The European Society for Pediatric Gastroenterology and Nutrition (ESPGHAN) Gastroenterology Committee has developed recommendations for using fecal calprotectin (FC) testing in gastrointestinal disorders in children, according to a position paper published in the Journal of Pediatric Gastroenterology and Nutrition.
The primary use of FC measurement is for the screening and monitoring of patients with inflammatory bowel disease (IBD) and to differentiate IBD from functional gastrointestinal disorders (FAPDs), stated the ESPGHAN committee. However, according to the group, FC should not be used for diagnosing patients with infantile colic or for differentiating between functional and organic constipation.
The ESPGHAN committee conducted a literature search in the PubMed, MEDLINE, EMBASE, and Cochrane databases until October 31, 2019 to identify all publications relating to FC or calprotectin, as well as those regarding calprotectin in the context of specific conditions including celiac disease, IBD, FAPDs, and others. Based on the available studies, the committee created 28 recommendations and reached a consensus on each one. The recommendations were then classified according to the quality of available evidence, including the methodology and outcomes assessed, and were given grades of strong, moderate, or weak.
The committee’s first recommendation concerns the collection and handling of stool samples. The group developed a moderate recommendation for collecting FC samples at any time of the day directly from the stool without any prior processing. Samples should not be obtained for FC measurements from diapers and nappies (especially when stool consistency is loose), or during/following bowel cleansing and/or lower endoscopy. Samples for FC measurements should not be kept for more than 3 days at room temperature before processing or for more than 7 days if they are refrigerated immediately.
The committee issued strong recommendations for using the same extraction methodology and test kit for measuring FC when diagnosing and assessing disease activity in an individual patient over time, and that each center’s laboratory establish its own normal values for FC.
Research has shown that FC values are generally higher in children than in adults, although no well-established cutoff levels exist for specific age ranges. FC levels depend on gestational and postnatal age, but they do not appear to be related to sex, noted the authors.
The committee strongly recommends the following when screening pediatric patients for evidence of gastrointestinal diseases: (1) always pay equal attention to the clinical context as well as to the absolute FC values; (2) do not use a cutoff level <100 µg/g for children aged <4 years owing to the wide variability in FC values detected in healthy children in this age range; and (3) exert caution when using a cutoff level of <50 µg/g (as recommended in adults) for children aged >4 years, as reference values in this age group have not been irrefutably established.
Research has shown that FC is a more effective screening tool for IBD in undiagnosed patients compared with blood inflammatory markers, such as C-reactive protein or erythrocyte sedimentation rate. Thus, FC could help select children for whom IBD needs to be evaluated, noted the authors.
The committee strongly recommends performing a diagnostic endoscopy in cases in which IBD is strongly suspected and not to wait for FC results if they cannot be obtained in a timely fashion, to avoid any delay in confirming the diagnosis. Additionally, FC should not be used as a prognostic marker in acute severe colitis.
The committee issued moderate recommendations for using FC levels after colectomy to screen for pouchitis and inflammation at the anastomosis, as well as to not use FC in babies with infantile colic.
The committee issued a strong recommendation to use FC to differentiate functional abdominal pain disorders from organic diseases. The authors issued a moderate recommendation against measuring FC in children with constipation, as it cannot differentiate between functional and organic causes, such as Hirschsprung disease.
Among several other moderate recommendations, the committee advises against the use of FC as a diagnostic tool or as a prognostic marker of cow’s milk protein allergy (CMPA) in children, and against the use of FC as a marker for the diagnosis or monitoring of children with celiac disease. In addition, the authors moderately recommend that clinicians be cautious when interpreting individual FC values as a marker of enteropathy in cystic fibrosis.
“There appears to be little value in using FC as a diagnostic tool or prognostic marker of CMPA, or for the diagnosis or monitoring of celiac disease,” stated the committee. “In children with cystic fibrosis, there is not enough evidence on a correlation between FC and enteropathy.”
The ESPGHAN group also advises against the use of FC in acute gastroenteritis, when distinguishing bacterial from viral gastroenteritis in children. Additionally, FC should not be used either alone or in combination with other inflammatory biomarkers when screening children with abdominal pain for the presence of acute appendicitis. Finally, FC measurements should not be used for screening or follow-up of children with Helicobacter pylori (H pylori) infection or H pylori–related diseases.
The committee moderately advises against the use of FC as a routine measurement in obese children, when no other clinical conditions relevant to its measurement is suspected. FC should also not be used to establish therapeutic efficacy in children with severe acute malnutrition.
The position paper also addresses other conditions, such as necrotizing enterocolitis (NEC), as research has shown that preterm infants with NEC have significant transient early increases in FC compared with healthy infants of the same gestational age. The committee issued a moderate recommendation to consider using serial FC measurements as a noninvasive screening tool to alert for the risk of developing NEC.
The ESPGHAN committee also advised against the use of FC measurements in children with autism, unless they have symptoms that are suggestive of conditions relevant to FC levels.
“FC measurement has seen an unprecedented rise in utility as a marker of gastrointestinal disease, specifically inflammation,” stated the committee. “There are, however, many considerations and limitations, which need to be defined and acknowledged before FC measurement is used to influence clinical management. This article has attempted to clarify these and provide the best evidence-based recommendations or, wherever not possible, expert consensus, for the use of FC. The use of FC should always be alongside and in support of good clinical judgment.”
Koninckx CR, Donat E, Benninga MA, et al. The use of fecal calprotectin testing in paediatric disorders: a position paper of the European Society for Paediatric Gastroenterology and Nutrition Gastroenterology Committee. J Pediatr Gastroenterol Nutr. 2021;72(4):617-640. doi: 10.1097/MPG.0000000000003046