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

  1. Charles Shey Wiysonge1,*,
  2. Muki Shey2,
  3. Eugene J Kongnyuy3,
  4. Jonathan AC Sterne4,
  5. Peter Brocklehurst5

Editorial Group: Cochrane HIV/AIDS Group

Published Online: 19 JAN 2011

Assessed as up-to-date: 13 SEP 2010

DOI: 10.1002/14651858.CD003648.pub3


How to Cite

Wiysonge CS, Shey M, Kongnyuy EJ, Sterne JAC, Brocklehurst P. Vitamin A supplementation for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.: CD003648. DOI: 10.1002/14651858.CD003648.pub3.

Author Information

  1. 1

    University of Cape Town, School of Child and Adolescent Health, Cape Town, South Africa

  2. 2

    University of Cape Town, Institute of Infectious Disease and Molecular Medicine (IIDMM), Cape Town, South Africa

  3. 3

    Liverpool School of Tropical Medicine, Child and Reproductive Health Group, Liverpool, UK

  4. 4

    University of Bristol, Department of Social Medicine, Bristol, UK

  5. 5

    University of Oxford, National Perinatal Epidemiology Unit, Headington, Oxford, UK

*Charles Shey Wiysonge, School of Child and Adolescent Health, University of Cape Town, Institute of Infectious Disease and Molecular Medicine, Anzio Road, Observatory, Cape Town, 7925, South Africa. charles.wiysonge@uct.ac.za. wiysonge@yahoo.com.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 19 JAN 2011

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Characteristics of included studies [ordered by study ID]
Coutsoudis 1999

MethodsDescribed as randomised double-blind.
Eight percent of mother-infant pairs lost to follow-up and excluded from the analysis.


Participants728 HIV-infected women enrolled at 17-39 weeks' gestation in KwaZulu-Natal Province of South Africa; 30.6% of whom had serum retinol levels < 20 µg/dl.


InterventionsDaily oral vitamin A (5000 IU retinyl palmitate and 30 mg beta-carotene) or placebo. At delivery, women in the vitamin A group received a dose of 200,000 IU of retinyl palmitate while the placebo arm received an identical placebo.


OutcomesStillbirths, HIV infection in the child, neonatal deaths, preterm birth, birthweight, low birthweight.


NotesNo woman received any antiretroviral therapy. It is not stated in the trial reports whether the women also received iron, folic acid, and/or chloroquine.


Risk of bias

BiasAuthors' judgementSupport for judgement

Adequate sequence generation?Unclear riskThe method used to generate the randomisation sequence is not described.

Allocation concealment?Unclear riskThe method used to conceal the treatment allocation is not described.

Blinding?
All outcomes
Low riskUse of identical placebo; diagnosis of HIV was done in the laboratory.

Incomplete outcome data addressed?
All outcomes
Low riskLess than 10% of women lost to follow-up and review authors do not believe that this was related to the outcome. Review authors do not believe this introduced bias.

Free of selective reporting?Low riskAll pre-specified outcomes reported in various publications from this trial.

Free of other bias?Unclear riskLimited by study design.

Fawzi 2002

MethodsRandomised, placebo-controlled, double-blind.
Five percent of mother-infant pairs were lost to follow-up and excluded from the analysis.


Participants1075 pregnant HIV-infected women enrolled at 12-27 weeks' gestation in Dar es Salam, Tanzania. Of 1085 women initially randomised, 10 were eventually excluded for either being HIV-negative (n=7) or nonpregnant (n=3). The prevalence of vitamin A deficiency (< 0.70 µmol/L) was about 34% during the second trimester.


InterventionsDaily oral dose of one of: vitamin A (30mg beta carotene + 5000 IU retinyl palmitate) alone, multivitamins ( 20mg B1, 20mg B2, 25mg B6, 100mg niacin, 50microg B12, 500mg C, 30 mg E, and 0.8 mg folic) plus vitamin A, multivitamins without vitamin A, or placebo. At delivery, women receiving any vitamin A were given an additional 200,000 IU oral dose of vitamin A while the others received an extra dose of placebo.


OutcomesStillbirths, HIV infection in child, preterm delivery, low birthweight, postpartum CD4 levels.


NotesIt is not mentioned in this trial whether any woman received antiretroviral therapy.
All women were given daily oral doses of iron and folic acid, and weekly doses of chloroquine.


Risk of bias

BiasAuthors' judgementSupport for judgement

Adequate sequence generation?Low riskComputer-generated sequence.

Allocation concealment?Low riskBlock randomisation; blocks of 20. At enrolment, each eligible woman was assigned the next numbered bottle of study drug

Blinding?
All outcomes
Low riskActive tablets and placebo indistinguishable, so that neither the subjects nor the investigators could identify which subjects were randomised to the same regimen.

Incomplete outcome data addressed?
All outcomes
Low riskLess than 10% of women lost to follow-up and review authors do not believe that this was related to the outcome. Review authors do not believe this introduced bias.

Free of selective reporting?Low riskAll outcomes specified in the goals of the study articles were reported on.

Free of other bias?Low riskReview authors do not believe that other biasses were introduced which could have affected study findings.

Friis 2004

MethodsRandomised, placebo-controlled, double-blind. One hundred and seventy-three (32.5%) HIV-infected women were lost to follow-up and excluded from the analysis.


Participants533 HIV-infected pregnant women enrolled at 22-35 weeks' gestation in Harare, Zimbabwe.


InterventionsDaily oral tablet containing either vitamin A (3000 micrograms retinol equivalents and 3.5 mg beta-carotene) and the recommended daily allowance of 11 micronutrients (1.5mg thiamine, 1.6mg riboflavin, 2.2mg B-6, 4.0micrograms B-12, 17mg niacin, 80mg C, 10micrograms D, 10mg E, 15mg zinc, 1.2micrograms copper, 65micrograms selenium), or placebo.


OutcomesMTCT of HIV, gestational length, birthweight, preterm delivery


NotesAll women received iron and folic acid as part of routine antenatal care. No woman received antiretroviral therapy. Information is not available on the HIV status of the children due to technical difficulties and problems with follow-up.


Risk of bias

BiasAuthors' judgementSupport for judgement

Adequate sequence generation?Low riskThe digits 0–5 in a computer-generated random sequence were replaced by 6 pre-assigned permuted blocks of 4: AABB, ABAB, ABBA, BABA, BBAA, and BAAB; the digits 6–9 were deleted.

Allocation concealment?Low riskContainers with active or placebo tablets, which were coded A or B, respectively, were delivered by the manufacturer (Almega, Ringsted, Denmark) together with the code in 2 sealed envelopes. Duplicate containers, which corresponded to the random sequence, were consecutively numbered from 1 to 1800. The study participants were numbered consecutively at recruitment.

Blinding?
All outcomes
Low riskParticipants, care givers, outcome assessors blind

Incomplete outcome data addressed?
All outcomes
High risk32.5% HIV-infected women were lost to follow-up and excluded from the analysis.

Free of selective reporting?High riskThe authors did not report data on MTCT of HIV, due to the high loss to follow-up (32.5%).

Free of other bias?Low riskReview authors do not believe that other biasses were introduced, over and above the high loss to follow-up and the selective reporting.

Humphrey 2006

MethodsRandomised, placebo-controlled trial.


Participants4495 mother-infants pairs who were part of the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) trial in Harare Zimbabwe. Mother-infant pairs were enrolled at 96 hours (or less) after delivery.


InterventionsA 2-by-2 factorial design with 4 treatment groups Aa, Ap, Pa, and Pp; where “A” was maternal vitamin A supplementation (400,000 IU), “P” was maternal placebo, “a” was infant vitamin A supplementation (50,000 IU), and “p” was infant placebo.


OutcomesPrimary outcome: breastfeeding–associated MTCT and HIV-free survival.

Secondary outcome: adverse effects in HIV-positive women or their infants.


NotesAll but 4 mothers initiated breastfeeding, no information on ART or cotrimoxazole prophylaxis.


Risk of bias

BiasAuthors' judgementSupport for judgement

Adequate sequence generation?Low riskComputer-generated blocks of 12.

Allocation concealment?Low riskConcealed envelopes with study number; link between number and treatment assignment kept at central location

Blinding?
All outcomes
Low riskParticipants, care providers, and outcome assessors blind to the treatment allocation.

Incomplete outcome data addressed?
All outcomes
Low riskLess than 10% of women lost to follow-up and review authors do not believe that this was related to the outcome. Review authors do not believe this introduced bias.

Free of selective reporting?Low riskOutcomes pre-specified in the protocol (NCT00198718) have been reported.

Free of other bias?Low riskReview authors do not believe that other biasses were introduced which could have affected study findings.

Semba 2002

MethodsRandomised controlled trial. Patients were assigned to treatment using computer-generated random numbers, and treatment was concealed by prepacking study supplements in sequentially numbered series assigned to study identification numbers. Sixty three women (9%) were lost to follow-up before delivery and excluded from the analyses. The 14 pairs of twins in the study were excluded from the birth weight and mortality analyses because twins are known to have lower birth weights and higher mortality rates.


Participants697 pregnant HIV-infected women enrolled at 18-28 week's gestation in Blantyre, Malawi. The prevalence of vitamin A deficiency (< 0.70 µmol/L) was 51% during the second trimester.


InterventionsAll women received orally administered daily doses of iron (30mg of elemental iron) and folate (400 µg) from enrolment until delivery. One-half of the women were randomised to receive daily doses of orally administered vitamin A (10,000 IU).


OutcomesStillbirths, HIV infection in child, preterm delivery, low birthweight, postpartum CD4 levels.


NotesAll women received oral vitamin A (100,000 IU) at 6 weeks postpartum, as per policy of the Malawi Ministry of Health.


Risk of bias

BiasAuthors' judgementSupport for judgement

Adequate sequence generation?Low riskTreatment assignment was determined by use of a computer’s random-number generator.

Allocation concealment?Low riskTreatment assignment was concealed by pre-packing study supplements in sequentially numbered series assigned to study identification numbers. Mothers were assigned an original study identification number at enrolment and were given the next sequentially numbered opaque bottle with supplements.

Blinding?
All outcomes
Low riskSupplements containing vitamin A, iron, and folate were identical in appearance to the supplements containing iron and folate.

Incomplete outcome data addressed?
All outcomes
Low riskLess than 10% of women lost to follow-up and review authors do not believe that this was related to the outcome. Review authors do not believe this introduced bias.

Free of selective reporting?Low riskAll outcomes specified in the goals of the study articles were reported on.

Free of other bias?Low riskReview authors do not believe that other biasses were introduced which could have affected study findings.

 
Characteristics of ongoing studies [ordered by study ID]
Chikobvu 2000

Trial name or titleBloemfontein Vitamin A Trial

Methods

Participants303 HIV-positive pregnant women from metropolitan Bloemfontein, South Africa. The majority (56%) lived in informal settlements, and all attended public health facilities. For the trial, women were asked to volunteer for HIV testing during their first antenatal visit. Pretest counselling was done in groups, and posttest counselling was done individually. Seropositive women were asked to participate in the trial.

InterventionsVitamin A supplementation versus placebo

OutcomesMTCT of HIV

Starting dateThe trial was conducted from September 1997 to December2000 in Bloemfontein, Free State, South Africa.

Contact informationChikobvuP@fshealth.gov.za

NotesAll trial participants gave separate informed consent for the trial. All patients were recruited by 1 study physician and received verbal or written information (Sesotho, English, or Afrikaans information sheets).

 
Comparison 1. Vitamin A supplementation versus no vitamin A supplementation

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

 1 HIV infection in child46517Risk Ratio (M-H, Random, 95% CI)1.04 [0.87, 1.24]

    1.1 Antenatal supplementation
32022Risk Ratio (M-H, Random, 95% CI)1.05 [0.78, 1.41]

    1.2 Postpartum supplementation
14495Risk Ratio (M-H, Random, 95% CI)0.99 [0.91, 1.09]

 2 HIV infection or death25536Risk Ratio (M-H, Fixed, 95% CI)1.04 [0.97, 1.11]

 3 Stillbirth42855Risk Ratio (M-H, Fixed, 95% CI)0.99 [0.68, 1.43]

 4 Preterm less than 34 weeks21578Risk Ratio (M-H, Random, 95% CI)0.69 [0.24, 2.00]

 5 Preterm less than 37 weeks32110Risk Ratio (M-H, Random, 95% CI)0.88 [0.65, 1.19]

 6 Low birth weight less than 2500g42606Risk Ratio (M-H, Fixed, 95% CI)0.83 [0.68, 1.01]

 7 Low birthweight less than 2000g21483Risk Ratio (M-H, Fixed, 95% CI)0.72 [0.41, 1.27]

 8 Birthweight31809Mean Difference (IV, Fixed, 95% CI)89.78 [84.73, 94.83]

 9 Maternal death1728Risk Ratio (M-H, Fixed, 95% CI)0.49 [0.04, 5.37]

 10 Postpartum CD4 count1727Mean Difference (IV, Fixed, 95% CI)-4.0 [-51.06, 43.06]

 11 Infant death1594Risk Ratio (M-H, Fixed, 95% CI)1.08 [0.78, 1.50]

12 Neonatal admission to neonatal unit00Risk Ratio (M-H, Fixed, 95% CI)Not estimable

 13 Death of child by 24 months21635Risk Ratio (M-H, Fixed, 95% CI)1.03 [0.88, 1.20]

14 Side effects in child00Risk Ratio (M-H, Fixed, 95% CI)Not estimable

 15 Later death of child1478Risk Ratio (M-H, Fixed, 95% CI)1.22 [0.53, 2.81]

16 Maternal post-partum infection00Risk Ratio (M-H, Fixed, 95% CI)Not estimable

17 Acceptance of supplementation00Risk Ratio (M-H, Fixed, 95% CI)Not estimable

 
Summary of findings for the main comparison. The effects of vitamin A supplementation of HIV infected women

The effects of vitamin A supplementation of HIV infected women

Patient or population: HIV infected women
Settings: low and middle-income countries
Intervention: vitamin A supplementation

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Controlvitamin A supplementation

HIV infection in child
Follow-up: 3-24 months
282 per 1000293 per 1000
(245 to 350)
RR 1.04
(0.87 to 1.24)
6517
(4 studies)
⊕⊕⊕⊝
moderate1

Still birth
Follow-up: median 20 weeks
37 per 100037 per 1000
(25 to 53)
RR 0.99
(0.68 to 1.43)
2855
(4 studies)
⊕⊕⊕⊝
moderate2

Preterm births
Follow-up: median 20 weeks
188 per 1000165 per 1000
(122 to 224)
RR 0.88
(0.65 to 01.19)
2110
(3 studies)
⊕⊕⊕⊝
moderate2

Low birth weight
Follow-up: median 20 weeks
146 per 1000121 per 1000
(99 to 147)
RR 0.83
(0.68 to 1.01)
2606
(4 studies)
⊕⊕⊕⊝
moderate2

Birth weight
Follow-up: median 20 weeks
The mean birth weight ranged across control groups from
2,805-3,069 grammes
The mean Birth weight in the intervention groups was
89.78 higher
(84.9 to 95.1 higher)
1809
(3 studies)
⊕⊕⊕⊕
high

Maternal death6 per 10003 per 1000
(0 to 32)
RR 0.49
(0.04 to 5.37)
728
(1 study)
⊕⊝⊝⊝
very low3

Child death by 24 months276 per 1000284 per 1000
(243 to 331)
RR 1.03
(0.88 to 1.20)
1635
(2 studies)
⊕⊕⊕⊝
moderate2

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Heterogeneity: P=0.02, I-square = 68%
2 Wide confidence intervals
3 One trial, with very wide confidence intervals
 
Table 1. Search String: PubMed (June 2010)

SearchDetails

#1Search 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"[MESH:NoExp]

#2Search (randomised controlled trial [pt] OR controlled clinical trial [pt] OR randomised [tiab] OR placebo [tiab] OR drug therapy [sh] OR randomly [tiab] OR trial [tiab] OR groups [tiab]) NOT (animals [mh] NOT humans [mh])

#3Search mother-to-child-transmission OR MTCT OR infectious disease transmission, vertical

#4Search caroten* OR retinoic OR retinol OR vitamin* OR vitamin A OR micronutrient*

#5Search #1 AND #2 AND #3 AND #4 Limits: Publication Date from 2007/01/01 to 2010/06/08

 
Table 2. Search string: EMBASE (June 2010)

SearchDetails

#1'human immunodeficiency virus infection'/exp OR 'human immunodeficiency virus infection'/de OR 'human immunodeficiency virus infection' OR 'human immunodeficiency virus'/exp OR 'human immunodeficiency virus'/de OR 'human immunodeficiency virus'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 immuno-deficiency virus':ti OR 'human immuno-deficiency virus':ab OR 'human immunedeficiency virus':ti OR 'human immunedeficiency virus':ab OR 'human immune-deficiency virus':ti OR 'human immune-deficiency virus':ab OR 'acquired immune-deficiency syndrome':ti OR 'acquired immune-deficiency syndrome':ab OR 'acquired immunedeficiency syndrome':ti OR 'acquired immunedeficiency syndrome':ab OR 'acquired immunodeficiency syndrome':ti OR 'acquired immunodeficiency syndrome':ab OR 'acquired immuno-deficiency syndrome':ti OR 'acquired immuno-deficiency syndrome':ab

#2random*: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 allocat*:ti OR allocat*:ab OR volunteer*:ti OR volunteer*:ab OR 'crossover procedure'/exp OR 'crossover procedure'/de OR 'crossover procedure'OR 'double-blind procedure'/exp OR 'double-blind procedure'/de OR 'double-blind procedure' OR 'single-blind procedure'/exp OR 'single-blind procedure'/de OR 'single-blind procedure' OR 'randomised controlled trial'/exp OR 'randomised controlled trial'/de OR 'randomised controlled trial'

#3'mother-to-child transmission' OR 'mother to child transmission' OR mtct OR 'vertical transmission'/de OR 'vertical transmission'

#4caroten* OR retinoicOR 'retinol'/de OR retinolOR vitamin*OR 'vitamin a'/de OR 'vitamin a'OR micronutrient*

#5#1 AND #2AND #3AND #4

#6#1 AND #2AND #3AND #4AND [humans]/lim AND [embase]/lim AND [1-1-2007]/sd NOT [8-6-2010]/sd

 
Table 4. Search String: PubMed (February 2008)

SearchDetails

#1Search 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]

#2Search randomised controlled trial [pt] OR controlled clinical trial [pt] OR randomised 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])

#3Search (DISEASE TRANSMISSION, VERTICAL) OR MTCT OR (MOTHER-TO-CHILD TRANSMISSION)

#4Search CAROTEN* OR RETINOIC OR RETINOL OR VITAMIN* OR MICRONUTRIENT*

#5Search PREGNANT OR PREGNANCY OR ANTEPARTUM OR PRENATAL OR ANTE-PARTUM OR PRE-NATAL OR PREPART*

#6Search #1 AND #2 AND #3 AND #4 AND #5 Limits: Publication Date from 2003 to 2008

 
Table 5. Search string: EMBASE (February 2008)

SearchDetails

#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 (((('randomised controlled trial'/exp OR 'randomised controlled trial') OR ('randomised controlled trial'/exp OR 'randomised controlled trial')) OR (('randomised controlled trial'/exp OR 'randomised controlled trial') OR ('randomised controlled trial'/exp OR 'randomised 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

#4caroten* OR retinoic OR ('retinol'/exp OR 'retinol') OR vitamin* OR micronutrient* AND [2003-2008]/py

#5pregnant 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 6. Search String: AIDSearch (February 2008)

SearchDetails

#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)

#4CAROTEN* OR RETINOIC OR RETINOL OR VITAMIN* OR MICRONUTRIENT*

#5PREGNANT 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 7. Search String: GATEWAY (February 2008)

SearchDetails

#1Search: (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])

#2Search: (randomised controlled trial [pt] OR controlled clinical trial [pt] OR randomised 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]))

#3Search: (DISEASE TRANSMISSION, VERTICAL) OR MTCT OR (MOTHER-TO-CHILD TRANSMISSION)

#4Search: CAROTEN* OR RETINOIC OR RETINOL OR VITAMIN* OR MICRONUTRIENT*

#5Search: 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