Introduction

Iron deficiency (ID) is common in children, mostly due to dietary insufficiency or heavy menstrual bleeding (HMB), but it can also be caused by acute gastrointestinal (GI) blood loss, inflammatory bowel disease (IBD), celiac disease/other malabsorptive disorders, and chronic kidney disease. Intravenous iron (IVI) is administered when oral iron is ineffective or poorly tolerated. Outcome comparisons of multiple IVI formulations in children are limited, with previous studies focusing on individual agents or specific populations. Our study compares the clinical efficacy and adverse effects of different IVI formulations used in children at our institution.

Methods

A retrospective chart review was conducted on subjects ≤21 years of age who received ≥1 dose of IVI therapy between July 2018 and June 2024 at a tertiary children's hospital. Patients receiving IVI as part of total parenteral nutrition and patients on dialysis were excluded. Data included demographics, indication of IVI, hemoglobin (Hgb) levels up to 1 month before and 7-30 days after IVI, ferritin levels up to 1 month before and 7-120 days after IVI, phosphorous levels 1-28 days after IVI, adverse effects within 48 hours after IVI, pre-medications, and post-medications for reactions. Statistical analysis was performed using Wilcoxon signed-rank test for paired analysis of pre/post treatment labs, Kruskal-Wallis test as well as linear mixed model for comparison of Hgb/ferritin improvement across IVI formulations, and Chi-square analysis as well as logistic mixed model for comparison of adverse effects.

Results

Our study included 344 patients, receiving a total of 661 IVI treatments [237(35.9%) iron sucrose (IS), 226(34.2%) iron dextran (IDx), 155(23.4%) ferric carboxymaltose (FCM), 41(6.2%) ferric gluconate (FG), 2(0.3%) ferumoxytol (FM)]. Each treatment consisted of ≥1 dose(s), for a total of 835 IVI doses (39% IS, 27.4% IDx, 27.4% FCM, 5.9% FG, 0.2% FM). Females compromised 68% of patients; 22 (6.4%) were <1 year, 63 (18.3%) 1-9 years and 259 (75.3%) were 10-21 years old. The IVI indications were poor GI absorption (381, 57.6%), ongoing blood loss (154, 23.3%), oral iron refractoriness (124, 18.8%), oral iron intolerance (80, 12.1%), inability to take oral medication (37, 5.6%), patient preference (28, 4.2%), and poor compliance (15, 2.3%), with ≥1 indication(s) per treatment.

Median Hgb improved from 9.1 g/dL to 10.9 g/dL (p< 0.001) across all IVI formulations, and IDx improved Hgb more compared to FG (p=0.033) and IS (p=0.003). Median ferritin improved from 6 ng/ml to 39 ng/ml (p<0.001) across all formulations, with both FCM and IDx increasing it more compared to IS and FG (all p values < 0.05). The findings remained significant in mixed linear models.

Adverse reactions occurred in 47 out of 835 (5.6%) doses, including 4 anaphylactic reactions (3 IDx and 1 FCM), 24 non-anaphylactic reactions needing post-medication (10 IDx, 4 FCM, 3 FG, 6 IS, 1 FM), and 19 non-anaphylactic reactions not requiring post-medication (11 IDx, 3 FCM, 1 FG, 4 IS, 0 FM). IDx was associated with a higher number of reactions needing post-medication (p= 0.02). For FCM treatments, 20/155 (12.9%) had phosphorous levels available and hypophosphatemia was seen in 9 of the 20 (45%) treatments.

Conclusion

In this large pediatric cohort, IDx and FCM had the greatest efficacy with Hgb and/or ferritin improvement, similar to previous studies comparing them individually to IS or oral iron. Adverse reactions were uncommon overall. IDx had a higher number of reactions compared to other IVI formulations, but its overall anaphylaxis risk is low (1.3% of all doses). With test dosing (done in children) followed by close monitoring, the benefits may outweigh the risks. Nearly half of the FCM treatments with available phosphorus levels had hypophosphatemia, re-affirming the importance of monitoring phosphorus for this known adverse effect of FCM. Limitations of this study include its retrospective nature and potential selection bias. Prospective studies in children are needed to validate our findings.

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2025
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