We aimed to identify factors associated with zinc protoporphyrin (ZPP) in children aged 1-3 years, and to assess the diagnostic performance and utility of ZPP, either alone or in combination with hemoglobin, in detecting iron deficiency.
We studied 338 Kenyan children aged 12-36 months, excluding those with fever and hemoglobin concentration <70g/L. We used multiple linear regression analysis to identify factors associated with ZZP. To assess diagnostic performance, we additionally excluded children with inflammation and Plasmodium infection. We analyzed receiver operating characteristics (ROC) curves, with plasma ferritin concentration <12µg/L as the reference for iron deficiency. We also developed models to assess the diagnostic utility of ZPP and hemoglobin concentration when screening for iron deficiency.
Whole blood ZPP and erythrocyte ZPP were independently associated with hemoglobin concentration, Plasmodium infection and plasma concentrations of soluble transferrin receptor, ferritin, C-reactive protein. In children without inflammation or Plasmodium infection, the prevalence of true iron deficiency was 32.1%, compared to 97.5% and 95.1% when assessed by whole blood ZPP >70µmol/mol. Addition of whole blood ZPP or erythrocyte ZPP to hemoglobin concentration increased the area-under-the-ROC-curve (84.0%, p=0.003, and 84.2%, p=0.001, respectively, versus 62.7%). A diagnostic score based on hemoglobin concentration and whole blood ZPP correctly ruled out iron deficiency in 37.4%-53.7% of children screened, depending on the true prevalence, with both specificity and negative predictive value =90%.
In young children without inflammation and Plasmodium infection, whole blood ZPP and erythrocyte ZPP have added diagnostic value in detecting iron deficiency compared to hemoglobin concentration alone.