Abstract: We included 13 studies involving 5810 participants from Latin America, Africa and Asia. We excluded 38 studies and identified six ongoing/unpublished trials. All trials compared the provision of MNP for point-of-use fortification with no intervention or placebo. No trials compared the effects of MNP versus iron-containing supplements (as drops, tablets or syrup). The sample sizes in the included trials ranged from 90 to 2193 participants. Six trials included participants younger than 59 months of age only, four included only children aged 60 months or older, and three trials included children both younger and older than 59 months of age. MNPs contained from two to 18 vitamins and minerals. The iron doses varied from 2.5 mg to 30 mg of elemental iron. Four trials reported giving 10 mg of elemental iron as sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), chelated ferrous sulphate or microencapsulated ferrous fumarate. Three trials gave 12.5 mg of elemental iron as microencapsulated ferrous fumarate. Three trials gave 2.5 mg or 2.86 mg of elemental iron as NaFeEDTA. One trial gave 30 mg and one trial provided 14 mg of elemental iron as microencapsulated ferrous fumarate, while one trial gave 28 mg of iron as ferrous glycine phosphate. In comparison with receiving no intervention or a placebo, children receiving iron-containing MNP for point-of-use fortification of foods had lower risk of anaemia prevalence ratio (PR) 0.66, 95% confidence interval (CI) 0.49 to 0.88, 10 trials, 2448 children; moderate-quality evidence) and iron deficiency (PR 0.35, 95% CI 0.27 to 0.47, 5 trials, 1364 children; moderate-quality evidence) and had higher haemoglobin (mean difference (MD) 3.37 g/L, 95% CI 0.94 to 5.80, 11 trials, 2746 children; low-quality evidence). Only one trial with 115 children reported on all-cause mortality (zero cases; low-quality evidence). There was no effect on diarrhoea (risk ratio (RR) 0.97, 95% CI 0.53 to 1.78, 2 trials, 366 children; low-quality evidence). Point-of-use fortification of foods with MNPs containing iron reduces anaemia and iron deficiency in preschool- and school-age children. However, information on mortality, morbidity, developmental outcomes and adverse effects is still scarce.

Plain-language summary: This review included 13 trials with 5810 participants from Latin America, Africa and Asia. All trials compared the provision of MNP for point-of-use fortification with no intervention or placebo. Six trials included participants younger than 59 months of age only, four included only children aged 60 months of age or older, and three trials included children both younger and older than 59 months of age. MNPs contained from two to 18 vitamins and minerals. We searched existing clinical trials in December 2016 and ongoing trials in April 2017. We also contacted relevant institutions for additional information upon publication of the protocol and in April 2017. The review found that children receiving iron-containing MNP for point-of-use fortification of foods were at significantly lower risk of having anaemia and iron deficiency and had higher haemoglobin concentrations. We did not find any positive or negative effect on diarrhoea or mortality, but the data on these two outcomes were very limited. We rated the overall quality of the evidence for the provision of multiple MNP versus no intervention or placebo as moderate for anaemia, iron deficiency and adverse effects. We judged the evidence to be of low quality for haemoglobin, mortality and diarrhoea, and to be very low-quality for ferritin. In general, the most common risk of bias in the studies was the lack of blinding for participants, personnel and outcome assessors. Point-of-use fortification of foods with MNPs containing iron reduces anaemia and iron deficiency in preschool- and school-age children and seems feasible for public health purposes. However, future research should aim to increase the body of evidence on mortality, morbidity, developmental outcomes and adverse effects. Due to the lack of trials, we were unable to determine at this time if this intervention has comparable effects to those observed with iron supplements (provided as drops, tablets or syrup).