Zinc supplementation for the promotion of growth and prevention of infections in infants less than six months of age.

Systematic review and meta-analysis of randomized trials in healthy, term infants under 6 months of age, predominantly breastfed, with studies conducted in developing countries and at least one developed country. Active-arm participants were infants enrolled from about 3 to 7 months of age in several trials, with one trial of full-term infants starting at 4 months and one combination trial in India starting at 4 months.

Zinc was given orally to infants in multiple randomized trials, most commonly as zinc sulfate 5 mg to 10 mg elemental zinc per day for 6 months; one trial used zinc 5 mg daily combined with riboflavin for 12 months. Comparators were placebo in most studies, and riboflavin alone in the combination-arm trial.

Zinc supplementation alone, and zinc combined with riboflavin, may improve infant growth and raise serum zinc levels, but evidence for infection prevention, mortality, and safety was limited. In one larger trial, zinc improved weight after 6 months (SMD 0.16 [0.00, 0.31]), weight-for-age z-score (MD 0.16 [0.07, 0.25]), and weight-for-length z-score (SMD 0.15 [0.02, 0.28]), while length was smaller and less consistent (SMD 0.07 [−0.08, 0.23]). Serum zinc increased in several trials, including 23.07 umol/L vs 15.79 umol/L at 6 months in one study (P<0.0001) and 18.4 (16.8–23) umol/L vs 15.3 (13.8–16.8) umol/L in another (P<0.001). Diarrhoea and lower respiratory tract infection were not clearly reduced, and mortality data were sparse. The review concluded that zinc may benefit growth, but clearer trials are needed.

Evidence was based on a small number of trials with varying doses, durations, ages, and settings, limiting consistency and generalizability. Mortality, morbidity, and adverse-event data were sparse or inconsistently reported, and several outcomes came from single studies. Some analyses had imprecision, and the zinc plus riboflavin finding was based on one trial only.