Double-Blind, Placebo-Controlled Trial Comparing Effects of Supplementation with Two Different Combinations of Micronutrients Delivered as Sprinkles on Growth, Anemia, and Iron Deficiency in Cambodian Infants

Double-blind, placebo-controlled randomized trial in Cambodian infants living in Tuk Phos district, Kompong Chhnang Province, Cambodia. Infants were enrolled at about 6 months of age; 204 eligible infants were randomized, with 68 assigned to MMN sprinkles, 68 to iron plus folic acid sprinkles, and 68 to placebo. Infants with severe anemia were excluded.

Daily sprinkle sachets were mixed into the infant's cooked complementary meal at home for 12 months, starting 7 +/- 2 days after the baseline blood assessment. One active regimen was iron(II) fumarate 12.5 mg plus folic acid 150 ug; the other added zinc 5 mg, vitamin C 50 mg, vitamin A 300 ug, and vitamin D3 7.5 ug to the same iron and folic acid base. Both active regimens were compared with placebo sprinkles.

Both active sprinkle regimens improved anemia-related outcomes versus placebo, but neither showed a clear growth advantage. Hemoglobin increased over 12 months in the MMN group by 8.2 g/L and in the FFA group by 8.3 g/L, while it decreased in the placebo group by 3.20 g/L; end-of-study hemoglobin was higher with both active regimens than placebo (P < 0.0001). Recovery from anemia was 53.8% with MMN and 52.9% with FFA versus 21.7% with placebo (P < 0.001). Ferritin rose slightly in the active groups but declined in placebo, and iron deficiency increased in placebo from 31% at baseline to 52% at end of study (P < 0.0001). Growth trajectories did not differ meaningfully among groups, and MMN did not outperform FFA on the main clinical outcomes.

Growth outcomes were not improved despite the micronutrient intervention, so the clinical benefit was limited to anemia and iron status. The subgroup with iron deficiency or iron deficiency anemia was small, which makes those recovery estimates imprecise. Arm-specific dietary and broader background nutrition data were limited, and the findings apply to infants from one province in Cambodia.