H/A: Micronutrient Supplementation (2009)

Citation:
 
Study Design:
Class:
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Quality Rating:
Research Purpose:

The purpose of this study was to determine whether supplementation of HIV-infected pregnant and lactating women with vitamins A and vitamins B, C and E was related to increased concentrations of vitamins B12, C and E during their infant's first six months of age.

Inclusion Criteria:
  • HIV-infected pregnant women attending pre-natal clinics in Dar Es Salaam, Tanzania
  • Between 12 and 27 weeks gestation at first clinic visit
  • Planning to stay in the city until delivery and then at least one year after delivery.
Exclusion Criteria:

Not stated.

Description of Study Protocol:

Recruitment

Women were recruited from four pre-natal clinics in Dar es Salaam, Tanzania.

Design

The study was a randomized clinical trial using a two-by-two factorial design. 

Blinding Used

All clinical and follow-up staff members were blinded to the treatment assignment.

Intervention 

Eligible women were randomly assigned in blocks of 20 to a daily oral dose of one of four regimens for the total duration of the followup:

  • Vitamin A and beta-carotene alone (30mg beta-carotene and 5,000 IU pre-formed vitamin A)
  • Multivitamins (excluding vitamin A and beta-carotene) that included 20mg thiamine (vitamin B1), 20mg riboflavin (vitamin B2), 25mg vitamin B6, 100mg niacin, 50mcg cobalamin (vitamin B12), 500mg vitamin C, 30mg vitamin E, 0.8mg folic acid
  • Vitamins provided in same doses as above
  • Placebo.

To maintain pills at a reasonable size, each daily dose was prepared in two tablets, each containing half the dose; tablets were packaged in identical coded bottles that contained 90 tablets each. At every visit, a new bottle of regimen was given to each woman, the used bottles were taken back, and the remaining pills were counted. At delivery, women in groups one and three received an additional oral dose of vitamin A (200,000 IU), and women in groups two and four were given a placebo.

All women received antenatal supplements of folic acid (5mg) and iron (120mg) according to the standard of prenatal care. All children received doses of vitamin A at six-month intervals according to standard of care in Tanzania (100,000 IU at six months and 20,000 IU at 12 months and thereafter). Active tablets and placebo were identical in size and color.

Antiretroviral therapy was not available at that time.

Statistical Analysis

The statistical significance of the differences in the mean concentration of vitamins at six weeks or six months between treatment arms was assessed using Wilcoxins's rank-sum tests, whereas treatment effects on the prevalence of vitamin deficiencies were tested using the Chi-Square test.

Data Collection Summary:

Timing of Measurements

Blood samples were collected from the infants at birth and at six weeks and six months post-natal visits.

Dependent Variables

  • Vitamin A levels in infants
  • Vitamin E levels in infants
  • Vitamin B12 levels in infants.

Independent Variables 

  • Vitamin A and beta-carotene alone (30mg beta-carotene and 5,000 IU pre-formed vitamin A)
  • Multivitamins (excluding vitamin A and beta-carotene) that included 20mg thiamine (vitamin B1), 20mg riboflavin (vitamin B2), 25mg vitamin B6, 100mg niacin, 50mcg cobalamin (vitamin B12), 500mg vitamin C, 30mg vitamin E, 0.8mg folic acid
  • Vitamins provided in same doses as above
  • Placebo. 

Control Variables

  • HIV-infected status
  • Antiretroviral therapy.

 

Description of Actual Data Sample:
  • Initial N: 716 mothers and their infants (171 received placebo; 180 received vitamin A; 181 received mulitvitamins; and 184 received vitamin A and multivitamins)
  • Attrition (final N): Same as above
  • Age: Average age of mothers was 25 years
  • Ethnicity: Lived in Dar es Salaam, Tanzania.

Other relevant demographics:

Mothers' average first pre-natal visit was at week 20. They had between five and eight years of education. Breastfeeding was almost universal in this population, with an average duration of  16 months (SD, seven months) and a prevalance of 95% at both six weeks and six months.

Anthropometrics

Serum vitamin E levels were signficantly higher in the Vitamin A-supplemented group vs. the no-vitamin-A group at baseline (22.6 micromol per L vs. 23.7micromol per L, P<0.05). Hemoglobin concentration was signficantly lower for the multivitamins (9.3g per L) vs. the no-multivitamins group (9.6g per L), P<0.05, at baseline.

Infants' birth weights in the multivitamin group was signficantly higher in the multivitamins group than the no-multivitamins group (3,109g vs. 2,979g, P<0.05). 12.4% of infants in the no-multivitamins group were classified as small for gestational age compared to 6.8 % in the multivitamins group (P<0.05).

Location

Dar es Salaam, Tanzania.

 

Summary of Results:

Vitamin Concentration

(6 weeks)

No Multivitamins

Mean (SD)

Multivitamins

Mean (SD)

P-value
Vitamin A (micromol per L) 0.50 (0.17) 0.45 (0.17) 0.0002
Vitamin E (micromol per L) 15.2 (6.5) 17.0 (7.7) 0.0008
Vitamin B12 (pmol per L) 247 (102) 423 (185) <0.0001

Vitamin Concentration

(Six Months)

 

No Multivitamins

Mean (SD)

 

Multivitamins

Mean (SD)

P-value
Vitamin A (micromol per L) 0.52 (0.19) 0.51(0.22) 0.27
Vitamin E (micromol per L) 14.6 (6.1) 15.7 (5.9) 0.004
Vitamin B12 (pmol per L) 286 (138) 413(165) <0.0001

  

Vitamin A Concentration (micromol per L) Mean (sd) No Vitamin A Vitamin A P-value
Six weeks 0.43 (0.16) 0.52(0.18) <0.0001
Six months 0.48 (0.19) 0.54(0.21) 0.0002

Other Findings

Maternal vitamin A supplementation increased serum retinol in the infants at six weeks (mean difference, 0.09micromol per L; P<0.0001) and six months (mean difference, 0.06micromol per L; P=0.0002), and decreased the prevalence of vitamin A deficiency, but had no impact on serum vitamins E or B12.

Multivitamins increased serum vitamin B12 at six weeks and six months (mean differences, 176micromol per L; P<0.001 and 127pmol per L; P<0.0001, respectively) and vitamin E (mean differences, 1.8micromol per L; P=0.0008 and 1.1micromol per L; P=0.004, respectively) and decreased the prevalence of vitamin B12 deficiency. 

 

 

 

 

Author Conclusion:

In conclusion, this study shows that supplementation with multivitamins during pregnancy and lactation to HIV-infected women is an effective strategy to improve the vitamin status of their infants.

Funding Source:
Government: National Institute of Child Health and Human Development, Fogarty International Center
Reviewer Comments:

Part of a large study evaluating the effects of micronutrient supplementation on HIV-infected women and their infants. Did not assess dietary intake of vitamins measured (this could have altered results). Did not assess vitamin C levels due to improper stabilization of serum samples.

Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? Yes
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? No
  6.6. Were extra or unplanned treatments described? No
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? ???
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes