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Vitamin A supplementation for postpartum women

  1. Julicristie M Oliveira-Menegozzo1,*,
  2. Denise P Bergamaschi2,
  3. Philippa Middleton3,
  4. Christine E East4

Editorial Group: Cochrane Pregnancy and Childbirth Group

Published Online: 6 OCT 2010

Assessed as up-to-date: 26 AUG 2010

DOI: 10.1002/14651858.CD005944.pub2

How to Cite

Oliveira-Menegozzo JM, Bergamaschi DP, Middleton P, East CE. Vitamin A supplementation for postpartum women. Cochrane Database of Systematic Reviews 2010, Issue 10. Art. No.: CD005944. DOI: 10.1002/14651858.CD005944.pub2.

Author Information

  1. 1

    School of Public Health, University of Sao Paulo, Department of Nutrition, São Paulo, SP, Brazil

  2. 2

    University of Sao Paulo, Departamento de Epidemiologia-Estatistica, Sao Paulo, Brazil

  3. 3

    The University of Adelaide, ARCH: Australian Research Centre for Health of Women and Babies, Discipline of Obstetrics and Gynaecology, Adelaide, South Australia, Australia

  4. 4

    Pregnancy Research Centre, Department of Perinatal Medicine, Royal Women's Hospital, Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia

*Julicristie M Oliveira-Menegozzo, Department of Nutrition, School of Public Health, University of Sao Paulo, Av Dr Arnaldo, 715, São Paulo, SP, Cep 01246-904, Brazil. julicristie@yahoo.com. cristie@usp.br.

Publication History

  1. Publication Status: New
  2. Published Online: 6 OCT 2010

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Characteristics of included studies [ordered by study ID]
Ayah 2007

MethodsRandomised, double blind, placebo controlled, 2 by 2 factorial trial.


ParticipantsWomen giving birth to a live single baby and their infants.
Bondo, Kenya.
N = 564 mothers and their infants.


InterventionsSingle dosage administered to mother within 24 hours of birth; single dosage to infant at 1-4 weeks of age.

All infants received 100,000 IU vitamin A at 8 months of age (after trial).

4 intervention groups:
1. Mother received 400,000 IU vitamin A and infant received 100,000 IU vitamin A as retinyl palmitate (n = 142).
2. Mother received 400,000 IU vitamin A and infant received placebo (n = 140).
3. Mother received placebo and infant received 100,000 IU vitamin A (n = 143).
4. Mother received placebo and infant received placebo (n = 139).


OutcomesMaternal serum retinol concentration, breast milk retinol concentration. Infant serum retinol concentration, vitamin A hepatic stores (MRDR).


NotesNo information regarding breastfeeding pattern was provided. However, at least some breastfeeding is implied by the analysis of breast milk retinol at 6 months for 63% of the women originally enrolled.

87.4% of follow up until 14 weeks, 77.1% of follow up until 26 weeks postpartum.

The prevalence of HIV infection among antenatal attendees was above 28% at the time of the study. However, the trial was conducted prior to availability of HIV testing and antiretrovirals for antenatal women in western Kenya. Thus, it was not possible to know the prevalence of HIV among recruited women.

Sample size calculation reported.


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?Yes"Two random sequences of X and Y were prepared, one for the mothers and one for the infants. Identification numbers from 1 to 700 were assigned consecutively to each of the two lists and mother-infant pairs of capsules were packaged in zip-lock bags numbered from 1 to 700 and kept in batches of ten."

Allocation concealment?Yes"The randomisation codes were concealed for the entire trial duration and only revealed after completion of data analysis."

Blinding?
All outcomes
Yes"...prepared and supplied the vitamin A and identical-looking placebo supplements as oily capsules in brown bottles coded as X or Y."

Incomplete outcome data addressed?
All outcomes
YesAll analyses were by intention-to-treat.

Free of selective reporting?NoNot all clinically relevant outcomes reported.

Free of other bias?NoSupported by Hoffmann-La Roche Ltd (Basel Switzerland).

Bhaskaram 2000

MethodsRandomised, double blind, placebo controlled trial.


ParticipantsHospital based study with postpartum women who did not receive any vitamin A supplements during pregnancy and had uncomplicated full term births.

Hyderabad, India.

102 mothers and their infants.


InterventionsSingle high dose to mother within 24 hours after birth.

2 intervention groups:
1. Mother received 200,000 IU vitamin A as retinyl palmitate (n = 50).
2. Mother received placebo (n = 52).


OutcomesInfant serum retinol concentration, breast milk retinol concentration, and corneal lesions.


NotesAll babies given oral polio vaccine within 72 hours after birth.
All infants breastfed, followed up at 6 months.

100% of follow up until 6 weeks, 87% followed up until 3 months, 46% followed up until 6 months.


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?UnclearRandomised, no detail provided.

Allocation concealment?UnclearNo detail provided.

Blinding?
All outcomes
YesBlinding: vitamin A and placebo coded by person not connected with the investigation.
Nurse administering dose unaware of code.

Incomplete outcome data addressed?
All outcomes
NoReasons for attrition and exclusions not reported. Intention-to-treat analyses not performed.

Free of selective reporting?NoNot all clinically relevant outcomes reported.

Free of other bias?UnclearSource of funding not mentioned. No mention of any research protocol published a priori.

Darboe 2007

MethodsRandomised, double blind, placebo controlled trial.


ParticipantsPostpartum women without severe peripartum difficulties or preterm birth, with newborns ≥ 2200 g with no congenital defects at birth.

Keneba and West Kiang, Gambia.

220 mothers and their infants.


InterventionsSingle or double high dose to mother at delivery (first dose) and within a week (second dose); and 3 high doses to infant at 2, 3 or 4 months.

All infants received 100,000 IU vitamin A at 9 months and 200,000 IU at 12 months postpartum.

2 intervention groups:

1. Mother received 400,000 IU vitamin A as retinyl palmitate and infant received 150,000 IU vitamin A (3 doses of 50,000 IU) (n = 110);
2. Mother received 200,000 IU and infant received placebo (3 doses) (n = 110).


OutcomesMaternal morbidity, and serum retinol and breast milk retinol concentration. Infant morbidity, haemoglobin concentration, and serum retinol concentration.


NotesNo information regarding breastfeeding pattern was provided. However, at least partial breastfeeding is implied by the reported analysis of breast milk retinol to 6 months in 88% of those enrolled.

89.5% of follow up until 12 months.


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?Yes"An independent senior scientist packed and labelled the supplements, and did a block randomisation procedure (16 per block) to allow for possible effects of season of
birth."

Allocation concealment?Yes"All members of the trial team were unaware of allocation until the data had been cleaned and locked."

Blinding?
All outcomes
Unclear"Vitamin A in vegetable oil and vegetable oil placebo were prepared by Hoffmann La Roche (Basel, Switzerland)."

Incomplete outcome data addressed?
All outcomes
YesReasons for attrition and exclusions were reported in detail, although intention-to-treat analysis was not performed.

Free of selective reporting?NoNot all clinically relevant outcomes reported

Free of other bias?YesTrial registered a priori (No. ISRCTN 98554309). The UK Medical Research Council funded the study, and laboratory analyses in Coleraine were supported by BASF
Aktiengesellschaft (Ludwigshafen, Germany).

Idindili 2007

MethodsRandomised, double blind, placebo controlled trial.


ParticipantsMothers resident in the study area that brought their infants for vaccination.

Ifakara, Tanzania.

780 mothers and their infants.


InterventionsSingle or double high dose to mother within 1 week after delivery; and 3 standard or higher doses to infant at 1, 2 or 3 months (DPT/OPV vaccination).

All infants received 100,000 IU vitamin A at measles vaccination (9 months).

2 intervention groups:

1. Mother received 200,000 IU vitamin A as retinyl palmitate and infant received 75,000 IU vitamin A (3 doses of 25,000 IU) (n = 390).
2. Mother received 400,000 IU vitamin A and infant received 150,000 IU vitamin A (3 doses of 50,000 IU) (n = 390).


OutcomesInfant morbidity, anaemia (packed cell volume), serum retinol concentration, vitamin A hepatic stores (MRDR), and breast milk retinol concentration.


NotesAt least 86% of infants were exclusively breastfed until 1 month.

81% of follow up until 3 months; 79.5% until 6 months; and 77.2% until 9 months.


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?Yes"Individual randomization was achieved by using a list of study numbers that had been randomly assigned to an intervention arm in blocks of 10, generated by the Data and
Safety Monitoring Board."

Allocation concealment?Yes"A compact disk containing the cleaned and locked database files was exchanged for the treatment randomization code, held by the Data and Safety Monitoring Board."

All members of the trial team were unaware of allocation until the data had been cleaned and locked.

Blinding?
All outcomes
Unclear"Vitamin A capsules providing different doses were manufactured by Accucaps Industries (Windsor, Canada) (25,000 and 50,000 IU) and RpScherer (Aprilia, Italy) (200,000 IU), and were supplied to the project by the WHO."

Not enough detail to judge whether participants were blinded.

Incomplete outcome data addressed?
All outcomes
NoReasons for attrition and exclusions not reported. Intention-to-treat analyses not performed.

Free of selective reporting?NoNot all clinically relevant outcomes reported.

Free of other bias?UnclearPost hoc analyses were conducted because of concerns that the capsules did not contain the necessary amount of vitamin A (in a sample of capsules vitamin degraded).

Supported by Immunization Vaccines & Biologicals (the World Health Organization and the United Nations Foundation), Sight&Life (Hoffman-la Roche Ltd), Micronutrient Initiative, the Canadian International Development Agency, and the United Nations Children’s Fund (UNICEF).

Newton 2005

MethodsRandomised, double blind, placebo controlled 2 x 2 factorial design trial.


ParticipantsWomen 3-4 weeks postpartum and their infants.

Kintampo, Brong Ahafo Region, Ghana.

N = 1085 mothers and their infants.


Interventions4 intervention groups.

1. Mother received 200,000 IU of vitamin A as retinyl palmitate at 3-4 weeks and infant received total of 75,000 IU (25,000 IU at 6, 10 and 14 weeks) (n = 274).

2. Mother received placebo at 3-4 weeks and infant received total of 75,000 IU (25,000 IU at 6, 10 and 14 weeks) (n = 265).

3. Mother received 200,000 IU of vitamin A as retinyl palmitate and infant received total of placebo (n = 269).

4. Mother received placebo and infant received placebo at 6, 10 and 14 weeks (n = 277).


OutcomesInfant serum antibody titers for polio and tetanus at 6 months of age, and infant mortality.


NotesNo information supplied regarding breastfeeding rates. The report's background outlined the evaluation of whether maternal supplementation alone could achieve adequate vitamin A status, without the need for infant supplementation. This suggests that women were breastfeeding.

Infant supplementation linked to time of administration of diphtheria pertussis tetanus and polio vaccinations.

It was confirmed with the first author that the mortality data in the study referred to infants.


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?Unclear"Mothers and infants were allocated to 1 of 4 treatment groups, using
a blocked randomization scheme."

Allocation concealment?UnclearDetails not provided.

Blinding?
All outcomes
Yes"The test and placebo capsules were identical in size colour and shape."

Incomplete outcome data addressed?
All outcomes
NoOnly infants of mothers for which blood sample was obtained in the end of the study were included in the analysis. Attrition was 34.6%.

Free of selective reporting?NoNot all clinically relevant outcomes were reported.

Free of other bias?UnclearEnrolment of participants was extended to higher than planned lost to follow-up. Sample size calculation provided, but unclear whether a protocol was published a priori. Supported by a grant from the Wellcome Trust.

RETIBETA Project

MethodsRandomised, double blind, placebo controlled trial.


ParticipantsCommunity-based study with women at 1-3 weeks after birth.
Matlab, Bangladesh.
220 mothers and their infants.


InterventionsSingle high dose to mother within 1-3 weeks after delivery of beta-carotene daily for 9 months.

3 intervention groups:
1. Mother received 200,000 IU of vitamin A as retinyl palmitate and placebo daily for 9 months postpartum (n = 74).
2. Mother received placebo and 7.8 mg (1,300 µg RE or 4,327 IU) of beta-carotene daily until 9 months postpartum (n = 73).
3. Mother received placebo and placebo daily until 9 months postpartum (n = 73).


OutcomesMaternal serum retinol, vitamin A hepatic stores (MRDR), and breast milk retinol concentration. Infant serum retinol concentrations, and vitamin A hepatic stores (MRDR) in a subsample of mothers and infants.


NotesAll Infants at least partially breastfed to 6 months of age.

87% ate complementary food during this period.

98% follow-up rates until 3 months, 95% until 6 months, and 92% until 9 months postpartum.


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?Yes"Before beginning the study, individual treatment codes and follow-up schedules were assigned to a sequence of identification numbers in blocks of 18 using a random number table"..."Each block contained all possible combinations of three treatment groups."

Allocation concealment?Yes"The study capsules were manufactured by Tischon Corporation (Salisbury, MD) and delivered to the field and to study participants coded as type A, B or C."

Blinding?
All outcomes
YesCapsules: packaged in blister pack strips. Vitamin A and placebo capsules differed in colour slightly - authors considered that foil packaging would reduce direct comparisons between groups. Beta-carotene and placebo capsules identical in colour.

Incomplete outcome data addressed?
All outcomes
NoReasons for attrition and exclusions not reported. Intention-to-treat analyses not performed.

Free of selective reporting?NoNot all clinically relevant outcomes were reported.

Free of other bias?UnclearSupported by cooperative agreements between The Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD, USA and the Office of Health and Nutrition, U.S. Agency for International Development, Washington, DC (DAN-5116-1-00-8051-00 and HRN-A-00-97-00015-00). Research protocol not published a priori.

Roy 1997

MethodsRandomised controlled trial.


ParticipantsPostpartum women.
Dhaka, Bangladesh.
50 mothers and their infants.


InterventionsSingle high dose to mother within 24 hours after birth.

2 intervention groups:

1. Mother received 200,000 IU vitamin A as retinyl palmitate plus 60 mg of iron daily for 9 months (n = 25).
2. Mother received 60 mg of iron daily for 9 months (n = 25).


OutcomesMaternal serum retinol, and breast milk retinol concentration. Infant morbidity.


NotesAll babies were breastfed until 6 months postpartum.

No information regarding breastfeeding pattern was provided.


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?UnclearWomen were randomly allocated to either the intervention or control group. No further details provided.

Allocation concealment?UnclearNo details provided.

Blinding?
All outcomes
NoWomen in the control group did not receive a placebo. No details provided about blinding of field workers, laboratory staff or investigators.

Incomplete outcome data addressed?
All outcomes
YesAll randomised participants were accounted for in the analysis.

Free of selective reporting?NoNot all clinically relevant outcomes were reported.

Free of other bias?UnclearStudy supported by the International Centre for Diarrhoeal Disease Research and the United States Agency for International Development. Research protocol not published a priori.

Stoltzfus 1993a

MethodsRandomised, double blind, placebo controlled trial.


ParticipantsWomen at 1-3 weeks postpartum.
Java, Indonesia.
153 mothers and their infants.


InterventionsSingle high dose to mother within 1-3 weeks after birth.

2 intervention groups:

1. Mother received 300,000 IU vitamin A as retinyl palmitate (n = 77).

2. Mother received placebo (n = 76).


OutcomesMaternal abnormal conjunctival impression cytology (CIC), breast milk retinol concentration, maternal serum retinol concentration. Infant serum retinol concentration, vitamin A hepatic stores (RDR).


NotesNo specific information regarding breastfeeding pattern was provided. However, the report's title, background and analysis of breast milk retinol to 8 months postpartum strongly suggest that infants received at least some breast milk for the duration of the study. Additionally, it is noted that the 3 women who stopped breastfeeding were not included in the 6 month follow-up.

88.9% follow-up rate until 6 months postpartum.


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?Unclear"Individual randomization to treatment codes A and B was done in blocks of eight according to the Moses-Oakford assignment algorithm."

Allocation concealment?Yes"The allocation of treatment codes A and B to vitamin A or placebo capsules was done by the Sight and Life Task Force, Hoffmann-LaRoche (Basel, Switzerland), who prepared the capsules."

Blinding?
All outcomes
YesVitamin A and placebo capsules "looked practically identical" and were prepared by "Sight and Life Task Force, Hoffmann-LaRoche" - in labelled foil packs. Participants, field workers, investigators and laboratory staff blinded to randomisation sequence until after field work complete.

Incomplete outcome data addressed?
All outcomes
NoReasons for attrition and exclusions not reported. Intention-to-treat analyses not performed.

Free of selective reporting?NoNot all clinically relevant outcomes were reported.

Free of other bias?UnclearSupported by a grant from the Thrasher Research Fund and a National Science Foundation Graduate Fellowship to Rebecca I. Stoltzfus. Study protocol not published a priori.

Venkatarao 1996

MethodsRandomised, double blind, placebo controlled trial.


ParticipantsWomen at 1-2 weeks after birth.
Tamil Nadu, India.
909 mothers and their infants.


InterventionsSingle high dose to mother within 1-2 weeks after birth; and high dose to infant at 6 months .

3 intervention groups:

1. Mother received 300,000 IU vitamin A as retinyl palmitate and Infant received 200,000 IU vitamin A (n = 301).

2. Mother received 300,000 IU vitamin A and Infant received placebo (n = 297).

3. Mother received placebo and Infant received placebo at 6 months of age (n = 311).


OutcomesInfant morbidity, and adverse effects.


Notes99.7% of infants were breast fed for at least 6 months. No information regarding breastfeeding pattern was provided.

75.8% follow-up rate until 12 months postpartum.


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?Unclear"...randomly allocated". No further details given.

Allocation concealment?Unclear" the Medical Officer...administered the appropriate capsules to the mother from the sealed envelope supplied by the Statistical Section at the Camp Office."

Blinding?
All outcomes
YesCapsules were "similar in colour". Infant syrup matched for colour and consistency.

Incomplete outcome data addressed?
All outcomes
NoExclusions and attrition were 23%. Intention-to-treat analyses not performed.

Free of selective reporting?NoNot all expected outcomes reported.

Free of other bias?UnclearSource of funding not provided. No mention of research protocol.

Vinutha 2000

MethodsRandomised, controlled trial.


ParticipantsPostpartum women (primigravid and second-gravid).
Mumbai, India.
109 mothers and their infants.


InterventionsSingle high dose to mother within 48 hours after delivery.

2 intervention groups:

1. Mother received 200,000 IU vitamin A as aquasol water miscible (n = 53).

2. Mother did not receive vitamin A or placebo (n = 56).


OutcomesMaternal serum retinol, breast milk retinol concentration. Infant serum retinol concentration.


NotesAll babies were exclusively breastfed.

77.1% follow-up rate until 3 months postpartum.


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?UnclearRandomised. No further details provided.

Allocation concealment?UnclearNo details provided.

Blinding?
All outcomes
NoWomen in the control group did not receive a placebo. No other details provided on blinding.

Incomplete outcome data addressed?
All outcomes
NoReasons for attrition and exclusions not reported. Intention-to-treat analyses not performed.

Free of selective reporting?NoNot all clinically relevant outcomes were reported.

Free of other bias?UnclearFunded by the Lokmanya Tilak Municipal Medical College and Hospital in Mumbai. Study protocol not published a priori.

WHO/CHD IVASSG

MethodsRandomised, double blind, placebo controlled, multicentre trial (India, Ghana, and Peru).


ParticipantsPostpartum women and their infants.
New Delhi, India; Brong Ahafo, Ghana; Lima, Peru.
7078 mothers and their infants.


InterventionsSingle high dose to mother within 21-42 days after birth in Ghana and 18-28 days after birth in Peru and India.

3 doses to infant during their DPT or OPV immunization (6, 10, 14 weeks) in Ghana, India and (2, 3 and 4 months) in Peru.

Multicentre trial - At 9 months, infants received 25,000 IU vitamin A with measles immunisation and infants from the control group received single high dose 100,000 IU vitamin A.

Ghana trial - At 6 months, infants received 25,000 IU vitamin A and infants from the control group received single high dose 100,000 IU vitamin A.

Multicentre trial - 2 intervention groups:

1. Mother received 200,000 IU vitamin A as retinyl palmitate and Infants received 100,000 IU vitamin A (4 doses 25,000 IU) (n = 3,522).

2. Mothers received placebo and Infants received placebo (3 doses) plus 100,000 IU vitamin A at 9 months (equivalent total dose received by group 1) (n = 3,556).

Ghana - 4 intervention groups:

1. Mother received 200,000 IU vitamin A as retinyl palmitate and Infants received 100,000 IU vitamin A (4 doses 25,000 IU) (n = 196).
2. Mother received placebo and Infants received vitamin A as per group 1 (n = 192).
3. Mother received vitamin A as per group 1 and Infants received placebo at times of immunisation, plus 100,000 IU vitamin A at 6 months (equivalent total dose received by groups 1 and 2) (n = 185).
4. Mothers received placebo and Infants received placebo (3 doses), plus 100,000 IU vitamin A at 6 months (equivalent total dose received by groups 1 and 2) (n = 194).


OutcomesMaternal serum retinol, breast milk retinol concentration. Infant mortality, morbidity, acute toxic effects, serum retinol concentration, vitamin A hepatic stores (MRDR).


NotesAt least 99.4% of infants were breastfed at enrolment. The sub-study that reported breast milk retinol gave these findings for 570 women, compared with 631 at 2 months, suggesting that the majority of infants were at least partially breast fed to 9 months.

74.9% follow-up rate until 12 months postpartum.

Before and periodically during the study standardisation exercises to assess agreement within and between observers were conducted for the main outcome variables.

Standardisation across sites (Ghana, India and Peru) was ensured by exchange visits.


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?Yes"Identification numbers were generated by computer at the data management centre at John Hopkins University in Baltimore, and assigned as random permuted blocks of size eight."

Allocation concealment?Yes"Three sealed copies of study codes were prepared and kept at WHO in Geneva, with the ethics committee of the All India Institute of Medical Sciences in New Delhi, and at the data management centre in Baltimore. Access was limited to one data manager, who had no direct involvement in the data analysis, and who prepared information requested by the treatment effects monitoring committee."

Blinding?
All outcomes
Yes"The supplements and placebo, in identical opaque gelatin capsules, were packaged in individually coded blister packs in Baltimore."

Incomplete outcome data addressed?
All outcomes
Yes"All analyses were by intent to treat from the time of first administration of study capsule to the mother."

Free of selective reporting?YesAll expected clinically relevant outcomes were reported.

Free of other bias?YesTrial supported by the Child Health and Development Division of WHO, the Johns Hopkins Family Health and Child Survival Cooperative Agreement (HRN 5986-A-00-6006-00) with funding from the United States Agency for International Development, and the Indian Council of Medical Research. A study protocol was not mentioned but study described in detail.

ZVITAMBO Study Group

MethodsRandomised, double blind, placebo controlled, 2 by 2 factorial trial.


ParticipantsPostpartum women without a life-threatening condition and their infants with birthweight ≥ 1500 g from urban maternity centres.
Harare, Zimbabwe.
N = 14,110 mothers and their infants.


InterventionsDouble high dose to mother within 96 hours of birth and single high dose to infant.

4 treatment groups:

1. Mother received 400,000 IU vitamin A as retinyl palmitate and infant received 50,000 IU vitamin A (n = 3529).

2. Mother received 400,000 IU vitamin A and infant received placebo (n = 3529).

3. Mother received placebo and infant received 50,000 IU vitamin A (n = 3530).

4. Mother received placebo and infant received placebo (n = 3522).


OutcomesMaternal mortality, morbidity, serum retinol concentration, haemoglobin concentration. Infant mortality, acute adverse effects (for 788 mother-infant pairs only), and serum retinol concentration.

Infant cause of death was determined from medical records when the death occurred in the hospital, or from a review of verbal autopsy information by study paediatrician.


NotesAll women initiated breastfeeding (97% started breastfeeding within 12 hours postpartum). 99.5% were still breastfeeding at 6 months and 85.8% at 12 months postpartum.


Risk of bias

ItemAuthors' judgementDescription

Adequate sequence generation?Yes"A separate team at Johns Hopkins University prepared the study capsule packets. Study identification numbers were randomly allocated to the treatment groups by computer in blocks of 12. The numbers were printed on adhesive labels and affixed to amber-colored zip-lock plastic bags that were packed with the assigned capsules. Capsule packets were prepared separately for each of the 4 treatment groups and were then merged into numeric order before shipping to Zimbabwe, where a series of packets were distributed to each recruitment site. As each mother-infant pair was recruited, the capsules in the next sequential bag were administered, and the associated study number was assigned to the pair."

Allocation concealment?Yes"Lists linking the study number to the treatment were kept in sealed envelopes and encrypted computer files."

Blinding?
All outcomes
Yes"Treatment and placebo capsules appeared identical."

"separate team at Johns Hopkins University prepared the study capsule packets" and "neither participants nor nurses who administered the capsules or assessed outcomes were aware of treatment group assignment."

Incomplete outcome data addressed?
All outcomes
No"Only infants of mothers who remained HIV-negative to 12 months postpartum were included in the current analysis."

Attrition was 11.3% (in both the vitamin A and placebo groups) for HIV-negative women (985/9562).

Adverse event data was only available for a subset of 788 mother-infant pairs.

The analyses were not by ITT.

Free of selective reporting?NoNot all clinically relevant outcomes were reported.

Free of other bias?Yes"The ZVITAMBO Project was primarily supported by the Canadian International Development Agency (R/C Project 690/M3688), the US Agency for International Development (cooperative agreement no. HRN-A-00-97-00015-00 between Johns Hopkins University and the Office of Health and Nutrition of the USAID), and a grant from the Bill and Melinda Gates Foundation (Seattle); additional support was provided by the Rockefeller Foundation (New York) and BASF (Ludwigshafen, Germany)."

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Ala-Houhala 1988Alternate allocation to the control or test group.

Basu 2003Alternate allocation to the control or test group.

Bezerra 2010Alternate allocation to the control or test group.

Canfield 2001Provision of vitamin A rich foods rather than vitamin A supplements.

De Pee 1995Provision of vitamin A rich foods rather than vitamin A supplements.

Filteau 1999Provision of vitamin A rich foods rather than vitamin A supplements.

Gossage 2000Provision of vitamin A rich foods rather than vitamin A supplements.

Khan 2007Provision of vitamin A rich foods rather than vitamin A supplements.

Lietz 2001Provision of vitamin A rich foods rather than vitamin A supplements.

Lietz 2006Provision of vitamin A rich foods rather than vitamin A supplements.

Ncube 2001Provision of vitamin A rich foods rather than vitamin A supplements.

NNIPS-2Long-term supplementation for women of reproductive age.

ObaapaVitALong-term supplementation for women of reproductive age.

Tchum 2006Alternate allocation to the control or test group.

 
Comparison 1. Supplement (vitamin A as retinyl, water miscible or beta-carotene) versus control (placebo, no treatment)

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

 1 Maternal mortality to six months1564Risk Ratio (M-H, Fixed, 95% CI)0.5 [0.09, 2.71]

    1.1 400,000 IU versus placebo
1564Risk Ratio (M-H, Fixed, 95% CI)0.5 [0.09, 2.71]

 2 Maternal fever at 3 months postpartumOther dataNo numeric data

    2.1 200,000 IU versus no treatment
Other dataNo numeric data

 3 Maternal respiratory tract infection at 3 months postpartumOther dataNo numeric data

    3.1 200,000 IU versus no treatment
Other dataNo numeric data

 4 Maternal diarrhoea at 3 months postpartumOther dataNo numeric data

    4.1 200,000 IU versus no treatment
Other dataNo numeric data

 5 Maternal adverse effects of supplementation1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    5.1 Headache within 30 hours of dosing: 400,000 IU versus placebo
1786Risk Ratio (M-H, Fixed, 95% CI)1.21 [0.74, 1.99]

    5.2 Blurred vision within 30 hours of dosing: 400,000 IU versus placebo
1786Risk Ratio (M-H, Fixed, 95% CI)1.64 [0.39, 6.82]

    5.3 Drowsiness within 30 hours of dosing: 400,000 IU versus placebo
1786Risk Ratio (M-H, Fixed, 95% CI)2.09 [0.91, 4.79]

    5.4 Nausea within 30 hours of dosing: 400,000 IU versus placebo
1786Risk Ratio (M-H, Fixed, 95% CI)1.38 [0.44, 4.31]

    5.5 Vomiting within 30 hours of dosing: 400,000 IU versus placebo
1786Risk Ratio (M-H, Fixed, 95% CI)0.33 [0.03, 3.14]

    5.6 Poor appetite within 30 hours of dosing: 400,000 IU versus placebo
1786Risk Ratio (M-H, Fixed, 95% CI)2.22 [0.69, 7.14]

    5.7 Abdominal pain within 30 hours of dosing: 400,000 IU versus placebo
1786Risk Ratio (M-H, Fixed, 95% CI)1.28 [0.95, 1.73]

 6 Maternal serum retinol (μmol/L) at 1.5 months postpartum1260Mean Difference (IV, Fixed, 95% CI)0.09 [-0.02, 0.20]

    6.1 HIV negative women: 400,000 IU versus placebo
1260Mean Difference (IV, Fixed, 95% CI)0.09 [-0.02, 0.20]

 7 Maternal serum retinol (mcmol/L) at 3 - 3.5 months postpartum4Mean Difference (IV, Random, 95% CI)Subtotals only

    7.1 200,000-400,000 IU versus placebo or no treatment
4660Mean Difference (IV, Random, 95% CI)0.11 [0.01, 0.20]

    7.2 200,000-300,000 IU versus placebo or no treatment
3258Mean Difference (IV, Random, 95% CI)0.17 [0.06, 0.28]

    7.3 400,000 IU versus placebo
1402Mean Difference (IV, Random, 95% CI)0.04 [-0.01, 0.09]

    7.4 Beta-carotene: 7.8 mg daily versus placebo
171Mean Difference (IV, Random, 95% CI)0.10 [-0.10, 0.30]

 8 Maternal serum retinol (mcmol/L) at 6 - 6.5 months postpartum4Mean Difference (IV, Random, 95% CI)Subtotals only

    8.1 200,000-400,000 IU versus placebo or no treatment
4551Mean Difference (IV, Random, 95% CI)0.05 [-0.07, 0.17]

    8.2 200,000-300,000 IU versus placebo or no treatment
3260Mean Difference (IV, Random, 95% CI)0.10 [-0.02, 0.23]

    8.3 400,000 IU versus placebo
1291Mean Difference (IV, Random, 95% CI)-0.02 [-0.08, 0.04]

    8.4 beta-carotene: 7.8mg daily versus placebo
168Mean Difference (IV, Random, 95% CI)0.05 [-0.22, 0.32]

 9 Maternal serum retinol (mcmol/L) at 9 months postpartum2Mean Difference (IV, Fixed, 95% CI)Subtotals only

    9.1 200,000-300,000 IU versus placebo or no treatment
2113Mean Difference (IV, Fixed, 95% CI)0.02 [-0.13, 0.17]

    9.2 beta-carotene: 7.8mg daily versus placebo
166Mean Difference (IV, Fixed, 95% CI)0.19 [-0.03, 0.41]

 10 Maternal low hepatic vitamin A stores 3 months postpartum (MRDR ≥ 0.06)1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    10.1 200,000 IU versus placebo
169Risk Ratio (M-H, Fixed, 95% CI)0.33 [0.15, 0.71]

    10.2 beta-carotene: 7.8 mg daily versus placebo
171Risk Ratio (M-H, Fixed, 95% CI)0.77 [0.47, 1.26]

 11 Maternal low hepatic vitamin A stores 5 - 6 months postpartum (MRDR ≥ 0.06)1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    11.1 200,000 IU versus placebo
171Risk Ratio (M-H, Fixed, 95% CI)0.94 [0.48, 1.85]

    11.2 beta-carotene: 7.8 mg daily versus placebo
168Risk Ratio (M-H, Fixed, 95% CI)0.56 [0.24, 1.32]

 12 Maternal low hepatic vitamin A stores 9 months postpartum (MRDR ≥ 0.06)1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    12.1 200,000 IU versus placebo
163Risk Ratio (M-H, Fixed, 95% CI)0.67 [0.34, 1.34]

    12.2 beta-carotene: 7.8 mg daily versus placebo
166Risk Ratio (M-H, Fixed, 95% CI)0.61 [0.30, 1.23]

 13 Maternal low hepatic vitamin A stores 3 months postpartum (RDR > 20%)1139Risk Ratio (M-H, Fixed, 95% CI)1.15 [0.41, 3.25]

    13.1 300,000 IU versus placebo
1139Risk Ratio (M-H, Fixed, 95% CI)1.15 [0.41, 3.25]

 14 Maternal low hepatic vitamin A stores 6 months postpartum (RDR > 20%)1139Risk Ratio (M-H, Fixed, 95% CI)2.15 [0.20, 23.16]

    14.1 300,000 IU versus placebo
1139Risk Ratio (M-H, Fixed, 95% CI)2.15 [0.20, 23.16]

 15 Breast milk retinol (mcmol/L) at 3 - 3.5 months postpartum5Mean Difference (IV, Random, 95% CI)Subtotals only

    15.1 200,000-400,000 IU versus placebo no treatment
5812Mean Difference (IV, Random, 95% CI)0.20 [0.08, 0.33]

    15.2 200,000-300,000 IU versus placebo no treatment
4390Mean Difference (IV, Random, 95% CI)0.27 [0.11, 0.43]

    15.3 400,000 IU versus placebo
1422Mean Difference (IV, Random, 95% CI)0.08 [0.03, 0.13]

    15.4 beta-carotene: 7.8 mg daily versus placebo
1145Mean Difference (IV, Random, 95% CI)0.02 [-0.14, 0.18]

 16 Breast milk retinol (mcmol/L) at 6 - 6.5 months postpartum4Mean Difference (IV, Random, 95% CI)Subtotals only

    16.1 200,000-400,000 IU versus placebo or no treatment
4679Mean Difference (IV, Random, 95% CI)0.19 [-0.01, 0.39]

    16.2 200,000-300,000 IU versus placebo or no treatment
3325Mean Difference (IV, Random, 95% CI)0.27 [-0.05, 0.60]

    16.3 400,000 IU versus placebo
1354Mean Difference (IV, Random, 95% CI)0.06 [0.01, 0.11]

    16.4 beta-carotene: 7.8 mg daily versus placebo
1138Mean Difference (IV, Random, 95% CI)0.12 [-0.09, 0.33]

 17 Breast milk retinol (mcmol/L) at 8 - 9 months postpartum3Mean Difference (IV, Random, 95% CI)Subtotals only

    17.1 200,000-300,000 IU versus placebo or no treatment
3307Mean Difference (IV, Random, 95% CI)0.15 [-0.15, 0.44]

    17.2 beta-carotene: 7.8 mg daily versus placebo
1135Mean Difference (IV, Random, 95% CI)0.21 [0.04, 0.38]

 18 Breast milk retinol (< 1.05 mcmol/L) at 3 months postpartum3Risk Ratio (M-H, Random, 95% CI)Subtotals only

    18.1 200,000-300,000 IU versus placebo or no treatment
3373Risk Ratio (M-H, Random, 95% CI)0.42 [0.19, 0.91]

    18.2 beta-carotene: 7.8 mg daily versus placebo
1145Risk Ratio (M-H, Random, 95% CI)0.95 [0.80, 1.14]

 19 Breast milk retinol (< 1.05 mcmol/L) at 6 months postpartum2Risk Ratio (M-H, Random, 95% CI)Subtotals only

    19.1 200,000-300,000 IU versus placebo
2275Risk Ratio (M-H, Random, 95% CI)0.65 [0.23, 1.90]

    19.2 beta-carotene: 7.8 mg daily versus placebo
1138Risk Ratio (M-H, Random, 95% CI)0.84 [0.67, 1.06]

 20 Breast milk retinol (< 1.05 mcmol/L) at 8-9 months postpartum2Risk Ratio (M-H, Random, 95% CI)Subtotals only

    20.1 200,000-300,000 IU versus placebo
2257Risk Ratio (M-H, Random, 95% CI)0.80 [0.48, 1.35]

    20.2 beta-carotene: 7.8mg daily versus placebo
1135Risk Ratio (M-H, Random, 95% CI)0.79 [0.63, 0.98]

 21 Breast milk retinol (< 0.28 mcmol/g of fat) at 3 months postpartum1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    21.1 200,000 IU versus placebo
1141Risk Ratio (M-H, Fixed, 95% CI)0.80 [0.63, 1.03]

    21.2 beta-carotene: 7.8mg daily versus placebo
1145Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.82, 1.23]

 22 Breast milk retinol (< 0.28 mcmol/g of fat) at 6 months postpartum2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    22.1 200,000 IU versus placebo
2813Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.71, 0.99]

    22.2 beta-carotene: 7.8mg daily versus placebo
1138Risk Ratio (M-H, Fixed, 95% CI)0.87 [0.71, 1.07]

 23 Breast milk retinol (< 0.28 mcmol/g of fat) at 9 months postpartum2Risk Ratio (M-H, Random, 95% CI)Subtotals only

    23.1 200,000 IU versus placebo
2699Risk Ratio (M-H, Random, 95% CI)0.87 [0.74, 1.02]

    23.2 beta-carotene: 7.8 mg daily versus placebo
1134Risk Ratio (M-H, Random, 95% CI)0.76 [0.62, 0.95]

 24 Maternal abnormal conjunctival impression cytology 3 months postpartum1148Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.55, 1.80]

    24.1 300,000 IU versus placebo
1148Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.55, 1.80]

 25 Maternal abnormal conjunctival impression cytology 6 months postpartum1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    25.1 300,000 IU versus placebo
1142Risk Ratio (M-H, Fixed, 95% CI)0.56 [0.27, 1.17]

 26 Infant mortality46170Risk Ratio (M-H, Fixed, 95% CI)1.14 [0.84, 1.57]

    26.1 deaths to 14 weeks: 400,000 IU versus placebo
1564Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.57, 1.74]

    26.2 deaths to 12 months: 300,000 IU versus placebo
1598Risk Ratio (M-H, Fixed, 95% CI)0.88 [0.34, 2.24]

    26.3 death to 6 months: 200,000 IU versus placebo
1407Risk Ratio (M-H, Fixed, 95% CI)1.54 [0.26, 9.10]

    26.4 deaths to 12 months: 400,000 IU versus placebo
14601Risk Ratio (M-H, Fixed, 95% CI)1.28 [0.83, 1.98]

 27 Infant diarrhoea (one or more episodes) to 12 months1456Risk Ratio (M-H, Fixed, 95% CI)1.02 [0.98, 1.06]

    27.1 300,000 IU versus placebo
1456Risk Ratio (M-H, Fixed, 95% CI)1.02 [0.98, 1.06]

 28 Infant diarrhoea episodes and durationOther dataNo numeric data

    28.1 200,000 IU versus no treatment
Other dataNo numeric data

 29 Infant gastroenteritis to 3 months1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    29.1 200,000 IU versus no treatment
184Risk Ratio (M-H, Fixed, 95% CI)8.44 [0.45, 158.40]

 30 Infant acute respiratory infection (one or more episodes) to 12 months1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    30.1 300,000 IU versus placebo
1456Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.96, 1.03]

 31 Infant upper respiratory tract infection to 3 months1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    31.1 200,000 IU versus treatment
184Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.22, 3.81]

 32 Infant acute respiratory tract infection episodes and durationOther dataNo numeric data

    32.1 200,000 IU versus no treatment
Other dataNo numeric data

 33 Infant febrile illness episodesOther dataNo numeric data

    33.1 200,000 IU versus no treatment
Other dataNo numeric data

 34 Infant adverse effects of supplementation29622Risk Ratio (M-H, Random, 95% CI)2.22 [1.01, 4.86]

    34.1 Bulging fontanelle: 200,000 IU versus placebo
19178Risk Ratio (M-H, Random, 95% CI)2.41 [0.85, 6.83]

    34.2 Bulging fontanelle: 400,000 IU versus placebo
1444Risk Ratio (M-H, Random, 95% CI)2.0 [0.61, 6.55]

 35 Infant serum retinol (µmol/L) at 2 - 3.5 months postpartum3Mean Difference (IV, Random, 95% CI)Subtotals only

    35.1 200,000-400,000 IU versus no treatment
3320Mean Difference (IV, Random, 95% CI)0.12 [-0.08, 0.33]

    35.2 200,000 IU versus placebo or no treatment
2156Mean Difference (IV, Random, 95% CI)0.19 [-0.04, 0.42]

    35.3 400,000 IU versus placebo
1164Mean Difference (IV, Random, 95% CI)0.02 [-0.03, 0.07]

 36 Infant serum retinol (µmol/L) at 5 - 6 months postpartum4Mean Difference (IV, Fixed, 95% CI)Subtotals only

    36.1 200,000-400,000 IU versus placebo
4465Mean Difference (IV, Fixed, 95% CI)Not estimable

    36.2 200,000-300,000 IU versus placebo
3324Mean Difference (IV, Fixed, 95% CI)0.04 [-0.01, 0.09]

    36.3 beta-carotene: 7.8 mg daily versus placebo
1139Mean Difference (IV, Fixed, 95% CI)0.03 [-0.04, 0.10]

    36.4 400,000 IU versus placebo
1141Mean Difference (IV, Fixed, 95% CI)0.06 [-0.02, 0.14]

 37 Infant low hepatic vitamin A stores 1.5 months postpartum (MRDR ≥ 0.06)1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    37.1 200,000 IU versus placebo
1600Risk Ratio (M-H, Fixed, 95% CI)1.11 [1.02, 1.21]

 38 Infant low hepatic vitamin A stores at 5 - 6.5 months postpartum3Risk Ratio (M-H, Random, 95% CI)Subtotals only

    38.1 200,000-400,000 IU versus placebo
3459Risk Ratio (M-H, Random, 95% CI)0.95 [0.79, 1.15]

    38.2 200,000-300,000 IU versus placebo
2270Risk Ratio (M-H, Random, 95% CI)0.69 [0.26, 1.84]

    38.3 400,000 IU versus placebo
1189Risk Ratio (M-H, Random, 95% CI)1.05 [0.90, 1.22]

    38.4 beta-carotene: 7.8 mg daily versus placebo
1139Risk Ratio (M-H, Random, 95% CI)0.91 [0.80, 1.02]

 
Analysis 1.2 Comparison 1 Supplement (vitamin A as retinyl, water miscible or beta-carotene) versus control (placebo, no treatment), Outcome 2 Maternal fever at 3 months postpartum.
Maternal fever at 3 months postpartum

StudyOutcomeSupplementControlP value

200,000 IU versus no treatment

Roy 1997Number of cumulative episodes;

(cumulative duration of illness in days)
10 (30);

n = 25
10 (28);

n = 25
Report states no significant difference

 
Analysis 1.3 Comparison 1 Supplement (vitamin A as retinyl, water miscible or beta-carotene) versus control (placebo, no treatment), Outcome 3 Maternal respiratory tract infection at 3 months postpartum.
Maternal respiratory tract infection at 3 months postpartum

StudyOutcomeSupplementControlP value

200,000 IU versus no treatment

Roy 1997Number of cumulative episodes;

(cumulative duration of illness in days)
23 (82);

n = 25
25 (125);

n = 25
Report states no significant difference

Roy 1997

 
Analysis 1.4 Comparison 1 Supplement (vitamin A as retinyl, water miscible or beta-carotene) versus control (placebo, no treatment), Outcome 4 Maternal diarrhoea at 3 months postpartum.
Maternal diarrhoea at 3 months postpartum

StudyOutcomeVitamin AControlP value

200,000 IU versus no treatment

Roy 1997Number of cumulative episodes;

(cumulative duration of illness in days)
10 (27);

n = 25
2 (15);

n = 25
Report states no significant difference

 
Analysis 1.28 Comparison 1 Supplement (vitamin A as retinyl, water miscible or beta-carotene) versus control (placebo, no treatment), Outcome 28 Infant diarrhoea episodes and duration.
Infant diarrhoea episodes and duration

StudyOutcomeSupplementNo treatmentSignificance

200,000 IU versus no treatment

Roy 1997Diarrhoea episodesRR/OR?? 0.12 (95% CI 0.09 to 0.15)0.11 (95% CI 0.08 to 0.14)P = 0.59

Roy 1997Diarrhoea duration0.74 (95% CI 0.53 to 0.95)0.71 (95% CI 0.50 to 0.92)P = 0.78

Roy 1997Child-weeks515522

 
Analysis 1.32 Comparison 1 Supplement (vitamin A as retinyl, water miscible or beta-carotene) versus control (placebo, no treatment), Outcome 32 Infant acute respiratory tract infection episodes and duration.
Infant acute respiratory tract infection episodes and duration

StudyOutcome / DetailsVitamin AControlSignificance

200,000 IU versus no treatment

Roy 1997Acute respiratory tract infection episodes

(mean episodes per child-week of observation)
0.42 (95% CI 0.38 to 0.46)0.45 (95% CI 0.41 to 0.49)P = 0.51

Roy 1997Acute respiratory tract infection duration

(duration (days) per child-week of observation)
3.1 (95% CI 2.7 to 3.5)3.7 (95% CI 3.25 to 4.15)P = 0.03

Roy 1997Child-weeks515522

 
Analysis 1.33 Comparison 1 Supplement (vitamin A as retinyl, water miscible or beta-carotene) versus control (placebo, no treatment), Outcome 33 Infant febrile illness episodes.
Infant febrile illness episodes

StudyOutcome / DetailsVitamin AControlSignificance

200,000 IU versus no treatment

Roy 1997Febrile illness episodes

(mean episodes per child-week of observation)
0.1 (95% CI 0.09 to 0.11)0.3 (95% CI 0.27 to 0.30)P < 0.002

Roy 1997Child-weeks515522

 
Comparison 2. Supplement (vitamin A as retinyl) high dose versus low dose

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

 1 Infant mortality1220Risk Ratio (M-H, Fixed, 95% CI)2.0 [0.37, 10.70]

    1.1 400,000 IU versus 200,000 IU
1220Risk Ratio (M-H, Fixed, 95% CI)2.0 [0.37, 10.70]

 2 Maternal serum retinol (ɥmol/L)2Mean Difference (IV, Fixed, 95% CI)Subtotals only

    2.1 400,000 IU versus 200,000 IU at 2 months postpartum
1193Mean Difference (IV, Fixed, 95% CI)0.02 [-0.10, 0.14]

    2.2 400,000 IU versus 200,000 IU at 3 months postpartum
1190Mean Difference (IV, Fixed, 95% CI)-0.06 [-0.28, 0.16]

    2.3 400,000 IU versus 200,000 IU at 6 months postpartum
2812Mean Difference (IV, Fixed, 95% CI)-0.00 [-0.14, 0.13]

    2.4 400,000 IU versus 200,000 IU at 9 months postpartum
1602Mean Difference (IV, Fixed, 95% CI)-0.09 [-0.26, 0.08]

 3 Breast milk retinol (< 1.05 ɥmol/L)1382Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.69, 1.36]

    3.1 400,000 IU versus 200,000 IU at 3 months postpartum
1190Risk Ratio (M-H, Fixed, 95% CI)1.25 [0.72, 2.17]

    3.2 400,000 IU versus 200,000 IU at 6 months postpartum
1192Risk Ratio (M-H, Fixed, 95% CI)0.81 [0.53, 1.25]

 4 Infant serum retinol (ɥmol/L ) at 2 months postpartum1134Mean Difference (IV, Fixed, 95% CI)0.02 [-0.05, 0.09]

    4.1 400,000 IU versus 200,000 IU
1134Mean Difference (IV, Fixed, 95% CI)0.02 [-0.05, 0.09]

 
Summary of findings for the main comparison. Vitamin A supplementation compared to placebo for postpartum mothers

Vitamin A supplementation compared to placebo for postpartum mothers

Patient or population: postpartum mothers
Settings:
Intervention: Vitamin A supplementation
Comparison: placebo

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

Assumed riskCorresponding risk

placeboVitamin A supplementation

Maternal mortality
Follow-up: mean 12 months
3 per 100013 per 1000
(2 to 5)2
HR 1.11
(0.81 to 1.51)
8577
(1 study)
⊕⊕⊝⊝
low3,4,5,6,7

Maternal morbidity: Infections (total days of illness per days of follow-up)
Follow-up: mean 3 months
See commentSee comment50
(1 study)
⊕⊝⊝⊝
very low8,9,10,11,12
30/2281 with vitamin A versus 28/2281 with placebo; no statistical comparison performed13

Maternal adverse effects after administration: vomiting8 per 10003 per 1000
(0 to 25)
RR 0.33
(0.03 to 3.14)
786
(1 study)
⊕⊕⊝⊝
low4,7,14

Maternal serum retinol (mcmol/L)
mcmol/L
Follow-up: 3-3.5 months
The mean maternal serum retinol (mcmol/l) in the control groups was
1.28 mcmol/L
The mean Maternal serum retinol (mcmol/L) in the intervention groups was
0.17 higher
(0.06 to 0.28 higher)
258
(3 studies)
⊕⊕⊝⊝
low15

Maternal low hepatic vitamin A stores (MRDR greater than or equal to 0.06)
Follow-up: 3 months
543 per 1000179 per 1000
(81 to 386)
RR 0.33
(0.15 to 0.71)
69
(1 study)
⊕⊕⊕⊝
moderate16,17,18

Maternal low hepatic vitamin A stores (RDR > 20%)
Follow-up: 3 months
87 per 1000100 per 1000
(36 to 283)
RR 1.15
(0.41 to 3.25)
139
(1 study)
⊕⊕⊕⊝
moderate19,20,21

*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; HR: Hazard 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 ZVITAMBO Study Group: The data for the number of deaths in the placebo group have been estimated from the original reference. The study did not report the number of deaths in the placebo group; we have estimated the figure using the reported number of participants in the placebo group, the total number of participants in both groups, the total number of deaths in both groups, and the hazard ratio of 1.11.
2 ZVITAMBO Study Group: The data for the number of deaths in the intervention group have been estimated from the original reference. The study did not report the number of deaths in the vitamin A group; we have estimated the figure using the reported number of participants in the vitamin A group, the total number of participants in both groups, the total number of deaths in both groups, and the hazard ratio of 1.11.
3 ZVITAMBO Study Group: The analysis was not by ITT, but the attrition rate was low (11%), and therefore a point has not been deducted for limitations in design
4 ZVITAMBO Study Group: One study only, therefore no inconsistency.
5 ZVITAMBO Study Group: Estimated rather than actual figures of mortality.
6 ZVITAMBO Study Group: Wide 95% confidence intervals that cross the line of no effect, which therefore does not exclude benefit or harm of vitamin A.
7 ZVITAMBO Study Group: Few events in trial.
8 Roy 1997: Unclear allocation concealment and unblinded control group (no placebo).
9 Roy 1997: No statistical analysis for comparison of vitamin A versus placebo.
10 Roy 1997: One study only, therefore no inconsistency.
11 Roy 1997: Maternal fever a proxy outcome for infectious morbidity.
12 Roy 1997: Few events in trial.
13 Roy 1997: Number of cumulative days of illness (numerator) and number of people days' follow-up (denominator). The number of people days has been extracted from the original reference.
14 ZVITAMBO Study Group: Unclear why only 766 women out of the 14,110 women randomised were included in the assessment of adverse effects.
15 RETIBETA, Roy 1997, Stoltzfus 1993a: Reasons for attrition were not reported, and no ITT analyses were performed, in RETIBETA and Stoltzfus 1993a. Unclear allocation concealment and unblinded control group (no placebo) in Roy 1997.
16 RETIBETA: Reasons for attrition were not reported, and no ITT analysis was performed; however, follow-up rates were greater than 90%, and therefore no point has been deducted.
17 RETIBETA: One study only, therefore no inconsistency.
18 RETIBETA: Few events in trial.
19 Stoltzfus 1993a: Reasons for attrition were not reported, and no ITT analysis was performed; however, follow-up rates were 89% at 6 months, and therefore no point has been deducted.
20 Stoltzfus 1993a: One study only, therefore no inconsistency.
21 Stoltzfus 1993a: Wide 95% confidence intervals that cross the line of no effect, which therefore does not exclude benefit or harm of vitamin A.