Optimal Enteral Iron Dosing in Preterm and Very-Low-Birth-Weight Infants: A Systematic Review and Meta-Analysis.
9 affiliations
- 1Pediatrics, Jordanian Royal Medical Services, Amman, JOR.
- 2Medicine and Surgery, Yarmouk University, Amman, JOR.
- 3Medicine and Surgery, University of Jordan, Amman, JOR.
- 4General Practice, Jameel Al Totangi Hospital, Amman, JOR.
- 5Medicine and Surgery, Mutah University, Amman, JOR.
- 6Quality Control Microbiology, Retaj Pharmaceutical Industry, Mafraq, JOR.
- 7Laboratory Medicine, The Hashemite University, Mafraq, JOR.
- 8Medicine and Surgery, Balqaa University, Amman, JOR.
- 9Medicine and Surgery, Marmara University, Istanbul, TUR.
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.
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BibTeX
@article{heissat2026optimal,
title = {{Optimal Enteral Iron Dosing in Preterm and Very-Low-Birth-Weight Infants: A Systematic Review and Meta-Analysis.}},
author = {Anas Heissat and Dana A Al-Jarrah and Hashem T Kanaan and Aya N Alqurneh and Amro Alrashdan and Ahmed M Abu Mahmoud and Shahed Yacoub and Mina H Baaji and Mohammad M Almahasneh and Mihar Raouf and Elaf Ibdah and Abdullah H Haider},
journal = {Cureus},
year = {2026},
month = sep,
doi = {10.7759/cureus.117030},
url = {https://europepmc.org/article/MED/42952599},
note = {CC BY},
}
RIS
TY - JOUR
TI - Optimal Enteral Iron Dosing in Preterm and Very-Low-Birth-Weight Infants: A Systematic Review and Meta-Analysis.
AU - Anas Heissat
AU - Dana A Al-Jarrah
AU - Hashem T Kanaan
AU - Aya N Alqurneh
AU - Amro Alrashdan
AU - Ahmed M Abu Mahmoud
AU - Shahed Yacoub
AU - Mina H Baaji
AU - Mohammad M Almahasneh
AU - Mihar Raouf
AU - Elaf Ibdah
AU - Abdullah H Haider
PY - 2026
DA - 2026/09/27
JO - Cureus
DO - 10.7759/cureus.117030
UR - https://europepmc.org/article/MED/42952599
AB - 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.
SN - 2168-8184
ER -