphate).

Length of the intervention: 3 months (groups 1 and 2) and 6 months (groups 3 and 4).

For the purposes of this review only groups 3 and 4 were compared.


OutcomesHaemoglobin, anthropometric measurements (height for age, weight, age and weight for height were Z-scores)


NotesArticle translated from French.

The supplements were administered between 8 and 10 am by local auxiliaries, under regular supervision of a member of the research team. 98% and 95% of the infants in group 3 and 4, respectively, received more than 90% of the expected total dose of iron.

Malaria endemicity not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskOnly children from groups 3 and 4 were randomly allocated to either daily or weekly supplementation. Method of sequence generation not described.

Allocation concealment (selection bias)Low riskNot described, but the trial included the provision of a placebo and multiple blinding.

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants: the nature of the treatment was unknown to the family of the infant; all the infants received identical looking syrups (with or without iron).

Personnel: community auxiliaries were not aware of the treatments.

Outcome assessors: Neither the people in charge of measurements researcher nor the data analysts were aware of the treatments.

Incomplete outcome data (attrition bias)
All outcomes
Low risk10 children did not complete the study, 4 because parents refused to continue, 3 due to address change and 4 because of low compliance (consumed less than 80% of the doses).

Selective reporting (reporting bias)High riskResults on growth not reported.

Other biasLow riskThe study appears to be free of other sources of bias.

Olsen 2000

MethodsRandomised, placebo-controlled, double-blind study. 2-arm design with individual randomisation.


Participants231 children, both sexes (99 females (43%)), aged 4-15 years (8.6 years in average), living in Luo villages of Asino, Ohala, and Pith-Kodhiambo in Kisumu district of Nyanza Province in western Kenya. Participants had moderately low blood haemoglobin concentrations (80-130 g/L for children 4-14 years of age or non-pregnant female >14 years of age and 80-135 g/Lif male and >14 years of age). Exclusion criteria: severe anaemia (Hb <80 g/L) or pregnant. Baseline prevalence of anaemia: 47.5%. Socioeconomic status not reported


InterventionsParticipants were allocated to one of the following groups:

Group 1 (n = 121): children received treatment twice weekly with a 60 mg of elemental iron (total of 120 mg of iron per week, as 200 mg of ferrous dextran);

Group 2 (n = 110): children received a placebo.

Length of the intervention: 12 months.


OutcomesHaemoglobin, serum ferritin (median and interquartile range, could not be extracted), reinfection rates and intensities of hookworm, Ascaris lumbricoides, Trichuris trichiura, and Schistosoma mansoni, compliance ("reasonable").


NotesAt baseline, any individual infected with any intestinal helminth. S. mansoni, and malaria were treated (only abstract says treated with malaria).

After baseline examination, each subject was given a container (labelled with the subject's name, study number and identification sticker) containing 50 tablets. At the end of each 4-month period, the number of tablets taken was registered, based on the number of remaining tablets. In order to encourage intake, field assistants visited every participant at least once a month. Tablet intake for the whole study period was 98.9% of the scheduled value, and 90.1% of the children each appeared to take between 80% and 120% of the scheduled number of tablets.

Iron supplementation had no effect on either reinfection rates or intensities in children. Multiple
logistic regression analyses controlling for baseline infection status confirmed the effect in adults of

Malaria endemic area.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskSimple randomisation using a programme written in advance.

Allocation concealment (selection bias)Low riskThe tablets were coded by the manufacturer and sealed envelopes containing the codes were kept closed until the end of the study.

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants: received identical pills and instructions

Personnel: envelopes revealing randomizations code not opened until analysis was complete.

Outcome assessors: envelopes revealing randomizations code not opened until analysis was complete.

Incomplete outcome data (attrition bias)
All outcomes
Low riskOf 231 randomised, one became pregnant and 30 lost to follow up. Lost equally distributed across both arms.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasUnclear riskBaseline intensity of A. Lumbricoides infection was higher in the placebo group than in the iron group. HIV not assessed at baseline, but at 4 months, and assumed to reflect baseline status; it is unclear what treatment was available for participants.

Palupi 1997

MethodsDouble-masked, randomised controlled field trial. 3-arm design with individual randomisation.


Participants299 children, both sexes (sex distribution not reported), aged 2-5 years, who were registered at the West Javanese village of Setia Asih. Of 344 potential subjects, parental permission was obtained for 299 children. No further inclusion or exclusion criteria mentioned. Baseline prevalence of anaemia: 36.7%. Socioeconomic status not reported.


InterventionsParticipants were allocated to one of the following groups:

Group 1 (n = 98): children received 30 mg elemental iron (as ferrous sulphate) once per week and anthelminthic treatment;

Group 2 (n = 96): children received 30 mg elemental iron (as ferrous sulphate) once per week and placebo for anthelminthic treatment;

Group 3 (n = 98): children received placebos for both iron supplements and anti-helminthic treatment. The placebo syrup did not contain ferrous sulphate, but was similar in taste and appearance to the iron-containing syrup.

Length of the intervention: 9 weeks

For the purpose of this review only groups 2 and 3 were compared.


OutcomesHaemoglobin, haemoglobin mean change, anaemia, anthropometric measurements (Height-for-age Z-score, Weight-for-age Z-score, Weight-for-height Z-score change), helminthic infection.


NotesThe anthelminthic tablets as well as the placebos were ingested under supervision of the researcher one week before iron supplementation started. The supplements were given to the children by their mothers and intake was not supervised by health centre staff or the researchers, but compliance was controlled by checking the iron content in the stool.

Z-scores used the National Center for Health Statistics data as a reference.

Malaria endemicity not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskChildren were randomly divided into three, equal-sized treatment groups. Method of sequence generation not described.

Allocation concealment (selection bias)Low riskMothers received a bottle with 100 mL glucose syrup. Although the concealment is not clearly described, this is a double-blind trial and its unlikely that there was a selection bias.

Blinding (performance bias and detection bias)
All outcomes
Low riskReported as double-masked trial.

Participants: were not aware of the treatment

Personnel: all mothers received a bottle with 100 mL glucose syrup containing or not iron.

Outcome assessors: unclear but probably blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low risk289 (out of 299) children remained; 10 (3%) dropped out because they had either moved or had become ill.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasLow riskThe study appears to be free of other sources of bias.

Roschnik 2003 (C)

MethodsCluster-randomised trial. 2-arm design with randomisation at school level and stratified by sponsorship status.


Participants1,160 children (752 followed up), both sexes (371 females (49.5%)), aged 7–8 years and 12-14 y. The study included 40 primary schools in the Mangochi District, Malawi. Baseline prevalence of anaemia: around 54%. Socioeconomic status not reported.


InterventionsSchools were randomly allocated to one of the following treatments:

Group 1 (20 schools, n = 640): children received 65 mg of elemental iron (as 200 mg ferrous sulphate) and 250 μg (0.25 mg) of folic acid once a week.

Group 2 (20 schools, n = 640): children received no intervention.

Length of the intervention: 15 weeks


OutcomesHaemoglobin concentration, bilharzia infection, school attendance, test scores

and drop-out rate and repetition rate (at the school level).  


NotesResults were stratified by age (<10 y, 10-14 y and 15+). For the purposes of this review we only included those data from children <10 years of age (192 in the intervention group and 190 in the control group), until we can obtain the data for all children <12 years.

A famine occurred in the region at the time of the study.

Each study group included 10 sponsorship schools and 10 non-sponsorship schools, 10 coastal and 10 upland schools. All children in Coastal intervention and comparison schools, where the prevalence of bilharzia was over 50%, were dewormed with Praziquantel (600mg) just after the baseline survey.

A vitamin A capsule (200,000 IU) was given to all children in standard 2 and below

63% of children took 10 iron tablets or more.

Analysis originally not adjusted by the effect of clustering. The effective sample was calculated by imputing the ICC from Roschnik 2004 (C), which has a similar study design; the estimated effective sample size was used in the analyses. 

Malaria endemicity not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk40 primary schools in the Mangochi District were randomly divided into the intervention (1st iron group) and comparison group (2nd iron group). Each group includes 10 sponsorship schools and 10 non-sponsorship schools. Method of sequence generation not specified.

Allocation concealment (selection bias)Low riskNot reported. Since the intervention was allocated at school level, it is unlikely there was a selection bias at the individual level.

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants: not reported.

Personnel: not reported

Outcome assessors: not reported.

Incomplete outcome data (attrition bias)
All outcomes
High risk1280 were randomised, 1160 had haemoglobin levels at baseline and 752 were followed up: 41.2% children lost to follow up

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasUnclear riskChildren attending sponsored schools responded better to the treatment.

Roschnik 2004 (C)

MethodsCluster-randomised trial. 2-arm design with randomisation at school level.


Participants1785 children (1510 followed up), both sexes (747 females (49.5%), aged 7–12 years. The study included 51 primary schools: 20 in Iloilo and 31 in Guimaras, Philippines. Baseline prevalence of anaemia: ˜15%. Socioeconomic status not reported.


InterventionsSchools were randomly allocated to one of the following treatments:

Group 1 (25 schools, unclear the number of children randomised): children received 108 mg of elemental iron (as 325 mg ferrous sulphate);

Group 2 (26 schools, unclear the number of children randomised): children received no intervention.

Length of the intervention: 10 weeks


OutcomesAnaemia, haemoglobin, haemoglobin change.


NotesSupplementation started between 1 and 7 weeks after the baseline survey and the second survey took place between 5 and 18 weeks after the end of the iron supplementation.

The consumption of each tablet was recorded by the teachers. Side effects were not recorded. All 10 iron tablets were taken by 93.4% of children.

67% of children were infected with one or more intestinal worms.

Malaria endemicity not reported.

Authors provided the ICC (0.1123) and design effect (4.35) to adjust data by the effect of clustering; the estimated effective sample size was used in the analyses. 


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskAll 51 schools were assigned to two groups using a random number table.

Allocation concealment (selection bias)Low riskNot reported. Since the intervention was allocated at school level, it is unlikely there was a selection bias at the individual level.

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants: not reported.

Personnel: not reported

Outcome assessors: not reported.

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk15.4% of attrition. Losses presumably higher among the control group as two schools were dropped out because they were unable to collect the baseline measurements within the month allotted.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasHigh riskThe second blood sample was withdrawn between 5 and 18 weeks after the end of the iron supplementation.

Fourteen of the 49 schools in the study had participated for about 2 months in the fortified rice programme: six in the intervention group and eight in the control group. The mean haemoglobin concentration of children in the 14 schools that had participated in the programme was slightly but significantly higher than that of children in the other 25 schools (126.4 g/L versus 125.0 g/L, P ¼ 0.031).

Analysis was not adjusted by the effect of clustering in data.

Schultink 1995

MethodsRandomised clinical trial. 2-arm design with individual randomisation.


Participants87 children, both sexes, aged 2-5 years, from Subdistrict Kelurahan Tenga of East Jakarta, Indonesia. The initial selection criterion was a haemoglobin concentration < 110 g/L. 96 children were invited to receive anthelmintic treatment before starting iron supplementation; only 87 accepted and were randomised.


InterventionsParticipants were allocated to one of the following groups:

Group 1 (n = 44): children were supplemented daily with 30 mg elemental iron (as ferrous sulphate dissolved in 5 mL syrup);

Group 2 (n = 43): children were supplemented twice a week with 30 mg elemental iron (as ferrous sulphate dissolved in 5 mL syrup) (total 60 mg of iron per week).

Length of the intervention: 8 weeks.


OutcomesHaemoglobin, ferritin, zinc protoporphyrin, mean changes of haematological variables (anaemia prevalence taken from Beaton 1999).


NotesParents and supervising health staff were instructed that each child should take 5 mL from the small bottle on Mondays and Fridays and 5 mL from the large bottle on the remaining days of the week using a standardized spoon for 8 wk. Bottles had similar appearance

Malaria endemicity not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSubjects were assigned at random to two groups. Method of sequence generation not described.

Allocation concealment (selection bias)Unclear riskNot reported.

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants: were not aware of the treatment

Personnel: all mothers received two small bottles (each 80 mL) and two large bottles (each 170 mL), each containing a syrup of similar appearance

Outcome assessors: supervising staff were not aware of the bottle content.

Incomplete outcome data (attrition bias)
All outcomes
High riskA complete set of data was obtained for 33 subjects in the group supplemented twice weekly (group 1) (75%) and for 32 subjects in the group supplemented daily (group 2) (74.4%).

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasHigh riskBaseline haemoglobin concentrations were different between groups.
The results include 25 children with Hb> 110 g/L and the initial description only mentions 16

Sen 2009 (C)

MethodsCluster-randomised controlled trial. 4-arm design with randomisation at school level.


Participants240 school age females, aged 9-13 years, attending four schools in Vadodara area of India. Females were excluded from the analysis if menstruation commenced. None of the Females were involved in athletic sports on a regular basis. Baseline prevalence of anaemia: 68.3%. Socioeconomic status not described in detail but participants were described as "underprivileged".


InterventionsSchools were allocated to one of the following groups:

Group 1 (n = 65): females received 100 mg elemental iron (as ferrous gluconate) and 500 μg (0.5 mg) folic acid folic acid oral once weekly;

Group 2 (n = 89): females received the same supplement twice weekly (200 mg of elemental iron per week);

Group 3 (n = 59): females received 100 mg elemental iron (as ferrous gluconate) daily;

Group 4 (n = 41): females received no supplement.

Length of the intervention: 1 year.

Groups 1 and 2 were combined and compared with groups 3 and 4 as appropriate.


OutcomesPhysical work capacity, haemoglobin change and adherence.


NotesMalaria endemicity not reported.

Analyses in this review include the estimated effective sample size only, after adjusting the data to account for the clustering effect.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskOf 17 schools meeting the inclusion criteria, 4 schools were selected randomly using a random numbers table. Once the four schools were selected, the chit system (chits representing school 1, 2, 3, 4) was used. The order of placing a school in a category was: the first school that is picked up (from the four) goes to daily; the chit is then put back; the next chit picked up goes to twice weekly; the next to once weekly and the one left over, to control so that all schools have an equal probability of being allocated to any of the four groups (information communicated by the author).

Allocation concealment (selection bias)Low riskNot reported. Since allocation was at school level it is unlikely that there is selection bias at individual level.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskParticipants, personnel and outcome assessors: Each school received a different intervention, although it is unclear if the intervention was blinded.

Incomplete outcome data (attrition bias)
All outcomes
High risk4 schools. In these schools a random sample of 240 children was selected. 163 had pre and postintervention data for work capacity (68% followed up). Females who started their periods were excluded from the analysis. For cognitive tests results relate to a sub-sample of 161 females available pre and post-test.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasHigh riskThe design effect was not taken into account in the analysis.

Siddiqui 2004

MethodsRandomised controlled trial with. 2-arm design with individual randomisation.


Participants60 children, both sexes (30 females (50%)), aged 5-10 years, attending a private school, blue collar workers, in Karachi Pakistan. Inclusion: anaemia (haemoglobin <110 g/L). Exclusion criteria: acute disease (diarrhoea, fever, cough, running nose) or history of chronic disease (joint pain, bleeding disorders). Socioeconomic status not described.


InterventionsParticipants were allocated to one of the following groups:

Group 1 (n = 30): Children took supplements containing 60 mg of elemental iron (as 200 mg ferrous sulphate) once a week for 2 months (8 doses total);

Group 2 (n = 30): Children took 60 mg of elemental iron supplements (as 200 mg ferrous sulphate) daily for 56 days.

Length of the intervention: ˜ 2 months (weekly dosing was 8 weeks but daily dosing only 56 days).


OutcomesHaemoglobin, hematocrit, serum iron, total iron binding capacity, serum ferritin.


NotesBoth groups de-wormed prior to start of study (mebendazole).

Malaria endemicity not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskChildren were randomly assigned to one of the groups. Method of sequence generation not described.

Allocation concealment (selection bias)Unclear riskNot reported.

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants: not reported.

Personnel: not reported.

Outcome assessors: not reported.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo losses.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasUnclear riskUnclear whether 60 participants reflected all anaemic children in the school or whether (and if so how) the 30 males and 30 females were selected out of all eligible students in the school. Age in weekly group significantly different than those in daily group. Did not assess or adjust/exclude iron status indicators for inflammation

Sinisterra 1997 (C)

MethodsCluster-randomised trial. 2-arm design with randomisation at school level (5 schools).


ParticipantsChildren (909 randomised, 842 followed up), both sexes (408 female (48%)), aged 6-13 years, attending rural schools in the district of Anton, Cocle, Panama. Exclusion criterion: severe anaemia (Hb ≤90 g/L) and clinical conditions that could affect iron status. Baseline prevalence of anaemia: approximately 42.4%. Socioeconomic status not explicitly reported.


InterventionsSchools received one of the following interventions:

Group 1 (n = 176 at follow up, number randomised not clear): children received daily 60 mg of elemental iron (as ferrous sulphate) and "nutricrema";

Group 2 (n = 210 at follow up, number randomised not clear): "nutricrema".

Group 3 (n = 225 at follow up, number randomised not clear): children received daily 60 mg of elemental iron (as ferrous sulphate) and "nutricrema" once a week;

Group 4 (composed by two schools n=195 at follow up, number randomised not clear): Milk plus a fortified cookie plus folic acid

Length of the intervention: 6 months

Only groups 1 and 3 were randomised and thus included in our analysis.


OutcomesAnaemia (Hg < 120 g/L), haemoglobin, attitudes, beliefs, growth.


NotesMalaria endemicity not reported.

We adjusted the results of this study to account for the effect of clustering in data; the estimated effective sample size was used in the analyses. 


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskGroups allocated by drawing of lots (communicated by the author).

Allocation concealment (selection bias)Low riskNot described. Since the intervention was allocated at school level, it is unlikely there was a selection bias at the individual level.

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants: Not reported

Personnel: Not reported

Outcom assessors: Not reported

Incomplete outcome data (attrition bias)
All outcomes
Low risk7.3% of losses to follow up. Unclear whether they were balanced across groups.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasHigh riskThe prevalence of anaemia among those receiving weekly supplementation was 20 percentage points higher than those receiving daily supplementation (54.7% vs 34.7%).

Soemantri 1997

MethodsRandomised controlled trial. 2-arm design with individual randomisation.


Participants97 children, both sexes (sex distribution not reported), aged 7-11 years, attending the primary school Batang, in Indonesia. Inclusion criteria: anaemia (Hb below 120 g/L); not taking iron supplements during the last six months; no evidence of hepatosplenomegaly, haemoglobinopathy, acute or chronic disease, severe anaemia. Baseline prevalence of anaemia: 67.36%. Socioeconomic status not reported.


InterventionsChildren were divided into 2 groups and randomly assigned

Group 1 (n = 52): children received daily 3 mg of iron per kilogram (as ferrous sulphate);

Group 2 (n = 45): children received once a week 3 mg of elemental iron per kilogram (as ferrous sulphate) (approximately 85 mg of iron per week).

Length of the intervention: 3 months.


OutcomesAnthropometric measurements (weight for age Z-score, height for age Z-score) and haemoglobin.


NotesThe solutions were given by the school teachers on school days with careful supervision.

All children with intestinal parasites were treated prior to supplementation.

Z-scores used the National Center for Health Statistics data as a reference.

Malaria endemicity not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskChildren were randomly assigned to the study groups. Method of sequence generation not described.

Allocation concealment (selection bias)Unclear riskNot described.

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants: not reported.

Personnel: not reported.

Outcome assessors: not reported.

Incomplete outcome data (attrition bias)
All outcomes
Low riskTwo children (3.8%) were excluded from the daily group because of gastrointestinal side effects.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasLow riskThe study appears to be free of other sources of bias.

Sungthong 2002

MethodsDouble-blind, randomised, placebo-controlled trial. 3-arm design with individual randomisation.


ParticipantsOf 50 government schools located outside the municipality, selected schools had to met the following criteria: 1) high prevalence of underweight according to school-records (no # or prevalence given to define "high"); 2) a least 150 students in school; 3) not >1 h away by car from research centre; 4) teachers willing to cooperate in study; 5) no previous iron supplementation programme implemented. Subsequently 2 schools selected.

397 school age children in grades 1-6 (9.7 years of age in average), both sexes (212 females (53%)) only those with written parental consent included. Excluded those with severe Iron deficiency anaemia (Hb equal or lower than 80 g/L and serum ferritin equal or lower than 20 μg/L) severe malnutrition weight-for-height <3rd percentile of Thai reference, chronic illness such as thalassaemia, haemolytic disease and physical handicaps. Participants assigned to group stratified by anaemia status. Baseline prevalence of anaemia:˜ 35%. This study took place in a socioeconomically disadvantaged community.


InterventionsParticipants were allocated to one of the following groups:

Group1 (n = 134): each child received 2 bottles with tablets, the first was to be taken on Monday only while the second was to be taken for the remaining days of the week (60 mg of elemental iron (as ferrous sulphate) weekly;

Group 2 (n = 140): each child received 2 bottles with tablets, the first was to be taken on Monday only while the second was to be taken for the remaining days of the week. Both bottles had 60 mg of elemental iron (as ferrous sulphate) daily);

Group 3 (n = 123): Same procedure as groups 1 and 2 but children received placebo. The tablets were similar in colour, shape, size, and taste as the iron tablets.

Length of the intervention: 16 weeks


OutcomesHaemoglobin, serum ferritin, mean changes of both, height, weight.


NotesThis area is free from malaria


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskChildren were stratified by anaemic status to balance the proportion of anaemic and non anaemic children across the intervention groups. The children were then assigned by simple random allocation within each stratum using a computer random number generator.

Allocation concealment (selection bias)Low riskTablets placed in packages labelled only with participants' name, content not known to any of the project personnel. 2 supplement packages similar in appearance: On Mondays received one packages which contained iron for daily and weekly group, but placebo for control group. Rest of week consumed tablets from other package, which were iron for daily group and placebos for weekly and placebo control group.

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants: neither parents nor participants knew the content of supplement packages.

Personnel: researchers did not know the content of supplement packages.

Outcome assessors: not reported but probably blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskOnly 6 of 397 enrolled lost to follow-up.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasUnclear riskBaseline prevalence of anaemia was different among study arms (39, 40 & 28%, for daily, weekly and placebo, respectively), but haemoglobin concentrations were not statistically different.

Tavil 2003

MethodsRandomised clinical trial. 2-arm design with randomisation at individual level.


Participants94 children aged 5 months to 6 years (median age was 18 months of age), both sexes (35 females (37.2%)), attending Dr Sami Ulus Children's Hospital in Ankara, Turkey, from December 1999 to December 2000. Inclusion criteria: iron deficiency anaemia (defined as haemoglobin (Hb) levels below 100 g/L, transferrin saturation levels below 12%, and ferritin levels below 12 ng/mL) and negative supplement intake during the past 3-4 weeks. Exclusion criteria: chronic, metabolic, and genetic diseases. Socioeconomic status not described.


InterventionsParticipants were randomly allocated to one of the following groups:

Group 1 (n = 48): children received daily 6 mg/kg of elemental iron as ferrous sulphate;
Group 2 (n = 46): children received 6 mg/kg of elemental iron as ferrous sulphate 2 days a week (Tuesday and Friday) (120 mg of iron per week). .

Twenty-three healthy children whose age and gender distribution were compatible with the other groups were included in the study as the control group. This group was not included in the analyses.

Length of the intervention: 2 months


OutcomesHaemoglobin, hematocrit; red blood cell count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, iron deficiency anaemia, serum iron, serum iron binding capacity, transferrin saturation, transferrin.


NotesMalaria endemicity not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskParticipants were randomly divided into two groups. Method of sequence generation not described.

Allocation concealment (selection bias)Unclear riskNot described.

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants: not reported.

Personnel: not reported.

Outcome assessors: not reported.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskIt is unclear the final number of participants per group. The report mentions that 'thirty three patients who had not been regularly conforming to the iron deficiency treatment as recommended or who were intolerant to the medication due to the side effects were excluded from the study. The patients presenting no increase in the Hb levels despite the iron treatment were reevaluated at the end of the first month, and those who were detected as thalassaemia traits were also excluded.' The tables do not present the final numbers.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasUnclear riskIt is unclear the failure rate of the intervention and whether the results are biased because of the exclusions.

Taylor 2001

MethodsDouble-blind randomised controlled trial. Factorial design (6 arms) with individual randomisation.


Participants425 children, both sexes (50% females), aged 6 -15 years (mean age 11.2 years), attending three rural primary schools in Kwa-Zulu Natal, South Africa.The sample was stratified by school, age and sex. Four children with anaemia were included in the study (Hb < 80 g/L) - all of these children were allocated to receive iron. Females over 12 years of age were excluded as the safety of albendazole in pregnancy has not been established. Socioeconomic status not reported although it was stated that the study was carried out in the third poorest province in South Africa. Anaemia at baseline was 35%.


InterventionsChildren were allocated to 1 of the following groups:

Group 1 (n = 56): children received 400 mg of albendazole weekly, 40 mg/kg of praziquantel weekly, and 65 mg of elemental iron (as 200 mg ferrous fumarate) plus 100 μg (0.1 mg) of folic acid weekly;

Group 2 (n = 60): children received 400 mg of albendazole weekly, 40 mg/kg of praziquantel weekly, and placebo for iron and folic acid weekly;

Group 3 (n = 60): children received 400 mg of albendazole for three days, 40 mg/kg of praziquantel weekly, and 65 mg of elemental iron (as 200 mg ferrous fumarate) plus 100 μg (0.1 mg) of folic acid weekly;

Group 4 (n = 57): children received 400 mg of albendazole for three days, 40 mg/kg of praziquantel weekly, and placebo for iron and folic acid weekly;

Group 5 (n = 101): children received placebo for albendazole, placebo for praziquantel and 65 mg of elemental iron (as 200 mg ferrous fumarate) plus 100 μg (0.1 mg) of folic acid weekly;

Group 6 (n = 91): children received only placebos.

For the purposes of this review only groups 5 and 6 were analysed.

Length of the intervention: 10 weeks, children were followed up for a year with measures at baseline, 6 months and 12 months.


OutcomesHeight, weight, full blood count, anaemia (could not be extracted), presence of malarial parasites, presence of hookworm infection, urine infection or presence of blood in urine.


NotesAll groups received interventions under supervision by teachers

It was reported that the area is endemic for malaria, schistosomiasis and hookworm.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised controlled trial, with individual randomisation. 6-arm trial (factorial design). Sample stratified by school, age and sex. Method of sequence generation not described.

Allocation concealment (selection bias)Low riskEach pupil’s treatment was individually packaged at each phase of the study. Both the field team and pupils were blinded as to the type of drugs used.

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants: all pupils were blinded to the type of supplement used.

Personnel: field team were blinded to the type of supplement used.

Outcome assessors: not reported.

Incomplete outcome data (attrition bias)
All outcomes
High risk428 children entered the study. 4 children who were anaemic at baseline were all allocated to receive iron treatment. It was stated that intention to treat analysis was not carried out as data was missing for children who were absent from school on the day specimens were collected. It was stated that the sample sizes varied at each phase of the study. There was considerable variation in the size of treatment groups - it was not clear why. The numbers available at each assessment point and missing data were not stated. The number with data on Hb at both 6 and 12 months follow up was 275 (64% of the original sample).

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasHigh riskIt was stated that groups were similar at baseline for prevalence of anaemia and other variables. Although the figure suggests there was considerable variation in mean Hb levels at baseline - although the differences between groups were not significant. Children with anaemia all received iron. The lack on information on attrition and missing data mean that results are difficult to interpret.

Thu 1999

MethodsDouble-blind, placebo-controlled trial. 2-arm design with randomisation at individual level.


Participants68 children, both sexes (88 females (54%)) 6–24 months of age, living in the Chi Lang Bac commune, Thanh Mien district, Hai Duong province in Vietnam. Exclusion criteria: infectious disease at the time of enrolment and a birth weight < 2.5 kg according to the birth record. Baseline prevalence of anaemia: ˜50%. Socioeconomic status not reported.


InterventionsParticipants were allocated to one of the following groups:

Group 1 (n = 55): children received daily 8 mg elemental iron (as ferrous sulphate), 5 mg elemental zinc(as zinc sulphate), 333 mg retinol, and 20 mg vitamin C 5 d/wk for 3 mo;

Group 2 (n = 54): children received 20 mg elemental iron (as ferrous sulphate), 17 mg zinc, 1700 mg retinol, and 20 mg vitamin C once a week (Thursdays); the rest of the week were given a placebo;

Group 3 (n = 54): children received a placebo Monday to Friday that was similar in colour and appearance to the supplement.

Length of the intervention: 12 weeks.


OutcomesHaemoglobin, serum retinol, zinc. weight and length (score z, measured 3 mo after the intervention ceased).


NotesThe syrup was put into the children’s mouth by syringe by a research staff member who visited the children daily between 0700 and 1000.

Before the start of the study, the acceptability of the syrup was tested in 12 children. Mothers of these children reported good acceptance and no side effects. Acceptability throughout the study remained good, and the children took all of the supplements as intended.

Z-scores used the National Center for Health Statistics data as a reference.

Malaria endemicity not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskChildren were randomly divided into 3 groups by using a table with randomly assorted digits.

Allocation concealment (selection bias)Low riskBlind supplementation was guaranteed by coding the 3 treatment groups as A, B, and C and by putting the syrups to be used for each group in bottles having a corresponding code. Neither the main researcher and his assistants nor the
mothers knew which supplement was represented by which code

Blinding (performance bias and detection bias)
All outcomes
Low riskBlind supplementation was guaranteed by coding the 3 treatment groups as A, B, and C and by putting the syrups to be used for each group in bottles having a corresponding code.

Participants: children received a placebo similar in colour and appearance to the supplement

Personnel: Neither the main researcher and his assistants nor the mothers knew which supplement was represented by which code.

Outcome assessors: Neither the main researcher and his assistants nor the mothers knew which supplement was represented by which code.

Incomplete outcome data (attrition bias)
All outcomes
Low riskOf the 168 children enrolled at baseline, complete data sets were available for 163 children for anthropometric data and for 160 children for biochemical data. Reasons for attrition included families’ moving to other places (n=3), mothers’ refusing further participation because of time limitations (n=2), and fear of blood collection (n=3).

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasLow riskThe study appears to be free of other sources of bias.

Verhoef 2002

MethodsDouble-blind, placebo-controlled trial. 2x2 factorial design with randomisation at individual level.


Participants328 children, both sexes (148 females (45%)), aged 2–36 months. The study was done during rainy seasons in the period 1998–2000 in Mtito Andei Division, Eastern Province, Kenya.

Children were randomly sampled. At screening, children were judged eligible for the study when they met the following criteria: the haemoglobin concentration was 60–110 g/L (anaemic); the axillary temperature was below 37·5C; there were no symptoms suggestive of malaria or anaemia, or any systemic illness occurring in combination with a blood dipstick test result indicating current or recent malarial infection; the parents intended to stay in the study area during the intervention period and gave their consent; no allergy to sulfa drugs was reported; and no sulfa drugs had been used in the previous 3 weeks. Children with a positive malaria dipstick test result but without symptoms of systemic illness were included.


InterventionsParticipants were randomly assigned to one of four groups

Group 1 (n = 82): children received intermittently sulphadoxine-pyrimethamine and iron supplement of 6 mg elemental iron (as ferrous fumarate) per kg body weight weekly (approximately 65 mg of elemental iron per week);

Group 2 (n = 82): children received intermittently sulphadoxine-pyrimethamine and iron placebo;

Group 3 (n = 82): children received intermittently sulphadoxine-pyrimethamine placebo and iron supplement of 6 mg elemental iron (as ferrous fumarate) per kg body weight weekly (approximately 65 mg of elemental iron per week);

Group 4 (n = 82): children received intermittently sulphadoxine-pyrimethamine placebo and iron placebo.

Iron was administered twice per week as ferrous fumarate in a suspension at a target dose of

Length of the intervention: 12 weeks

For the purposes of this review, groups 1 and 3 were combined (iron) and compared with the combination of groups 2 and 4 (no iron).


OutcomesMalaria attacks, adverse drug reactions, anaemia, iron deficiency, serum ferritin (could not be extracted) and difference in mean haemoglobin change from that of placebo (we calculated final haemoglobin concentrations).


NotesSulphadoxine-pyrimethamine was administered by the clinical officer employed by the project once every 4 weeks at therapeutic doses. Iron was administered by community health-workers.

Children in all groups were under intense health surveillance throughout the intervention period.

Malaria transmission is highly seasonal in this area


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskBalanced block randomisation (41 blocks). The allocation schedule was generated by one of the researchers for each block, by means of tables with randomised permutations, and only after acceptance of all children making up a block.

Allocation concealment (selection bias)Low riskThe order of the children listed in each block was concealed from the person generating the allocation schedule. Both placebos and active compounds were administered as suspensions that were indistinguishable in taste and appearance. Bottles were colour-coded, but none of the field
investigators was aware of the code until after crude analysis and a plan for further analysis had been prepared.

Blinding (performance bias and detection bias)
All outcomes
Low riskSee above.

Incomplete outcome data (attrition bias)
All outcomes
Low riskOf 328 children undergoing randomisation, 307 (94%) completed the trial and 21 (6%) did not (migrated or moved temporarily from the study area, 13; parents withdrew consent, three; developed severe anaemia, one; died, one; developed malaria but treated elsewhere, one; unknown reasons, two). Balanced losses to follow-up.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasLow riskThe study appears to be free of other sources of bias.

Yang 2004 (C)

MethodsCluster-randomised trial. 3-arm trial with randomisation at classroom level.


Participants353 preschool children, both sexes 58 females (44.7%), aged 3–6 years, attending a kindergarten in Baotou City. Inclusion criterion: absence of major diseases, haemoglobin 90-140g/L.


InterventionsClassrooms were allocated to one of the following groups:

Group 1 (n = 120): children received tablets containing 30 mg elemental iron: 5 mg zinc, 300 μg vitamin A, 50 mg vitamin C: 7.5 μg vitamin D3, 150 μg (0.15 mg) folic acid five times every week (Monday to Friday);
Group 2 (n = 120): children received the same tablets as group 1 only once a week;
Group 3 (n = 113): children received a placebo similar in colour and appearance to the iron supplement tablets. Placebo was given daily

Length of the intervention: 14 weeks


OutcomesHaemoglobin, serum ferritin, erythrocyte protoporphyrin, iron deficiency (serum ferritin <30 μg/L), height-for-age Z-scores, weight-for-age Z-scores).


NotesStudy translated from Chinese. We attempted to contact the author to validate the extraction

Teachers and nurses received iron supplement tablets from kindergarten doctors and helped children to take the tablets with semi-liquid food. All groups have the same food in the kindergarten except for the tablets.

We adjusted the results of this study to account for the effect of clustering in data; the estimated effective sample size was used in the analyses. 

Malaria endemicity not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskChildren were randomly assigned to the treatment or the control according to their classroom. Method of sequence generation not described.

Allocation concealment (selection bias)Low riskEvery week, teachers and nurses received iron supplement tablets from kindergarten doctors and helped children to take the tablets. Since the intervention was allocated at classroom level, it is unlikely there was a selection bias at the individual level.

Blinding (performance bias and detection bias)
All outcomes
Low riskParticipants: children received a placebo similar in colour and appearance to the supplement

Personnel: Every week, teachers and nurses received iron supplement tablets from kindergarten doctors.

Outcome assessors: Unclear

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskLosses to follow up not reported.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasUnclear riskThe data was not adjusted by the effect of clustering.

Young 2001

MethodsRandomised controlled trial. 2-arm with individual randomisation after stratifying children by anaemia status.


Participants577 Malawian children, both sexes (sex distribution not reported), 15 and 60 months of age, were enrolled as they attended the mobile child health clinic in their area. Exclusion criteria:children with severe anaemia (Hb < 70 g/L). Baseline prevalence of anaemia: 83%. Socioeconomic status not reported.


InterventionsChildren were allocated to one of the following groups:

Group 1 (n = 73 at follow up): children received 60 mg of iron once a week;

Group 2 (n = 73 at follow up) children received 60 mg of elemental iron (as ferrous sulphate) plus 7500 IU vitamin A, 45 mg vitamin C, 600 IU vitamin D3, 3 mg vitamin B1, 1.5 mg B2 and 22.5 mg vitamin B3 once a week;

Group 3 (n = 85 at follow up): children received 60 mg of elemental iron (as ferrous sulphate) daily.

Groups 1 and 2 were combined and reported independently for the relevant subgroup analysis.

Length of the intervention: 12 weeks


OutcomesHaemoglobin concentration.


NotesAll children received treatment for hookworm at baseline with albendazole.

Adherence to the treatment, as reported by guardians along with a monthly tablet count, was similar in each group, approximately 52%. Reported adverse effects ranged from 2.7% to 9.4%, with the weekly iron/vitamin group reporting the least adverse effects and the daily iron group the most.

Malaria endemicity not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe children were stratified according to haemoglobin (Hb) levels (using the HemoCue) and then randomised. Method of sequence generation not described.

Allocation concealment (selection bias)Unclear riskSupplements were administered by guardian but unclear whether he/she was aware of which treatment was being administered

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants: Not reported.

Personnel: Not reported.

Outcome assessors: Not reported.

Incomplete outcome data (attrition bias)
All outcomes
High riskAttrition of 60% (n=346). No description of why more than half of the sample was lost to follow-up.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasLow riskThe study appears to be free of other sources of bias.

Yurdakok 2004

MethodsRandomised control trial. 3 arm design with individual randomisation.


Participants79 infants, both sexes (sex distribution not reported), 4 months of age at baseline, identified for potential enrolment at Hacettepe University Ihsan Dogramaci Children's Hospital Well Baby Clinic, Ankara Turkey. Inclusion criteria: 1) gestational age more than 37 weeks, 2) birthweight >2500g, 3) singleton birth, 4) no congential malformation,5) no perinatal disease, 6) breast milk as the only source of food on admission, 7) no history of iron supplementation or therapy, 8) no known hematologic disorder of mother-infant pairs, 9) mother intended to breasted exclusively until 6 months of age and to continue breastfeeding with introduction of complementary foods no earlier than 7 months of age. Infants or mothers with iron deficiency or iron deficiency anaemia identified at baseline were excluded from the study. Baseline prevalence of anaemia: unknown. Socioeconomic status not reported.


InterventionsInfants were randomised to one of the following groups:

Group 1 (n = 27): infants received daily 1 mg/kg/d iron (as ferrous sulphate);

Group 2 (n = 27): infants received 7 mg of iron/kg/week (as ferrous sulphate) every Tuesday. The whole dose was divided into three, but all iron was provided only once a week (approximately 45 mg of elemental iron per week);

Group 3 (n = 25): infants received no supplementation.

The dose was adjusted monthly according to infant's weight.

Length of the intervention: 3 months


OutcomesHaemoglobin, mean corpuscular volume, red cell distribution width, transferrin saturation, serum ferritin and adverse effects; Iron Deficiency or Iron Deficiency Anaemia are reported together.


NotesMothers gave supplement at home in morning one hour before breastfeeding (this seems difficult to control/estimate, as it seems to assume there is no night nursing or on demand feeding).

Malaria endemicity not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised trial. Method of sequence generation not described.

Allocation concealment (selection bias)Unclear riskNot reported.

Blinding (performance bias and detection bias)
All outcomes
High riskParticipants: Not reported.

Personnel: Not reported.

Outcome assessors: Not reported.

Incomplete outcome data (attrition bias)
All outcomes
Low risk12 of 79 (15%) did not finish the study. 3 mothers withdrew from the study. Mothers that introduced complementary foods early or gave other milks (not breast milk) were removed from study (n=5), non-compliance for iron supplementation were removed from the study (n=2). Infants who contracted infectious disease were removed (n=2). Withdrawns did not significantly differ across three groups. No differences at baseline between those who completed the study and those who did not.

Selective reporting (reporting bias)Unclear riskThere is insufficient information to permit judgement.

Other biasLow riskThe study appears to be free of other bias.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Agarwal 2003Prospective study conducted in government schools in Northeast Delhi. 2088 adolescent females participated in the study, with 702 females receiving daily iron-folate supplementation, 695 females on weekly iron-folate supplementation and 691 females serving as controls. The authors concluded that though the weekly regimen took longer, it was as effective and practical as daily regimens in raising haemoglobin levels.

This study was excluded because the authors looked only at adolescent females, which is out of the scope of this review.

Ahmed 2001Randomised, double-blind, placebo-controlled study in a 2x2 factorial design conducted in urban Bangladesh. Female postmenarchal adolescent subjects were randomised to a placebo (for vitamin A and for iron/folic acid), vitamin A only, iron and folic acid only, and iron, folic acid and vitamin A weekly for 12 weeks. Haemoglobin concentrations were raised significantly more in response to iron and folic acid and iron, folic acid, and vitamin A when compared to vitamin A alone or to placebo.

This study was excluded because the study evaluated post-menarchal females specifically, which is out of the scope of this review.

Ahmed 2005Randomised double-blind clinical trial conducted in Bangladesh. Anemic (haemoglobin < 120 g/L) females (n=197) aged 14-18 y from rural schools in Dhaka District were entered into a randomised double-blind trial and received twice-weekly supplements of iron and folic acid or multiple micronutrients (15 micronutrients, including iron and folic acid) for 12 wk. In conclusion, twice-weekly MMN supplementation for 12 wk significantly improved the status of the micronutrients assessed but was not more efficacious than was supplementation with iron and folic acid alone in improving the hematologic status of anaemic adolescent females.

The study was excluded because the authors did not compare intermittent iron supplementation versus daily/placebo and hence the study is out of the scope of this review.

Avila-Jimenez 2011Randomised trial conducted in Mexico City, Mexico. The trial included 1,699 healthy, at term, singleton babies during their first year of life and excluded those with low weight at birth, unknown gestational age, bleeding disorder or any other medical conditions that may be associated with anaemia (i.e., malabsorption).

Children were randomly assigned to receive a daily, weekly (7 mg/dose) or monthly dose of supplements containing 30 mg elemental iron (as either ferrous sulphate or aminochelate iron), for one year.

The study was excluded because the authors compared two intermittent iron supplementation regimens and such comparison is out of the scope of this review.

Azeredo 2010A prospective population study performed in the city of Viçosa, Southeastern Brazil, in 2007-8. A total of 103 non-anaemic children, aged between six and 18 months of age, were included and divided into two supplementation groups: daily dosage (group 1, n=34) and weekly dosage (group 2, n=69). After six months of supplementation, the daily dosage was found to be more effective than the weekly scheme to prevent anaemia in infants.

The study was excluded because it was not randomised.

Beasley 2000Single-blind randomised trial performed in three rural villages of the Muheza district of Tanzania. Females between the ages of 12-18 were randomised to a treatment 12 doses of ferrous sulphate or a control of 12 doses of vitamin B12 over the 16 weeks following anti-helminthic treatment. The use of a strict placebo was not allowed due to ethical reasons. The authors found a significantly greater improvement in serum ferritin in the iron supplemented group but no significant differences in haemoglobin when compared to the control group.

This study was excluded because the study evaluated adolescent females which is out of the scope of this review.

Briars 2003Randomised clinical trial performed in Dunedin, New Zealand. Free-living healthy adult women of childbearing age (n=138) were randomised to receive a 2,800 μg (2.8 mg) folic acid weekly, a daily 400 μg (0.4 mg) folic acid supplement, or placebo. Authors found that a weekly high-dose folic acid supplement was as effective as a daily supplement in lowering homocysteine concentrations.

The study was excluded because vitamin and minerals were given as foodlets and they are out of the scope of this review.

Februhartanty 2002Single-blind experimental community study carried out in Kupang, East Nusa Tenggara, Indonesia. Postmenarchal adolescent females (n=150) were randomised to weekly iron supplementation, placebo, or supplementation during 4 consecutive days of their menstrual cycle. The authors found that weekly iron supplementation for 16 weeks led to a greater improvement in haemoglobin concentration, compared with supplementation during four consecutive days of menstruation.

This study was excluded because supplementation was administered to only postmenarchal adolescent females which is out of the scope of this review.

Hafeez 1998Randomised trial conducted at Combined Military Hospital (CMH), Lahore, Pakistan, from January 1996 to June 1996. 130 children aged 1-6 years (average 27 months), both sexes, with iron deficiency anaemia (Hb 110 g/L) were divided into 2 subgroups, group A in which children received daily oral dosage of 6 mg/kg of elemental iron as ferrous gluconate and group B, in which children received the same dosage of iron on three consecutive days per week. The intervention lasted 2 months. Haemoglobin and ferritin concentrations increased in both groups with no differences between them.

The study was excluded because the intermittent supplements were given on consecutive days.

Hop 2005Randomised, double-blind, placebo-controlled trial conducted in Vietnam. Infants aged 6-12 mo (n=138) were allocated to one of the following groups: daily multiple micronutrient, daily placebo, weekly multiple micronutrient, or daily iron supplements. All were supplemented for 6 mo, 7 d/wk, under supervision. DMM supplementation had the best overall performance of the micronutrient supplements tested; it reduced the rate of length–growth faltering and had the best hematinic effect.

The study was excluded because vitamin and minerals were given as foodLETs and they are out of the scope of this review.

Jackson 2003The objectives of this study were to ascertain whether, short-term supplementation with iron and folic acid could reduce anaemia and iron deficiency, and be well tolerated by adolescent females over an 8-week period. It included 608 postmenarchal adolescent schoolgirls with mild to moderate anaemia. The females were randomly assigned to three groups (iron alone, folic acid alone, and iron with folic acid) and given weekly supplements for eight weeks. Iron and folic acid tablets contained 60 mg elemental iron (as ferrous sulphate) and 3500 μg (3.5 mg) folic acid, respectively. A fourth group of females who had normal Hb concentrations and received no treatment was also included at baseline and after eight weeks.
Authors found that the females receiving iron (alone or in combination) had greater mean rise in Hb than females who received folic acid alone. Eight weeks of supplements given on a weekly basis were well tolerated, causing few symptoms and was effective in reducing anaemia by 30-40%.

The study was excluded because the control group was not randomised. Also the control group had normal Hb values while the females receiving the intervention were anaemic.

Jaleel 2004Prospective study that included 90 apparently healthy individuals. They were divided into 3 groups of 30 subjects each. First group comprised of male subjects of age between 25-45 years, second group was of postmenopausal women of age between 46-65 years and third group of reproductive age group that is between 15-45 years. Each group was further divided into 3 subgroups of 10 male subjects, 10 postmenopausal and 10 women of reproductive age groups. The first subgroup was given iron supplements (as ferrous
sulphate 300 mg) daily. The second subgroup received supplementation (as ferrous sulphate 300 mg) on weekly basis that is 6 times for 36 days and third subgroup received iron supplements in double dose (ferrous sulphate 600 mg) on weekly basis that is 6
times for 36 days. It was concluded, that 600mg of iron given on a weekly gave similar results as that of subjects receiving 300 mg on a daily basis.

This study was excluded because the populations assessed are out of the scope of this review.

Jayatissa 1999In Sri Lanka 36% of all adolescents have inadequate iron intakes. Daily and weekly iron supplementation of 659 adolescent schoolgirls, divided into three groups, was studied in an eight-week double-blind trial. One group received 60 mg of elemental iron, 250 μg (0.25 mg) of folic acid, and 100 mg of vitamin C daily. The second group was given the same doses on a weekly basis. The third group was given a placebo. All of the participants were de-wormed at the beginning of the study. Anaemia was more common among older adolescents. Haemoglobin levels increased significantly at the end of the study. The prevalence of anaemia was reduced from 25% to 9.5% by weekly supplementation and from 18.5% to 8.6% by daily supplementation. The difference in haemoglobin levels between the two groups receiving supplementation was not significant.

The study was excluded because it is not clear whether is randomised or not. Based on the methods the selection of participants was at random but not the allocation of the intervention.

Kanal 2005This was a community trial in which social marketing and community mobilization approaches were applied to introduce weekly iron-folic acid supplementation to prevent anaemia in Cambodian women of reproductive age. The programme was implemented in three very different environments: secondary schoolgirls, women working in garment factories in the vicinity of Phnom Penh, and women in rural villages. All three groups of women showed substantial improvements in knowledge about the causes, consequences, and prevention of anaemia, and the large majority reported interest in continuing to take the supplements.

The study was excluded because it was not randomised.

Kapur 2003A community-based trial that compared the effect of nutrition education and/or iron supplementation (weekly) on iron status of 400 children, 9-36 months, living in an urban slum in Delhi.

Children and care takers were selected by using a random number table. Children were assigned to one of the following groups. Group 1, received nutrition education. Group 2, received supplements with 20 mg elemental iron. Group 3, received nutrition education with supplementation with 20 mg elemental iron and Group 4, control given placebo.

To ensure objectivity and to avoid spill over effect, specifically with respect to nutrition education, caution was maintained in forming groups and allocation of subjects therein. Subjects from the Anganwadis in Block A (A1, A2, A3 and A4) and Block B (including B1, B2, B3, B4, B5 and B6) (which were more or less adjoining) were allocated to experimental groups 3 (NE+ S) and 4 (NE), where nutrition education was a component.  Control and Experimental group 2 (supplementation group), on the other hand, included subjects from Block C (including C1, C2 and C3),  Block D (including D1, D2 and D3) and  Block E (including E1, E2, E3, E4 and E5) which are situated at a distance of about 1 - 2 Km  from the Experimental groups 3 and 4 (information provided by the author).

The intervention program was of four months duration, with a treatment phase of 8 wk followed by 8 wk of no treatment.There was no significant effect of any of the intervention at 8 weeks. At 16 wk, there was significant positive effect of nutrition education group (p less than 0.05).

This study was excluded because the allocation was not at random.

Kianfar 2000A randomised trial comparing the effects of daily and intermittent iron supplementation regimens in adolescent schoolgirls in the areas of Zahedan and Rasht, Iran. 1853 subjects were selected by stepwise random sampling and randomised to a daily group, supplemented with 50 mg elemental iron per day, a once weekly group supplemented with 50 mg elemental iron and a twice weekly group, also supplemented with 50 mg elemental iron. The authors concluded that the once and twice weekly regimens were effective in treating anaemia but that the daily schedule was more effective at increasing iron stores than a weekly dose in the short-term.

This study was excluded because it evaluated adolescent females which is out of the scope of this review.

Lechtig 2006This paper is one of a series of papers that describes the experiences of a multiple micronutrient intervention programme implemented in poor urban mothers and their young children of Chiclayo, Peru. It summarizes the lessons learned for consideration of future programming.

The study was excluded because the authors gave foodlets and that intervention is out of the scope of this review.

Leenstra 2009A double-blind, randomised controlled study using a factorial design carried out in primary schools in Kisumu, Western Kenya. The study aimed to evaluate the effect of weekly iron and vitamin A supplementation on haemoglobin, iron status,and malaria and non-malaria morbidity in adolescent schoolgirls. Weekly iron supplementation was found to greatly increase haemoglobin levels in menstruating and iron-deficient females but not in iron-replete and non menstruating females.

This study was excluded because it looked only at adolescent school females between the ages of 12-18 years which is out of the scope of this review.

Lima 2006A controlled, community-based intervention was carried out with 378 infant to evaluate the impact of weekly treatment with ferrous sulphate on haemoglobin level, morbidity and nutritional status in a sample of anaemic infants from Zona da Mata Meridional in the state of Pernambuco, Brazil. Participating infants were divided into three groups: two received 45 mg of elemental iron weekly, from 12 to 18 months of life (69 children with moderate/severe anaemia, and 111 with mild anaemia); the third group was composed of 65 non-anaemic children, who received no intervention. The remaining 133 children constituted the control group. Less than half the children receiving ferrous sulphate recovered from anaemia at the end of follow-up while 40.3% of the children without anaemia at baseline, who did not receive treatment, developed anaemia.

The study was excluded because it was not randomised.

Lin 2001270 rural preschool children aged 3-7 years with low levels of vitamin A and iron living in Beijing, China. Participants were divided into four groups based on their determinations: control, lower serum vitamin A, lower iron, and both lower iron and serum vitamin A. Forty-one subjects who had lower iron and lower serum vitamin A (< 1.12 mumol/L) were divided into two groups: one of them supplemented with 30 mg elemental iron (as ferrous sulphate 0.15 g) once a day for 8 weeks, and the other group supplemented with iron and 12,500 IU vitamin A twice a week for 8 weeks. Authors concluded that supplementation with vitamin A and iron was helpful to improve body iron nutritional status and immunological function obviously in preschool children with iron-deficiency and sub-clinical deficiency of vitamin A.

The study was excluded because the daily and weekly groups did not receive the same nutrients.

López de Romaña 2005Randomised, double-blind, masked, controlled trial conducted in Peru. Infants aged 6 to 12 mo (n=313) were assigned to receive either a daily dose of iron, a daily dose of multiple micronutrients, a weekly dose of multiple micronutrients, or a placebo for 6 mo. None of the supplements tested prevented growth faltering or the morbidities common during infancy. The daily multiple micronutrient intervention was the most efficacious for preventing anaemia, iron, and zinc deficiencies, 15%, 20%, and 50% of this group still remained anaemic, zinc deficient, and iron deficient, respectively, at the end of the study.

The study was excluded because vitamin and minerals were given as foodLETs and they are out of the scope of this review.

López de Romaña 2006Randomised community trial undertook in 26 Peruvian communities with stunting rates above the average. Households were selected if they had at least one child under 5 years of age and at least one woman or adolescent females of childbearing age (12 through 44 years). A total of 866 households (448 in the intervention group and 418 in the comparison group-unclear) were selected. Women received Nutrivit capsules while children received Foodlets. Authors concluded that weekly supplementation with multi-micronutrients had a protective effect on the haemoglobin levels of both women and adolescent females of childbearing age and children under 5 years of age.

The study was excluded because vitamin and minerals were given as foodlets and they are out of the scope of this review.

Menendez 1997Randomized clinical trial in Tanzania. Newborns (n=832) were randomly assigned to group DI, receiving daily oral iron (2 mg/kg daily) plus weekly Deltaprim (3.125 mg pyrimethamine plus 25 mg dapsone); group IP, receiving iron plus weekly placebo; group DP, receiving daily placebo plus weekly Deltaprim; or group PP. supplementation was given from 8 to 24 weeks of age, and the weekly chemoprophylaxis from 8 to 48 weeks. The groups that received iron supplementation had a lower frequency of severe anaemia.

The study was excluded because only the malaria prophylaxis was given on a weekly basis.

Mwanakasale 2009Placebo-controlled intervention trial conducted in Nchelenge district in Luapula province of Zambia. Children between 9 and 15 years of age received once a week either 200 mg of ferrous sulphate or 100 mg of vitamin C. Both study groups received a single dose of praziquantel at baseline and the follow-up lasted 9 months.

The study was excluded because it was not randomised.

Perrin 2002It is a commentary paper on Shah 2002.

Risonar 2008242 Filipino schoolchildren aged 6–12 years with haemoglobin (Hb) concentration <120 g/L and enrolled for school year 2003–2004. UNICEF iron-folate tablets containing 60 mg elemental iron and 400 μg (0.40 mg) folic acid were given weekly through directly observed supplementation by the teachers for 27 weeks. The intervention reduced anaemia prevalence among anaemic schoolchildren and resulted in high compliance to and coverage of iron supplementation.

The study was excluded because it does not have a control group.

Rivera 1998Report that presents the results of a regional program providing weekly iron supplements to school-age children attending 30 schools, between 1995 and 1997, in Chiriqui, Panama,

This study was excluded because the study design (pre-post without a control group) is out of the scope of this review.

Schümann 2009Randomised doubly-masked, placebo-controlled trial undertook in Cambodia. Children aged 6-24 months (n= 250) received twice-weekly administration of 3 RDAs of iron and folic acid, with and without a complement of 2 RDAs of 11, and 1 RDA of 3 additional essential micronutrients as compared to a placebo control (PlbCON) given as foodLETs. Supplementation of micronutrients along with iron and folic acid mitigates the excess morbidity of iron-folate alone, without reducing its efficacy in correcting anaemia and building iron stores.

The study was excluded because vitamin and minerals were given as foodLETs and they are out of the scope of this review.

Shah 2002Randomised-controlled trial of healthy adolescent females in government female schools of Dharan, Nepal. The study aimed to compare the effectiveness of weekly versus daily iron folate supplementation. Females (n=209) were randomised to either a daily iron-folate group, a weekly iron-folate group, or a placebo group which did not receive any tablets. The authors concluded that once weekly iron folate supplementation was an effective alternative to daily regimens.

The study was excluded because it evaluated only adolescent females which is not in the scope of this review.

Sharma 2000Randomised experimental trial of adolescent females in poor communities in urban areas of Delhi and rural parts of Rajasthan. Subjects were randomised to either daily iron folate supplementation, weekly iron folate supplementation or weekly iron folate with vitamin C. The authors concluded that the response of haemoglobin levels was greater following daily iron folate supplementation when compared to weekly iron supplementation, but that the addition of vitamin C led to greater increases in haemoglobin than administration of iron and folate alone.

This study was excluded because it evaluated only adolescent females which is out of the scope of this review.

Shobha 2003Randomised trial of 244 adolescent females at an Andhra Pradesh residential social welfare school in the Ranga Reddy district of India. Females were stratified by anaemia status and then randomly assigned to either a daily or twice weekly supplementation regimen. Supervised administration of iron twice weekly was found to be similarly advantageous as daily supplementation in this population.

This study was excluded because it evaluated only adolescent females which is out of the scope of this review.

Smuts 2005Randomised trial undertook in South Africa. Infants aged 6-12 mo (n=265) were individually randomised to 1 of 4 intervention groups a daily multiple micronutrient supplement, a daily placebo supplement; a multiple micronutrient supplement 1 d of the week and placebo supplement on the other days of the week, and a daily iron supplement . For 6 mo, the blinded supplements were provided to mothers at monthly health clinic sessions, and consumption was verified during weekly household visits by community health workers, when morbidity was also checked. The DMM was the most effective intervention tested, not only for improving anaemia but also for improving iron, zinc, riboflavin, and tocopherol status.

The study was excluded because vitamin and minerals were given as foodlets and they are out of the scope of this review.

Soekarjo 2004A school-based grade-randomised intervention was conducted in rural and urban, East Java, Indonesia among adolescents. 1757 females and 1859 males were randomised to weekly supplementation (650 mg iron, 250 μg (0.25 mg) folic acid), weekly vitamin A supplementation (10,000 IU), or both, were compared to a group not receiving any supplements. Weekly iron supplementation was not effective at raising haemoglobin levels, likely due to poor compliance and side effects.

This study was excluded because it evaluated an exclusively adolescent population, which is out of the scope of this review.

Sotelo-Cruz 200220 anaemic children aged 2 to 5 years living in Hermosillo, Mexico. Group A received oral ferrous sulphate twice a day whereas group B received the some dose per kilogram of weight like that of group A once a week for three months. Haemoglobin concentrations improved in both groups.

The study was excluded because it is not randomised.

Tee 1999Study that investigated whether long-term, weekly iron folate supplements administered at school would improve haemoglobin and ferritin concentrations in adolescent females, including those with mild-to-moderate anaemia and haemoglobin concentrations indicating borderline anaemia. 266 females with haemoglobin concentrations of 80–119.9 g/L (group A) and 358 females with haemoglobin concentrations of 120–130 g/L (group B) who were otherwise healthy. Two hundred sixty-six females in group A and 268 females in group B were randomly assigned to receive either 60 or 120 mg iron plus 3500 μg (3.5 mg) folic acid weekly for 22 wk. Ninety of the females in group B were randomly assigned to receive only 5000 μg (5 mg) folic acid weekly. Authors concluded that long-term, weekly iron-folate supplementation was found to be a practical, safe, effective, and inexpensive method for improving iron nutrition in adolescent schoolgirls.

Study was excluded because children in both arms were given iron on a weekly basis. Group C did not receive supplements but was not followed up.

Tomashek 2001Randomised double-blind study, in which 215 anaemic children, initially treated for malaria and helminth infection, received 12 weeks of thrice-weekly oral iron and folic acid. Group I received placebo and chloroquine treatment for symptomatic malaria infection (i.e., no presumptive anti-malarial treatment given). Group II received placebo and monthly presumptive treatment with sulphamethoxazole-pyrimethamine (SP). Group III also received
monthly SP and thrice-weekly vitamins A and C (VAC). Mean haemoglobin concentration increased from 66 to 102 g/L, with no significant differences among groups.

Study was excluded because all the participants were given iron and folic acid on a weekly basis.

UNICEF 2006Report that presents the results of a National program providing weekly iron supplements (ferrous fumarate) to infants and pregnant women living in priority districts in the Republic of Panama.

This study was excluded because the study design (pre-post without a control group) is out of the scope of this review.

Vir 2008Study performed in school and non-school females aged 11 to 18 years that aimed to assess the effectiveness of weekly iron-folic acid supplementation in reducing the prevalence of anaemia in adolescent females. The project provided weekly iron-folic acid tablets, family life education, and deworming tablets every 6 months to 150,700 adolescent school females and non-school females of a total district population of 3,647,834. Groups were not evaluated simultaneously. In 4 years, the overall prevalence of anaemia was reduced from 73.3% to 25.4%. Hemoglobin levels and anaemia prevalence were influenced significantly at 6 months. No difference in the impact on haemoglobin or anaemia prevalence was observed between supervised and unsupervised females.

The study was excluded because it was not randomised.

Wijaya-Erhardt 2007A double-blind, randomised, placebo-controlled trial. Indonesian infants.
aged 6–12 mo were randomly allocated to 1 of 4 groups: daily multiple-micronutrients food like tablets (foodlets), weekly multiple-micronutrient foodlets, daily iron foodlets, or daily placebo Data were obtained at baseline and 23 wk. DI and daily multiple-micronutrients foodlets are efficacious in improving and weekly multiple-micronutrient is efficacious in maintaining iron stores.

The study was excluded because vitamin and minerals were given as foodlets and they are out of the scope of this review.

Zavaleta 2000A randomised, double-blind, placebo-controlled study conducted among adolescent school females in Lima, Peru. 312 adolescents females were randomly assigned to either 60mg ferrous sulphate Mon-Friday (daily), 60 mg of ferrous sulphate twice weekly with placebo 3 times per week, or a placebo five days per week. Both iron supplementation regimens were found to be effective at reducing iron deficiency and the daily supplementation schedule was found to be more effective at raising haemoglobin concentration and reducing anaemia.

This study was excluded because it evaluated adolescent females which is out of the scope of this review.

 
Characteristics of studies awaiting assessment [ordered by study ID]
Husseini 1999

MethodsCluster-randomised trial. 2-arm design with randomisation at village level.

Participants822 children, both sexes, 5 to 26 months (average age 17.5 months). Inclusion criterion: haemoglobin <90 g/L

InterventionsVillages were allocated to one of the following groups>

Group 1: children received 20 mg of iron daily;

Group 2: children received 25 mg of iron once a week;

Length of the intervention: 18 months with visits every 4 weeks.

Intervention supervised and unsupervised.

OutcomesAnaemia, haemoglobin, ferritin

NotesInformation obtained from Beaton 1999

Kargarnovin 2010

MethodsRandomised trial. 2-arm design with individual randomisation.

Participants160 anaemic infants, both sexes, 6-24 months living in the South of Tehrna, Iran.

InterventionsChildren were allocated to one of the following groups:

Group 1 (n=80): children were given daily containing 40 mg of elemental iron (as ferrous sulphate);

Group 1 (n=80): children were given 40 mg of elemental iron (as ferrous sulphate) once a week on Friday mornings.

Length of the intervention: 6 months.

OutcomesHaemoglobin, erythrocyte volume, total iron binding capacity, transferrin saturation, serum transferrin

NotesArticle written in Farsi. The author was contacted to obtain the information.

Figure 2 is not available in PDF and the author has been contacted to obtain this information.

The article concludes that weekly administration of iron compared with daily consumption seems superior due to similar effects, better compliance of mothers and lower costs for the treatment of anaemia in infants between 6 and 24 months

Reid 2001

MethodsDouble-blind randomised trial. 3 arm study with randomisation at individual level.

Participants125 Mexican preschoolers with low Hb, age 12-40 months of age

InterventionsParticipants were allocated to one of the following treatments:

Group 1: placebo

Group 2: iron (Fe),

Group 3: iron + B-12 (Fe+B-12), or

Group 4: multiple micronutrients (MM = iron, vitamin B12, vitamin B2, vitamin B6, vitamin A, vitamin E, folic acid zinc, cooper). Doses were 2 x RDA, 3 times/wk, under supervision.

Length of the intervention: 3 months

OutcomesAnaemia, haematocrit, ferritin, retinol, serum B12

NotesThis study has not been published. If the data is made available to us, we will include it in future updates of the review.

 
Characteristics of ongoing studies [ordered by study ID]
Zeeba Zaka-ur-Rab 2010

Trial name or titleA clinical trial to compare the effects of daily versus intermittent iron supplementation on markers of oxidative stress and anti-oxidant status in children with iron deficiency anaemia 

MethodsRandomised, controlled trial.

Method of generating randomisation sequence: random number table.

Method of allocation concealment: sequentially numbered, sealed, opaque envelopes

Blinding and masking:Outcome Assessor Blinded   

Participants150 children between 1-15 years of age with iron deficiency anaemia. Exclusion criteria: children with history of fever within last 4 weeks, acute or chronic medical disorders, hemolytic anaemia, haemoglobin <6gm%, patients receiving iron/vitamin/mineral supplements (including herbal drugs), blood transfusion within 8 weeks.

InterventionsIntervention: sodium feredetate: 6 mg/kg daily;

Control: sodium feredetate: 6 mg/kg on day 1 and day 4.

Length of the intervention: 8 weeks.

OutcomesChanges in malonyl dialdehyde, oxidized glutathione, superoxide dismutase, glutathione peroxidase, catalase, changes in hemo globin, serum ferritin, total iron binding capacity and serum iron.

Timepoint: 8 weeks 

Starting dateDate of first enrolment:  02-03-2009

Contact informationDr. Zeeba Zaka-ur-Rab  

Deptt. of Pediatrics, J.N. Med. College, A.M.U.

2, Wazir Manzil, Luxmibai Marg, 202 001 Aligarh, UTTAR PRADESH India 

Tel: 0571 -2402928

Email:  zzrab@yahoo.co.in

Notes

 
Comparison 1. Intermittent iron supplementation versus placebo or no intervention: children 0 - 12 years

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Anaemia (ALL)101824Risk Ratio (M-H, Random, 95% CI)0.51 [0.37, 0.72]

 2 Anaemia (by dose of elemental iron in the intermittent group)101824Risk Ratio (M-H, Random, 95% CI)0.51 [0.37, 0.72]

    2.1 25 mg or less/week
2157Risk Ratio (M-H, Random, 95% CI)0.15 [0.06, 0.37]

    2.2 Greater than 25 mg to 75 mg/week
61256Risk Ratio (M-H, Random, 95% CI)0.54 [0.37, 0.80]

    2.3 Greater than 75 mg/week
2411Risk Ratio (M-H, Random, 95% CI)0.71 [0.48, 1.04]

 3 Anaemia (by duration of the intervention)101824Risk Ratio (M-H, Random, 95% CI)0.51 [0.37, 0.72]

    3.1 0 to three months
51456Risk Ratio (M-H, Random, 95% CI)0.63 [0.49, 0.82]

    3.2 More than three months
5368Risk Ratio (M-H, Random, 95% CI)0.37 [0.14, 1.02]

 4 Anaemia (by type of compound)101824Risk Ratio (M-H, Random, 95% CI)0.51 [0.37, 0.72]

    4.1 Ferrous sulphate
91517Risk Ratio (M-H, Random, 95% CI)0.47 [0.30, 0.75]

    4.2 Ferrous fumarate
1307Risk Ratio (M-H, Random, 95% CI)0.61 [0.49, 0.74]

   4.3 Other
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 5 Anaemia (by anaemia status at baseline)101824Risk Ratio (M-H, Random, 95% CI)0.51 [0.37, 0.72]

    5.1 Anaemic
2424Risk Ratio (M-H, Random, 95% CI)0.30 [0.07, 1.38]

    5.2 Non-anaemic
164Risk Ratio (M-H, Random, 95% CI)0.78 [0.27, 2.31]

    5.3 Mixed/unknown
71336Risk Ratio (M-H, Random, 95% CI)0.59 [0.41, 0.85]

 6 Anaemia (by intermittent regimen)101824Risk Ratio (M-H, Random, 95% CI)0.51 [0.37, 0.72]

    6.1 One supplement a week
91517Risk Ratio (M-H, Random, 95% CI)0.47 [0.30, 0.75]

    6.2 Other intermittent regimen
1307Risk Ratio (M-H, Random, 95% CI)0.61 [0.49, 0.74]

 7 Anaemia (by sex)101824Risk Ratio (M-H, Random, 95% CI)0.55 [0.41, 0.73]

    7.1 Girls
1248Risk Ratio (M-H, Random, 95% CI)0.75 [0.59, 0.95]

    7.2 Boys
1253Risk Ratio (M-H, Random, 95% CI)0.81 [0.66, 1.00]

    7.3 Mixed/unknown
91323Risk Ratio (M-H, Random, 95% CI)0.46 [0.30, 0.70]

 8 Anaemia (by nutrient)101824Risk Ratio (M-H, Random, 95% CI)0.51 [0.37, 0.72]

    8.1 Iron alone
61074Risk Ratio (M-H, Random, 95% CI)0.48 [0.31, 0.74]

    8.2 Iron + folic acid
2593Risk Ratio (M-H, Random, 95% CI)0.83 [0.66, 1.03]

    8.3 iron + vitamin C
150Risk Ratio (M-H, Random, 95% CI)0.06 [0.00, 0.97]

    8.4 Iron + multiple micronutrients
1107Risk Ratio (M-H, Random, 95% CI)0.16 [0.06, 0.44]

 9 Haemoglobin (ALL)193032Mean Difference (IV, Random, 95% CI)5.20 [2.51, 7.88]

 10 Haemoglobin (by by dose of elemental iron in the intermittent group)193032Mean Difference (IV, Random, 95% CI)5.20 [2.51, 7.88]

    10.1 25 mg or less/week
3324Mean Difference (IV, Random, 95% CI)8.19 [-4.01, 20.38]

    10.2 Greater than 25 mg to 75 mg/week
122059Mean Difference (IV, Random, 95% CI)5.45 [2.31, 8.58]

    10.3 Greater than 75 mg/week
4649Mean Difference (IV, Random, 95% CI)1.84 [0.25, 3.44]

 11 Haemoglobin (by duration of the intervention)193032Mean Difference (IV, Random, 95% CI)5.20 [2.51, 7.88]

    11.1 0 to three months
71616Mean Difference (IV, Random, 95% CI)5.16 [2.82, 7.51]

    11.2 More than three months
121416Mean Difference (IV, Random, 95% CI)5.13 [0.90, 9.36]

 12 Haemoglobin (by type of compound)193032Mean Difference (IV, Random, 95% CI)5.20 [2.51, 7.88]

    12.1 Ferrous sulphate
142288Mean Difference (IV, Random, 95% CI)5.57 [2.21, 8.92]

    12.2 Ferrous fumarate
2432Mean Difference (IV, Random, 95% CI)7.03 [3.36, 10.71]

    12.3 Other
3312Mean Difference (IV, Random, 95% CI)2.03 [-0.26, 4.33]

 13 Haemoglobin (by anaemia status at baseline)193032Mean Difference (IV, Random, 95% CI)5.20 [2.51, 7.88]

    13.1 Anaemic
2422Mean Difference (IV, Random, 95% CI)13.17 [3.07, 23.26]

    13.2 Non-anaemic
164Mean Difference (IV, Random, 95% CI)2.0 [-2.46, 6.46]

    13.3 Mixed/unknown
162546Mean Difference (IV, Random, 95% CI)4.35 [1.88, 6.82]

 14 Haemoglobin (by intermittent regimen)193032Mean Difference (IV, Random, 95% CI)5.15 [2.52, 7.79]

    14.1 One supplement a week
152256Mean Difference (IV, Random, 95% CI)5.61 [2.13, 9.09]

    14.2 Other intermittent regimen
5776Mean Difference (IV, Random, 95% CI)3.67 [1.05, 6.28]

 15 Haemoglobin (by sex)193032Mean Difference (IV, Random, 95% CI)5.17 [2.56, 7.77]

    15.1 Girls
1248Mean Difference (IV, Random, 95% CI)4.0 [0.83, 7.17]

    15.2 Boys
1253Mean Difference (IV, Random, 95% CI)3.70 [0.58, 6.82]

    15.3 Mixed/unknown
182531Mean Difference (IV, Random, 95% CI)5.31 [2.40, 8.22]

 16 Haemoglobin (by nutrient)193032Mean Difference (IV, Random, 95% CI)4.83 [2.25, 7.41]

    16.1 Iron alone
111699Mean Difference (IV, Random, 95% CI)4.41 [1.32, 7.50]

    16.2 Iron + folic acid
4756Mean Difference (IV, Random, 95% CI)3.36 [1.51, 5.21]

    16.3 iron + zinc
177Mean Difference (IV, Random, 95% CI)-1.60 [-8.09, 4.89]

    16.4 Iron + vitamin C
150Mean Difference (IV, Random, 95% CI)20.70 [17.51, 23.89]

    16.5 Iron + multiple micronutrients
4450Mean Difference (IV, Random, 95% CI)5.47 [0.32, 10.61]

 17 Iron deficiency (ALL)3431Risk Ratio (M-H, Random, 95% CI)0.24 [0.06, 0.91]

 18 Ferritin (ALL)5550Mean Difference (IV, Random, 95% CI)14.17 [3.53, 24.81]

 19 Ferritin (by dose of elemental iron in the intermittent group)5550Mean Difference (IV, Random, 95% CI)14.17 [3.53, 24.81]

    19.1 25 mg or less/week
1148Mean Difference (IV, Random, 95% CI)4.60 [-0.89, 10.09]

    19.2 Greater than 25 mg to 75 mg/week
4402Mean Difference (IV, Random, 95% CI)17.77 [8.21, 27.34]

   19.3 Greater than 75 mg/week
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 20 Ferritin (by duration of the supplementation)5550Mean Difference (IV, Random, 95% CI)14.17 [3.53, 24.81]

    20.1 0 to three months
135Mean Difference (IV, Random, 95% CI)15.80 [-1.23, 32.83]

    20.2 More than three months
4515Mean Difference (IV, Random, 95% CI)13.82 [1.84, 25.81]

 21 Ferritin (by type of compound)5550Mean Difference (IV, Random, 95% CI)14.17 [3.53, 24.81]

    21.1 Ferrous sulphate
4476Mean Difference (IV, Random, 95% CI)16.28 [4.68, 27.87]

   21.2 Ferrous fumarate
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    21.3 Other
174Mean Difference (IV, Random, 95% CI)2.46 [-14.37, 19.29]

 22 Ferritin (by anaemia status at baseline)5550Mean Difference (IV, Random, 95% CI)14.17 [3.53, 24.81]

   22.1 Anaemic
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    22.2 Non-anaemic
174Mean Difference (IV, Random, 95% CI)2.46 [-14.37, 19.29]

    22.3 Mixed/unknown
4476Mean Difference (IV, Random, 95% CI)16.28 [4.68, 27.87]

 23 Ferritin (by supplementation regimen)5550Mean Difference (IV, Random, 95% CI)14.17 [3.53, 24.81]

    23.1 One supplement a week
4497Mean Difference (IV, Random, 95% CI)10.14 [1.74, 18.53]

    23.2 Other intermittent regimen
153Mean Difference (IV, Random, 95% CI)27.80 [22.88, 32.72]

 24 Ferritin (by sex)5550Mean Difference (IV, Random, 95% CI)14.17 [3.53, 24.81]

   24.1 Girls
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

   24.2 Boys
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    24.3 Mixed/unknown
5550Mean Difference (IV, Random, 95% CI)14.17 [3.53, 24.81]

 25 Ferritin (by nutrient)5550Mean Difference (IV, Random, 95% CI)11.41 [2.71, 20.11]

    25.1 Iron alone
4379Mean Difference (IV, Random, 95% CI)16.25 [5.41, 27.09]

   25.2 Iron + folic acid
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    25.3 Iron + zinc
153Mean Difference (IV, Random, 95% CI)5.50 [-3.91, 14.91]

    25.4 Iron + multiple micronutrients
2118Mean Difference (IV, Random, 95% CI)3.80 [-4.96, 12.56]

 26 All cause morbidity (ALL)1194Risk Ratio (M-H, Random, 95% CI)0.26 [0.03, 2.24]

 27 Any side effects (ALL)153Risk Ratio (M-H, Fixed, 95% CI)3.87 [0.19, 76.92]

 28 Nausea164Risk Ratio (M-H, Random, 95% CI)2.82 [0.12, 66.82]

 29 Adherence (ALL)2289Risk Ratio (M-H, Random, 95% CI)1.04 [0.98, 1.09]

 30 Mental development scale (ALL)1172Mean Difference (IV, Random, 95% CI)2.0 [-2.40, 6.40]

 31 Orientation engagement (ALL)1172Mean Difference (IV, Random, 95% CI)8.40 [-1.79, 18.59]

 32 Emotional regulation (ALL)1172Mean Difference (IV, Random, 95% CI)-2.5 [-11.58, 6.58]

 33 Motor quality (ALL)1172Mean Difference (IV, Random, 95% CI)15.60 [7.66, 23.54]

 34 Psychomotor development index (ALL)1172Mean Difference (IV, Random, 95% CI)6.90 [1.35, 12.45]

 35 IQ (ALL)1252Mean Difference (IV, Random, 95% CI)-3.00 [-5.96, -0.04]

 36 Thai language (ALL)1208Mean Difference (IV, Random, 95% CI)-0.30 [-0.50, -0.09]

 37 Mathematics (ALL)1233Mean Difference (IV, Random, 95% CI)-0.27 [-0.44, -0.10]

 38 WAZ3366Std. Mean Difference (IV, Random, 95% CI)-0.03 [-0.33, 0.27]

 39 HAZ3366Mean Difference (IV, Random, 95% CI)0.03 [-0.04, 0.10]

 
Comparison 2. Intermittent iron supplementation versus daily iron supplementation: children 0 - 12 years

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Anaemia (ALL)6980Risk Ratio (M-H, Random, 95% CI)1.23 [1.04, 1.47]

 2 Anaemia (by dose of elemental iron in the intermittent group)6980Risk Ratio (M-H, Random, 95% CI)1.23 [1.04, 1.47]

    2.1 25 mg or less/week
2404Risk Ratio (M-H, Random, 95% CI)1.20 [0.98, 1.47]

    2.2 Greater than 25 mg to 75 mg/week
4576Risk Ratio (M-H, Random, 95% CI)1.34 [0.96, 1.88]

   2.3 Intermittent group: greater than 75 mg/week
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 3 Anaemia (by duration of the supplementation)6980Risk Ratio (M-H, Random, 95% CI)1.23 [1.04, 1.47]

    3.1 0 to three months
2172Risk Ratio (M-H, Random, 95% CI)1.24 [0.55, 2.77]

    3.2 More than three months
4808Risk Ratio (M-H, Random, 95% CI)1.23 [1.03, 1.47]

 4 Anaemia (by type of compound)6980Risk Ratio (M-H, Random, 95% CI)1.23 [1.04, 1.47]

    4.1 Ferrous sulphate
6980Risk Ratio (M-H, Random, 95% CI)1.23 [1.04, 1.47]

   4.2 Ferrous fumarate
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

   4.3 Other
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 5 Anaemia (by anaemia status at baseline)6980Risk Ratio (M-H, Random, 95% CI)1.23 [1.04, 1.47]

    5.1 Anaemic
2183Risk Ratio (M-H, Random, 95% CI)0.96 [0.50, 1.82]

   5.2 Non-anaemic
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    5.3 Mixed/unknown
4797Risk Ratio (M-H, Random, 95% CI)1.26 [1.05, 1.51]

 6 Anaemia (by supplementation regimen)6980Risk Ratio (M-H, Random, 95% CI)1.23 [1.04, 1.47]

    6.1 One supplement a week
4549Risk Ratio (M-H, Random, 95% CI)1.18 [0.97, 1.43]

    6.2 Other intermittent regimen
2431Risk Ratio (M-H, Random, 95% CI)1.49 [1.02, 2.19]

 7 Anaemia (by sex)6980Risk Ratio (M-H, Random, 95% CI)1.23 [1.04, 1.47]

   7.1 Girls
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

   7.2 Boys
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    7.3 Mixed/unknown
6980Risk Ratio (M-H, Random, 95% CI)1.23 [1.04, 1.47]

 8 Anaemia (by nutrient)6980Risk Ratio (M-H, Random, 95% CI)1.23 [1.04, 1.47]

    8.1 Iron alone
4507Risk Ratio (M-H, Random, 95% CI)1.17 [0.97, 1.42]

    8.2 Iron + folic acid
1366Risk Ratio (M-H, Random, 95% CI)1.55 [1.02, 2.36]

    8.3 Iron + multiple micronutrients
1107Risk Ratio (M-H, Random, 95% CI)1.31 [0.31, 5.57]

 9 Haemoglobin (ALL)192851Mean Difference (IV, Random, 95% CI)-0.60 [-1.54, 0.35]

 10 Haemoglobin (by dose of elemental iron in the intermittent group)182751Mean Difference (IV, Random, 95% CI)-0.62 [-1.60, 0.37]

    10.1 25 mg or less/week
3536Mean Difference (IV, Random, 95% CI)-2.42 [-4.18, -0.66]

    10.2 Greater than 25 mg to 75 mg/week
132078Mean Difference (IV, Random, 95% CI)-0.58 [-1.62, 0.45]

    10.3 Greater than 75 mg/week
2137Mean Difference (IV, Random, 95% CI)1.00 [-4.68, 6.68]

 11 Haemoglobin (by duration of the supplementation)192842Mean Difference (IV, Random, 95% CI)-0.38 [-1.26, 0.50]

    11.1 0 to three months
111455Mean Difference (IV, Random, 95% CI)0.47 [-0.91, 1.84]

    11.2 More than three months
81387Mean Difference (IV, Random, 95% CI)-1.14 [-2.07, -0.22]

 12 Haemoglobin (by type of compound)192851Mean Difference (IV, Random, 95% CI)-0.60 [-1.54, 0.35]

    12.1 Ferrous sulphate
172733Mean Difference (IV, Random, 95% CI)-0.60 [-1.60, 0.40]

   12.2 Ferrous fumarate
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    12.3 Other
2118Mean Difference (IV, Random, 95% CI)-0.46 [-4.24, 3.32]

 13 Haemoglobin (by anaemia status at baseline)192851Mean Difference (IV, Random, 95% CI)-0.61 [-1.54, 0.32]

    13.1 Anaemic
7957Mean Difference (IV, Random, 95% CI)-0.76 [-2.59, 1.07]

    13.2 Non-anaemic
3166Mean Difference (IV, Random, 95% CI)0.79 [-1.42, 2.99]

    13.3 Mixed/unknown
101728Mean Difference (IV, Random, 95% CI)-0.76 [-2.00, 0.48]

 14 Haemoglobin (by supplementation regimen)192851Mean Difference (IV, Random, 95% CI)-0.70 [-1.70, 0.30]

    14.1 One supplement a week
141612Mean Difference (IV, Random, 95% CI)-0.25 [-1.57, 1.07]

    14.2 Other intermittent regimen
81239Mean Difference (IV, Random, 95% CI)-1.42 [-3.02, 0.19]

 15 Haemoglobin (by sex)192851Mean Difference (IV, Random, 95% CI)-0.60 [-1.54, 0.35]

    15.1 Girls
142Mean Difference (IV, Random, 95% CI)-2.0 [-5.43, 1.43]

   15.2 Boys
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    15.3 Mixed/unknown
182809Mean Difference (IV, Random, 95% CI)-0.53 [-1.51, 0.46]

 16 Haemoglobin (by nutrient)192851Mean Difference (IV, Random, 95% CI)-0.59 [-1.52, 0.35]

    16.1 Iron alone
152144Mean Difference (IV, Random, 95% CI)-0.51 [-1.61, 0.59]

    16.2 Iron + folic acid
2408Mean Difference (IV, Random, 95% CI)-2.26 [-4.30, -0.22]

    16.3 Iron + multiple micronutrients
3299Mean Difference (IV, Random, 95% CI)0.61 [-2.04, 3.26]

 17 Iron deficiency (ALL)176Risk Ratio (M-H, Random, 95% CI)4.0 [1.23, 13.05]

 18 Ferritin (ALL)10902Mean Difference (IV, Random, 95% CI)-4.19 [-9.42, 1.05]

 19 Ferritin (by dose of elemental iron in the intermittent group)9802Mean Difference (IV, Random, 95% CI)-4.34 [-10.20, 1.53]

   19.1 by dose of elemental iron in the intermittent group: 25 mg or less/week
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    19.2 by dose of elemental iron in the intermittent group: greater than 25 mg to 75 mg/week
9802Mean Difference (IV, Random, 95% CI)-4.34 [-10.20, 1.53]

   19.3 by dose of elemental iron in the intermittent group: greater than 75 mg/week
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 20 Ferritin (by duration of the supplementation)10902Mean Difference (IV, Random, 95% CI)-4.19 [-9.42, 1.05]

    20.1 by duration of the supplementation: 0 to three months
6442Mean Difference (IV, Random, 95% CI)-1.06 [-6.62, 4.51]

    20.2 by duration of the supplementation: more than three months
4460Mean Difference (IV, Random, 95% CI)-9.58 [-23.08, 3.93]

 21 Ferritin (by type of compound)10902Mean Difference (IV, Random, 95% CI)-4.19 [-9.42, 1.05]

    21.1 by type of compound: ferrous sulphate
9826Mean Difference (IV, Random, 95% CI)-3.85 [-9.28, 1.59]

   21.2 by type of compound: ferrous fumarate
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    21.3 by type of compound: other
176Mean Difference (IV, Random, 95% CI)-9.03 [-23.95, 5.89]

 22 Ferritin (by anaemia status at baseline)10902Mean Difference (IV, Random, 95% CI)-4.93 [-9.98, 0.12]

    22.1 by anaemia status at baseline: anaemic
5285Mean Difference (IV, Random, 95% CI)-2.94 [-12.23, 6.34]

    22.2 by anaemia status at baseline: non-anaemic
3167Mean Difference (IV, Random, 95% CI)-2.67 [-5.89, 0.54]

    22.3 by anaemia status at baseline: mixed/unknown
3450Mean Difference (IV, Random, 95% CI)-9.42 [-23.19, 4.35]

 23 Ferritin (by supplementation regimen)10902Mean Difference (IV, Random, 95% CI)-4.48 [-9.68, 0.71]

    23.1 by supplementation regimen: one supplement a week
7595Mean Difference (IV, Random, 95% CI)-7.34 [-16.12, 1.44]

    23.2 by supplementation regimen: other intermittent regimen
5307Mean Difference (IV, Random, 95% CI)-0.93 [-3.94, 2.08]

 24 Ferritin (by sex)10902Mean Difference (IV, Random, 95% CI)-4.19 [-9.42, 1.05]

   24.1 by sex: girls
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

   24.2 by sex: boys
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    24.3 by sex: mixed/unknown
10902Mean Difference (IV, Random, 95% CI)-4.19 [-9.42, 1.05]

 25 Ferritin (by nutrient)10902Mean Difference (IV, Random, 95% CI)-4.19 [-9.42, 1.05]

    25.1 By nutrient: iron alone
9826Mean Difference (IV, Random, 95% CI)-3.85 [-9.28, 1.59]

   25.2 By nutrient: iron + folic acid
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    25.3 By nutrient: iron + multiple micronutrients
176Mean Difference (IV, Random, 95% CI)-9.03 [-23.95, 5.89]

 26 Increase in steps climbed (ALL)165Mean Difference (IV, Random, 95% CI)-5.0 [-13.34, 3.34]

 27 All cause morbidity (ALL)2599Risk Ratio (M-H, Random, 95% CI)0.96 [0.83, 1.12]

 28 Diarrhoea (ALL)2122Risk Ratio (M-H, Random, 95% CI)1.17 [0.60, 2.28]

 29 Any side effects (ALL)4895Risk Ratio (M-H, Random, 95% CI)0.60 [0.19, 1.87]

 30 Adherence (ALL)51130Risk Ratio (M-H, Random, 95% CI)1.23 [0.98, 1.54]

 31 IQ (ALL)1252Mean Difference (IV, Random, 95% CI)-3.00 [-5.96, -0.04]

 32 Thai language (ALL)1208Mean Difference (IV, Random, 95% CI)-0.30 [-0.50, -0.09]

 33 Mathematics (ALL)1233Mean Difference (IV, Random, 95% CI)-0.27 [-0.44, -0.10]

 34 HAZ3279Std. Mean Difference (IV, Random, 95% CI)-0.26 [-0.80, 0.28]

 
Comparison 3. Intermittent iron supplementation versus placebo or no intervention: children 0 - 59 months

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Anaemia (ALL)4658Risk Ratio (M-H, Random, 95% CI)0.43 [0.23, 0.80]

 2 Anaemia (by dose of elemental iron in the intermittent group)4658Risk Ratio (M-H, Random, 95% CI)0.43 [0.23, 0.80]

    2.1 25 mg or less/week
2157Risk Ratio (M-H, Random, 95% CI)0.15 [0.06, 0.37]

    2.2 Greater than 25 mg to 75 mg/week
2501Risk Ratio (M-H, Random, 95% CI)0.61 [0.51, 0.74]

   2.3 Greater than 75 mg/week
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 3 Anaemia (by duration of the supplementation)4658Risk Ratio (M-H, Random, 95% CI)0.43 [0.23, 0.80]

    3.1 0 to three months
3608Risk Ratio (M-H, Random, 95% CI)0.48 [0.27, 0.85]

    3.2 More than three months
150Risk Ratio (M-H, Random, 95% CI)0.06 [0.00, 0.97]

 4 Anaemia (by type of compound)4658Risk Ratio (M-H, Random, 95% CI)0.43 [0.23, 0.80]

    4.1 Ferrous sulphate
3351Risk Ratio (M-H, Random, 95% CI)0.26 [0.07, 1.03]

    4.2 Ferrous fumarate
1307Risk Ratio (M-H, Random, 95% CI)0.61 [0.49, 0.74]

   4.3 Other
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 5 Anaemia (by anaemia status at baseline)4658Risk Ratio (M-H, Random, 95% CI)0.43 [0.23, 0.80]

    5.1 Anaemic
1307Risk Ratio (M-H, Random, 95% CI)0.61 [0.49, 0.74]

   5.2 Non-anaemic
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    5.3 Mixed/unknown
3351Risk Ratio (M-H, Random, 95% CI)0.26 [0.07, 1.03]

 6 Anaemia (by intermittent regimen)4658Risk Ratio (M-H, Random, 95% CI)0.43 [0.23, 0.80]

    6.1 One supplement a week
3351Risk Ratio (M-H, Random, 95% CI)0.26 [0.07, 1.03]

    6.2 Other intermittent regimen
1307Risk Ratio (M-H, Random, 95% CI)0.61 [0.49, 0.74]

 7 Anaemia (by sex)4658Risk Ratio (M-H, Random, 95% CI)0.43 [0.23, 0.80]

   7.1 Girls
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

   7.2 Boys
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    7.3 Mixed/unknown
4658Risk Ratio (M-H, Random, 95% CI)0.43 [0.23, 0.80]

 8 Anaemia (by nutrient)4658Risk Ratio (M-H, Random, 95% CI)0.43 [0.23, 0.80]

    8.1 Iron alone
2501Risk Ratio (M-H, Random, 95% CI)0.61 [0.51, 0.74]

   8.2 Iron + folic acid
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    8.3 iron + vitamin C
150Risk Ratio (M-H, Random, 95% CI)0.06 [0.00, 0.97]

    8.4 Iron + multiple micronutrients
1107Risk Ratio (M-H, Random, 95% CI)0.16 [0.06, 0.44]

 9 Haemoglobin (ALL)91254Mean Difference (IV, Random, 95% CI)6.45 [2.36, 10.55]

 10 Haemoglobin (by dose of elemental iron in the intermittent group)91254Mean Difference (IV, Random, 95% CI)6.45 [2.36, 10.55]

    10.1 25 mg or less/week
3324Mean Difference (IV, Random, 95% CI)8.19 [-4.01, 20.38]

    10.2 Greater than 25 mg to 75 mg/week
6930Mean Difference (IV, Random, 95% CI)5.50 [2.64, 8.36]

   10.3 Greater than 75 mg/week
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 11 Haemoglobin (by duration of the supplementation)91254Mean Difference (IV, Random, 95% CI)6.45 [2.36, 10.55]

    11.1 0 to three months
4643Mean Difference (IV, Random, 95% CI)6.64 [3.01, 10.27]

    11.2 More than three months
5611Mean Difference (IV, Random, 95% CI)6.16 [-1.55, 13.87]

 12 Haemoglobin (by type of iron compound)91254Mean Difference (IV, Random, 95% CI)6.45 [2.36, 10.55]

    12.1 Ferrous sulphate
7873Mean Difference (IV, Random, 95% CI)6.54 [1.44, 11.63]

    12.2 Ferrous fumarate
1307Mean Difference (IV, Random, 95% CI)8.0 [5.00, 11.00]

    12.3 Other
174Mean Difference (IV, Random, 95% CI)4.06 [-1.32, 9.44]

 13 Haemoglobin (by anaemia status at baseline)91254Mean Difference (IV, Random, 95% CI)6.45 [2.36, 10.55]

    13.1 Anaemic
1307Mean Difference (IV, Random, 95% CI)8.0 [5.00, 11.00]

   13.2 Non-anaemic
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    13.3 Mixed/unknown
8947Mean Difference (IV, Random, 95% CI)6.25 [1.60, 10.90]

 14 Haemoglobin (by supplementation regimen)91254Mean Difference (IV, Random, 95% CI)6.45 [2.36, 10.55]

    14.1 One supplement a week
6699Mean Difference (IV, Random, 95% CI)7.35 [0.92, 13.77]

    14.2 Other intermittent regimen
3555Mean Difference (IV, Random, 95% CI)4.68 [1.28, 8.08]

 15 Haemoglobin (by sex)91254Mean Difference (IV, Random, 95% CI)6.45 [2.36, 10.55]

   15.1 Girls
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

   15.2 Boys
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    15.3 Mixed/unknown
91254Mean Difference (IV, Random, 95% CI)6.45 [2.36, 10.55]

 16 Haemoglobin (by nutrient)91254Mean Difference (IV, Random, 95% CI)6.01 [2.13, 9.89]

    16.1 Iron alone
5744Mean Difference (IV, Random, 95% CI)3.81 [1.61, 6.01]

   16.2 Iron + folic acid
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    16.3 Iron + multiple micronutrients
5510Mean Difference (IV, Random, 95% CI)8.46 [0.60, 16.32]

 17 Iron deficiency (ALL)3431Risk Ratio (M-H, Random, 95% CI)0.24 [0.06, 0.91]

 18 Ferritin (ALL)4310Mean Difference (IV, Random, 95% CI)13.15 [-2.28, 28.59]

 19 Ferritin (by dose of iron in the intermittent group)4310Mean Difference (IV, Random, 95% CI)13.15 [-2.28, 28.59]

    19.1 25 mg or less/week
1148Mean Difference (IV, Random, 95% CI)4.60 [-0.89, 10.09]

    19.2 Greater than 25 mg to 75 mg/week
3162Mean Difference (IV, Random, 95% CI)16.91 [0.99, 32.82]

   19.3 Greater than 75 mg/week
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 20 Ferritin (by duration of the supplementation)4310Mean Difference (IV, Random, 95% CI)13.15 [-2.28, 28.59]

    20.1 0 to three months
135Mean Difference (IV, Random, 95% CI)15.80 [-1.23, 32.83]

    20.2 More than three months
3275Mean Difference (IV, Random, 95% CI)12.34 [-6.19, 30.87]

 21 Ferritin (by type of iron compound)4310Mean Difference (IV, Random, 95% CI)13.15 [-2.28, 28.59]

    21.1 Ferrous sulphate
3236Mean Difference (IV, Random, 95% CI)16.12 [-1.81, 34.05]

   21.2 Ferrous fumarate
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    21.3 Other
174Mean Difference (IV, Random, 95% CI)2.46 [-14.37, 19.29]

 22 Ferritin (by anaemia status at baseline)4310Mean Difference (IV, Random, 95% CI)13.15 [-2.28, 28.59]

   22.1 by anaemia status at baseline: anaemic
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    22.2 by anaemia status at baseline: non-anaemic
174Mean Difference (IV, Random, 95% CI)2.46 [-14.37, 19.29]

    22.3 by anaemia status at baseline: mixed/unknown
3236Mean Difference (IV, Random, 95% CI)16.12 [-1.81, 34.05]

 23 Ferritin (by supplementation regimen)4310Mean Difference (IV, Random, 95% CI)13.15 [-2.28, 28.59]

    23.1 One supplement a week
3257Mean Difference (IV, Random, 95% CI)5.37 [0.39, 10.36]

    23.2 Other intermittent regimen
153Mean Difference (IV, Random, 95% CI)27.80 [22.88, 32.72]

 24 Ferritin (by sex)4310Mean Difference (IV, Random, 95% CI)13.15 [-2.28, 28.59]

   24.1 Girls
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

   24.2 Boys
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    24.3 Mixed/unknown
4310Mean Difference (IV, Random, 95% CI)13.15 [-2.28, 28.59]

 25 Ferritin (by nutrient)4310Mean Difference (IV, Random, 95% CI)11.15 [-1.92, 24.22]

    25.1 Iron alone
3144Mean Difference (IV, Random, 95% CI)15.70 [-2.68, 34.08]

   25.2 Iron + folic acid
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    25.3 Iron + multiple micronutrients
2166Mean Difference (IV, Random, 95% CI)4.58 [-2.27, 11.43]

 26 All cause morbidity (ALL)1194Risk Ratio (M-H, Random, 95% CI)0.26 [0.03, 2.24]

 27 Any side effects (ALL)153Risk Ratio (M-H, Random, 95% CI)3.87 [0.19, 76.92]

 28 Adherence (ALL)2289Risk Ratio (M-H, Random, 95% CI)1.04 [0.98, 1.09]

 29 Mental development scale (ALL)1172Mean Difference (IV, Random, 95% CI)2.0 [-2.40, 6.40]

 30 Orientation engagement (ALL)1172Mean Difference (IV, Random, 95% CI)8.40 [-1.79, 18.59]

 31 Emotional regulation (ALL)1172Mean Difference (IV, Random, 95% CI)-2.5 [-11.58, 6.58]

 32 Motor quality (ALL)1172Mean Difference (IV, Random, 95% CI)15.60 [7.66, 23.54]

 33 Psychomotor development index (ALL)1172Mean Difference (IV, Random, 95% CI)6.90 [1.35, 12.45]

 34 HAZ2302Mean Difference (IV, Random, 95% CI)0.04 [-0.03, 0.11]

 
Comparison 4. Intermittent iron supplementation versus daily iron supplementation: children 0 - 59 months

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Anaemia (ALL)3770Risk Ratio (M-H, Random, 95% CI)1.26 [1.05, 1.51]

 2 Haemoglobin (ALL)142270Mean Difference (IV, Random, 95% CI)-0.75 [-1.80, 0.29]

 3 Haemoglobin (by dose of elemental iron in the intermittent group)142438Mean Difference (IV, Random, 95% CI)-0.82 [-1.82, 0.18]

    3.1 25 mg or less/week
3536Mean Difference (IV, Random, 95% CI)-2.42 [-4.18, -0.66]

    3.2 Greater than 25 mg to 75 mg/week
111902Mean Difference (IV, Random, 95% CI)-0.45 [-1.59, 0.68]

   3.3 Greater than 75 mg/week
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 4 Haemoglobin (by duration of supplementation)142270Mean Difference (IV, Random, 95% CI)-0.75 [-1.80, 0.29]

    4.1 0 to three months
91309Mean Difference (IV, Random, 95% CI)-0.15 [-1.66, 1.36]

    4.2 More than three months
5961Mean Difference (IV, Random, 95% CI)-1.53 [-2.95, -0.11]

 5 Haemoglobin (by type of compound)142270Mean Difference (IV, Random, 95% CI)-0.75 [-1.80, 0.29]

    5.1 Ferrous sulphate
132194Mean Difference (IV, Random, 95% CI)-0.85 [-1.91, 0.21]

   5.2 Ferrous fumarate
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    5.3 Other
176Mean Difference (IV, Random, 95% CI)1.96 [-3.05, 6.97]

 6 Haemoglobin (by anaemia status at baseline)142270Mean Difference (IV, Random, 95% CI)-0.75 [-1.80, 0.29]

    6.1 Anaemic
5834Mean Difference (IV, Random, 95% CI)-0.57 [-2.81, 1.68]

    6.2 Non-anaemic
2113Mean Difference (IV, Random, 95% CI)1.99 [-0.72, 4.70]

    6.3 Mixed/unknown
71323Mean Difference (IV, Random, 95% CI)-1.20 [-2.22, -0.19]

 7 Haemoglobin (by supplementation regimen)142270Mean Difference (IV, Random, 95% CI)-0.72 [-1.71, 0.27]

    7.1 One supplement a week
91054Mean Difference (IV, Random, 95% CI)-0.23 [-1.67, 1.21]

    7.2 Other intermittent regimen
71216Mean Difference (IV, Random, 95% CI)-1.14 [-2.57, 0.29]

 8 Haemoglobin (by sex)142270Mean Difference (IV, Random, 95% CI)-0.75 [-1.80, 0.29]

   8.1 Girls
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

   8.2 Boys
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    8.3 Mixed/unknown
142270Mean Difference (IV, Random, 95% CI)-0.75 [-1.80, 0.29]

 9 Haemoglobin (by nutrient)142270Mean Difference (IV, Random, 95% CI)-0.75 [-1.80, 0.29]

    9.1 Iron alone
101490Mean Difference (IV, Random, 95% CI)-0.80 [-2.05, 0.46]

    9.2 Iron + folic acid
1366Mean Difference (IV, Random, 95% CI)-2.40 [-4.94, 0.14]

    9.3 Iron + multiple micronutrients
3414Mean Difference (IV, Random, 95% CI)0.57 [-1.84, 2.98]

 10 Iron deficiency (ALL)176Risk Ratio (M-H, Random, 95% CI)4.0 [1.23, 13.05]

 11 Ferritin (ALL)8582Mean Difference (IV, Random, 95% CI)-3.10 [-6.59, 0.39]

 12 Ferritin (by dose of elemental iron in the intermittent subgroup)8582Mean Difference (IV, Random, 95% CI)-2.22 [-6.03, 1.59]

   12.1 25 mg or less/week
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    12.2 Greater than 25 mg to 75 mg/week
8582Mean Difference (IV, Random, 95% CI)-2.22 [-6.03, 1.59]

   12.3 Greater than 75 mg/week
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 13 Ferritin (by duration of supplementation)8582Mean Difference (IV, Random, 95% CI)-3.10 [-6.59, 0.39]

    13.1 0 to three months
5382Mean Difference (IV, Random, 95% CI)-3.02 [-7.91, 1.87]

    13.2 More than three months
3200Mean Difference (IV, Random, 95% CI)-1.63 [-5.88, 2.62]

 14 Ferritin (by type of compound)8582Mean Difference (IV, Random, 95% CI)-3.10 [-6.59, 0.39]

    14.1 Ferrous sulphate
7506Mean Difference (IV, Random, 95% CI)-2.69 [-6.42, 1.05]

   14.2 Ferrous fumarate
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    14.3 Other
176Mean Difference (IV, Random, 95% CI)-9.03 [-23.95, 5.89]

 15 Ferritin (by anaemia status at baseline)8582Mean Difference (IV, Random, 95% CI)-3.70 [-8.25, 0.86]

    15.1 Anaemic
4225Mean Difference (IV, Random, 95% CI)-4.47 [-15.45, 6.52]

    15.2 Non-anaemic
3167Mean Difference (IV, Random, 95% CI)-2.67 [-5.89, 0.54]

    15.3 Mixed/unknown
2190Mean Difference (IV, Random, 95% CI)-1.53 [-5.23, 2.17]

 16 Ferritin (by supplementation regimen)8582Mean Difference (IV, Random, 95% CI)-3.27 [-7.87, 1.33]

    16.1 One supplement a week
5291Mean Difference (IV, Random, 95% CI)-6.21 [-12.98, 0.55]

    16.2 Other intermittent regimen
4291Mean Difference (IV, Random, 95% CI)-0.81 [-3.89, 2.27]

 17 Ferritin (by sex)8582Mean Difference (IV, Random, 95% CI)-3.10 [-6.58, 0.39]

   17.1 Girls
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

   17.2 Boys
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    17.3 Mixed/unknown
8582Mean Difference (IV, Random, 95% CI)-3.10 [-6.58, 0.39]

 18 Ferritin (by nutrient)8582Mean Difference (IV, Random, 95% CI)-3.10 [-6.59, 0.39]

    18.1 Iron alone
7506Mean Difference (IV, Random, 95% CI)-2.69 [-6.42, 1.05]

   18.2 Iron + folic acid
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    18.3 Iron + multiple micronutrients
176Mean Difference (IV, Random, 95% CI)-9.03 [-23.95, 5.89]

 19 All cause morbidity (ALL)1522Risk Ratio (M-H, Random, 95% CI)0.98 [0.82, 1.16]

 20 Diarrhoea (ALL)145Risk Ratio (M-H, Random, 95% CI)2.88 [0.12, 67.03]

 21 Any side effects (ALL)4895Risk Ratio (M-H, Random, 95% CI)0.60 [0.19, 1.87]

 22 Adherence (ALL)31185Risk Ratio (M-H, Random, 95% CI)1.29 [1.15, 1.45]

 23 HAZ1109Std. Mean Difference (IV, Random, 95% CI)-0.15 [-0.52, 0.23]

 24 WAZ1109Std. Mean Difference (IV, Random, 95% CI)-0.44 [-0.82, -0.06]

 
Comparison 5. Intermittent iron supplementation versus placebo or no intervention: children 5 - 12 years

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Anaemia (ALL)61166Risk Ratio (M-H, Random, 95% CI)0.54 [0.33, 0.90]

 2 Anaemia (by dose)61166Risk Ratio (M-H, Random, 95% CI)0.54 [0.33, 0.90]

   2.1 25 mg or less/week
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    2.2 Greater than 25 mg to 75 mg/week
4755Risk Ratio (M-H, Random, 95% CI)0.47 [0.21, 1.02]

    2.3 Greater than 75 mg/week
2411Risk Ratio (M-H, Random, 95% CI)0.71 [0.48, 1.04]

 3 Anaemia (by duration)61166Risk Ratio (M-H, Random, 95% CI)0.54 [0.33, 0.90]

    3.1 0 to three months
2848Risk Ratio (M-H, Random, 95% CI)0.77 [0.67, 0.89]

    3.2 More than three months
4318Risk Ratio (M-H, Random, 95% CI)0.44 [0.16, 1.24]

 4 Anaemia (by type of compound)61166Risk Ratio (M-H, Random, 95% CI)0.54 [0.33, 0.90]

    4.1 Ferrous sulphate
61166Risk Ratio (M-H, Random, 95% CI)0.54 [0.33, 0.90]

   4.2 Ferrous fumarate
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

   4.3 Other
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 5 Anaemia (by anaemia status at baseline)61166Risk Ratio (M-H, Random, 95% CI)0.54 [0.33, 0.90]

    5.1 Anaemic
1117Risk Ratio (M-H, Random, 95% CI)0.14 [0.07, 0.27]

    5.2 Non-anaemic
164Risk Ratio (M-H, Random, 95% CI)0.78 [0.27, 2.31]

    5.3 Mixed/unknown
4985Risk Ratio (M-H, Random, 95% CI)0.73 [0.54, 0.98]

 6 Anaemia (by intermittent regimen)61166Risk Ratio (M-H, Random, 95% CI)0.54 [0.33, 0.90]

    6.1 One supplement a week
61166Risk Ratio (M-H, Random, 95% CI)0.54 [0.33, 0.90]

   6.2 Other intermittent regimen
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 7 Anaemia (by sex)61166Risk Ratio (M-H, Random, 95% CI)0.59 [0.40, 0.86]

    7.1 Girls
1248Risk Ratio (M-H, Random, 95% CI)0.75 [0.59, 0.95]

    7.2 Boys
1253Risk Ratio (M-H, Random, 95% CI)0.81 [0.66, 1.00]

    7.3 Mixed/unknown
5665Risk Ratio (M-H, Random, 95% CI)0.49 [0.24, 1.01]

 8 Anaemia (by nutrient)61166Risk Ratio (M-H, Random, 95% CI)0.54 [0.33, 0.90]

    8.1 Iron alone
4573Risk Ratio (M-H, Random, 95% CI)0.39 [0.17, 0.90]

    8.2 Iron + folic acid
2593Risk Ratio (M-H, Random, 95% CI)0.83 [0.66, 1.03]

   8.3 Iron + multiple micronutrients
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 9 Haemoglobin (ALL)101778Mean Difference (IV, Random, 95% CI)4.04 [0.30, 7.78]

 10 Haemoglobin (by dose of elemental iron in the intermittent group)101778Mean Difference (IV, Random, 95% CI)4.04 [0.30, 7.78]

   10.1 25 mg or less/week
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    10.2 Greater than 25 mg to 75 mg/week
61129Mean Difference (IV, Random, 95% CI)5.24 [-0.78, 11.26]

    10.3 Group: greater than 75 mg/week
4649Mean Difference (IV, Random, 95% CI)1.84 [0.25, 3.44]

 11 Haemoglobin (by duration of the supplementation)101778Mean Difference (IV, Random, 95% CI)4.04 [0.30, 7.78]

    11.1 0 to three months
3973Mean Difference (IV, Random, 95% CI)3.13 [1.49, 4.77]

    11.2 More than three months
7805Mean Difference (IV, Random, 95% CI)4.38 [-1.20, 9.96]

 12 Haemoglobin (by type of iron compound)101778Mean Difference (IV, Random, 95% CI)4.04 [0.30, 7.78]

    12.1 Ferrous sulphate
71415Mean Difference (IV, Random, 95% CI)4.59 [-0.30, 9.47]

    12.2 Ferrous fumarate
1125Mean Difference (IV, Random, 95% CI)3.4 [-4.09, 10.89]

    12.3 Other
2238Mean Difference (IV, Random, 95% CI)1.79 [-1.25, 4.84]

 13 Haemoglobin (by anaemia status at baseline)101778Mean Difference (IV, Random, 95% CI)4.04 [0.30, 7.78]

    13.1 Anaemic
1115Mean Difference (IV, Random, 95% CI)18.30 [15.55, 21.05]

    13.2 Non-anaemic
164Mean Difference (IV, Random, 95% CI)2.0 [-2.46, 6.46]

    13.3 Mixed/unknown
81599Mean Difference (IV, Random, 95% CI)2.37 [1.17, 3.57]

 14 Haemoglobin (by supplementation regimen)101868Mean Difference (IV, Random, 95% CI)4.04 [0.45, 7.62]

    14.1 One supplement a week
91647Mean Difference (IV, Random, 95% CI)4.43 [0.21, 8.65]

    14.2 Other intermittent regimen
2221Mean Difference (IV, Random, 95% CI)1.17 [-1.27, 3.61]

 15 Haemoglobin (by sex)101778Mean Difference (IV, Random, 95% CI)4.03 [0.51, 7.55]

    15.1 Girls
1248Mean Difference (IV, Random, 95% CI)4.0 [0.83, 7.17]

    15.2 Boys
1253Mean Difference (IV, Random, 95% CI)3.70 [0.58, 6.82]

    15.3 Mixed/unknown
91277Mean Difference (IV, Random, 95% CI)4.05 [-0.37, 8.46]

 16 Haemoglobin (by nutrient)101778Mean Difference (IV, Random, 95% CI)4.04 [0.30, 7.78]

    16.1 Iron alone
61022Mean Difference (IV, Random, 95% CI)4.98 [-0.71, 10.68]

    16.2 Iron + folic acid
4756Mean Difference (IV, Random, 95% CI)2.91 [0.65, 5.16]

   16.3 Iron + multiple micronutrients
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 17 Ferritin (ALL)1240Mean Difference (IV, Random, 95% CI)16.6 [11.12, 22.08]

 18 All cause morbidity (ALL)1194Risk Ratio (M-H, Random, 95% CI)0.26 [0.03, 2.24]

 19 Any side effects (ALL)153Risk Ratio (M-H, Random, 95% CI)3.87 [0.19, 76.92]

 20 Nausea164Risk Ratio (M-H, Random, 95% CI)2.82 [0.12, 66.82]

 21 IQ (ALL)1252Mean Difference (IV, Random, 95% CI)-3.00 [-5.96, -0.04]

 22 Thai language (ALL)1208Mean Difference (IV, Random, 95% CI)-0.30 [-0.50, -0.09]

 23 Mathematics (ALL)1233Mean Difference (IV, Random, 95% CI)-0.27 [-0.44, -0.10]

 24 Increase in steps climbed (ALL)160Mean Difference (IV, Random, 95% CI)8.0 [-0.72, 16.72]

 25 WAZ164Std. Mean Difference (IV, Random, 95% CI)-0.24 [-0.74, 0.25]

 26 HAZ164Mean Difference (IV, Fixed, 95% CI)-0.24 [-0.69, 0.21]

 
Comparison 6. Intermittent iron supplementation versus daily iron supplementation: children 5 - 12 years

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Anaemia (ALL)2145Risk Ratio (M-H, Random, 95% CI)0.95 [0.47, 1.91]

 2 Haemoglobin (ALL)5581Mean Difference (IV, Random, 95% CI)-0.31 [-2.59, 1.97]

 3 Haemoglobin (by dose of elemental iron)5581Mean Difference (IV, Random, 95% CI)-0.31 [-2.59, 1.97]

   3.1 25 mg or less/week
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    3.2 Greater than 25 mg to 75 mg/week
3444Mean Difference (IV, Random, 95% CI)-1.10 [-3.01, 0.80]

    3.3 Intermittent group: greater than 75 mg/week
2137Mean Difference (IV, Random, 95% CI)1.00 [-4.68, 6.68]

 4 Haemoglobin (by duration of the supplementation)5581Mean Difference (IV, Random, 95% CI)-0.31 [-2.59, 1.97]

    4.1 0 to three months
2155Mean Difference (IV, Random, 95% CI)0.32 [-6.54, 7.18]

    4.2 More than three months
3426Mean Difference (IV, Random, 95% CI)-0.64 [-2.12, 0.84]

 5 Haemoglobin (by type of compound)5581Mean Difference (IV, Random, 95% CI)-0.31 [-2.59, 1.97]

    5.1 Ferrous sulphate
4539Mean Difference (IV, Random, 95% CI)0.04 [-2.63, 2.71]

   5.2 Ferrous fumarate
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    5.3 Other
142Mean Difference (IV, Random, 95% CI)-2.0 [-5.43, 1.43]

 6 Haemoglobin (by baseline prevalence of anaemia)5581Mean Difference (IV, Random, 95% CI)-0.31 [-2.59, 1.97]

    6.1 Anaemic
3271Mean Difference (IV, Random, 95% CI)0.37 [-3.44, 4.17]

   6.2 Non-anaemic
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    6.3 Mixed/unknown
2310Mean Difference (IV, Random, 95% CI)-1.22 [-3.08, 0.63]

 7 Haemoglobin (by supplementation regimen)5581Mean Difference (IV, Random, 95% CI)-0.31 [-2.59, 1.97]

    7.1 by supplementation regimen: one supplement a week
5581Mean Difference (IV, Random, 95% CI)-0.31 [-2.59, 1.97]

   7.2 by supplementation regimen: other intermittent regimen
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 8 Haemoglobin (by sex)5581Mean Difference (IV, Random, 95% CI)-0.31 [-2.59, 1.97]

    8.1 Girls
142Mean Difference (IV, Random, 95% CI)-2.0 [-5.43, 1.43]

   8.2 Boys
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    8.3 Mixed/unknown
4539Mean Difference (IV, Random, 95% CI)0.04 [-2.63, 2.71]

 9 Haemoglobin (by nutrient)5581Mean Difference (IV, Random, 95% CI)-0.31 [-2.59, 1.97]

    9.1 Iron alone
4539Mean Difference (IV, Random, 95% CI)0.04 [-2.63, 2.71]

    9.2 Iron + folic acid
142Mean Difference (IV, Random, 95% CI)-2.0 [-5.43, 1.43]

   9.3 By nutrient: iron + multiple micronutrients
00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 10 Ferritin (ALL)2320Mean Difference (IV, Random, 95% CI)-11.57 [-38.75, 15.61]

 11 All cause morbidity (ALL)177Risk Ratio (M-H, Random, 95% CI)0.92 [0.68, 1.24]

 12 Diarrhoea (ALL)177Risk Ratio (M-H, Random, 95% CI)1.12 [0.56, 2.22]

 13 Adherence (ALL)2245Risk Ratio (M-H, Random, 95% CI)1.29 [0.44, 3.75]

 14 IQ (ALL)1252Mean Difference (IV, Random, 95% CI)-3.00 [-5.96, -0.04]

 15 Thai language (ALL)1208Mean Difference (IV, Random, 95% CI)-0.30 [-0.50, -0.09]

 16 Mathematics (ALL)1233Mean Difference (IV, Random, 95% CI)-0.27 [-0.44, -0.10]

 17 Increase in steps climbed (ALL)165Mean Difference (IV, Random, 95% CI)-5.0 [-13.34, 3.34]

 18 HAZ2170Std. Mean Difference (IV, Random, 95% CI)-0.32 [-1.26, 0.63]

 19 WAZ2170Std. Mean Difference (IV, Random, 95% CI)0.09 [-0.21, 0.39]

 20 WAZ2302Std. Mean Difference (IV, Random, 95% CI)0.04 [-0.34, 0.41]

 
Summary of findings for the main comparison. Intermittent use of iron supplements versus placebo or no intervention in children younger than 12 years of age

Patient or population: children under 12 years of age
Settings: community settings
Intervention: intermittent supplementation with iron alone or with other nutrients
Comparison: placebo or no intervention

OutcomesRelative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)

Anaemia (haemoglobin below a cut-off defined by trialists, taking into account the age and altitude)

 
RR 0.51
(0.37–0.72)
1824
(10 studies)
⊕⊕⊕⊝
moderate1

Haemoglobin (g/L)MD 5.20
(2.51–7.88)
3032

 (19 studies)
⊕⊕⊝⊝
low2,3

Iron deficiency (using ferritin concentrations)RR 0.24
(0.06–0.91)

 
431
(3 studies)
⊝⊝⊝⊝
very low2,3,4

Iron status (ferritin (μg/L)MD 14.17
(3.53–24.81)
550
(5 studies)
⊕⊕⊝⊝
low2,3

Iron deficiency anaemia Not estimable0
(0 studies)
None of the trials reported on this outcome

All-cause mortalityNot estimable0
(0 studies)
None of the trials reported on this outcome

CI, confidence interval; RR, risk ratio; MD, mean difference.

*GRADE Working Group grades of evidence:
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We have moderate confidence in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of the effect.

1There was high statistical heterogeneity. Given the large and consistent effect (RR 0.51; 95% CI 0.37–0.72) we have refrained from downgrading even though three of the nine studies are at high risk of bias.

2 High statistical heterogeneity but results were consistent.
3 Some studies lacked blinding and clear methods of allocation.

4 Wide confidence intervals.

Note: For cluster-randomised trials the analyses only include the estimated effective sample size, after adjusting the data to account for the clustering effect.

 
Summary of findings 2. Intermittent versus daily use of iron supplements in children younger than 12 years of age

Patient or population: children under 12 years of age
Settings: community settings
Intervention: intermittent supplementation with iron alone or with other micronutrients
Comparison: daily supplementation with iron alone or with other micronutrients

OutcomesRelative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)

Anaemia (haemoglobin below a cut-off defined by trialists, taking into account the age and altitude)RR 1.23
(1.04–1.47)
980
(6 studies)
⊕⊕⊝⊝

low1,2

Haemoglobin (g/L)MD –0.60
(–1.54-0.35)
2851

(19 studies)
⊕⊕⊝⊝

low1,3

Iron deficiency (using ferritin concentrations)RR 4.00
(1.23–13.05)

 
76
(1 study)
⊝⊝⊝⊝
very low4

Iron status (ferritin (µg/L)MD –4.19

(–9.42- 1.05)

 
902

(10 studies)
⊕⊕⊝⊝

low1 3

Iron deficiency anaemia Not estimable0
(0 studies)
None of the trials reported on this outcome

MortalityNot estimable0
(0 studies)
None of the trials reported on this outcome

CI, confidence interval; RR, risk ratio; MD, mean difference.

*GRADE Working Group grades of evidence:
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We have moderate confidence in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of the effect.

1 Some studies lacked blinding and clear methods of allocation.

2 Wide confidence intervals.

3 High heterogeneity but results were mostly consistent.

4 Only one trial with unclear methods to generate the random sequence and conceal the allocation. Wide confidence intervals.

Note: For cluster-randomised trials the analyses only include the estimated effective sample size, after adjusting the data to account for the clustering effect.

 
Table 1. Intermittent iron supplementation versus placebo or no intervention by age group

OutcomeComparison 3

Children 0 to 59 months

Relative effect
(95% CI)


Number of trials and effective sample size
Comparison 5

Children 60 months and older

Relative effect
(95% CI


Number of trials and effective sample size

AnaemiaRR 0.43

(0.23 to 0.80)

4 trials, 658 children
RR 0.54,

(0.33 to 0.90)

6 trials, 1166 children

Haemoglobin (g/L)MD 6.45

(2.36 to 10.55)

9 trials, 1254 children
MD 4.04

(0.30 to 7.78)

10 trials, 1778 children

4.04 [0.30, 7.78]

Iron deficiency (using ferritin concentrations)RR 0.24

(0.06 to 0.91)

3 trials, 431 children
None of the trials reported

on this outcome

Ferritin (μg/L)MD 13.15

(-2.28 to 28.59)

4 trials, 310 children
MD 16.60

(11.12 to 22.08)

1 trial, 240 children

AdherenceRR 1.04

(0.98 to 1.09)

2 trials, 289 children 
None of the trials reported

on this outcome

 
Table 2. Intermittent versus daily iron supplementation by age group

OutcomeComparison 4

Children 0 to 59 months

Relative effect
(95% CI)


Number of trials and effective sample size
Comparison 6

Children 60 months and older

Relative effect
(95% CI)


Number of trials and effective sample size

AnaemiaRR 1.26

(1.05 to 1.51)

3 trials, 770 children
RR 0.95

(0.47 to 1.91)

2 trials, 145 children

Haemoglobin (g/L)MD -0.75

(-1.80 to 0.29)

14 trials, 2270 children

 
MD -0.31

(-2.59 to 1.97)

5 trials, 581 children

Iron deficiencyRR 4.00

(1.23 to 13.05)

1 trial, 76 children
None of the trials reported

on this outcome

Ferritin (μg/L)MD -3.10

(-6.59 to 0.39)

8 trials, 582 children
MD -11.57

(-38.75 to 15.61)

2 trials, 320 children

AdherenceRR 1.29

(1.15 to 1.45)

3 trials, 1185 children
RR 1.29

(0.44 to 3.75)

2 trials, 245 children