SELECTED LABORATORY BASED BIOMARKERS FOR ASSESSING VITAMIN A DEFICIENCY IN INFANTS AND CHILDREN A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

BackgroundIn 2013, the World Health Organization estimated 190 million preschool aged children (6-59 months), and 19 million pregnant women were affected by vitamin A deficiency. It is difficult to identify subclinical vitamin A deficiency before overt clinical symptoms develop, as serum retinol levels are homeostatically regulated until liver stores become significantly depleted. Therefore, common blood tests will not indicate a subclinical deficiency. In order to improve diagnostic accuracy of vitamin A status indicators, we need non invasive biomarkers that are also sensitive and specific. MethodsThis systematic review focuses on infants and children under the age of 5 years. We searched for studies that measured vitamin A status by at least one reference standard (liver biopsy or isotope dilution) and one index test (serum/plasma retinol, serum/plasma retinol binding protein, or relative dose response/modified relative dose response). Data was extracted from studies that met the inclusion criteria via Jotform. Methodological quality of included studies was assessed using QUADAS 2 (Whiting 2011). 2x2 tables were constructed to calculate sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios. Forest plots were created to compare sensitivity and specificity between studies. ResultsThe initial search returned 34,574 references. After title/abstract and full text screening, 11 were included in the final review. 4 of these studies were included in meta-analysis. Due to small sample sizes, sensitivity and specificity estimates for each study had large confidence intervals. The most reliable estimates of sensitivity/specificity were from Zaklama 1972, the only included study that had participants in each category (TP, FP, TN, FN) for calculation. DiscussionMore research is needed to truly assess the diagnostic accuracy of common biomarkers used in this population. Researchers should focus on using isotope dilution as a reference standard to allow more diverse populations and clinical conditions to be studied. BIOGRAPHICAL SKETCH