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Optimal Enteral Iron Dosing in Preterm and Very-Low-Birth-Weight Infants: A Systematic Review and Meta-Analysis

Year: 2026

Type: review

Study designs: Systematic Review, Meta-Analysis

Abstract: Preterm and very-low-birth-weight (VLBW) infants are particularly vulnerable to iron deficiency because of reduced fetal iron accretion, rapid postnatal growth, and phlebotomy losses, while excessive iron exposure may increase oxidative stress. The optimal enteral iron regimen therefore remains uncertain. We systematically reviewed randomized and non-randomized studies evaluating enteral iron dose, timing of initiation, formulation, or supplementation versus a comparator in preterm and eligible low-birth-weight infants. PubMed, Scopus, Web of Science, and supplementary sources were searched from inception through 21 June 2026. Two reviewers independently screened records, extracted data, and assessed risk of bias. Twenty-six reports representing 25 studies and 2,549 participants met the inclusion criteria. Quantitative synthesis was feasible for a limited subset of sufficiently comparable outcomes. Earlier versus later iron initiation was associated with higher hemoglobin in the primary random-effects analysis [mean difference (MD) 0.85 g/dL, 95% confidence interval (CI) 0.54 to 1.16; I² = 0%]; however, this finding was not robust in small-sample sensitivity analysis. No clear difference was observed for blood-transfusion requirement [risk ratio (RR) 0.38, 95% CI 0.07 to 2.17; I² = 69.5%] or reticulocyte count (MD -2.64 ×10⁹/L, 95% CI -30.97 to 25.69; I² = 80.3%). Given the limited quantitative evidence base, substantial uncertainty for several outcomes, and low-to-very-low certainty of evidence, firm conclusions regarding the optimal enteral iron regimen cannot be drawn. Further adequately powered comparative trials are needed to clarify the optimal dose and timing of supplementation.

Source: Cureus

DOI: 10.7759/cureus.117030