Evaluation and Management of Iron Deficiency in Children Undergoing Intestinal Rehabilitation-A Position Paper From the NASPGHAN Intestinal Rehabilitation Special Interest Group.

Iron deficiency (ID) is the most common nutritional deficiency affecting children undergoing intestinal rehabilitation (IR). Patients may be asymptomatic or present with nonspecific symptoms including fatigue, irritability, and dizziness. The diagnosis of ID in this population can be complicated by the coexistence of systemic inflammation or other nutritional deficiencies which may mimic ID. Many routinely available laboratory tests lack specificity and no consensus on screening is available. Success in oral and enteral treatment is impeded by poor tolerance of iron formulations in a population already challenged with intolerance. Newer parenteral iron formulations exhibit excellent safety profiles, but their role in repletion in this population remains unclear. The following report, compiled by a multidisciplinary group of providers caring for children undergoing IR and representing the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Special Interest Group for Intestinal Rehabilitation, seeks to address these challenges. After discussing iron physiology and population-specific pathophysiology, we make recommendations on iron intake, iron status assessment, and evaluation for alternative causes of anemia. We then provide recommendations on iron supplementation and treatment of ID anemia specific to this nutritionally vulnerable population.

Pitfalls of iron supplementation in parenteral nutrition admixtures for children with intestinal failure.

BACKGROUND: Pediatric patients with intestinal failure are at increased risk for iron deficiency. Supplementation is not routinely included in parenteral nutrition solutions. There is currently limited research related to the safety of iron supplementation in parenteral nutrition and for intravenous forms used in patients with intestinal failure. Current American Society for Parenteral and Enteral Nutrition and ESPGHAN guidelines promote the use of enteral iron, acknowledging the risks of using iron supplementation within parenteral nutrition admixtures. METHODS: We review a patient case and the current available literature related to iron in parenteral nutrition. RESULTS: Five major concerns are identified: peroxidation reactions, incompatibility, hypersensitivity, infection risk, and iron overload. CONCLUSION: We propose an argument against the preferential use of iron supplementation within parenteral nutrition in children with intestinal failure when enteral supplementation or intermittent parenteral infusion may be sufficient.

Bacterial overgrowth assessment and treatment among pediatric intestinal rehabilitation and nutrition support providers: An international survey of clinical practice patterns.

BACKGROUND: Small bowel bacterial overgrowth (SBBO) is a common, but difficult to diagnose and treat, problem in pediatric short bowel syndrome (SBS). Lack of clinical consensus criteria and unknown sensitivity and specificity of bedside diagnosis makes research on this potential SBS disease modifier challenging. The objective of this research was to describe clinical care of SBBO among international intestinal rehabilitation and nutrition support (IR&NS) providers treating patients with SBS. METHODS: A secure, confidential, international, electronic survey of IR&NS practitioners was conducted between March 2021 and May 2021. All analyses were conducted in the R statistical computing framework, version 4.0. RESULTS: Sixty percent of respondents agreed and 0% strongly disagreed that abdominal pain, distension, emesis, diarrhea, and malodorous stool, were attributable to SBBO. No more than 20% of respondents strongly agreed and no more than 40% agreed that any sign or symptom was specific for SBBO. For a first-time diagnosis, 31 practitioners agreed with use of a 7-day course of a single antibiotic, with a majority citing grade 5 evidence to inform their decisions (case series, uncontrolled studies, or expert opinion). The most common first antibiotic used to treat a new onset SBBO was metronidazole, and rifaximin was the second most commonly used. One hundred percent of respondents reported they would consider a consensus algorithm for SBBO, even if the algorithm may be divergent from their current practice. CONCLUSION: SBBO practice varies widely among experienced IR&NS providers. Development of a clinical consensus algorithm may help standardize care to improve research and care of this complex problem and to identify risks and benefits of chronic antibiotic use in SBS.

Enteral ferric citrate absorption is dependent on the iron transport protein ferroportin.

Ferric citrate is approved as an iron replacement product in patients with non-dialysis chronic kidney disease and iron deficiency anemia. Ferric citrate-delivered iron is enterally absorbed, but the specific mechanisms involved have not been evaluated, including the possibilities of conventional, transcellular ferroportin-mediated absorption and/or citrate-mediated paracellular absorption. Here, we first demonstrate the efficacy of ferric citrate in high hepcidin models, including Tmprss6 knockout mice (characterized by iron-refractory iron deficiency anemia) with and without adenine diet-induced chronic kidney disease. Next, to assess whether or not enteral ferric citrate absorption is dependent on ferroportin, we evaluated the effects of ferric citrate in a tamoxifen-inducible, enterocyte-specific ferroportin knockout murine model (Villin-Cre-ERT2, Fpnflox/flox). In this model, ferroportin deletion was efficient, as tamoxifen injection induced a 4000-fold decrease in duodenum ferroportin mRNA expression, with undetectable ferroportin protein on Western blot of duodenal enterocytes, resulting in a severe iron deficiency anemia phenotype. In ferroportin-deficient mice, three weeks of 1% ferric citrate dietary supplementation, a dose that prevented iron deficiency in control mice, did not improve iron status or rescue the iron deficiency anemia phenotype. We repeated the conditional ferroportin knockout experiment in the setting of uremia, using an adenine nephropathy model, where three weeks of 1% ferric citrate dietary supplementation again failed to improve iron status or rescue the iron deficiency anemia phenotype. Thus, our data suggest that enteral ferric citrate absorption is dependent on conventional enterocyte iron transport by ferroportin and that, in these models, significant paracellular absorption does not occur.

Nutrition Deficiencies in Children With Intestinal Failure Receiving Chronic Parenteral Nutrition.

BACKGROUND: Home parenteral nutrition (PN) is a lifesaving therapy for children with intestinal failure (IF). Our aims were to describe the prevalence of micronutrient deficiencies (vitamin D, zinc, copper, iron, selenium) in a diverse population of children with IF receiving PN and to identify and characterize risk factors associated with micronutrient deficiencies, including hematologic abnormalities. METHODS: Data were collected on 60 eligible patients through retrospective chart review between May 2012 and February 2015. Descriptive statistics included frequencies, medians, interquartile ranges (IQRs), and odds ratios (ORs). Statistical analyses included χ2 , Fisher's exact, t tests, and logistic, univariate, and multivariate regressions. RESULTS: Patients were primarily young (median age, 3.3 years; IQR, 0.7-8.4), Latino (62%), and male (56%), with short bowel syndrome (70%). Of 60 study patients, 88% had ≥1 deficiency and 90% were anemic for age. Of 51 patients who had all 5 markers checked, 59% had multiple deficiencies (defined as ≥3). Multivariate analysis shows multiple deficiencies were associated with nonwhite race (OR, 9.4; P = .012) and higher body mass index z score (OR, 2.2; P = .016). Children with severe anemia (hemoglobin <8.5 g/dL) made up 50% of the cohort. Nonwhite race (OR, 6.6; P = .037) and zinc deficiency (OR, 11; P = .003) were multivariate predictors of severe anemia. CONCLUSIONS: Micronutrient deficiency and anemia are overwhelmingly prevalent in children with IF using chronic PN. This emphasizes the importance of universal surveillance and supplementation to potentially improve quality of life and developmental outcomes. Future research should investigate how racial disparities might contribute to nutrition outcomes for children using chronic PN.