Systematic Review and Meta-Analysis of the Relative Dose-Response Tests to Assess Vitamin A Status

Abstract

Vitamin A (VA) is an essential nutrient often lacking in the diets of people in developing countries. Accurate biomarkers of VA status are vital to inform public health policy and monitor interventions. The relative dose-response (RDR) and modified-RDR (MRDR) tests are semi-quantitative screening tests for VA deficiency that have been used in Demographic and Health Surveys and VA intervention studies. A systematic review and meta-analysis of sensitivity and specificity were conducted to summarize the physiological evidence to support the RDR tests as methods to assess VA status and investigate the impact of different pathological and physiological states on the tests. A total of 190 studies were screened for inclusion, with 21 studies comparing the RDR tests with the gold-standard biomarker, liver VA concentration (68% and 80% sensitivity and 85% and 69% specificity for the RDR and MRDR, respectively). Nearly all studies with VA interventions in VA-deficient populations demonstrated a response of the tests to VA intake that would be expected to improve VA status. The impacts of chronic liver disease, protein malnutrition, age, pregnancy and lactation, infection and inflammation, and various other conditions were examined in 51 studies. The RDR and MRDR tests were reported to have been used in 39 observational studies, and the MRDR has been used in at least 6 national micronutrient surveys. The RDR and MRDR are sensitive tests for determining population VA status and assessing VA interventions. Although they are robust to most physiological and pathological states, caution may be warranted when using the tests in neonates, individuals with chronic liver disease, and those with protein or iron malnutrition. Research on further improvements to the tests to increase accessibility, such as sampling breast milk instead of blood or using intramuscular doses in subjects with malabsorption, will allow wider adoption. This review was registered with PROSPERO as CRD42019124180.