A Randomized Trial of Quadruple-Fortified Salt for Anemia and Birth Defects Prevention in Southern India: Protocol Design and Methods.

BACKGROUND

Women of reproductive age are at an increased risk of anemia and micronutrient deficiencies. Evidence supports the role of periconceptional nutrition in the development of neural tube defects (NTDs) and other pregnancy complications. Vitamin B12 deficiency is a risk factor for NTDs and may modify folate biomarkers that predict NTD risk at the population level. There is an interest in mandatory fortification with vitamin B12 and folic acid for anemia and birth defect prevention. However, there are limited population-representative data needed to inform policy and guidelines.

OBJECTIVES

This randomized trial will be conducted to evaluate the efficacy of quadruple-fortified salt (QFS; iron, iodine, folic acid, vitamin B12) in 1,000 households in Southern India.

METHODS

Women 18 to 49 y who are not pregnant or lactating and reside within the catchment area of our community-based research site in Southern India will be screened and invited to participate in the trial. After informed consent, women and their households will be randomized to receive one of the following 4 interventions: 1) double-fortified salt (DFS; iron, iodine), 2) DFS + folic acid (iron, iodine, folic acid), 3) DFS + vitamin B12 (iron, iodine, vitamin B12), or 4) DFS + folic acid and vitamin B12 (QFS; iron, iodine, folic acid, vitamin B12) for 12 mo. Structured interviews will be conducted by trained nurse enumerators to collect sociodemographic, anthropometric, dietary, health, and reproductive history data. Biological samples will be collected at baseline, midpoint, and endpoint. Whole blood will be analyzed for hemoglobin using Coulter Counter. Total vitamin B12 will be measured by chemiluminescence; red blood cell folate and serum folate will be evaluated using the World Health Organization-recommended microbiologic assay.

CONCLUSIONS

The results of this randomized trial will help to evaluate the efficacy of QFS to prevent anemia and micronutrient deficiencies. Clinical trial registration numbers: NCT03853304 and Clinical Trial Registry of India REF/2019/03/024479.

REGISTRATION NUMBER: NCT03853304 and REF/2019/03/024479.