Treatment targeting pediatric inflammatory bowel disease-associated anemia: experience from a single tertiary center

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Clin Exp Pediatr. 2025;68(9):722-731

Publication date (electronic) : 2025 June 10

doi : https://doi.org/10.3345/cep.2025.00640

Ana S.C. Fernandes, MD^,1,2, Sara Azevedo, MD^1,2, Ana Rita Martins, RN¹, Ana Isabel Lopes, MD, PhD^1,2

¹Pediatric Department, University Hospital Santa Maria, Lisbon Medical Centre, Lisbon, Portugal

²Medical Faculty, University of Lisbon, Lisbon, Portugal

Corresponding author: Ana S.C. Fernandes. Hospital de Santa Maria, Av. Prof. Egas Moniz MB, 1649-028 Lisboa, Portugal Email: anascfernandes@gmail.com

Received 2025 March 13; Revised 2025 May 5; Accepted 2025 May 15.

Abstract

Introduction

Anemia is one of the most common extraintestinal complications of inflammatory bowel disease (IBD), both at diagnosis and during follow-up [1-3]. In IBD patients, anemia often has a complex and multifactorial etiology, in which several factors may play a role:

(1) iron deficiency anemia (IDA), resulting from mucosal inflammation, chronic gastrointestinal blood losses, sometimes exceeding iron absorption capacity, impaired iron absorption in the duodenum or upper jejunum of Crohn disease patients, anorexia/malnutrition, and dietary restrictions;

(2) anemia of inflammation and chronic disease – inflammation induces hepcidin synthesis in the liver, which binds and inactivates ferroportin, inhibiting the export of iron from the intracellular compartment to the plasma for peripheral utilization, resulting in disturbed iron deposit distribution with retention in erythrocytes and macrophages. Additionally, hepcidin inhibits iron absorption by enterocytes. Active inflammation also leads to upregulation of ferritin and downregulation of transferrin, which result in lower transferrin-bound plasma iron, ineffective iron transport, and inadequate iron delivery to the bone marrow, leading to functional iron deficiency, direct inhibition of erythropoiesis (mediated by interferon-γ) and inhibition of erythropoietin production (by 1L-1, TNF-α, IL-6);

(3) drug induced anemia (myelosuppressive effect of drugs, myelodysplasia, impaired folic acid absorption; impaired iron absorption caused by treatment with proton pump inhibitors, hemolysis);

(4) other vitamin deficiencies (e.g. vitamin B12, folic acid deficiency).

Among these, IDA and anemia of chronic disease (ACD) are the most common etiologies [4,5].

Several studies have evaluated the prevalence of anemia and iron deficiency in pediatric IBD patients, both at diagnosis and during follow-up. Reported prevalence of anemia ranges from 44% to 78% at diagnosis, and 20% to 61% at follow-up (usually 1- or 2-year follow-up) [6-14], exceeding the reported prevalence in adults. Abnormal inflammatory markers, such as elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), low albumin, low body mass index, acute onset of severe disease, active disease, Crohn disease with colonic/ileocolonic involvement, and extensive ulcerative colitis (UC) have been pointed as risk factors for anemia in IBD pediatric patients [9,10,13,15]. Reported prevalence of iron deficiency in pediatric IBD patients ranges from 39%–95% at diagnosis [7,8,13-17], and 27%–70% at 1- to 2-year follow-up [8,14]. Wikholm et al. [17], reported a high prevalence of iron deficiency (85%) even in IBD children in clinical and biochemical remission. Thus, reported evidence indicates that expectant management of anemia and iron deficiency in IBD patients is clearly insufficient.

Anemia and iron deficiency are frequently overlooked, due to their insidious onset, lack of standardized screening practices, concerns with tolerability, adverse events, or costs of iron formulations. IDA and ID are frequently asymptomatic or manifest with nonspecific symptoms such as irritability, headaches, fatigue and exercise intolerance, dizziness, anorexia, impairment of cognitive function, restricted growth, epithelial alterations (cheilitis, atrophic glossitis, hair loss). These impact significantly on quality of life and contribute to the disease burden [5]. Danko et al. [18] reported a positive correlation between correction of IDA with intravenous (IV) iron and improvement of health-related quality of life scores in pediatric IBD patients, even in those in clinical remission.

Currently, there has been a paradigm shift in clinical practice, with the recent publication of consensus and position papers, recommending a proactive approach strategy, involving prevention, earlier screening, monitoring and treatment of IBD associated anemia in children [5,19]. Oral iron preparations can be used as the first-line treatment in mild IDA, especially in IBD patients in remission, who have not been previously intolerant to oral iron formulations. They have the advantages of low-cost, safety, noninvasiveness and at home administration, but the disadvantages of poor tolerability (nausea, vomiting, abdominal pain, and diarrhea are more common than with IV iron treatment), compliance problems, deficient absorption (especially in active IBD), and possible pernicious impact on inflammation and microbiome [4,5,19-23]. On the other hand, IV iron replacement has been shown to be safe and effective both in adult and pediatric IBD patients and is now the recommended treatment for IDA in IBD patients with active disease, moderate to severe anemia or intolerance to oral iron, allowing fast anemia correction and repletion of iron stores, showing a higher efficacy in achieving a hemoglobin (Hb) response of at least 2.0 g/dL than oral iron preparations [5,19-21]. Two IV iron preparations are available at our center: iron sucrose (IS) and ferric carboxymaltose (FCM), approved below and above the age of 14, respectively. Side effects of these formulations include local inflammation at the injection site (e.g., pain, erythema), nausea, dizziness and rare, but potentially serious, allergic reactions. Other reported side effects of IS include muscle cramps, dysgeusia, diarrhea or constipation, headache, arthralgia and hypotension, while FCM has been associated with hypertension, flushing, and hypophosphatemia.

In pediatric patients with IBD and anemia, data regarding the optimal therapeutic pathway are still lacking. We report our cumulative experience (single tertiary referral center) with IV iron treatment (IS and FCM), in a retrospective cohort of children with IBD associated iron deficiency and anemia. This study further contributes to the existing evidence of safety and efficacy of IV iron formulations used in these patients, while adding up evidence of a longer follow-up period (10 years of experience, median follow-up 5.5 years).

Methods

This is a single center retrospective study, including pediatric patients with IBD aged 1–19 years treated with IV iron—IS < 14 years, FCM ≥ 14 years—for IDA or evidence of iron deficiency, between March 2011 and March 2021 at the Gastroenterology Unit of the Santa Maria Hospital, in Lisbon, Portugal. Patients were treated according to the Unit Protocol. The diagnosis of IBD was confirmed by standard clinical, imaging and histological criteria.

IV iron was considered first-line treatment (as opposed to oral iron) for all pediatric IBD patients with Hb>6 g/dL (with hemodynamic stability and no cardiovascular disease or other comorbidities), in accordance with the Portuguese Consensus on Anemia in Pediatric Inflammatory Bowel Disease [19]. Additionally, patients with concomitant vitamin B12 or folate deficiency, patients receiving oral iron throughout the study period and pregnant patients were excluded from the study.

Anemia was defined according to World Health Organization [24] criteria: Hb<11 g/dL in children aged between 6 months and 5 years, Hb<11.5 g/dL in children aged between 6 and 11 years, Hb<12.0 g/dL for girls above 12 and boys between 12 and 13 years, and Hb<13 g/dL for boys above the age of 14.

Iron deficiency was defined as serum ferritin<30 μg/L in the absence of inflammation, or serum ferritin<100 μg/L in the presence of inflammation (elevated CRP or ESR) and/or transferrin saturation (TSAT) <16%.

Patients treated at the outpatient clinic and patients treated opportunistically during their inpatient admission for several reasons were both considered.

Written informed consent was obtained for all patients or their caretakers at the time of IV iron treatment, regarding treatment and study participation. The study followed the norms established by the Ethics Committee of Hospital de Santa Maria – Centro Hospitalar Lisboa Norte, EPE.

Demographic and clinical data recorded for each participant included: IBD type (Crohn disease, Ulcerative Colitis or IBD-unclassified), IBD phenotype (Paris classification), sex, age at the time of IBD diagnosis and at the time of IV iron treatment, disease activity assessed with the Pediatric Crohn’s Disease Activity Index (PCDAI) or the Pediatric Ulcerative Colitis Activity Index (PUCAI) at the time of treatment and posttreatment evaluations, IBD treatment at the time of treatment and posttreatment evaluations.

Laboratory parameters recorded included Hb, hematocrit, red blood cell distribution width, platelets, albumin, ESR, CRP, serum ferritin (s-ferritin), TSAT and calprotectin both at the time of iron deficiency diagnosis/treatment and at the follow-up evaluation 4–12 weeks after IV iron administration.

The total dose of IV iron administered was determined according to the Ganzoni formula: iron (mg) = weight (kg) × [target Hb-real Hb (g/dL)] × 2,4 + iron stores. Iron stores: ≥35-kg body weight: 500 mg, <35 kg: 15 mg/kg. FCM dosage was determined according to the simplified scheme using body weight as recommended by the European Consensus on the Diagnosis and Management of Iron Deficiency and Anaemia in Inflammatory Bowel Diseases [25].

When IS was used, the total dose was divided in several infusions according to need (first dose 5 mg/kg up to a maximum of 100 mg, subsequent doses 5 to 7 mg/kg/dose, maximum 200 mg at weekly intervals).

According to the unit’s protocol, in order to identify adverse reactions associated with IV iron treatment, parameters such as blood pressure, heart rate, oxygen saturation and temperature were recorded before, during and after each infusion by a trained pediatric nurse, and any adverse reactions were closely monitored by questioning and physical examination. When discharged, all patients were asked to report any adverse events in the following week to the nursing or medical staff (available by phone). At the follow-up visit, patients were questioned about symptoms and physically examined.

The primary outcome was the treatment efficacy and safety. For patients with IDA, efficacy was defined as a ≥2 g/dL increase in Hb and/or normalization of Hb up to 12 weeks after treatment. For patients with iron deficiency without anemia, efficacy was defined as TSAT or s-ferritin normalization.

Statistical methods: statistical descriptive analysis. Continuous variables were expressed with mean and/or median and interquartile range (IQR). Adverse events were reported descriptively using frequency and percentage.

Results

1. Demographic and clinical data

During the 10-year study period, 132 pediatric patients with IBD were being followed and 63 (47%) were treated with IV iron, at least once (Fig. 1). Their baseline demographics and clinical characteristics are shown in (Table 1). Thirty patients were male (47.6%), the median age at the time of first IV iron administration was 14.6 years, 41 (65.1%) had Crohn disease, 15 (23.8%) had UC, and 7 (11.1%) had IBD-unclassified.

Fig. 1.

Number of patients in follow-up during the study period, number of patients treated with intravenous iron included in the study, and number of administered treatments. IBD, inflammatory bowel disease

Table 1.

Summary of baseline demographics and clinical characteristics of patients with inflammatory bowel disease treated with intravenous iron (N=63)

In this 10-year period, 103 patients were newly diagnosed with IBD, 48 of which (48 of 103) received IV iron. Considering only the newly diagnosed IBD patients, ID or IDA affected 21.4% at the time of IBD diagnosis and recurred in 5.8% one year later. In newly diagnosed patients, the first IV iron administration occurred after a median time of 2.4 months (0–32.7 months) after the diagnosis.

At the end of the study period, the median time since IBD diagnosis in these 63 patients was 6.0 years (0.2–20.2 years), and the median follow-up since their first IV iron administration was 5.5 years (2 months 10 years).

In this 10-year period, 104 IV iron administrations were performed: 63 (60.6%) administrations of FCM in a single infusion, and 41 (39.4%) of IS (the total dose per each of these 41 courses was divided into 3–5 infusion episodes). Most treatments took place in the ambulatory regimen (86 of 104, 82.7%). In 23 cases (22.1%), the patients were treated during IBD presentation, and in 10 of these IV iron was administered while hospitalized.

Table 2 shows clinical activity scores before and after IV iron administration in Crohn disease and UC patients, evaluated by PCDAI and PUCAI, respectively. Sixty-one of the 104 IV iron administrations occurred in patients with Crohn disease, most of which had PCDAI scores compatible with inactive (32 patients) or moderately active disease (23 patients). At the time of the 27 IV iron administrations to UC patients, most patients PUCAI score was also compatible with inactive (14 patients) or mild disease (7 patients). Only 12 patients had scores compatible with moderate-severe activity (6 with Crohn disease and 6 with UC). Calprotectin levels at the time of treatment were available in 57 cases and suggested active inflammation in most patients (982 μg/g; IQR, 430–2,878 μg/g).

Table 2.

Clinical activity scores before and after intravenous (IV) iron administration (N=104)

There was a global reduction of the activity scores from pre- to posttreatment evaluations, even in the group of patients with moderate-severe activity, in which PCDAI score median diminished from 40 to 6.25 and PUCAI score median reduced from 52.5 to 20. Similarly, from pre- to posttreatment evaluations, there was a reduction in median ESR (from [38.2; IQR, 22.0–67.5] to [24; IQR, 11–42]) and CRP (from [0.6 mg/dL; IQR, 0.07–3.32 mg/dL] to [0.36 mg/dL; IQR, 0.07–1.06 mg/dL]). Calprotectin levels from both pre- and posttreatment evaluations were only available in 39 treatment courses, in which a reduction from pre- to posttreatment evaluations was also noted (from [941 μg/g; IQR, 526–3,637 μg/g] to [840 μg/g; IQR, 213–1,494 μg/g]).

Most patients (37 of 63, 58.7%) received a single IV iron course during the study period. The remaining 26 (41.3%) had recurrent iron deficiency, requiring 2 (18 of 63, 28.6%), 3 (4 of 63, 6.3%), 4 (1 of 63, 1.6%) or 5 (3 of 63, 4.8%) courses of treatment. In patients with recurrent iron deficiency (26 of 63, 41,3%) and, thus, need for recurrent IV iron treatment, the median follow-up since their first IV iron administration was 5.7 years (1.2–9.7 years), and the median interval between IV iron administration courses was 1.4 years (IQR, 0.6–2.6 years). In these patients with recurrent iron deficiency, median activity scores at the time of recurrent treatment were 8.75 (IQR, 5–15) for patients with Crohn disease and 0 (IQR, 0–23.75) for patients with UC. Relevant changes in IBD treatment (dose escalation/ shift to different drugs) occurred at some point following 16 of 26 (61.5%) of these IV iron treatment courses, and 2 patients with UC were submitted to colectomy.

The median IV iron dose administered per treatment course was 800 mg (IQR, 500–1,000 mg), and the median cumulative dose administered per patient in the 10 years study period was 1,000 mg (IQR, 700–1,400 mg; range 350–4,700 mg).

Discussion

IDA requiring IV iron treatment affected 47% of the IBD patients treated at this single center, 21.4% of the IBD patients at the time of diagnosis and recurred in 6 of 103 (5.8%) at 1 year follow-up. The prevalence value found is within the range that has been reported in literature: Aljomah et al. [12] reported an IDA prevalence of 28.85% at IBD diagnosis and 15.38% at 1 year follow-up; Goodhand et al. [7] reported a prevalence of IDA of 69.5% in children and 44% in adolescents, and another Portuguese cohort, by Carvalho et al. [11], reported IDA affected 43,5% of children at IBD diagnosis and 21.7% at 1-year follow-up.

Increasing evidence supports proactive treatment of IDA in pediatric IBD, and the safety and efficacy of newer IV iron preparations such as FCM and IS.

IS treatment for IDA in pediatric IBD patients has been retrospectively studied by several groups, with reported efficacy in the correction of IDA ranging from 52.3%–68.8%, and minor adverse reactions in up to 6.6% of infusion treatments [26-28]. Experience with IV FCM for IDA treatment in pediatric IBD has also been retrospectively studied by several groups, although efficacy criteria have not always been defined nor uniform. Improvement or correction of hematinic indices in IDA occurred in 62.5%–100% of patients in the studies by Laass et al. [29], Tan et al. [30], Cococcioni et al. [31], and Papadopoulos et al. [32], with non–life-threatening adverse reactions noted in up to 5,6% of patients (mild rash/urticaria, mild oedema of palms and fingers). Finally, a prospective study by Carman et al. [33] reported the treatment of 101 pediatric IBD patients (age 6–18 years) for ID or IDA with FCM. Treatment was effective in 64% of the patients treated for IDA and 81% of the patients treated for ID. The reported efficacy in this study was very similar to our experience: 66.7%–67.6% efficacy in IDA treatment, 77.8% efficacy in ID treatment.

In our 10-year experience with a total of 104 IV iron treatment courses, there was one adverse reaction during IS infusion in a 5-year-old boy, consisting of exanthema and hypotension. These results further contribute to the safety and efficacy data regarding IV iron treatment in pediatric IBD. The similar efficacy with both IV iron formulations and the single adverse reaction registered do not allow comparative conclusions to be drawn between the two. However, it should be noted that IS has the disadvantage of a low maximum dose per infusion, usually requiring multiple separate infusions in each treatment course, with the associated economic, time and emotional costs for the child, the family and healthcare services. Despite being approved in Europe only for children above the age of 14, the previously mentioned studies report FCM’s efficacy and safety in much younger IBD patients, allowing a higher single dose administration.

At the time of IV iron treatment, most patients in our cohort had mild or inactive disease according to clinical activity scores. However, calprotectin levels, when available, suggested active inflammation. There was a global reduction of the activity scores and inflammatory markers (ESR, CRP) from pre- to posttreatment evaluations, even in the group of patients who initially showed moderatesevere activity. This reduction may indicate that disease activity was successfully controlled in most patients between the 2 evaluations. Unfortunately, calprotectin levels from both pre- and posttreatment evaluations were only available in 39 treatment courses (in which a reduction from pre- to posttreatment evaluations was also noted). Therefore, we must consider that, despite low clinical activity scores and low serum inflammatory markers at the time of treatment, iron deficiency may be an early sign of disease activity, which was corroborated by calprotectin levels, when available.

The 33 patients in which IV iron treatment did not reach efficacy were similar to the whole cohort in terms of IBD phenotype, clinical activity scores and calprotectin levels. Low clinical activity scores, low inflammatory markers, and similar calprotectin levels, suggest that treatment failures cannot be fully accounted for by active inflammation. This was also the case in the studies by Stein et al. [28], Cococcioni et al. [31], Papadopoulos et al. [32], and Danko and Wiedecamp [34], in which treatment response could not be fully explained by disease activity and/or location. In comparison to the adult IBD population, other factors inherent to the pediatric age, such as growth and nutrient requirements, make it particularly vulnerable to ID.

The estimation of iron deficit in our patients was calculated using Ganzoni formula. This formula has been increasingly criticized for being “inconvenient, prone to error” and the fact that it “underestimates” iron requirements [25]. In fact, after IV iron treatment for IDA, our patients’ median ferritin rose to 93.4 ng/mL (IQR, 53.9–159.1 ng/mL), a value far below the European Crohn's and Colitis Organisation (ECCO) consensus recommendation of 400 μg/L (400 ng/mL) to prevent recurrence of anemia, and far below the 800 μg/L safety limit to prevent iron overload [25]. Thus, underestimation of iron needs may have been an important contribution to treatment failure and ID or IDA recurrence.

During the 10 years of study, recurrent ID with or without anemia, affected 26 patients (41.3%), with median interval of 1.4 years between IV iron administration courses. This is higher than the recurrence rate reported in other pediatric studies which had, however, a shorter follow-up: Papadopoulos et al. [32] reported a 14.6% recurrence of IDA over 38 months, Tan et al. [30] reported a 29.4% recurrence over 46 months, with a median interval of 12 months between IV iron treatment courses, Cococcioni et al. [31] reported a 35.2% recurrence during 5 years of follow-up with a median interval of 37.9 weeks (approximately 8.5 months) between IV iron courses, and in a previous prospective 40 months study in our Unit a 31.6% recurrence of IDA was identified, with a median 15.5 month period between treatments [35]. Kulnigg et al. [36], in a 5-year study in the adult population, identified anemia recurrence in 50% of patients after 10 months of treatment. Table 3 contains key findings from relevant studies on Pediatric Inflammatory Bowel Disease associated IDA and the study of Kulnigg et al. [36] in the adult population.

Table 3.

Comparison of findings of relevant studies

Both inadequate response to treatment and rapid recurrence of anemia require attention to IBD activity. Inflammatory markers may not always adequately reflect disease activity, and careful reassessment (clinical, imaging and/or endoscopic) may be necessary. As a matter of fact, even though most of our patients with recurrent ID or IDA had IBD activity scores compatible with inactive or mild disease at the time of retreatment, calprotectin levels, when available, suggested active inflammation, relevant changes in IBD treatment (dose escalation/shift to different drugs) were made after IV iron treatment in 16 of 26 patients (61.5%) and 2 patients with UC were submitted to colectomy, suggesting that ID may have been one of the first signs of disease activity. Furthermore, when new biomarkers, such as soluble transferrin receptor (sTfR) and the index sTfR/log ferritin, become generally available and standardized, they may be helpful in distinguishing IDA from ACD more precisely in patients with chronic inflammatory diseases such as IBD. These 2 biomarkers were identified as the best predictors of ID in a group of 75 children with IBD, in comparison to other classical biomarkers such as erythrocyte indexes, serum iron, ferritin, transferrin and transferrin saturation [37].

According to the ECCO consensus, after successful treatment of IDA with IV iron, patients should be monitored for recurrent ID every 3 months for at least a year and every 6 to 12 months thereafter, and retreatment should be initiated as soon as serum ferritin drops below 100 μg/L or Hb drops below 12 or 13 g/dL (according to gender). Adequate treatment of IBD is also crucial to prevent recurrence, which should always be regarded as a potential indicator of persistent intestinal disease activity, even in the absence of symptoms or inflammatory markers rise [25]. Considering the frequent recurrence of ID and IDA in children, these recommendations may also be appliable to children, even though there is currently no consensus on the treatment of pediatric IBD patients with nonanemic ID. Oral iron can be an option in patients with ID or mild anemia, inactive IBD and no known intolerance to oral iron. A new formulation, ferric maltol, designed to optimize the absorption and tolerability of oral iron, has been approved for the treatment of adults with ID, with or without anemia. It has also been investigated in adolescents above the age of 10, with promising results. With this more stable molecule, unabsorbed iron remains chelated in the ironmaltol complex and is excreted in feces, thereby reducing the risk of mucosal oxidative damage from free iron and reactive hydroxyl radicals. Additionally, no significant changes in the microbiome have been found following treatment with ferric maltol [38].

The main limitations of our study are associated with its retrospective design. There was some missing information, and minor adverse events might not have been reported or documented. Posttreatment laboratorial evaluations were done opportunistically 4–12 weeks after IV iron treatment, at the next follow-up visit. Thus, improvement or worsening of Hb and iron profile could have been influenced by underlying disease activity and diet. There was no comparison group treated with placebo or oral iron, the latter of which might have been adequate in some patients with mild or inactive IBD. However, it should be noted that in the cases treated with FCM, a single dose administered opportunistically at a scheduled visit to the outpatient clinic allows a simple, practical, faster, safe, and efficient treatment of ID.

Prospective randomized clinical trials are needed to determine the best iron formulation, optimize iron treatment dosing, eliminate confounding factors that might influence treatment efficacy and clarify the impact of IDA and nonanemic ID treatment on the course of IBD and patient outcomes, in order to improve ID and IDA management in pediatric IBD.

In conclusion, ID and IDA are common complications of IBD. In our cohort, we found an IDA prevalence of 47%, within the range that has been reported in literature, but higher recurrence rates (41.3%), probably explained by our longer follow-up period.

Treatment efficacy was 66.7% (FCM) to 67.6% (IS) in IDA, and 77.8% in ID without anemia, and one adverse reaction was noted (hypotension and rash) with IS, adding to the existing evidence that FCM and IS are safe and effective treatments for iron deficiency in pediatric IBD.

Most patients in our cohort had mild or inactive disease activity scores and low serum inflammatory markers at the time of IV iron treatment, but calprotectin levels, when available, suggested active inflammation. This suggests that the former may not always adequately and timely reflect disease activity, and that ID may be an early sign of active disease.

The posttreatment median ferritin levels reached in our patients—93.4 ng/mL (IQR, 53.9–159.1 ng/mL)—far below the ECCO consensus recommendation of 400 ng/mL to prevent recurrence of anemia, add to the evidence that Ganzoni formula likely underestimates pediatric patients’ iron needs and better formulas are required to estimate iron deficit.

Based on the results found in this study, we propose the following adjustments to clinical practice:

• Adopt the ECCO consensus recommendation to monitor patients for recurrent ID, after successful treatment of IDA with IV iron, every 3 months for at least a year and every 6 to 12 months thereafter

• Adopt the ECCO consensus recommendation for retreatment with iron as soon as serum ferritin drops below 100 μg/L or Hb drops below 12 or 13 g/dL (according to gender)

• In the absence of alternative formulas proven superior to Ganzoni formula for calculating iv iron dosing, we suggest aiming at the ECCO consensus recommendation of ferritin levels of 400 ng/mL to prevent recurrence of anemia. This will require a prospective experimental approach.

• In cases of treatment failure with IV iron or early recurrence of ID or IDA, it is essential to reassess patients thoroughly for signs of active disease, including clinical signs and symptoms, systemic inflammation markers (CRP and ESR), calprotectin, imaging findings, complemented by endoscopy, when necessary

• Point-of-care endoscopy ultrasound has recently become available in our Unit. This has proved to be a safe, noninvasive, quick, cost-effective and accurate tool, performed at patient’s bedside, requiring no fasting or intestinal preparation, and allowing real-time decision making [39,40]. Through earlier detection of active, yet subclinical, disease activity, this promising tool may allow timely treatment adjustments, with positive changes in disease progression and prevention of morbidity.

Published evidence strongly encourages proactive screening, monitoring and treatment of IDA in IBD. Our findings add to the growing evidence that support the safety and efficacy of IV iron treatment in the management of pediatric IBD patients, contributing with representative data from a particularly longer follow-up than most previous pediatric studies.

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