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Updated: Jun 30, 2026
A Point-of-Care Method with Integrated Decision Support Tool to Estimate Anemia at Population Level
Published on: January 19, 2024
Nonlinear dose-response relationship between serum ferritin and anemia in Chinese children: a matched case-control
Yan Sun1, Yi-Ya Liu1, Hong-Bo Li1
1Institute of Public Health Surveillance and Evaluation, Guizhou Center for Disease Control and Prevention, Guiyang, China.
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 (P-trend = 0.011). RCS analysis confirmed a significant non-linear relationship (P-nonlinearity <0.001). A significant sex interaction was observed (P-interaction = 0.006). Stratified analysis revealed a strong inverse association in females (e.g., Q4 vs. Q1: OR = 0.36, 95% CI: 0.18-0.73) but no significant association in males. The prediction model incorporating SF, age, sex, BMI, and CRP had an AUC of 0.61 and demonstrated good calibration (Brier score = 0.182; Hosmer-Lemeshow p = 0.358).
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.
