Neural tube defects (NTDs) are severe birth defects primarily due to maternal folate insufficiency during early pregnancy, although maternal vitamin B12 deficiency has also been proposed as a possible contributor. NTDs pose a significant public health burden in Ethiopia, where the prevalence ranges from 60 to 166 cases per 10,000 births, depending on the study, far exceeding the global average of 19 per 10,000 births. Folate insufficiency is also prevalent among Ethiopian women of reproductive age (WRA), with 74.6% having red blood cell (RBC) folate levels below the recommended threshold of 748 nmol/L; and 15% of WRA have vitamin B12 deficiency. Although mandatory fortification of wheat flour with folic acid has successfully reduced NTD prevalence globally, Ethiopia has limited production of fortifiable wheat flour, which reaches only 30% of the population, largely in urban areas. Fortifying iodized salt with folic acid and potentially with vitamin B12 offers a promising solution due to salt’s universal accessibility and Ethiopia’s established iodization infrastructure. This dissertation addresses critical gaps in knowledge to support the implementation of folic acid fortification of iodized salt. The objectives were to: 1) evaluate the quality of Ethiopian and imported salts, including moisture, iodine, and heavy metal concentrations, and assess the stability of folic acid and iodine in fortified salt; 2) examine salt procurement and utilization practices and assess the acceptability of double-fortified salt (DFS) containing iodine and folic acid and triple-fortified salt (TFS) containing iodine, folic acid, and vitamin B12; and 3) determine the serum folate cutoff that corresponds to the RBC folate threshold used for predicting NTD risk and evaluate its performance.
The first study evaluated the quality of Ethiopian and imported salts and assessed the stability of folic acid and iodine in salts stored under varied storage conditions. Fifty-four Ethiopian salt samples (categorized by four packaging types) and 10 imported salts were analyzed for moisture, iodine, and heavy metal contents. All moisture levels met the acceptable limit of 3%, but 25% of the Ethiopian salts exceeded the iodine standard (20–40 ppm) and contained elevated copper (>2 ppm), iron (>10 ppm), lead (>2 ppm), and aluminum (>5 ppm). Imported salts met all quality standards. Stability analysis showed folic acid retention of 82.1%, 79.5%, and 73.4% at 25°C, 35°C, and 45°C, respectively, after six months of storage, while iodine retention exceeded 94% across all temperatures. These findings confirm the feasibility of dual fortification, but highlight the need for quality assurance, improved packaging, and robust monitoring systems to address local salt quality issues.
The second study examined household salt procurement and utilization practices and assessed the acceptability of DFS and TFS among Ethiopian WRA. Surveys of 840 women in urban (Addis Ababa) and rural (Gimbichu Woreda) areas explored salt preferences, purchasing practices, and sensory acceptability using a three-point hedonic scale. Women were the primary salt purchasers (rural: 72.8%, urban: 97.4%). Rural women preferred coarse salt (76.1%), while urban women favored fine salt (42.4%) or both types (30.0%). All salts received favorable sensory ratings (≥2.1), with fine salt preferred for all characteristics (P<0.05). While iodized salt (IS) scored slightly higher than DFS and TFS, willingness to purchase DFS and TFS was greater among rural women (DFS: 79.2%, TFS: 73.0%) than urban women (DFS: 65.0%, TFS: 63.8%). These findings highlight the high acceptability of DFS and TFS and emphasize the need for mandatory fortification of both coarse and fine salts to ensure nationwide coverage.
The third study determined the serum folate cutoff corresponding to the RBC folate threshold (748 nmol/L) for predicting NTD risk. Biomarker data from 1,570 Ethiopian WRA who participated in the 2015 Ethiopian National Micronutrient Survey were analyzed. Serum and RBC folate were measured using the CDC microbiological assay. Serum folate cutoffs were identified via unadjusted and adjusted regression models and ROC curve analysis. Ethiopian-specific cutoffs of 15.3 nmol/L (unadjusted), 15.2 nmol/L (adjusted), and 17.9 nmol/L (ROC-derived) were identified. Regression-based cutoffs balanced sensitivity (~76%) and specificity (~62%), while the ROC-derived cutoff improved sensitivity (~83%) but reduced specificity (~50%). The serum folate cutoff from Southern India (~37 nmol/L) showed high sensitivity (~98%) but poor specificity (~15%), when applied to Ethiopian data leading to elevated false positives. Ethiopian cutoffs demonstrated fair discriminatory performance (AUC: 0.665–0.686), highlighting the need for population-specific thresholds. Serum folate remains a practical alternative where RBC folate measurement is not feasible, but RBC folate should be prioritized as the gold-standard biomarker.
In conclusion, fortifying iodized salt with folic acid and vitamin B12 is a feasible, practical, and acceptable intervention to address Ethiopia’s high burden of NTDs, maternal folate insufficiency, B12 deficiency and related morbidities. Policy efforts should focus on implementing mandatory fortification of both coarse and fine salts, strengthening quality control systems, ensuring proper packaging to maintain stability, and establishing robust monitoring frameworks to track industry compliance and program impact. In countries opting to collect serum folate alone for population assessments, population-specific cutoffs for estimating NTD risk should be determined. However, the sub-optimal predictive performance of serum folate thresholds underscores the need to prioritize RBC folate where feasible. These measures offer a sustainable strategy to improve folate status, reduce NTDs, and combat micronutrient deficiencies in Ethiopia.
