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Article

The Effect of Ferric Carboxymaltose on Fibroblast Growth Factor 23 (FGF23) in Children with Iron Deficiency Anemia Due to Gastrointestinal Diseases

by
Maria Ntoumpara
1,
Elpis Mantadakis
2,
Lemonia Skoura
3,
Paraskevi Panagopoulou
1,
Elpida Emmanouilidou-Fotoulaki
1,
Eleftheria Parasidou
3,
Paraskevoula Koutra
3 and
Maria Fotoulaki
1,*
1
4th Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, “Papageorgiou” General Hospital, 56403 Thessaloniki, Greece
2
Department of Pediatrics, Democritus University of Thrace, Faculty of Medicine, University General Hospital of Alexandroupolis, 68100 Alexandroupolis, Greece
3
Department of Microbiology, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
*
Author to whom correspondence should be addressed.
Hemato 2024, 5(4), 448-458; https://doi.org/10.3390/hemato5040034
Submission received: 25 October 2024 / Revised: 21 November 2024 / Accepted: 25 November 2024 / Published: 28 November 2024
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Abstract

:
Background: Hypophosphatemia is a known side-effect of parenteral iron administration, especially after intravenous ferric carboxymaltose (FCM). Fibroblast growth factor 23 (FGF23) is thought to play an important role in the pathophysiology of serum phosphate homeostasis. This study aimed to investigate the effects of FCM on FGF23 serum levels in FCM-treated pediatric patients with iron deficiency (ID)/iron deficiency anemia (IDA) caused by gastrointestinal diseases. Methods: Over 30 months, FGF23 serum levels were assessed prospectively in children with ID/IDA due to gastrointestinal diseases and treated with FCM infusion. Serum levels of intact FGF23 (iFGF23) were assessed and correlated to phosphate serum levels and factors of bone metabolism. Blood sampling was performed in three phases: before FCM infusion, 7–10 days after FCM infusion, and 6–8 weeks after FCM infusion. Results: A total of 42 FCM infusions were given to 35 children (20 girls) with a mean age (±SD) of 12.2 (±4.03) years (range: 2–16 years). The median levels of iFGF23 did not show a significant difference across the three phases (p = 0.56). No significant correlation was found between iFGF23 levels and 25-hydroxyvitamin D/parathyroid hormone/serum phosphate/serum calcium/alkaline phosphatase. No significant change was noted between pre- and post-treatment serum phosphate levels. However, four children (11.42%) developed asymptomatic and transient hypophosphatemia. Conclusions: No significant difference was found between pre-and post-FCM infusion serum iFGF23 levels and bone metabolism parameters. An increase of iFGF23 serum levels 7–10 days after FCM infusion was noted in patients with hypophosphatemia.

1. Introduction

Intravenous (IV) iron is an established therapeutic modality for the treatment of iron deficiency anemia (IDA) in adults. Its indications include intolerance to or inefficacy of orally administered iron, functional iron deficiency (ID) [1], and inflammatory bowel disease (IBD) [2]. The latest generation of IV iron preparations [ferric carboxymaltose (FCM), ferumoxytol (which is not commercially available), iron isomaltoside/ferric derisomaltose (IIM)] have shown a favorable safety profile and excellent efficacy [3,4], but there is limited experience in children <14 years of age [5]. The US Food and Drug Administration (FDA) approved FCM in 2021 [6] for pediatric patients aged >1 year who are either intolerant to or have an unsatisfactory response to oral iron administration. A similar approval followed in Europe. FCM was the first of the new formulations to be approved for rapid administration in large doses, as it is a stable iron complex, and no test dose is required [3].
Among the adverse events (AEs) associated with FCM administration, transient hypophosphatemia is one of the most common [7]. Regarding the pathophysiological mechanism of hypophosphatemia, a significant and sustained increase in fibroblast growth factor 23 (FGF23) levels, a hormone with a key role in phosphate homeostasis, has been described [8]. The biologically active form of FGF23 (intact FGF23, iFGF23) suppresses the action of sodium phosphate cotransporters (NaPi2a and NaPi2c) in renal proximal tubule epithelial cells and increases urinary phosphate excretion [8]. High levels of iFGF23 also reduce the activation of 25-hydroxyvitamin D and decrease serum calcium [9]. This can cause secondary hyperparathyroidism, which maintains renal phosphate loss through the phosphaturic effects of parathyroid hormone [10]. Both inflammation and ID have been described as regulators of systemic FGF23 synthesis and secretion [11,12].
The present study aimed to investigate the effects of FCM on iFGF23 serum levels in children with ID/IDA due to gastrointestinal diseases.

2. Materials and Methods

We conducted a prospective study evaluating the fluctuation of serum phosphate levels, corresponding serum levels of iFGF23, and bone metabolism parameters in FCM-treated Greek pediatric patients with gastrointestinal conditions who presented with ID/IDA. The Aristotle University of Thessaloniki Medical School Ethics Committee approved the study. Informed consent for the administration of FCM, sample collection, and anonymized data recording was obtained from the parents of all participating children.
Τhe iron deficit was calculated according to the Ganzoni formula [13], and FCM infusion (Ferinject®, Vifor SA, Neuilly-sur-Seine, France) was administered according to published guidelines. Corticosteroids and antihistamines were not allowed before the infusion, as most AEs of FCM are mild and self-limited, and to avoid vasoactive reactions associated with premedication that could be misinterpreted as causally related to FCM [4]. In our study, AEs were graded (grade I to V) according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) [14]. Serum analysis and complete blood count were measured immediately after sample collection. Biological sampling was performed in three phases: before FCM infusion (Phase I), 7–10 days after the infusion (Phase II), and 6–8 weeks after the infusion (Phase III). Serum samples collected at each phase were centrifuged, and the supernatant was stored at −80 °C. All samples were analyzed simultaneously, and the serum levels of iFGF23 were measured by an ELISA assay (Kainos Laboratories, Tokyo, Japan). The estimated glomerular filtration rate (eGFR) was calculated using the Schwartz formula [15]. With regard to serum phosphate concentration, hypophosphatemia was defined as mild, moderate, or severe for serum phosphate levels of <2.5 mg/dL, <2.0 mg/dL, and <1.0 mg/dL, respectively [16,17]. A schematic diagram of the method and materials used in the study is depicted in the vertical flowchart in Scheme 1.
Descriptive statistical analysis for all variables of interest was performed using mean and standard deviation (SD) for normally distributed variables and median and interquartile range (IQR) for the remaining variables. A complete case analysis was performed to manage missing values. For the analysis of repeated measurements, the non-parametric Friedman test was used for variables not normally distributed (iFGF23, ALP, Ca), and a one-way ANOVA for repeated measurements was used when the data were normally distributed (Phos). Finally, a paired sample t-test was used to compare the means of 25(OH)D and PTH, which were available in two phases (Phase I and Phase III). Accordingly, the Wilcoxon Signed Rank test was used for the comparison of the non-parametric variables (sTfR) between two phases (Phase I and Phase III). Correction for multiple comparisons was made using the Bonferroni method. Spearman’s Rank Correlation was used to investigate the linear correlation between iFGF23 and bone metabolism parameters. Serum iFGF23 levels were compared between children who developed hypophosphatemia and those who did not, with a serum phosphate cut-off value of 2.5 mg/dL. An a priori power analysis was conducted using G*Power version 3.1 to determine the minimum sample size required to test the effect of iFGF23 on serum phosphate levels. Results indicated that a sample size of six ensures that a two-sided test with α = 0.05 has 80% power to detect a large effect in matched pairs. The level of statistical significance was set at 0.05. Statistical analysis was performed using SPSS v. 29, and the graphs were created using R software v. 4.2.3 (2023-03-15 ucrt).

3. Results

3.1. Participants

A total of 35 children (20 girls), with a mean age (±SD) of 12.2 (±4.03) years [median (range): 14 (2–16) years] were included. Seventeen patients were <14 years old. Baseline characteristics and biochemical parameters of the study population are presented in Table 1. The underlying diseases causing ID/IDA were: IBD, celiac disease, severe cow’s milk allergy, feeding problems, and eosinophilic esophagitis. The distribution of these diseases among our patients is presented in Table 2. Six patients (one with Crohn’s disease, two with ulcerative colitis, one with celiac disease, and two with feeding problems) needed an additional FCM infusion. A single patient with Crohn’s disease needed a third FCM infusion within the study period.

3.2. Intact FGF23 (iFGF23)

Serum iFGF23 levels were measured in three phases, as previously described. The median (range) of iFGF23 was 56.53 (25.77, 852.46) pg/mL (Phase I), 56.60 (14, 273) pg/mL (Phase II), and 50.57 (10.65, 228.79) pg/mL (Phase III). Median iFGF23 levels did not significantly differ across the three phases (p = 0.56) (Figure 1). No linear correlation was found between iFGF23 and bone metabolism parameters after FCM infusion: 25(OH)D (p = 0.72 Phase III), PTH (p = 0.67 Phase III), Phos (p = 0.34 Phase II, p = 0.45 Phase III), Ca (p = 0.47 Phase II, p = 0.59 Phase III), ALP (p = 0.41 Phase II, p = 0.39 Phase III). Serum iFGF23 levels before, 7–10 days after, and 6–8 weeks after FCM infusion were individually evaluated in children who developed hypophosphatemia (N = 4). The comparative iFGF23 trend for children with low and normal serum phosphate is shown in the violin plots of Figure 2 and Figure 3, respectively. A further evaluation of serum iFGF23 levels was performed among patients with IBD, as the presence of inflammation interferes with FGF23 levels [11,12,18]. A significant difference was noted in CRP in all three phases (p = 0.023 Phase I, p = 0.014 Phase II, p = 0.008 Phase III), where CRP was higher in IBD patients. However, no significant difference was found for serum iFGF23 levels.

3.3. Ca, Phos, ALP

The distributions of ALP, Ca, and Phos did not show significant differences between the three phases (p = 0.09, p = 0.059, and p = 0.16, respectively).

3.4. PTH and 25(OH)D

Levels of PTH and 25(OH)D were evaluated between Phase I and III and showed no significant difference (p = 0.23 and p = 0.89, respectively).

3.5. sTfR, TIBC, Hb

Levels of sTfR presented a significant decrease following FCM IV infusion (z = −2.98, p = 0.003 with a medium effect size r = 0.41). The same was true for TIBC (p = 0.01), while Hb increased, as expected, after the FCM infusions (p < 0.001).

3.6. Adverse Events (AEs)

Four patients (three aged > 14 years old, and one toddler) experienced mild skin rashes and were treated with antihistamines (grade I–II, CTCAE, version 5.0). No severe immediate or delayed hypersensitivity reactions (i.e., abdominal pain, hypotension, nausea, vomiting, or wheezing) were recorded. Furthermore, regarding the serum phosphate levels, although there was no significant change between pre- and post-FCM, a 15-year-old girl developed moderate, asymptomatic, and transient hypophosphatemia after the third FCM infusion. In contrast, a 15-year-old girl, a 16-year-old girl, and a 15-year-old boy developed mild, asymptomatic, and transient hypophosphatemia after the first FCM infusion. Serum phosphate returned to baseline by Day 21 in three patients and by Day 42 in the 15-year-old boy.

4. Discussion

In our prospective study, we present data on serum phosphate, iFGF23, and bone metabolism parameters of a cohort of 35 children aged 2–16 years with ID/IDA of gastrointestinal etiology who received FCM over 30 months. Parenteral iron is an established therapeutic modality for the management of refractory IDA in adults, especially in IBD patients [2]. In these patients, the prevalence of anemia approaches 30–40% and ID has been identified as the major cause of anemia [2]. Oral iron administration in IBD patients may not be effective due to poor absorption from the inflamed mucosa, while intraluminal iron can adversely affect the intestinal microbiota [7,19,20]. Iron, as a pro-oxidant, is an important nutrient for many bacteria, exacerbating sepsis in laboratory animals [21]. However, an increase in infectious risk after parenteral iron administration has not been described [22]. Moreover, IV iron preparations completely bypass the intestinal hepcidin-ferroportin pathway that controls iron absorption. Hepcidin, after binding to ferroportin, triggers endocytosis of the complex and degradation of ferroportin [23]. Therefore, increased hepcidin levels account for the reduced iron absorption seen in inflammatory conditions.
Among parenteral iron formulations, FCM has shown a good safety profile and efficacy [3]. Especially in studies performed in adults with IBD, FCM has prevented the recurrence of anemia compared with placebo [24]. Moreover, according to a systematic review with network meta-analysis, FCM proved to be the most effective and better tolerated IV iron product in adults with IBD [7]. In our study, 14 out of 35 (40%) patients had IBD and received 18 out of 42 (42, 8%) FCM infusions.
Regarding hypophosphatemia, one of the commonly reported AEs of FCM, the pooled incidence of hypophosphatemia among adult patients, according to randomized clinical trials included in systematic reviews and meta-analyses, is approximately 50% [16,25,26]. However, in a prospective observational study of patients with IBD, FCM-induced hypophosphataemia occurred in 71.2% [27], whereas in the PHOSPHARE-IDA randomized clinical trial, the rate was 74.4% (87/117) [28]. According to a recent post hoc pooled analysis of 45 clinical trials, FCM-induced hypophosphatemia is temporary and without severe clinical manifestations [29]. However, there is evidence that this is not always the case [16,30,31,32]. Wolf et al. reported that 11.3% of FCM-treated patients developed severe hypophosphatemia (serum phosphate < 1 mg/dL) and 40% (46/115) had persistent hypophosphatemia on Day 35, including 12 of 13 who developed severe hypophosphatemia [33]. Persistent hypophosphatemia, even beyond five weeks, has also been described [25,27].
Recent studies performed in pediatric patients have confirmed the safety and efficacy of FCM [34,35,36,37]. In one of the first studies in pediatric patients with IBD and other enteropathies who were treated with FCM, Laass et al. [38] observed significant improvement in hemoglobin values within 5–12 weeks without any serious AEs. Powers et al. in a retrospective analysis where FCM was administered in children with IDA [39], described minor transient complications in 7/116 FCM infusions. Tan et al. also reported positive results when FCM was used in pediatric patients [35]. Moreover, Mantadakis and Roganovic reported encouraging results from 15 pediatric and adolescent patients from Greece and Croatia, with no AEs recorded [36]. Additionally, in a multicenter, randomized, active-controlled study (NCT03523117), severe AEs (CTCAE grades 3, 4, and 5) in patients who received FCM were <3% [40]. Regarding hypophosphatemia, in this clinical trial, the mean phosphate levels decreased in both cohorts that received FCM at 7.5 mg/kg and at 15 mg/kg at 72 h post-dose infusion. Serum phosphate returned to baseline by Day 14 in the first group and by Day 28 in the second group [40]. In a retrospective, observational study, Posod et al. described hypophosphatemia after the first FCM dose in 16.7% of the treated patients [41]. In a cohort of children with IBD and concomitant IDA, Cococcioni et al. described post-FCM hypophosphatemia in 25/94 patients (~26%). Hypophosphatemia was mild, except for two patients who developed severe hypophosphatemia [42]. Finally, Kirk et al. reported a rate of asymptomatic hypophosphatemia of 14% after 313 infusions, administered in 40 patients ≤ 21 years old [43]. Hence, FCM-induced hypophosphatemia appears to be much less common in children compared to adults.
In our study, there was no significant change between pre- and post-treatment serum phosphate levels, but four children (11.42%) (two patients with IBD and two with celiac disease) developed asymptomatic and transient hypophosphatemia. A 15-year-old girl developed moderate hypophosphatemia (1.1 mg/dL) after the third FCM infusion, while three adolescents developed mild hypophosphatemia after the first FCM infusion. None of them exhibited symptoms such as weakness and fatigue [26]. Hypophosphatemia resolved within 21 days in three patients, and serum phosphate levels returned to baseline by Day 42 in all patients.
A significant and sustained increase of FGF23, a hormone that plays a key role in phosphate homeostasis, was first reported in 2009 in a patient with iron-induced hypophosphatemia [44]. This association was later confirmed in a prospective study [45]. Since these early publications, there have been many reports of hypophosphatemia associated with parenteral iron [16], including iron sucrose and FCM [16,26,46,47], which are responsible for most cases in Europe and North America. Hypophosphatemia after FCM administration has been explained by a 3- to 6-fold increase in FGF23 [48], starting on the first day after FCM infusion. The proposed mechanism by which FCM acutely elevates iFGF23 is that the carbohydrate iron carrier in FCM inhibits the cleavage of iFGF23, which is normally upregulated in ID through increased FGF23 gene transcription [9,48,49]. FCM-induced hypophosphatemia caused by significant increases in iFGF23 has been associated with significant changes in markers of bone metabolism [33].
In our study, we found no significant changes in iFGF23 levels and the levels of Phos, Ca, ALP, 25(OH)D, and PTH after FCM infusion. In addition, iFGF23 levels were not different in patients with low or normal phosphate levels. The results of the present study, however, support the expected increase in iFGF23 levels in patients who developed hypophosphatemia. As shown in Figure 2, iFGF23 levels follow a different trend, with an increase in Phase II (7–10 days after infusion). In contrast, Figure 3 shows no similar trend, as iFGF23 levels remain stable before, 7–10 days after, and 6–8 weeks after FCM infusion. Considering that only four children developed hypophosphatemia, the lack of significance of the results could be attributed to an insufficient sample size. It should be noted, however, that even with low statistical power, iFGF23 seems to have an impact on phosphate levels, as previously proposed. No significant correlation between iFGF23 and phosphate concentrations, either in pathological conditions [50] and in health [51,52], has been described. Baroncelli et al. attributed the lack of correlation in healthy subjects to the non-regulation of iFGF23 by circulating phosphate. Conversely, they described an inverse correlation of iFGF23 with phosphate concentration in patients with X-linked hypophosphatemia, supporting the idea that FGF23 excess impairs the regulation of phosphate metabolism [53].
Serum iFGF23 levels in healthy Greek children were measured using the same ELISA assay as in this study, and were found to be lower [iFGF23; 35 pg/mL (8.8, 120)] [18] compared to our study. Moreover, although iFGF23 serum levels in children vary with age, being higher in infancy and adolescence and lower in childhood and adulthood, the age-related variation in iFGF23 levels is questionable [51,53]. Baroncelli et al. described that infancy and puberty are characterized by the highest iFGF23 plasma concentrations [53]. It should be noted, however, that the comparisons of FGF23 levels described in the literature may be unreliable due to the large heterogeneity of values, cut-offs, and the sensitivity of the assays used [54].
Finally, our data provide further evidence of the safety and efficacy of FCM. Four patients (three patients > 14 years old and one toddler) developed mild skin rashes (grades I–II) and were treated with antihistamines. With regards to efficacy, as expected, sTfR and TIBC levels presented a significant decrease following FCM infusion, while post-FCM Hb levels increased.
Our study is limited by the relatively small sample size due to the strict inclusion criteria used. Furthermore, our patients had heterogeneous underlying gastrointestinal diseases. Hence, patient comparisons based on age, disease, or laboratory findings were limited.

5. Conclusions

FCM administration appears effective and safe as a treatment for ID/IDA in pediatric patients with gastrointestinal diseases. In our study, we found no significant difference between pre- and post-FCM serum phosphate levels. Four out of 35 patients (11.42%) developed transient and asymptomatic hypophosphatemia. Furthermore, we found no significant difference between pre- and post-FCM-infusion serum iFGF23 levels and no correlation between serum iFGF23 and serum PTH, 25(OH)D, ALP, calcium, or phosphate levels. However, we noted that iFGF23 levels increased 7–10 days after infusion in patients who developed hypophosphatemia. More prospective studies of FCM administration in pediatric patients are required to confirm the incidence of FCM-induced hypophosphatemia and its mechanisms.

Author Contributions

M.N.: Investigation, Data Curation, Resources, Visualization, Writing—Original Draft, Statistical Analysis; E.M.: Conceptualization, Methodology, Validation, Writing—Review and Editing, Project Administration; L.S.: Resources, Methodology; P.P.: Methodology, Visualization; E.E.-F.: Statistical Analysis, Data Curation, Visualization; E.P. and P.K.: Resources and Visualization; M.F.: Conceptualization, Data Curation, Supervision, Methodology, Validation, Writing—Review and Editing. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki and was approved by the Ethics Committee of Aristotle University of Thessaloniki (Protocol Code: 1483; Date of approval: 19 October 2021).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The data presented in this study are available on request from the corresponding author.

Conflicts of Interest

The authors declare no conflicts of interest.

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Hemato 05 00034 sch001
Scheme 1. A schematic diagram of the method and materials used in the study. Sample collection was performed in three phases as displayed in the vertical flowchart [phosphate (Phos), calcium (Ca), alkaline phosphatase (ALP), urea, creatinine, alanine transaminase (ALT), aspartate aminotransferase (AST), ferritin, total iron-binding capacity (TIBC), 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (PTH), C-reactive protein (CRP), and soluble Transferrin Receptor (sTfR)].
Scheme 1. A schematic diagram of the method and materials used in the study. Sample collection was performed in three phases as displayed in the vertical flowchart [phosphate (Phos), calcium (Ca), alkaline phosphatase (ALP), urea, creatinine, alanine transaminase (ALT), aspartate aminotransferase (AST), ferritin, total iron-binding capacity (TIBC), 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (PTH), C-reactive protein (CRP), and soluble Transferrin Receptor (sTfR)].
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Figure 1. Distribution of serum iFGF23 levels in three phases using R software. Median serum iFGF23 levels did not significantly differ across the three phases (p = 0.56).
Figure 1. Distribution of serum iFGF23 levels in three phases using R software. Median serum iFGF23 levels did not significantly differ across the three phases (p = 0.56).
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Figure 2. Violin plots for serum iFGF23 levels of patients with hypophosphatemia (N = 4) after FCM infusion. A graphically different trend is noted, with an iFGF23 increase 7–10 days after infusion.
Figure 2. Violin plots for serum iFGF23 levels of patients with hypophosphatemia (N = 4) after FCM infusion. A graphically different trend is noted, with an iFGF23 increase 7–10 days after infusion.
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Figure 3. Violin plots for serum iFGF23 levels of patients with normal serum phosphate after FCM infusion. No similar trend is observed in patients with hypophosphatemia. Serum iFGF23 levels remain stable before, 7–10 days after, and 6–8 weeks after FCM infusion.
Figure 3. Violin plots for serum iFGF23 levels of patients with normal serum phosphate after FCM infusion. No similar trend is observed in patients with hypophosphatemia. Serum iFGF23 levels remain stable before, 7–10 days after, and 6–8 weeks after FCM infusion.
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Table 1. Baseline demographic and biochemical parameters of the participants.
Table 1. Baseline demographic and biochemical parameters of the participants.
VariableMean ± SD or
Median (Min, Max)		Normal Reference Range *
(According to Our Laboratory)
Age (years)14 (2, 16)-
eGFR (mL/min/1.73 m2)135.82 (110.87, 225)-
Serum Phos (mg/dL)4.36 ± 0.624.5–5.5
Serum Ca (mg/dL)9.4 (8, 14)8.4–10.2
Creatinine (mg/dL)0.6 ± 0.120.57–1.11
Urea (mg/dL)22.11 ± 7.6410–50
ALP (U/L)116 (39, 362)<300
ALT (U/L)16 (7, 110)5–34
AST (U/L)24 (10, 84)0–55
Ferritin (ng/mL)4.94 (0.5, 435)9.29–58.7
TIBC (μg/dL)354 ± 63.72300–400
sTfR (mg/L)2.2 (1.13, 9.92)0.83–1.76
PTH (pg/mL)38.27 ± 18.2818.5–88
25(OH)D (ng/mL)20.45 ± 10.9730–150
Hb (g/L)10.74 ± 2.5512–15.4
MCV (fl)75.36 ± 12.9580–98
MCH (pg)26.1 (13, 33)27–33
MCHC (g/dL)32.7 (26.7, 35.7)31.5–35
RDW (%)14.1 (10.7, 21.9)11.5–14.5
CRP (mg/dL)0.16 (0.04, 17.8)<0.5
iFGF23 (pg/mL)56.53 (25.77, 852.46)8–120 **
* Normal ranges may differ by age/gender; ** According to Gkentzi et al. [18]; Serum iFGF23 levels were measured in healthy Greek children using the same ELISA assay used in our study.
Table 2. Underlying gastrointestinal causes of ID/IDA of the children included in the study.
Table 2. Underlying gastrointestinal causes of ID/IDA of the children included in the study.
Underlying DiseasesNumber of
Patients
IBD14
   -Crohn’s disease    12
   -Ulcerative colitis    2
Celiac disease8
Cow’s milk allergy3
Feeding problems8
Eosinophilic esophagitis2
Total35
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Ntoumpara, M.; Mantadakis, E.; Skoura, L.; Panagopoulou, P.; Emmanouilidou-Fotoulaki, E.; Parasidou, E.; Koutra, P.; Fotoulaki, M. The Effect of Ferric Carboxymaltose on Fibroblast Growth Factor 23 (FGF23) in Children with Iron Deficiency Anemia Due to Gastrointestinal Diseases. Hemato 2024, 5, 448-458. https://doi.org/10.3390/hemato5040034

AMA Style

Ntoumpara M, Mantadakis E, Skoura L, Panagopoulou P, Emmanouilidou-Fotoulaki E, Parasidou E, Koutra P, Fotoulaki M. The Effect of Ferric Carboxymaltose on Fibroblast Growth Factor 23 (FGF23) in Children with Iron Deficiency Anemia Due to Gastrointestinal Diseases. Hemato. 2024; 5(4):448-458. https://doi.org/10.3390/hemato5040034

Chicago/Turabian Style

Ntoumpara, Maria, Elpis Mantadakis, Lemonia Skoura, Paraskevi Panagopoulou, Elpida Emmanouilidou-Fotoulaki, Eleftheria Parasidou, Paraskevoula Koutra, and Maria Fotoulaki. 2024. "The Effect of Ferric Carboxymaltose on Fibroblast Growth Factor 23 (FGF23) in Children with Iron Deficiency Anemia Due to Gastrointestinal Diseases" Hemato 5, no. 4: 448-458. https://doi.org/10.3390/hemato5040034

APA Style

Ntoumpara, M., Mantadakis, E., Skoura, L., Panagopoulou, P., Emmanouilidou-Fotoulaki, E., Parasidou, E., Koutra, P., & Fotoulaki, M. (2024). The Effect of Ferric Carboxymaltose on Fibroblast Growth Factor 23 (FGF23) in Children with Iron Deficiency Anemia Due to Gastrointestinal Diseases. Hemato, 5(4), 448-458. https://doi.org/10.3390/hemato5040034

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