• A composite score based on the sum of all distinct episodes of diarrhea, dysentery and lower respiratory tract infections [ Time Frame: 2 distinct and consecutive phases of 6 months each ] [ Designated as safety issue: No ]
  

• Incidence of death and fever without a source [Safety] [ Time Frame: 2 distinct and consecutive phases of 6 months each ] [ Designated as safety issue: No ]
  
• Change in haemoglobin concentration after Sprinkles supplementation [Efficacy] [ Time Frame: 2 distinct and consecutive phases of 6 months each ] [ Designated as safety issue: No ]
  

Iron deficiency (ID) affects many children in developing countries. Anemia and impaired brain development are its most significant consequences. These may be prevented by giving oral iron supplements (OIS), such as Sprinkles. ID treatment was controversial because high dose parenteral iron therapy is strongly associated with severe infections when given to severely malnourished children. Many studies have since demonstrated the safety of low dose OIS. WHO guidelines reflect this finding: population-wide iron supplementation campaign (PWISC), without prior screening, is recommended when ID prevalence is ≥ 40%.

However, a gap in the safety evidence has been identified: children with moderate or severe malnutrition (MSM) are strikingly absent from the studies performed to date to investigate the link between OIS and infectious morbidities. In this context, PWISC may have unrecognized deleterious effects when the prevalence of MSM is high, since safety is assumed, but incorrectly extrapolated from available evidence.

We wish to emphasize an additional concern with regards to safety studies published thus far: all were designed as superiority trials. In this context, it is statistically incorrect to conclude that failure to show a significant difference between iron and placebo means that their respective side-effect profiles are similar.