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Vitamin A for non-measles pneumonia in children

  1. Taixiang Wu1,*,
  2. Juan Ni2,
  3. Jiafu Wei2

Editorial Group: Cochrane Acute Respiratory Infections Group

Published Online: 20 JUL 2005

Assessed as up-to-date: 3 AUG 2010

DOI: 10.1002/14651858.CD003700.pub2

How to Cite

Wu T, Ni J, Wei J. Vitamin A for non-measles pneumonia in children. Cochrane Database of Systematic Reviews 2005, Issue 3. Art. No.: CD003700. DOI: 10.1002/14651858.CD003700.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 Hospital, Sichuan University, Department of Clinical Epidemiology, 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: 20 JUL 2005

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Characteristics of included studies [ordered by study ID]
Fawzi 1998

MethodsRandomised block design, placebo controlled trial. Double-blind. Baseline was similar


ParticipantsChildren between 6 and 60 months of age admitted to hospital with pneumonia as diagnosed by a paediatrician on the presence of cough and one or more of the following signs: respiratory rates >= 40 breaths (50 breaths for infants between the ages of 6 and 11 months) per minute, chest retractions, inability to eat or drink, the presence of decreased air entry, crackling sounds or dullness to percussion


InterventionsChildren in vitamin A group received a dose of vitamin A at admission according to the age. Children > 1 year and infants were administered 1 ml (200,000 IU) and 0.5 ml (100,000 IU) of a vitamin A solution, respectively


OutcomesClinical outcomes: mortality, duration of hospitalization, time with rapid respiratory rate (> 40 breaths/minute), time with fever (> 37.8 C), time with hypoxia (PO2 < 90%)


NotesSetting: Tanzania


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?UnclearThe randomisation was described as "eligible children were randomly assigned in blocks of 20 to receive a dose of vitamin A or placebo", but how the allocation sequence was generated did not described in detail

Allocation concealment?UnclearNot mentioned

Blinding?
All outcomes except mortality
YesThe treatment regimens were prepared especially for the study, and the batch code was retained by the manufacturer until the end of the study

Incomplete outcome data addressed?
All outcomes except mortality
Yes

Liu 1997

MethodsBoth 'completed random method' and double-blind was mentioned


Participants4 groups with different interventions (selenium) were selected. Data in vitamin A group and placebo group were extracted. 18 children in vitamin A group and 21 in placebo group. All children were younger than 14 years old


InterventionsChildren in vitamin A group received a dose of vitamin A 150,000 IU orally


OutcomesVariate outcomes were used; we only extracted data from those that matched the inclusion criteria for this review:
1. clearance time of fever
2. remission time of cough
3. remission time of positive finding of auscultation
4. remission days of positive finding at chest X-ray


NotesSetting: Youyi Hospital, Beijing.


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?Unclear"Completed random method" was mentioned but lacked a detailed description

Allocation concealment?NoNot concealment mentioned

Blinding?
All outcomes except mortality
YesDouble-blinding

Incomplete outcome data addressed?
All outcomes except mortality
No

Nacul 1997

MethodsBlock randomisation, placebo controlled; double-blind. The baseline was broadly similar


ParticipantsChildren aged 6 to 59 months with a clinical diagnosis either admitted to hospital or treated as outpatients. The diagnosis of pneumonia was made after taking a detailed history and looking for signs of lung infection such as fever, tachypnoea, signs of dyspnoea and consolidation


InterventionsChildren received a dose of vitamin A on admission to the trial and then again the following day. Children > 1 year and infants were administered 200,000 IU and 100,000 IU of vitamin A respectively. Children who received vitamin A supplements in the preceding month received a capsule (100,000 IU) on admission only


OutcomesClinical outcomes: mortality, episode of pneumonia, fever, tachypnoea, lung complications, other complications, hospital admission (for outpatients only), antibiotic change, vomiting, diarrhea, irritability, bulging fontanelle


NotesSetting: Recife, north east Brazil


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?Unclear"Children were individually randomized into one of the two treatment groups. The randomisation was blocked into groups of four". There was no description for how the sequence was generated

Allocation concealment?UnclearNo description about allocation concealment

Blinding?
All outcomes except mortality
YesThe vitamin A or placebo capsules were put into small brown envelopes labelled with identification numbers

Incomplete outcome data addressed?
All outcomes except mortality
Yes

Rodriguez 2005

MethodsRandomised block design, placebo controlled trial. Double-blind


ParticipantsChildren between 2 and 59 months of age admitted to hospital with clinical pneumonia (confirmed by X-ray). Clinical pneumonia was defined as the presence of elevated respiratory rate (> 40/minute in children aged > 12 to 59 months; > 50/minute in children aged 2 to 12 months), fever (axial temperature > 37.5 C), cough or chest indrawing or both, and low oxygen saturation (pulse oximetry level < 90%), and at least one clinical sign by auscultation (for example, rales, wheezing, diminished breath sounds, bronchial breath sounds, or pleural rub)


InterventionsChildren in vitamin A group received a dose of vitamin A 50,000 IU orally in children aged 2 to 12 months; 100,000 IU orally in children aged > 12 to 59 months


OutcomesClinical outcomes: mortality, time to remission of signs, the duration of respiratory sign, resolution of focal infiltrates at 72 hours


NotesSetting: Baca Ortiz Children's Hospital, Quito, Ecuador


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?YesThe allocation sequence was generated by a random number table

Allocation concealment?YesThe Ethical Committee of the Corporacio´n Ecuatoriana de Biotecnología held the blinded randomisation codes in a secure place. The study code was not broken until all the data were entered and the initial analyses performed

Blinding?
All outcomes except mortality
YesDouble-blinding

Incomplete outcome data addressed?
All outcomes except mortality
Yes48 children (16.7%) were lost to follow-up during the course of the study

Stephensen 1998

MethodsRandomised block design, placebo controlled trial. Double-blind


ParticipantsChildren between 3 months and 10 years of age with a principal diagnosis of pneumonia (confirmed by X-ray) admitted as inpatients to the paediatrics ward. A purified protein derivative (PPD) skin test was applied at the time of admission to the paediatrics ward and was read 48 hours later. 47 in vitamin A group and 48 in placebo group


InterventionsChildren < 1 year received 100,000 IU (2 ml of water-miscible preparation) of vitamin A on admission to the study and 50,000 IU (1 ml) on the second day of hospitalization. Children >= 1 year of age received 200,000 IU (4 ml) on the first day and 100,000 (2 ml) on the second day


OutcomesClinical outcomes: temperature, heart rate, respiratory rate, presence or absence of retractions, occurrence of central cyanosis, percent of blood oxygen saturation, use of supplemental oxygen
Other: food consumed, mother's impression of child's appetite


NotesSetting: Lima, Peru


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?UnclearDid not mention any means of sequence generation, but block randomisation was mentioned

Allocation concealment?UnclearDid not mention any means of allocation concealment

Blinding?
All outcomes except mortality
YesDouble-blinding

Incomplete outcome data addressed?
All outcomes except mortality
YesIn placebo group 3 participants were excluded after randomisation due to positive PPD tests, 2 participants were withdrawn from additional data collection because of complications of their infection at day 10 (placebo) and day 14 (vitamin A). One participant was withdrawn from the placebo group during the first hospital day because of medical complications

Zhang 1999

MethodsQuasi-randomised parallel design, placebo-controlled trial. Children were allocated into two groups by the order of admission. No blinding


Participants80 children between 1 and 3 years old with recurrent bronchopneumonia were equally allocated to two groups. Diagnosis of pneumonia was confirmed by X-ray


InterventionsSame routine therapy, including antibiotics, anti-symptoms drugs, given in both groups. Oxygen was given for children with hypoxic and digitalis was given for children with heart failure. In addition to these, vitamin A was added for the vitamin A group with 10,000 IU, b.i.d. orally for 6 days, then 1500 IU/d for 20 days


OutcomesShort-term effect:
1. Marked improvement: all symptoms of pneumonia improved within 6 days, whilst no positive finding at chest X-ray
2. Improvement: 7 to 9 days after treatment, all of symptoms in remission and no positive finding at chest X-ray
3. Slight improvement: symptoms in remission after more than 10 days, but no change at chest X-ray

Long-term effects:
1. Marked improvement: no recurrence of bronchopneumonia during 1 year post-treatment
2. Improvement: bronchopneumonia recurred 1 to 2 times during 1 year post-treatment
3. No improvement: bronchopneumonia recurred 3 times or more during 1 year post-treatment


NotesSetting: Sihong County, Jiangsu, China


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?NoQuasi-randomisation

Allocation concealment?NoD - Not used

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Anonymous 1991Patients had pneumonia complicated by measles

Barreto 1994Vitamin A administered prior to pneumonia diagnosis

Basu 2003Vitamin A administered prior to pneumonia diagnosis

Bhandari 1997Vitamin A administered prior to pneumonia diagnosis

Biesalski 2001Not a RCT

Biswas 1994Vitamin A administered prior to pneumonia diagnosis

Bresee 1996Participants included were children with lower respiratory tract diseases not just pneumonia

Buyukgebiz 1990Clinical outcomes not reported

Chen 2005The study compared the efficacy of vitamin A administered intravenously and orally

Coles 2001Vitamin A administered prior to pneumonia diagnosis

Coutsoudis 2000Vitamin A administered prior to pneumonia diagnosis

Daulaire 1992Vitamin A administered prior to pneumonia diagnosis

Dibley 1996Vitamin A administered prior to pneumonia diagnosis

Donnen 1998Vitamin A administered prior to pneumonia diagnosis

Dowell 1996Participants included were children with lower respiratory tract diseases not just pneumonia

Dudley 1997Not a RCT

Fauveau 1992Not a RCT

Fawzi 1995Vitamin A administered prior to pneumonia diagnosis

Fawzi 1999Duplicate patient groups

Fawzi 2000Duplicate patient groups

Fu 2005Not a RCT

Ghana VAST team 1993Vitamin A administered prior to pneumonia diagnosis

Hadi 1999Vitamin A administered prior to pneumonia diagnosis

Humphrey 1996Vitamin A administered prior to pneumonia diagnosis

Julien 1999Paticipants included were children with lower respiratory tract diseases not just pneumonia

Junhong 1997Not a RCT

Kao 1996Although 'randomized allocation' was mentioned, by asking the trial author we understand that the method of randomisation was 'convenience' allocation; not a real RCT

Kartasasmita 1995Vitamin A administered prior to pneumonia diagnosis

Khandait 2000Not a RCT

Kjolhede 1995Subjects included were children with lower respiratory tract diseases - not just pneumonia but also bronchiolitis

Li 2004Not a real RCT, although 'randomisation' was mentioned

Lie 1993Vitamin A administered prior to pneumonia diagnosis

Lin 1999'Random' was mentioned, but by asking the trial author we discovered that 'random' meant 'sampling' so this was not a RCT

Liu 2002Not a RCT

Lloyd 1991Not a RCT

Long 2006Vitamin A administered prior to pneumonia diagnosis

Long 2007Vitamin A administered prior to pneumonia diagnosis

Ma 2000'Randomised allocation' was mentioned, but by asking the trial author we discovered they performed a convenience allocation

Mahalanabis 2001Not a RCT

Qin 1999'Randomised' was mentioned. We asked the trial authors and understood that the method of randomisation was 'convenience' allocation, not a real RCT

Quinlan 1996Participants included were children with lower respiratory tract disease rather than pneumonia

Rahman 2001Vitamin A administered prior to pneumonia diagnosis

Rahmathullah 1991Vitamin A administered prior to pneumonia diagnosis

Ramakrishnan 1998Not a RCT

Roy 1997Vitamin A administered prior to pneumonia diagnosis

Ruz 1995Vitamin A administered prior to pneumonia diagnosis

Semba 1993Vitamin A administered prior to pneumonia diagnosis

Semba 1995Not a RCT

Semba 1999Not a RCT

Sempertegui 1999Vitamin A administered prior to pneumonia diagnosis

Shah 1994Not a RCT

Si 1997Patients had pneumonia complicated by measles

Stansfield 1993Vitamin A administered prior to pneumonia diagnosis

Stephensen 2002Clinical outcomes not reported

Tomkins 2000Not a RCT

Velasquez 1995Clinical outcomes not reported

Vijayaraghavan 1990Vitamin A administered prior to pneumonia diagnosis

Villamor 2000aNot a RCT

Villamor 2000bDuplicate patient groups

Wang 2003aNot a real RCT

Wang 2003bDuplicate publication of Wang 2003a, and not a real RCT

West 1991Vitamin A administered prior to pneumonia diagnosis

Willumsen 1997Not a RCT

Winkler 2005Vitamin A administered prior to pneumonia diagnosis

Wu 2000'Randomised' was mentioned, but by asking the trial author we understand that the method of randomisation was 'convenience' allocation; not a real RCT

Yang 2002Non-randomised controlled study

Ying 1998Although 'randomized' was mentioned, we asked the trial author and understand that the method of randomisation was 'convenience' allocation; not a real RCT

Zhen 2003'Randomised' was mentioned, we asked the trial author and understand that the method of randomisation was 'convenience' allocation; not a real RCT

 
Comparison 1. Vitamin A versus control

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

 1 Mortality during hospitalisation31446Peto Odds Ratio (Peto, Fixed, 95% CI)1.29 [0.63, 2.66]

 2 Time with signs of pneumonia and treatment issues (continuous)4Mean Difference (IV, Fixed, 95% CI)Subtotals only

    2.1 Time with fever
3958Mean Difference (IV, Fixed, 95% CI)-1.11 [-5.66, 3.44]

    2.2 Time with rapid respiratory rate, > 40 breaths/min/day
2926Mean Difference (IV, Fixed, 95% CI)0.03 [-0.32, 0.38]

    2.3 Time with hypoxia, PO2 < 95% per day
2926Mean Difference (IV, Fixed, 95% CI)0.07 [-0.21, 0.34]

    2.4 Length of hospitalisation (days)
2779Mean Difference (IV, Fixed, 95% CI)0.08 [-0.43, 0.59]

    2.5 Time with positive findings on auscultation
2278Mean Difference (IV, Fixed, 95% CI)-0.54 [-1.14, 0.05]

    2.6 Time with cough
138Mean Difference (IV, Fixed, 95% CI)-2.0 [-3.51, -0.49]

    2.7 Time with positive findings at x-ray
139Mean Difference (IV, Fixed, 95% CI)0.90 [-1.10, 2.90]

 3 Time with signs of pneumonia and treatment issues (dichotomous)2Odds Ratio (M-H, Fixed, 95% CI)Subtotals only

    3.1 Short-term effects: slight improvement
180Odds Ratio (M-H, Fixed, 95% CI)0.06 [0.01, 0.30]

    3.2 Long-term effects: no improvement (number of recurrences)
180Odds Ratio (M-H, Fixed, 95% CI)0.12 [0.03, 0.46]

    3.3 Change of antibiotic required
1472Odds Ratio (M-H, Fixed, 95% CI)0.65 [0.42, 1.01]

 4 Adverse events2Odds Ratio (M-H, Fixed, 95% CI)Subtotals only

    4.1 Vomiting
2430Odds Ratio (M-H, Fixed, 95% CI)0.77 [0.45, 1.33]

    4.2 Diarrhoea
1405Odds Ratio (M-H, Fixed, 95% CI)0.57 [0.31, 1.05]

    4.3 Bulging fontanelles
1186Odds Ratio (M-H, Fixed, 95% CI)8.25 [0.44, 155.37]

    4.4 Irritability
1306Odds Ratio (M-H, Fixed, 95% CI)0.93 [0.56, 1.57]

 5 Time with fever, tachypnoea and hypoxaemia of pneumonia (serum retinol > 200 ug/L)152Mean Difference (IV, Fixed, 95% CI)-61.40 [-119.10, -3.70]