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Background Male infants exhibit a higher risk of iron deficiency (ID) than females, yet the underlying mechanisms remain unclear. Given that rapid postnatal growth may deplete iron stores and males typically experience faster early development, this study aimed to test whether rapid weight gain (WG) during the first 6 months mediates the association between male sex and ID risk at 6 months. Methods We conducted a retrospective cohort study of healthy term infants born at Sichuan Provincial Women’s and Children’s Hospital in Chengdu, China, between January 2023 and June 2024. Associations among sex, WG, and ID were examined using logistic regression, adjusting for selected covariates and feeding type. Mediation analysis used SPSS PROCESS macro (Model 4) to estimate the indirect effect of sex on ID via WG with bootstrapped 95% confidence intervals. Results This study included 355 infants (55.5% male), with a median WG of 4.9 kg. Total ID occurred in 22.5% of infants, with the highest incidence observed in exclusively breastfed males (36%). After adjusting for covariates and feeding type, male infants exhibited greater WG than females ( β = 0.61 kg, 95%CI: 0.44 to 0.78, p 0.001) and had higher odds of ID (aOR = 2.13, 95%CI: 1.23 to 3.70, p = 0.007). Further adjustment for WG attenuated the sex-ID association (aOR = 1.57, 95%CI: 0.88 to 2.83, p = 0.129), while WG remained independently associated with ID risk (aOR = 1.63 per kg, 95%CI: 1.17 to 2.27, p = 0.004). Mediation analyses revealed that WG partially mediated this association (indirect effect = 0.30; bootstrapped 95% CI: 0.11 to 0.54), accounting for 40% of the total effect. Conclusion Male infants exhibited elevated ID risk at 6 months, with postnatal greater WG partially explaining this association. Our findings underscore the need for sex-specific guidelines on the introduction of complementary foods and on iron supplementation, particularly for rapidly growing, exclusively breastfed males before 6 months. Prospective trials should evaluate iron dosing strategies aligned with growth trajectories before clinical implementation.
Ge et al. (2026) studied this question.