Influence of Inflammation on Assessing Iron-Deficiency Anemia in Cuban Preschool Children

Anemia is a public health problem worldwide and is most prevalent in preschool children, for whom it is the most frequent cause of nutritional deficits. In turn, iron deficiency is the main cause of anemia, affecting 43% of children globally. Previous studies in Cuba show rates of iron deficiency in preschool children between 38.6% and 57.6%, higher in infants (71.2% to 81.1%). WHO recommends using serum ferritin as an indicator of iron deficiency accompanied by acute (C-reactive protein) and chronic (a1-acid glycoprotein) inflammation biomarkers.

Assess how inflammation affects measuring and reporting of iron-deficiency anemia rates in Cuban preschool children.

Data were obtained from serum samples contained in the National Anemia and Iron Deficiency Survey, and included presumably healthy preschool Cuban children (aged 6-59 months). Serum samples were collected from 1375 children from randomly selected provinces in 4 regions of the country from 2014 through 2018. We examined the association between ferritin and two inflammatory biomarkers: C-reactive protein and a1-acid glycoprotein. Individual inflammation-adjusted ferritin concentrations were calculated using four approaches: 1) a higher ferritin cut-off point (⟨30 g/L); 2) exclusion of subjects showing inflammation (C-reactive protein ⟩5 mg/L or a1-acid glycoprotein ⟩1 g/L); 3) mathematical correction factor based on C-reactive protein or a1-acid glycoprotein; and 4) correction by regression with the method proposed by the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia Group. We estimated confidence intervals of differences between unadjusted prevalence and prevalence adjusted for inflammation by each method.

The proportion of children with inflammation according to C-reactive protein concentrations >5 mg/L was lower (11.1%, 153/1375) than the proportion measured according to the concentrations of a1-acid glycoprotein, at >1 g/L (30.8%, 424/1375). The percentage of children with high concentrations of at least one of the aforementioned biomarkers was 32.7% (450/1375). Thus, each correction method increased the observed prevalence of iron deficiency compared to unadjusted estimates (23%, 316/1375). This increase was more pronounced when using the internal regression correction method (based only on C-reactive protein) or the method based on a higher cut-off point. Adjustment using all four methods changed estimated iron deficiency prevalence, increasing it from 0.1% to 8.8%, compared to unadjusted values.

One-third of preschool children had biomarkers indicating elevated inflammation levels. Without adjusting for inflammation, iron deficiency prevalence was underestimated. The significant disparity between unadjusted and inflammation-adjusted ferritin when using some approaches highlights the importance of selecting the right approach for accurate, corrected measurement. The internal regression correction approach is appropriate for epidemiological studies because it takes into account inflammation severity. However, other models should be explored that account for inflammation and also provide better adjusted ferritin concentrations.