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 the effect of multivitamin supplementation on hemoglobin concentrations and the risk of anemia among HIV-infected women and their children.

Inclusion Criteria:

HIV-infected pregnant women in Dar es Salaam, Tanzania.

 

Exclusion Criteria:

Unknown (stated in another published article).

Description of Study Protocol:

Recruitment

Pregnant women were enrolled during a two-year period starting in April, 1995 and they (and their children after delivery) were followed until the end of the study in August, 2003.

Design

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

  • Vitamin A and beta-carotene alone (30mg beta-carotene and 5,000 IU preformed 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 and 0.8mg folic acid
  • Vitamins provided in same doses as above
  • Placebo.

Blinding Used

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

Intervention

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 the 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.

Statistical Analysis

The Kruskal-Wallis test was used for continuous variables and the chi-square test for categorical variables. All analyses were based on the intent-to-treat principle and P-values were two-sided.

Data Collection Summary:

Timing of Measurements

Participants were followed through monthly visits to a study clinic where physicians performed a physical examination. A study nurse inquired about the health of the woman and child in the preceding period. Blood samples from the women were taken at baseline and at six-month intervals.

Dependent Variables

  • Hemoglobin concentration of mother
  • Hemoglobin concentration of children
  • Relative risk of anemia for mothers
  • Relative risk of anemia for children.

Independent Variables

Multivitamin supplementation (preformed vitamin A and beta-carotene; vitamins B, C, E; preformed vitamin A and beta-carotene, and vitamins B, C, E; placebo).

Control Variables

  • HIV status
  • Antiretroviral medications.

 

Description of Actual Data Sample:
  • Initial N: 1,078 pregnant women
  • Attrition (final N): 1,042
  • Age: 24.8±4.9.

Anthropometrics

  • There were no significant differences between the four groups with regards to age, gestational week, education, number of prior pregnancies, weight, height, CD4 count, hemoglobin concentration, anemia, iron deficiencies and plasma vitamin A and E levels at baseline
  • There were no significant differences in compliance between the four groups at the end of the study
  • There were no significant differences in infant feeding practices across the four groups.

Location

Dar es Salaam, Tanzania. 

Summary of Results:

 Other Findings

  • Women who received multivitamins had hemoglobin concentrations 0.33g per dL higher than women who were not given multivitamins during the whole period (P=0.07)
  • Hemoglobin concentrations of children of mothers on multivitamins were 0.18g per dL higher than children of mothers not on multivitamins (P=0.0002)
  • At birth, the difference in hemoglobin concentrations among children of mothers in the vitamin A and beta-carotene group on average was -0.08g per dL compared with children whose mothers did not receive vitamin A and beta-carotene (P=0.008)
  • By six months of age, hemoglobin concentrations of children of mothers in the multivitamins-only group were 0.36g per dL higher than among children of mothers given placebo (P=0.06)
  • Hemoglobin concentrations of children born to mothers who received multivitamins including vitamin A and beta-carotene, or vitamin A and beta-carotene alone, were not significantly different from children of mothers in the placebo group
  • Children born to mothers in the multivitamin group had a reduced risk of severe microcytic hypochromic anemia (RR: 0.60; 95% CI: 0.42, 0.85; P=0.004)
  • The risk of microcytic hypochromic anemia was reduced 30% in the multivitamins-alone child group compared to the placebo group  (RR: 0.70; 95% CI: 0.51, 0.95; P=0.02)
  • Macrocytic anemia was significantly less likely to occur among children of women in the multivitamins-alone group (RR: 0.37; 95% CI: 0.18, 0.79; P=0.01).
Author Conclusion:

Multivitamin supplementation provided during pregnancy and in the post-partum period resulted in significant improvements in hematologic status among HIV-infected women and their children, which provides further support for the value of multivitamin supplementation in HIV-infected adults.

Funding Source:
Government: National Institute of Child Health and Human Development, City of Dar es Salaam Regional Health Authority;Tanzanian National AIDS Control Program
University/Hospital: Muhimbili University College of Health Sciences;Muhimbili National Hospital;Harvard School of Public Health
Reviewer Comments:

Large sample size, well-designed study.

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? ???
  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? Yes
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.) Yes
  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? Yes
  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? ???
  6.6. Were extra or unplanned treatments described? ???
  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? Yes
  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? Yes
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