Iron deficiency is the most frequent nutritional deficiency in pediatrics, and oral iron is the first-line treatment. In some cases, oral iron supplementation may be insufficient, leading to the use of parenteral iron formulations.1 Traditionally, the first-line agent for intravenous delivery has been iron sucrose,2 whose main limitation is the need to administer several doses. This has prompted development of novel iron formulations, such as ferric carboxymaltose.3 This agent, widely used in the adult population due to its optimal safety profile, tolerability, and possibility of administering fewer doses, had been used off-label in pediatric patients until its approval for pediatric use by the United States Food and Drug Administration (FDA) in 2021.

We conducted a retrospective, observational, descriptive, and analytical cohort study to assess the efficacy and safety of ferric carboxymaltose in pediatric patients treated in a tertiary care hospital. The sample comprised 36 patients (with administration of a total of 52 doses), aged 12 months to 16 years (mean, 11.5 years; SD, 4.3), and managed between 2014 and 2022.

Quantitative variables were summarized as mean and standard deviation if the data followed a normal distribution, and otherwise as median and interquartile range (IQR). We assessed normality with the Kolmogorov-Smirnov test (n > 50) or the Shapiro-Wilk test (n ≤ 50). The data were compared with the paired t test (normal distribution) or the Wilcoxon signed-rank test (non-normal distribution). We defined statistical significance as a P value of less than 0.05, and the statistical analysis was performed with IBM SPSS Statistics, version 27.

In the sample under study (n = 36), gastrointestinal disorders were the leading cause of iron deficiency (75%), with a predominance of inflammatory bowel disease (IBD) (53%): Crohn disease (n = 8), ulcerative colitis (n = 8) and indeterminate colitis (n = 3). The most frequent alternative causes (25%) were neurologic (n = 3), dermatological (n = 2), postsurgical (n = 2) and isolated cases of renal disease and metrorrhagia.

Considering the total of 52 administered doses, the most frequent symptoms preceding infusion were asthenia (21%) and headache (7.7%), which are common manifestations of iron-deficiency anemia. There was also one case of alopecia, which is associated with iron deficiency.

The median dose of ferric carboxymaltose was 500 mg (IQR, 312.5–500), equivalent to 12.6 mg/kg (IQR, 10.6–16.4). The median doses by age group were: 12.8 mg/kg (IQR, 10.6–15.7) in children aged 0–5 years; 14.2 mg/kg (IQR, 9.4–20.7) in children aged 6–11 years; and 12.2 mg/kg (IQR, 10.6–14.0) in children aged 11 years and older (maximum dose, 1000 mg). All doses were administered in full as a single infusion. Additional doses were administered separately and several months apart.

Laboratory tests at the time of first follow-up after infusion (median, 13 days; IQR, 4.0–29.5) evinced significant increases in all measured markers (P < .001) (Tables 1 and 2).

The stratified analysis (by age, sex, ethnicity, and etiology) showed significant improvement in hemoglobin and ferritin levels in most subgroups. However, the increase in ferritin levels was not significant in the Arab ethnic group, probably due to the small size of this subset. Similarly, there were no statistically significant differences in patients with Crohn disease (P = .089 for hemoglobin and P = .074 for ferritin). This could be explained by the administration of doses that were suboptimal in terms of achieving a complete hematologic response, elevated baseline ferritin levels in some patients in relation to the role of this marker as an acute-phase reactant, and the presence of an inflammatory component associated with anemia of chronic disease, which would primarily affect hemoglobin (Tables 1 and 2).

There were no serious adverse reactions, with a single documented adverse event in the form of mild self-limited urticaria.

Both our case series and the previous literature3 support the use of ferric carboxymaltose as the optimal choice for intravenous iron delivery in the pediatric population, as it allows administration of high doses over a short period of time with an excellent safety profile. In our experience, the treatment was well tolerated, without serious adverse reactions. However, the safety evaluation was limited to clinical variables and did not include serum phosphate monitoring for detection of hypophosphatemia, an adverse effect with a reported incidence of less than 25%4 that is usually subclinical. Although cases of severe post-infusion hypophosphatemia requiring treatment have been reported,5 the clinical relevance of serum phosphate monitoring is still under debate, and monitoring is mainly recommended for patients with risk factors, such as malabsorption.4–6

In conclusion, our findings, consistent with the previous literature, support the use of ferric carboxymaltose as an effective and safe option for intravenous treatment of iron deficiency in the pediatric population.