Evaluation of the newly proposed Vitamin A supplementation regimen for postpartum mothers using 3,4-didehydroretinol acetate in Modified Relative Dose Response (MRDR) assay.

Investigators:

• S.K. Tchum, S. Newton and S. Owusu-Agyei.(Kintampo Health Research Centre, Health Research Unit, Ghana Health Service, Ghana.)

• S. A. Tanumihardjo ( Department of Nutritional Sciences, University of Wisconsin,) Madison, U.S.A.

Background

Vitamin A deficiency (VAD) is a public health problem in many developing countries. Assessing vitamin A (VA) status is important in determining which population groups are at risk for deficiency. Dietary surveys are inappropriate for determining VA status because multiple factors affect the absorption and utilization of pro-VA carotenoids and preformed VA. Biochemical assessment of VA status is not straightforward because serum retinol concentrations (RE) are homeostatically controlled and can be depressed by infection. However, other indicators of VA status have been developed. The Modified Relative Dose Response (MRDR) test, one of the sensitive indicators of VA status, has been designed to assess the total body reserves of VA in lactating women

Hypothesis

• In women who are given 400,000 IU of vitamin A, the length of protection from vitamin A depletion is increased but not doubled.

• The length of protection from vitamin A depletion is not extended to 5 months.

Objective

To determine the length of time mothers are protected against depletion after receiving either 400,000 IU of vitamin A in two doses of 200,000 IU 24 hours apart or one dose of 200,000 IU.

Methods

This is an individually randomised alternate weekly-randomised controlled trial of a sample size of 168 postpartum mothers at selected villages in Kintampo District of the Brong-Ahafo Region in Ghana.

The trial mothers are visited at home about 7 to 10 days after delivery and recruited into the trial using the established procedures at Kintampo Health Research Centre. This involves an earlier meeting of the potential trial subjects together with their heads of household or elder(s) and soliciting their agreement to participate inthe trial after reading to them a prepared information sheet written in their local language. This explains the purpose of the study, the study procedures, the obligations of investigators and what will be required of participants if they agree to participate. Opportunity is given for questions and for checking that the information provided has been understood. Mothers are then asked to indicate their consent to participate by appending their signatures or other personal mark to a prepared declaration.

After this, the mothers are issued with a study ID card bearing their details; including their unique study ID’s.

The selected postpartum mothers were recruited six weeks after delivery at these selected villages in Ghana. All the women were tested for their baseline MRDR. They were then divided into three groups of 56 women in each group and randomly assigned to a follow-up MRDR assessment at 1, 3 or 5 months after receipt of one of the two oral doses of 200,000IU (control group) and 400,000IU (intervention group). The MRDR test involves giving a single oral dose of vitamin A containing, 8.8µmol of 3,4-didehydroretinyl acetate and then taking a single finger prick blood sample of 500ul, 5 hours after dosing. The blood samples were centrifuged and the serum separated from the blood cells by means of a transfer pipette into a 1.5ml amber tube. The serum samples were kept frozen until all collections have been completed. They were air-freighted to a laboratory in University of Wisconsin (UW), Department of Nutritional Sciences, Madison, U.S.A. for analysis. MRDR analysis was carried on the serum samples;

The MRDR test was used at 1, 3 and 5 months after dosing to assess changes in vitamin A status, through analyses using the High Performance Liquid Chromatography (HPLC) method. The data collected from the field and the laboratory are being analysed.

Long-term goal

The long-term goal of this project is to establish public health programs that will improve the health of women globally by determining safe and effective methods to improve vitamin A status. By improving the vitamin A status of mothers, mortality and morbidity of children will be reduced. The project will be completed by mid-October, 2005.

Results:

The baseline serum retinol concentration and MRDR values were 1.4 ± 0.5 μmol/L and 0.048 ± 0.037, respectively. A significant improvement in VA status occurred within the treatment groups as assessed by the MRDR test at each time point (P < 0.0034), and both the 200,000 and 400,000 IU doses maintained VA adequacy for 5 mo. Serum retinol concentrations were not different between and within the two treatment groups at any of the times tested (P > 0.60).

Conclusion:

The postpartum mothers had marginally depleted VA liver reserves at baseline as assessed by the MRDR test. Liver reserves of VA significantly improved in both treatment groups and improvement was maintained for at least 5 months.

Project funder

The International Atomic Energy Agency (IAEA) funded this study.

Contact: Kofi.Tchum@ghana-khrc.org