Recurrent Infections as an Independent Determinant of Childhood Iron-Deficiency Anemia Within a...

Iron-deficiency anemia (IDA) is common in young children in developing countries, where recurrent infections (RIs) are also endemic. It was evaluated whether RI is an independent determinant of IDA using inflammation-adjusted serum ferritin (ISF), rather than viewing IDA as purely nutritional.

A prospective case-control study of children aged 6-59 months was conducted. Iron-deficiency anemia (IDA) was defined by anemia and iron deficiency using ISF derived from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) approach; controls had normal hematology and ISF. Recurrent infection (RI) within the previous 12 months was ascertained from medical records. Multivariable regression estimated adjusted odds ratios (aORs) for IDA, controlling for nutritional and social covariates; model performance was assessed by discrimination, calibration, and comparative fit.

Three hundred children were analyzed (100 with IDA, 200 controls). In multivariable analysis, RI remained independently associated with IDA (aOR=2.29), alongside delayed complementary feeding (aOR=7.12), non-maternal caregiving (aOR=21.02), and low-iron diet (aOR=2.69). A dose-response with infection breadth was observed: infections at ≥2 sites tripled the odds of IDA (P-trend= .007). In phenotype-specific models, recurrent respiratory and gastrointestinal infections were independently associated with IDA (aOR: 2.26 and 2.22, respectively). Adding RI slightly increased discrimination (AUC=0.902; ΔAUC=+0.008) but significantly improved model fit versus the model without RI (likelihood-ratio χ2(1) = 5.14; P=.023; DeLong P = .26).

Recurrent infection (RI) was an independent, dose-related determinant of childhood IDA beyond inflammation and nutrition, supporting a dual nutrition-inflammation framework and the inclusion of infection control in anemia strategies.