Nonlinear dose-response relationship between serum ferritin and anemia in Chinese children: a matched case-control study.

Objectives: This study aimed to investigate the dose-response relationship between serum ferritin (SF) and anemia risk in Chinese children and adolescents, with a specific focus on potential non-linearity and effect modification by sex. Methods: A 1:3 age- and sex-matched case-control study was conducted, comprising 175 anemia cases and 525 controls selected from a national school-based surveillance system. Anemia was diagnosed using WHO altitude-adjusted hemoglobin cutoffs. SF was measured by electrochemiluminescence immunoassay. The association was analyzed using unconditional logistic regression, with adjustment for confounders (age, sex, BMI, C-reactive protein) guided by a directed acyclic graph. The dose-response shape was modeled with restricted cubic splines (RCS), and a sex-SF interaction term was tested. Model performance was evaluated by the area under the ROC curve (AUC), calibration plot, and Brier score. Results: In the fully adjusted model, compared to the lowest quartile (Q1), the second (Q2: OR = 0.39, 95% CI: 0.23-0.66) and fourth (Q4: OR = 0.51, 95% CI: 0.30-0.85) quartiles of SF were associated with a significantly lower anemia risk, with a significant inverse linear trend ( Conclusion: SF exhibits a non-linear, inverse association with anemia risk in Chinese children and adolescents, which is significantly modified by sex, being pronounced only in females. These findings highlight the importance of considering both non-linear dynamics and sex-specific factors in the assessment and management of pediatric anemia.