Vitamin A supplementation for reducing the risk of mother‐to‐child transmission of HIV infection

Charles Shey Wiysonge; Muki Shey; Eugene J Kongnyuy; Jonathan AC Sterne; Peter Brocklehurst

doi:10.1002/14651858.CD003648.pub2

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Analysis 1.1

Comparison 1 Vitamin A supplementation versus no vitamin A supplementation, Outcome 1 HIV infection in child.

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Analysis 1.2

Comparison 1 Vitamin A supplementation versus no vitamin A supplementation, Outcome 2 HIV infection or death.

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Analysis 1.3

Comparison 1 Vitamin A supplementation versus no vitamin A supplementation, Outcome 3 Stillbirth.

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Analysis 1.4

Comparison 1 Vitamin A supplementation versus no vitamin A supplementation, Outcome 4 Preterm less than 34 weeks.

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Analysis 1.5

Comparison 1 Vitamin A supplementation versus no vitamin A supplementation, Outcome 5 Preterm less than 37 weeks.

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Analysis 1.6

Comparison 1 Vitamin A supplementation versus no vitamin A supplementation, Outcome 6 Low birth weight less than 2500g.

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Analysis 1.7

Comparison 1 Vitamin A supplementation versus no vitamin A supplementation, Outcome 7 Low birthweight less than 2000g.

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Analysis 1.8

Comparison 1 Vitamin A supplementation versus no vitamin A supplementation, Outcome 8 Birthweight.

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Analysis 1.9

Comparison 1 Vitamin A supplementation versus no vitamin A supplementation, Outcome 9 Maternal death.

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Analysis 1.10

Comparison 1 Vitamin A supplementation versus no vitamin A supplementation, Outcome 10 Postpartum CD4 count.

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Analysis 1.11

Comparison 1 Vitamin A supplementation versus no vitamin A supplementation, Outcome 11 Infant death.

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Analysis 1.13

Comparison 1 Vitamin A supplementation versus no vitamin A supplementation, Outcome 13 Death of child by 24 months.

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Analysis 1.15

Comparison 1 Vitamin A supplementation versus no vitamin A supplementation, Outcome 15 Later death of child.

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Table 1. Search String: PubMed

Search	Details
#1	Search HIV Infections[MeSH] OR HIV[MeSH] OR hiv[tw] OR hiv‐1[tw] OR hiv‐2[tw] OR hiv1[tw] OR hiv2[tw] OR hiv infect[tw] OR human immunodeficiency virus[tw] OR human immunedeficiency virus[tw] OR human immuno‐deficiency virus[tw] OR human immune‐deficiency virus[tw] OR ((human immun) AND (deficiency virus[tw])) OR acquired immunodeficiency syndrome[tw] OR acquired immunedeficiency syndrome[tw] OR acquired immuno‐deficiency syndrome[tw] OR acquired immune‐deficiency syndrome[tw] OR ((acquired immun*) AND (deficiency syndrome[tw])) OR "sexually transmitted diseases, viral"[MH]
#2	Search randomized controlled trial [pt] OR controlled clinical trial [pt] OR randomized controlled trials [mh] OR random allocation [mh] OR double‐blind method [mh] OR single‐blind method [mh] OR clinical trial [pt] OR clinical trials [mh] OR ("clinical trial" [tw]) OR ((singl* [tw] OR doubl* [tw] OR trebl* [tw] OR tripl* [tw]) AND (mask* [tw] OR blind* [tw])) OR ( placebos [mh] OR placebo* [tw] OR random* [tw] OR research design [mh:noexp] OR (comparative study) OR (comparative studies) OR (evaluation studies) OR follow‐up studies [mh] OR prospective studies [mh] OR control* [tw] OR prospectiv* [tw] OR volunteer* [tw]) NOT (animals [mh] NOT human [mh])
#3	Search (DISEASE TRANSMISSION, VERTICAL) OR MTCT OR (MOTHER‐TO‐CHILD TRANSMISSION)
#4	Search CAROTEN* OR RETINOIC OR RETINOL OR VITAMIN* OR MICRONUTRIENT*
#5	Search PREGNANT OR PREGNANCY OR ANTEPARTUM OR PRENATAL OR ANTE‐PARTUM OR PRE‐NATAL OR PREPART*
#6	Search #1 AND #2 AND #3 AND #4 AND #5 Limits: Publication Date from 2003 to 2008

Table 1. Search String: PubMed

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Table 2. Search string: EMBASE

Search	Details
#1	(('human immunodeficiency virus infection'/exp OR 'human immunodeficiency virus infection') OR ('human immunodeficiency virus infection'/exp OR 'human immunodeficiency virus infection')) OR ((('human immunodeficiency virus'/exp OR 'human immunodeficiency virus') OR ('human immunodeficiency virus'/exp OR 'human immunodeficiency virus'))) OR ((('b cell lymphoma'/exp OR 'b cell lymphoma') OR ('b cell lymphoma'/exp OR 'b cell lymphoma'))) OR (hiv:ti OR hiv:ab) OR ('hiv‐1':ti OR 'hiv‐1':ab) OR ('hiv‐2':ti OR 'hiv‐2':ab) OR ('human immunodeficiency virus':ti OR 'human immunodeficiency virus':ab) OR ('human immunedeficiency virus':ti OR 'human immunedeficiency virus':ab) OR ('human
#2	(random:ti OR random:ab) OR (factorial:ti OR factorial:ab) OR (cross?over:ti OR cross?over:ab OR crossover:ti OR crossover:ab) OR (placebo:ti OR placebo:ab) OR (((doubl:ti AND blind:ti) OR (doubl:ab AND blind:ab))) OR (((singl:ti AND blind:ti) OR (singl:ab AND blind:ab))) OR (assign:ti OR assign:ab) OR (volunteer:ti OR volunteer:ab) OR (((('crossover procedure'/exp OR 'crossover procedure') OR ('crossover procedure'/exp OR 'crossover procedure')) OR (('crossover procedure'/exp OR 'crossover procedure') OR ('crossover procedure'/exp OR 'crossover procedure')))) OR (((('double‐blind procedure'/exp OR 'double‐blind procedure') OR ('double‐blind procedure'/exp OR 'double‐blind procedure')) OR (('double‐blind procedure'/exp OR 'double‐blind procedure') OR ('double‐blind procedure'/exp OR 'double‐blind procedure')))) OR (((('single‐blind procedure'/exp OR 'single‐blind procedure') OR ('single‐blind procedure'/exp OR 'single‐blind procedure')) OR (('single‐blind procedure'/exp OR 'single‐blind procedure') OR ('single‐blind procedure'/exp OR 'single‐blind procedure')))) OR (((('randomized controlled trial'/exp OR 'randomized controlled trial') OR ('randomized controlled trial'/exp OR 'randomized controlled trial')) OR (('randomized controlled trial'/exp OR 'randomized controlled trial') OR ('randomized controlled trial'/exp OR 'randomized controlled trial')))) OR (allocat:ti OR allocat*:ab) AND [2003‐2008]/py
#3	'mother‐to‐child transmission' OR mtct OR 'vertical disease transmission' AND [2003‐2008]/py
#4	caroten* OR retinoic OR ('retinol'/exp OR 'retinol') OR vitamin* OR micronutrient* AND [2003‐2008]/py
#5	pregnant OR ('pregnancy'/exp OR 'pregnancy') OR antepartum OR ('ante partum') OR antenatal OR ('ante natal') OR prenatal OR ('pre natal') AND [2003‐2008]/py
#6	#1 AND #2 AND #3 AND #4 AND #5

Table 2. Search string: EMBASE

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Table 3. Search String: AIDSearch

Search	Details
#1	(HIV INFECTIONS) OR HIV OR HIV OR HIV‐1* OR HIV‐2* OR HIV1 OR HIV2 OR (HIV INFECT) OR (HUMAN IMMUNODEFICIENCY VIRUS) OR (HUMAN IMMUNEDEFICIENCY VIRUS) OR (HUMAN IMMUNO‐DEFICIENCY VIRUS) OR (HUMAN IMMUNE‐DEFICIENCY VIRUS) OR ((HUMAN IMMUN) AND (DEFICIENCY VIRUS)) OR (ACQUIRED IMMUNODEFICIENCY SYNDROME) OR (ACQUIRED IMMUNEDEFICIENCY SYNDROME) OR (ACQUIRED IMMUNO‐DEFICIENCY SYNDROME) OR (ACQUIRED IMMUNE‐DEFICIENCY SYNDROME) OR ((ACQUIRED IMMUN*) AND (DEFICIENCY SYNDROME)) OR (SEXUALLY TRANSMITTED DISEASES, VIRAL)
#2	((RANDOMIZED CONTROLLED TRIAL) OR (CONTROLLED CLINICAL TRIAL) OR (RANDOMIZED CONTROLLED TRIALS) OR (RANDOM ALLOCATION) OR (DOUBLE‐BLIND METHOD) OR (SINGLE‐BLIND METHOD) OR (CLINICAL TRIAL) OR (CLINICAL TRIALS) OR ("CLINICAL TRIAL") OR ((SINGL* OR DOUBL* OR TREBL* OR TRIPL* AND (MASK* OR BLIND* )) OR PLACEBOS OR PLACEBO* OR RANDOM* OR (COMPARATIVE STUDY) OR (EVALUATION STUDIES) OR (FOLLOW‐UP STUDIES) OR (PROSPECTIVE STUDIES) OR CONTROL* OR PROSPECTIV* OR VOLUNTEER*)) NOT (ANIMALS NOT HUMAN )
#3	(MOTHER‐TO‐CHILD TRANSMISSION) OR MTCT OR (VERTICAL DISEASE TRANSMISSION)
#4	CAROTEN* OR RETINOIC OR RETINOL OR VITAMIN* OR MICRONUTRIENT*
#5	PREGNANT OR PREGNANCY OR ANTEPARTUM OR (ANTE‐PARTUM) OR ANTENATAL OR (ANTE‐NATAL) OR PRENATAL OR (PRE‐NATAL)
#6	#1 AND #2 AND #3 AND #4 AND #5

Table 3. Search String: AIDSearch

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Table 4. Search String: GATEWAY

Search	Details
#1	Search: (HIV Infections[MeSH] OR HIV[MeSH] OR hiv[tw] OR hiv‐1[tw] OR hiv‐2[tw] OR hiv1[tw] OR hiv2[tw] OR hiv infect[tw] OR human immunodeficiency virus[tw] OR human immunedeficiency virus[tw] OR human immuno‐deficiency virus[tw] OR human immune‐deficiency virus[tw] OR ((human immun) AND (deficiency virus[tw])) OR acquired immunodeficiency syndrome[tw]) AND (acquired immunedeficiency syndrome[tw] OR acquired immuno‐deficiency syndrome[tw] OR acquired immune‐deficiency syndrome[tw] OR ((acquired immun*) AND (deficiency syndrome[tw])) OR "sexually transmitted diseases, viral"[MH])
#2	Search: (randomized controlled trial [pt] OR controlled clinical trial [pt] OR randomized controlled trials [mh] OR random allocation [mh] OR double‐blind method [mh] OR single‐blind method [mh] OR clinical trial [pt] OR clinical trials [mh] OR ("clinical trial" [tw]) OR ((singl* [tw] OR doubl* [tw] OR trebl* [tw] OR tripl* [tw]) AND (mask* [tw] OR blind* [tw]))) OR (( placebos [mh] OR placebo* [tw] OR random* [tw] OR research design [mh:noexp] OR (comparative study) OR (comparative studies) OR (evaluation studies) OR follow‐up studies [mh] OR prospective studies [mh] OR control* [tw] OR prospectiv* [tw] OR volunteer* [tw]) NOT (animals [mh] NOT human [mh]))
#3	Search: (DISEASE TRANSMISSION, VERTICAL) OR MTCT OR (MOTHER‐TO‐CHILD TRANSMISSION)
#4	Search: CAROTEN* OR RETINOIC OR RETINOL OR VITAMIN* OR MICRONUTRIENT*
#5	Search: PREGNANT OR PREGNANCY OR ANTEPARTUM OR PRENATAL OR ANTE‐PARTUM OR PRE‐NATAL OR PREPART*
#6	#1 and #2 and #3 and #4 and #5 Limit: 2003:2008

Table 4. Search String: GATEWAY

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Comparison 1. Vitamin A supplementation versus no vitamin A supplementation

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 HIV infection in child Show forest plot	3	2022	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.78, 1.41]

2 HIV infection or death Show forest plot	1	1041	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [0.97, 1.27]

3 Stillbirth Show forest plot	4	2855	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.68, 1.43]

4 Preterm less than 34 weeks Show forest plot	2	1578	Risk Ratio (M‐H, Random, 95% CI)	0.69 [0.24, 2.00]

5 Preterm less than 37 weeks Show forest plot	3	2110	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.65, 1.19]

6 Low birth weight less than 2500g Show forest plot	4	2606	Risk Ratio (M‐H, Fixed, 95% CI)	0.83 [0.68, 1.01]

7 Low birthweight less than 2000g Show forest plot	2	1483	Risk Ratio (M‐H, Fixed, 95% CI)	0.72 [0.41, 1.27]

8 Birthweight Show forest plot	3	1809	Mean Difference (IV, Fixed, 95% CI)	89.78 [84.73, 94.83]

9 Maternal death Show forest plot	1	728	Risk Ratio (M‐H, Fixed, 95% CI)	0.49 [0.04, 5.37]

10 Postpartum CD4 count Show forest plot	1	727	Mean Difference (IV, Fixed, 95% CI)	‐4.0 [‐51.06, 43.06]

11 Infant death Show forest plot	1	594	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.78, 1.50]

12 Neonatal admission to neonatal unit	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
13 Death of child by 24 months Show forest plot	2	1635	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.88, 1.20]

14 Side effects in child	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
15 Later death of child Show forest plot	1	478	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [0.53, 2.81]

16 Maternal post‐partum infection	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
17 Acceptance of supplementation	0	0	Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 1. Vitamin A supplementation versus no vitamin A supplementation

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