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Vitamin A for preventing acute lower respiratory tract infections in children up to seven years of age

  1. Hengxi Chen2,
  2. Qi Zhuo3,
  3. Wei Yuan3,
  4. Juan Wang3,
  5. Taixiang Wu1,*

Editorial Group: Cochrane Acute Respiratory Infections Group

Published Online: 23 JAN 2008

Assessed as up-to-date: 29 JUN 2010

DOI: 10.1002/14651858.CD006090.pub2


How to Cite

Chen H, Zhuo Q, Yuan W, Wang J, Wu T. Vitamin A for preventing acute lower respiratory tract infections in children up to seven years of age. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD006090. DOI: 10.1002/14651858.CD006090.pub2.

Author Information

  1. 1

    West China Hospital, Sichuan University, Chinese Cochrane Centre, Chinese Clinical Trial Registry, Chinese Evidence-Based Medicine Centre, INCLEN Resource and Training Centre, Chengdu, Sichuan, China

  2. 2

    West China Second University Hospital, West China Women's and Children's Hospital, Department of Obstetrics and Gynecology, Chengdu, Sichuan, China

  3. 3

    West China Hospital, Sichuan University, Chengdu, Sichuan, China

*Taixiang Wu, Chinese Cochrane Centre, Chinese Clinical Trial Registry, Chinese Evidence-Based Medicine Centre, INCLEN Resource and Training Centre, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan, 610041, China. txwutx@hotmail.com.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 23 JAN 2008

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Characteristics of included studies [ordered by study ID]
Barreto 1994

MethodsRandomised, double-blind, placebo-controlled clinical trial


Participants1240 children aged 6 to 48 months. The baseline was comparable. The inclusion criteria: children between 6 and 48 months. The exclusion criteria: active xerophthalmia, measles within the previous 30 days, high-dose vitamin A supplementation in the previous 6 months, weight-for-age less than 60% of the statistical median


InterventionsVitamin A group received 100,000 IU every 4 months for 1 year for children younger than 12 months and 200,000 IU for the older children. The placebo group only received placebo


Outcomes1. ALRI incidence
2. Mean daily prevalence of respiratory signs and symptoms


NotesThis study was conducted in Serrinha, capital of the state of Bahia, where the climate is hot and dry. The pubic health services there are inadequate. The biochemical deficiency (serum vitamin A concentration < 0.35 mmol/L) rate in children is 7.4%, shown in an earlier survey. According to WHO criteria, vitamin A deficiency should be considered a pubic health problem in this area. Children were visited 3 times per week for 1 year, so the recall period was 48 to 72 hours. The person-time of the vitamin A group and the control group were 203,252 child-days and 201,656 child-days, respectively. The total loss in follow-up time was 10.3%, equally distributed between the control and vitamin A group. Migration away from the area was the main reason for loss to follow up. The sample size of 1240 was estimated to give a power of 90% to detect a 15% reduction in the incidence of diarrhoea.


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?UnclearOnly mentioned "randomly assigned"

Allocation concealment?YesOnly an external investigator had the codes for the individually wrapped and numbered capsules

Blinding?
All outcomes
YesDouble-blind

Incomplete outcome data addressed?
All outcomes
No9 children excluded from the trial because of severe weight loss.

Free of selective reporting?NoNot all the pre-specified outcomes were reported

Free of other bias?YesThere were no significant differences between groups

Bhandari 1994

MethodsRandomised, double-blind, placebo-controlled clinical trial. The randomisation method was simple randomisation scheme drawn up by the WHO


Participants900 children aged 12 to 60 months who resided in the slum area attending the government clinic with diarrhoea duration 7 days or less and weight for height 70% or more of the median were included. Exclusion criteria: presence of signs of vitamin A deficiency, had received a large dose of vitamin A in the past 6 months, had the likelihood to migrate out of the slum area, had associated illness, had been enrolled in the study within the past 6 months and refused consent. The baseline line of two group were comparable


InterventionsThe vitamin A group received 200,000 IU vitamin A; the placebo group received only placebo. They were followed up 90 days after recovery


OutcomesIncidence of ALRI


NotesThis study was conducted at Govindpuri, an urban slum area in south Delhi where vitamin A had not been given to people in the preceding 3 years. The sample size estimate was 358 children per group based on detecting 25% reduction in the prevalence of acute LRTIs with 90% power and 5% significance. The researchers increased the sample size by 25% to allow for attrition. Children were visited every 3 days until 90 days after they recovered from the diarrhoea. The final results were data according to 842 children, 422 in vitamin A group. 5 were for withdrawing consent, 46 for being unavailable for more than 30 days, and 7 for fast breathing related to tuberculosis, cardiac disease or severe anaemia. The child 90-day of follow up for vitamin A group and placebo group was 410 and 409


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?YesThe randomisation was done using a simple randomisation scheme

Allocation concealment?UnclearNot mentioned

Blinding?
All outcomes
YesDouble-blind

Incomplete outcome data addressed?
All outcomes
No58 participants were excluded. 5 withdrew consent, 46 were unavailable for more than 30 study days, 7 for persistent fast breathing due to tuberculosis.

Free of selective reporting?NoNot all the pre-specified outcomes were reported

Free of other bias?YesThere were no significant differences between groups

Dibley 1996

MethodsRandomised, double-blind, placebo-controlled trial. Randomisation was done with 1:1 allocation ratio in blocks of 8 based on a table of random permutations of integers. Treatments were given once every 4 months for 6 treatment cycles


Participants1405 children aged 6 to 47 months. The inclusion criteria: children between 6 to 47 months. Exclusion criteria: those with cerebral palsy, epilepsy, flaccid paralysis, mental retardation, congenital or rheumatic heart disease were permanently excluded. Those with weight-for-height more than 3.00 SD below the WHO growth reference mean or acute xerophthalmia were excluded for one cycle and treated with high-dose vitamin A and then included. Demographic, clinical and nutritional characteristics at the baseline were the same, and the groups remained balance at the start of each of the other 5 cycles. Compliance was equally high in both group, on average, 89% of the age-eligible children received a treatment


InterventionsVitamin A group: 206,000 IU of retinyl ester plus 37 IU vitamin E or 103,000 IU retinyl ester plus 17 IU vitamin E if less than 12 months of age; the control group: placebo that contained 17 or 37 IU vitamin E on the age of the subject


OutcomesIncidence of ALRI


NotesThis study was conducted in 34 rural villages located on the southern coast of Central Java in Indonesia, with high prevalence of subclinical vitamin A deficiency. 4.6% migrated and 3.5% withdrew before the end of the treatment cycle. Morbidity surveillance was 96% and 97% in placebo and vitamin A group respectively. Less than 2% of the daily morbidity records were missing. Children were visited every other day for 6 cycles. The longest recall period allowed was 4 days. Observed child-days of ALRI of vitamin A group and control group were 280,186 and 273,630


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?UnclearRandomisation procedure was described as "based on a table of random permutations of integers"

Allocation concealment?UnclearNot mentioned

Blinding?
All outcomes
YesAll investigator, field and laboratory staff, and participants were masked to the treatment code

Incomplete outcome data addressed?
All outcomes
NoLess than 2% of the daily morbidity records were missing

Free of selective reporting?NoNot all the pre-specified outcomes were reported

Free of other bias?YesThere were no significant differences between groups

Donnen 1998

MethodsRandomised, double-blind, placebo-controlled clinical trial


Participants900 children aged 0 to 72 months hospitalized in the Lwiro Pediatric Hospital for protein-energy malnutrition. Children were not eligible for inclusion in the study if they had been admitted to the hospital in a coma, if their parents or legal guardians had refused their participation, or if they had taken vitamin A capsules within the previous 4 months. Consecutively in the Lwiro Pediatric Hospital were included in the trial. The baselines of the 2 groups were comparable


Interventions1) The high-dose treatment group received 200,000 IU vitamin A (100,000 IU if aged < 12 months) orally on the day of admission and a placebo on every subsequent day during hospitalization
2) The low-dose treatment group received 5,000 IU vitamin A every day until discharge
3) The placebo group received a placebo every day during hospitalization


OutcomesIncidence of ALRI


NotesThis study was conducted in the health district of Katana, province of South Kivu in Congo, with population mainly poor farmers. Children were visited every day until they were discharged from the hospital. Protein-energy malnutrition reduces the absorption of vitamin A and synthesis and release of retinol binding protein, it always coexists with vitamin A deficiency. 73.9% to 78.5% of the study sample at baseline were found to have deficient serum retinol concentrations (< 0.35 mmol/L)


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?UnclearOnly mentioned "randomly assigned"

Allocation concealment?UnclearNot mentioned

Blinding?
All outcomes
Yes"Double-blind". Paediatrician was the only one with access to the allocation list

Incomplete outcome data addressed?
All outcomes
YesNo participants lost to follow up

Free of selective reporting?NoNot all the pre-specified outcomes were reported

Free of other bias?YesThere were no significant differences between groups

Long 2006

MethodsRandomised, double-blind, placebo-controlled clinical trial. The randomisation sequence was generated by using a random-number table by project personnel. It was stratified allocation


Participants736 children aged 6 to 15 months living in a peri-urban area of Mexico City. 336 children were in vitamin A group and placebo group. The baseline of the participants was not significantly different between the 4 groups. Those who had diseases causing immuno-suppression, had digestive disease that alter the absorption of micronutrients and those who were taking vitamin supplements were excluded


InterventionsThey were assigned to 1 of 4 groups:
1) Vitamin A group that received 20,000 IU retinol every 2 months for children aged <= 1 year or 45,000 IU for children aged > 1 year
2) Zn group that received a daily dose equivalent to 20 mg elemental Zn as zinc methionine
3) A group that received both the zinc supplement and the vitamin A as above
4) A placebo group


OutcomesPrevalence of respiratory tract infections:
1) Cough alone
2) Cough and fever
3) Cough and rapid respiratory rate


NotesThis study was conducted in La Magdalena Atlicpac, Mexico. About 12% of the children there were classified as having a height-for-age z score below -2. Children were visited twice a week for 1 year. 93 children were lost to follow up or were excluded, 736 children were followed for 12 months (181 in the zinc group, 192 in the vitamin A + zinc group, 180 in the vitamin A group, and 183 in the placebo group). Child-year of follow up in vitamin A group and placebo group were 153.9 and 155.1. The loss to follow up in the vitamin A group and control group was 20 (10%) and 17 (8.5%) respectively. The sample size of 200 per children per group was estimated by assuming that the diarrhoeal disease rate was 3 episodes per child per year with a power of 80% and 95% significance level and an expected loss to follow up of 20%


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?UnclearOnly mentioned "randomized trial"

Allocation concealment?UnclearNot mentioned

Blinding?
All outcomes
YesDouble-blind

Incomplete outcome data addressed?
All outcomes
NoThe loss to follow up in the vitamin A group and control group were 20 (10%) and 17 (8.5%), respectively

Free of selective reporting?NoNot all the pre-specified outcomes were reported

Free of other bias?YesThere were no significant differences between the groups

Rahman 2001

MethodsRandomised, parallel groups design, double-blind


Participants800 children aged 12 to 35 months


InterventionsChildren were randomized to receive 1 of 4 treatments: zinc, vitamin A, both zinc and vitamin A, or placebo
The zinc group received 5 ml zinc syrup (20 mg elemental zinc) daily for 14 days and a placebo capsule on day 14
The vitamin A group received 5 ml placebo syrup daily for 14 days and a 200,000 IU (60 mg) vitamin A capsule on day 14
The zinc plus vitamin A group received 5 ml zinc syrup daily for 14 days and a 200,000 IU vitamin A capsule on day 14
The placebo group received 5 ml placebo syrup daily for 14 days and a placebo capsule on day 14


OutcomesIncidence and prevalence of acute lower respiratory infection and diarrhoea


NotesThere were no significant differences between groups


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?UnclearThere was no description about the method of randomisation for generating the allocation sequence

Allocation concealment?YesThe randomisation code was kept sealed until the completion of the study

Blinding?
All outcomes
YesDouble-blind

Incomplete outcome data addressed?
All outcomes
No135 (17%) were excluded from the study or dropped out. Of these 135 children, 85 (11% of total) were excluded because they had received vitamin A after enrolment during the “National vitamin A week” campaign in Bangladesh.
49 (6%) children were lost to follow up or had fewer than 90 days of observation period, and one child was excluded owing to a complicated illness

Free of selective reporting?NoNot all the pre-specified outcomes were reported

Free of other bias?UnclearThere were no significant differences between the groups

Rahmathullah 1991

MethodsThe article stated it was a randomized, controlled, masked clinical trial. Due to varied population density in the area where this study took place, the researchers used a cluster-sampling design. 206 clusters were formed, and the majority of them consisted of 50 to 100 children 6 to 60 month of age. The article did not state clearly how the clusters were randomly assigned to the control or vitamin A group


Participants15,419 children 6 to 60 months of age were included in the study. The baseline of the 2 groups was comparable on the following characteristics: age and sex, 1-month history of diarrhoea and respiratory disease, anthropometric indexes of nutritional status, xerophthalmia status, 5-year retrospective history of mortality of children under 5, household economic, household hygienic status, and serum retinol levels. Exclusion for analysis: receiving a high-dose supplement of vitamin A because of xerophthalmia at baseline, midterm, or final examination (n = 2687); missing receiving the supplement for > 7 consecutive weeks or for > 4 weeks on four occasions (n = 1874).


InterventionsHalf the children received weekly doses of 8333 IU vitamin A and 20 mg vitamin E (treated) and 20 mg vitamin E the other half (control). Any children diagnosed with xerophthalmia at baseline, midterm, or final examination was given a high-dose (60,000 ug) supplement of vitamin A and continued in their study


OutcomesIncidence of lower respiratory tract infections


NotesSetting: the study was carried out in 3 drought-prone Panchayat Unions, which are poor in economy and environment, of the Trichy district of Tamil Nadu in southern India. Children were visited once a week for 52 weeks. All morbidity data were analysed both without exclusion (N = 15,419, intention-to treat analysis) and with exclusion (N = 10858). The article stated that no significant changes in RR occurred when each of the exclusions was applied. The data presented in the article were based on an intention-to-treat analysis. On average > 90% of the children were contacted each week, and the lowest coverage in any single week was 88%. 11% had clinical evidence of xerophthalmia while about 38% had serum retinol concentrations <= 0.35 mmol/L at baseline


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?UnclearOnly mentioned "randomized"

Allocation concealment?UnclearNot mentioned

Blinding?
All outcomes
YesOnly mentioned "masked"

Incomplete outcome data addressed?
All outcomes
NoOn average > 90% of the children were contacted each week, and the lowest coverage in any single week was 88%

Free of selective reporting?NoNot all the pre-specified outcomes were reported

Free of other bias?YesThere were no significant differences between groups

Sempertegui 1999

MethodsA randomized, placebo-controlled, double-blind trial. Identical flasks containing vitamin A or placebo were numbered from 1 to 400 by members of the study team in Boston, Massachusetts. The local Ethical Committee of the Ecuadorian Biotechnology Corporation in Quito did not know the identity of the active or placebo flasks, because they did not have the code. Then, this committee assigned each flask to a specific child from a random list by using a table of random numbers. After randomisation, the ethical committee received the confidential code from Boston and kept it for the remainder of the study, when it was revealed


ParticipantsAll study participants were children 6 to 36 months of age living in the neighbourhood. All children (N = 613) between 6 to 36 months of age were considered eligible. Age was verified through birth certificates. To decrease the drop-out rate, the researchers selected those children who reliably stayed at home or at day care centres during weekdays (N = 525), and then they excluded children whose families had lived in the neighbourhood for < 1 year (N = 60). Children who had been given multivitamins in the last 3 months also were excluded (N = 6). A total of 459 children were available for entry into the study. These children were examined by an ophthalmologist for signs of xerophthalmia. No cases of xerophthalmia were found. Finally, 400 children completing the basal anthropometric test were included. The baselines of the 2wo groups were comparable


InterventionsChildren in the supplement-treated group received a weekly dose of 10,000 IU of vitamin A (3000 mg of retinol) for 40 weeks, and children in the non-supplement group received a weekly placebo for the same period


OutcomesThe incidence of ALRI: defined as tachypnea (respiratory rate 40 /min) and/ or lower respiratory tract secretions (alveolar or bronchoalveolar) assessed by thoracic auscultation with 1 or more of the following symptoms: cough, fever and chest retractions


NotesThis study was conducted in the northwestern region of the Quito, Ecuador, which represented most Ecuadorian high Andean slums with substantial rates of malnutrition and subclinical vitamin A deficiency. Children were visited weekly. The total person-time of follow up of vitamin A group and control group was 5719 child-weeks and 5707 child-weeks. The researchers assumed that the incidence of diarrhoeal disease in this area was 46 episodes per 1000 child-weeks. The sample sizes of 200 children per group were based on detecting a 25% reduction in the incidence of diarrhoea with 80% power and 2-tailed 0.05 significance, and it allowed for 30% annual drop-out. The reported yearly incidence of acute respiratory tract infections is similar to that of acute diarrhoeal, so the researchers inferred that this sample sizes of 200 children in each group were likely to be sufficient


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?YesAllocation sequence was generated by using a random number table

Allocation concealment?YesThe ethics committee received the confidential code and kept it for the remainder of the study until it was revealed

Blinding?
All outcomes
YesDouble-blind

Incomplete outcome data addressed?
All outcomes
No50 children from the supplement-treated group and 44 from the non-supplement group were lost to follow up

Free of selective reporting?NoNot all the pre-specified outcomes were reported

Free of other bias?YesThere were no significant differences between groups

Stansfield 1993

MethodsA randomized, placebo-controlled, double-blind trial


Participants11,124 children aged 6 to 83 months. Those with corneal changes consistent with vitamin A deficiency, with measles and those had received vitamin A within the past 4 months were excluded. The baseline of the 2 groups was comparable


InterventionsThe vitamin A group received 100,000 IU supplements every 4 months for 3 distribution cycle for those 6 to 11 months and 200,000 IU for the older, while the other group only received placebo


Outcomes2 week prevalence of signs of respiratory tract infections: cold, cough and rapid breathing


NotesThis study was conducted at north west of Haiti with a high prevalence of malnutrition and xerophthalmia. 72% (7958) of total 11,124 participants received at least 2 doses, and 38% (4178) received 3 doses. Children were visited every 2 weeks for 12 months


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?UnclearOnly mentioned "random"

Allocation concealment?UnclearNot mentioned

Blinding?
All outcomes
YesDouble-blind

Incomplete outcome data addressed?
All outcomes
UnclearNot mentioned

Free of selective reporting?NoNot all the pre-specified outcomes were reported

Free of other bias?YesThere were no significant differences between groups

VAST 1993

MethodsRandomised double-blind controlled trial. Randomisation was by individuals in the Health Study


ParticipantsThe Health Study included 1455 children aged 6 to 59 months. Inclusion: children 6 to 59 months. Children born from 1986 were included in the Health Study. Excluded: children with active xerophthalmia or measles were excluded from the trial as soon as they were confirmed


InterventionsChildren were randomly assigned either 200,000 IU retinol equivalent (100,000 IU under 12 months) or placebo every 4 months


OutcomesMean daily prevalence of sighs of lower respiratory tract infections:
1) daytime cough
2) tired ribs (severe respiratory illness)
3) difficulty in breathing
4) rapid breathing


NotesThis study was conducted in guinea savannah area of Ghana with a sub-Sahelian climate. The study populations were rural and their main staple foods are deficient in carotenoids and vitamin A. Vitamin A deficiency and xerophthalmia were recognised as problems locally. Children were visited weekly for 1 year. 1455 children in the Health Study were followed up for 1185 child-years (596 for vitamin A group and 589 for control group), of whom, 1287 (88.5%) survived, 26 (1.8%) died, 14 (1.0%) developed measles, 4 (0.3%) withdrew consent, and 119 (8.2%) were lost to follow up


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?UnclearRandomisation was carried out by an independent statistician

Allocation concealment?YesThe randomisation code was kept by an independent statistician

Blinding?
All outcomes
YesTriple-blinded

Incomplete outcome data addressed?
All outcomes
Yes14 (1.0%) developed measles, 4 (0.3%) withdrew consent, and 119 (8.2%) were lost to follow up

Free of selective reporting?NoNot all the pre-specified outcomes were reported

Free of other bias?YesThere were no significant differences between groups

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

An 2000Random allocation mentioned, but trial authors allocated participants

Biswas 1994Discussed the prevention of ARI but not LRTIs

Chang 2006Included children aged < 11 years hospitalized with 215 ALRI episodes

Cherian 2001The trial focused on recurrent respiratory infections, not preventing ALRI

Chowdhury 2002Included children aged < 10 years

Coutsoudis 1991The participants had measles-related pneumonia

Coutsoudis 1995The participants were HIV positive

Coutsoudis 2000This study focused on low birth weight neonates, and should be included in another Cochrane Review (Brian 2007)

Daulaire 1992Did not discuss the preventative effect of vitamin A on LRTIs

Dudley 1997Did not discuss the preventative effect of vitamin A on LRTIs

Fawzi 1998Did not discuss the preventative effect of vitamin A on LRTIs

Fawzi 1999The participants involved had HIV infection

Fawzi 2000The participants involved had HIV infection

Fawzi 2003The participants involved had HIV infection

Hussey 1990The participants had measles-related pneumonia

Jiang 2009aDiscussed the treatment but not prevention

Jiang 2009bDiscussed the prevention of diarrhoea following pneumonia

Jin 2003The inventions used were vitamin A with other supplementation versus placebo

Julien 1999Discussed the prevention of ARIs but not LRTIs

Kao 1996Random allocation mentioned, but trial authors allocated participants

Kartasasmita 1995Discussed the prevention of ARI but not LRTIs

Kjolhede 1995The research was not about LRTIs

Li 2005Random allocation mentioned, but trial authors allocated participants

Liang 2005Random allocation mentioned, but trial authors allocated participants

Liu 2003Random allocation mentioned, but trial authors allocated participants

Liu 2004Interventions included vitamin A with other supplementation but not vitamin A alone

Lu 2000Interventions included vitamin A with other supplementation but not vitamin A alone

Ma 1998Interventions included vitamin A with other supplementation but not vitamin A alone

Ma 2003Interventions included vitamin A with other supplementation but not vitamin A alone

Mahalanabis 2002Involved treatment not prevention of LRTIs

Mahalanabis 2004Involved treatment not prevention of LRTIs

Nacul 1997Prevention of LRTIs with vitamin A not discussed

Nacul 1998The study dealt with vitamin A supplementation for ARI and subsequent follow up in terms of recurrence of symptoms

Ogaro 1993Participants involved complicated with measles infection

Quinlan 1996Prevention of LRTIs with vitamin A not discussed

Rahman 1996Discussed the prevention of ARI but not LRTIs

Rodriguez 2005Discussed treatment, not preventing LRTIs

Rosales 1994Prevention of LRTIs with vitamin A not discussed

Rosales 1996The participants had measles-related pneumonia

Rosales 2002The participants had measles-related pneumonia

Si 1997Prevention of LRTIs with vitamin A not discussed

Song 2000The interventions included vitamin A with other supplementation but not vitamin A alone

Stephensen 1998Prevention of LRTIs with vitamin A not discussed

Tan 2002Random allocation mentioned, but participants actually allocated optionally by the authors (confirmed by telephoning the author)

Venkatarao 1996Discussed the prevention of ARI but not LRTIs

Vijayaraghavan 1990Discussed the prevention of ARI but not LRTIs

Villamor 2002Participants involved also had HIV infections

Villamor 2005Participants involved also had HIV infections

Wang 1993Random allocation mentioned, but trial authors allocated participants

Wang 1995Random allocation mentioned, but trial authors allocated participants

Wang 1997Not blinded

Wang 1999Random allocation mentioned, but trial authors allocated participants

Yan 1992Random allocation mentioned, but trial authors allocated participants

Yang 1995Random allocation mentioned, but trial authors allocated participants

Yang 2003The interventions included vitamin A with other supplementation but not vitamin A alone

Yang 2005Random allocation mentioned, but trial authors allocated participants

Zar 2003Participants with HIV infection were included

Zhang 1997Random allocation mentioned, but trial authors allocated participants

Zhang 1999Discussed the combined effect of vitamin A with other supplementation

Zhang 2000Interventions included vitamin A with other supplementation but not vitamin A alone

Zhang 2002Interventions included vitamin A with other supplementation but not vitamin A alone

 
Characteristics of studies awaiting assessment [ordered by study ID]
Donnen 2007

MethodsRandomised, double-blind controlled trial

Participants604 and 610 Senegalese hospitalized children

InterventionsA high-dose vitamin A supplement (200,000 IU) on admission, the second a daily low-dose vitamin A supplement (5000 IU daily) during hospitalization

OutcomesSurvival, incidence of respiratory disease, duration of respiratory infection, duration and incidence of diarrhoea, mortality

Notes

Long 2007

MethodsRandomised controlled trial

ParticipantsA total of 188 children, aged 6 to 15 months, from peri-urban, marginalised communities of Mexico City

InterventionsVitamin A or placebo

OutcomesThe incidence and duration of respiratory tract infections

Notes

Swami 2007

MethodsRandomised controlled trial

Participants27,642 (98.7%) and 31,762 (88.0%) children were included respectively in Chandigarh. A random sample of 276 children from the intervention area and 252 children from control area in the age group of 1 to 5 years were followed

InterventionsMass supplementation of vitamin A solution

OutcomesThe average annual episodes of ARI

Notes

 
Comparison 1. Vitamin A versus placebo

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

 1 Incidence of acute LRTI in community-based trials3Incidence of ALRI (Random, 95% CI)Subtotals only

    1.1 Age <= 5
3Incidence of ALRI (Random, 95% CI)1.13 [0.88, 1.43]

    1.2 Mega dose
2Incidence of ALRI (Random, 95% CI)1.13 [0.80, 1.60]

    1.3 Low dosage
1Incidence of ALRI (Random, 95% CI)1.16 [0.77, 1.76]

    1.4 Under weight
1Incidence of ALRI (Random, 95% CI)0.38 [0.17, 0.85]

    1.5 Stunted
1Incidence of ALRI (Random, 95% CI)0.48 [0.21, 1.12]

    1.6 Normal
1Incidence of ALRI (Random, 95% CI)2.22 [1.25, 3.95]

 2 Prevalence of symptoms of acute LRTI1Prevalence (Random, 95% CI)Totals not selected

    2.1 Overall cough
1Prevalence (Random, 95% CI)Not estimable

    2.2 Cough with difficulty in breathing
1Prevalence (Random, 95% CI)Not estimable

    2.3 Cough with fever
1Prevalence (Random, 95% CI)Not estimable

 
Table 1. Incidence of acute lower respiratory infections of community-based trials (original data)

StudyVitamin A groupPlacebo groupRR

Barreto 1994Incidence: 0.002686 per child-daysIncidence: 0.002757 per child-days0.97 (0.86 to 1.09)

Dibley 1996Incidence: 0.0002668 per child-daysIncidence: 0.0003712 per child-days1.39 (1.003 to 1.931)

Sempertegui 1999 (underweight)Incidence: 8.5 per 1000 child-weeksIncidence: 22.3 per 1000 child-weeks0.38 (0.17 to 0.85)

Sempertegui 1999 (stunted)Incidence: 4.7 per 1000 child-weeksIncidence: 9.8 per 1000 child-weeks0.48 (0.21 to 1.12)

Sempertegui 1999 (normal)Incidence: 9.8 per 1000 child-weeksIncidence: 4.4 per 1000 child-weeks2.21 (1.24 to 3.39)

 
Table 2. Donnen 1998: morbidity during hospitalisation related to respiratory tract infections

SymptomsHigh-doseLow-dosePlacebo

ALRI1

Never99.3%98.6%98.6%

>= 1 episodes0.7%1.4%1.4%

ALRI2

Never98.6%99.0%99.3%

>= 1 episodes1.4%1.0%0.7%

Fever

Never90.6%92.7%92.1%

>= 1 episodes9.4%7.3%7.9%

 ALRI = acute lower respiratory infection
 
Table 3. Rahman 2001: incidence and prevalence of acute lower respiratory infections

IncidencePrevalence



GroupEpisodes ALRIPerson-years at risk infectionIncidenceRate ratio

(95%CI)
Days with

illness
Person-yearsPrevalenceRate ratio

(95% CI)

Acute lower respiratory infection

Zinc

(n = 345)
17255.0031.141.62

(1.16 to 2.25)
78756.3225.102.07

(1.76 to 2.44)

Vitamin A

(n = 334)
13753.7620.931.06

(0.74 to 1.53)
58054.7273.871.20

(0.99 to 1.45)

Placebo

(n = 161)
5625.8360.791.021126.2152.941.0

Interaction of zinc and vitamin A0.75

(0.46 to 1.20)
0.58

(0.46 to 0.73)

Severe acute lower respiratory infection

Zinc

(n = 345)
17255.0031.141.62

(1.16 to 2.25)
78756.3225.102.07

1.76 to 2.44)

Vitamin A

(n = 334)
13753/7620.931.06

(0.74 to 1.53)
58054.7273.871.20

(0.99 to 1.45)

Placebo

(n = 161)
5625.8360.791.021126.2152.941.0

Interaction of zinc and vitamin A0.66

(0.33 to 1.31)
0.56

(0.39 to 0.80)

 
Table 4. Rahmathullah 1991: number of episodes of acute lower respiratory infections/number of children

AgeVitamin APlaceboRate ratio95% CI

<= 11 mo0.0060.061.010.58 to 1.76

12 to 35 mo0.050.050.980.58 to 1.66

>= 36 mo0.040.041.050.55 to 2.00

 
Table 5. Bhandari 1994: incidence of acute lower respiratory infections over 90 days

AgeVitamin APlaceboRelative risk

All children0.440.411.07 (0.92 to 1.26)

Age <= 23 months0.590.491.19 (0.99 to 1.43)

Age > 23 months0.330.340.98 (0.75 to 1.26)

 
Table 6. Barreto 1994: mean daily prevalence of respiratory symptoms

SymptomsVitamin APlaceboRate ratioP

Cough0.24290.23880.990.57

Cough + fever0.02890.02820.990.90

Cough + IRR0.01240.01290.960.74

 IRR = instantaneous respiratory rate
 
Table 7. VAST 1993: mean daily prevalence of signs or symptoms

SymptomsVitamin APlaceboPrevalence ratioP

Daytime cough13.2%13.0%1.020.67

"Tied ribs" (severe respiratory illness)1.1%1.1%0.980.86

Difficulty breathing1.2%1.2%0.960.70

Rapid breathing1.1%1.3%0.810.11

 
Table 8. Stansfield 1993: risk ratio for 2-week prevalence of morbidity by age group

Age group (months)ColdCoughRapid breathing

<11 (817; 660)0.99 (0.93 to 1.06)1.00 (0.90 to 1.12)1.18 (0.97 to 1.45)

12-23 (1206; 1001)1.05 (1.00 to 1.11)1.07 (0.98 to 1.18)1.25 (1.04 to 1.50)

24-35 (1210; 966)1.10 (1.05 to 1.16)1.15 (1.05 to 1.26)1.05 (0.88 to 1.26)

36-47 (1181; 930)1.00 (0.95 to 1.06)1.02 (0.93 to 1.12)1.23 (1.00 to 1.51)

48-59 (1069; 921)1.09 (1.02 to 1.15)1.13 (1.03 to 1.25)1.20 (0.97 to 1.47)

60-71 (896; 809)0.98 (0.92 to 1.04)1.02 (0.92 to 1.14)1.19 (0.94 to 1.50)

72-83 (711; 540)1.05 (0.98 to 1.12)1.06 (0.93 to 1.20)1.03 (0.79 to 1.34)

 
Table 9. Stansfield 1993: 2-week prevalence of morbidity

SymptomVitamin APlaceboRate ratio

Cough48%45%1.18 (1.09 to 1.27)

Rapid breathing18%15%1.18 (1.09 to 1.27)

 
Table 10. Prevalence of symptoms of acute lower respiratory infections (original data)

StudyVitamin A groupPlacebo groupRR

Long 2006 (overall cough)Prevalence: 481/153.9 per child-yearsPrevalence: 539/155.1 per child-years0.90

Long 2006 (cough with difficulty breathing)Prevalence: 5/153.9 per child-yearsPrevalence: 10/155.1 per child-years0.50

Long 2006 (cough with fever)Prevalence: 146/153.9 per child-yearsPrevalence: 142/155.1 per child-years1.04