Adding zinc to supplemental iron and folic acid does not affect mortality and severe morbidity in young children.

This was a large community-based randomized trial in urban north and northwest Delhi, India, enrolling young children aged 1 to 23 months from low-to-middle-income urban neighborhoods. In the zinc plus IFA arm, 47,110 children were randomized; in the IFA-only arm, 47,249 children were randomized. Children were followed for 12 months for hospitalization and mortality outcomes.

The active regimen was an oral daily zinc plus iron and folic acid tablet for 12 months: 10 mg elemental zinc, 12.5 mg iron, and 50 mg folic acid. Infants younger than 6 months received half a tablet dissolved in expressed breast milk; older children received 1 tablet daily in breast milk or clean water. The comparison group received iron and folic acid without zinc.

Adding zinc to iron and folic acid did not improve severe morbidity or survival. All-cause hospitalizations were similar between the zinc plus IFA and IFA-only groups: 980 versus 916 admissions, 25 versus 23 admissions per 1000 child-years, rate ratio 1.08 (0.98, 1.19). Mortality was also unchanged: 326 versus 321 deaths, 8.3 versus 8.2 deaths per 1000 child-years, hazard ratio 1.02 (0.87, 1.19). Cause-specific hospitalization estimates for diarrhea, pneumonia, and other causes were likewise not significantly different, supporting the conclusion of no meaningful overall benefit from adding zinc.

The intervention was tested only in urban Delhi children, which may limit generalizability to other settings. Outcomes were focused on hospitalizations and mortality, so potential benefits on biochemical or functional zinc status were not assessed. The authors also noted that iron-zinc interactions or the zinc dose used may have attenuated any effect.