Trends of Fecal Calprotectin and Lactoferrin Results for Infants

Abstract

Calprotectin and lactoferrin can be measured in stool to test for inflammation in the gastrointestinal tract associated with inflammatory bowel disease (IBD) versus irritable bowel syndrome (IBS). The clinical specificity of these markers decreases in children versus adults because of the broader differential diagnosis for intestinal inflammation in children. Surprisingly, these tests are frequently ordered for infants (age = 0 years). Therefore, we wanted to assess our historical data in order to understand how infant calprotectin and lactoferrin concentrations change over time and review literature for the potential differential diagnosis for intestinal inflammation in infants. Data were analyzed on 19,543 infants/toddlers ages 0 to 2 years who had a stool test result of either the quantitative ELISA calprotectin PhiCal assay (Eurospital) or qualitative ELISA Lactoferrin Chek assay (Techlab). For the quantitative calprotectin test, the averages and medians were graphed over time in infants. And for the qualitative lactoferrin test, the positivity rate was graphed over time in infants. Both were compared to toddlers of ages 1 to 2 years old. The average level of calprotectin in neonates (0-1 months old) was 336 ± 348 μg/g with a median of 192 μg/g. While these values were dramatically above the adult normal reference range of 0 to 50 μg/g, the average level decreased over time to 119 ± 218 μg/g with a median of 39 μg/g for toddlers 2 years old. The presence of elevated lactoferrin was detected in 89% of neonates versus 34% of toddlers age 2 years. These trends demonstrate that both calprotectin and lactoferrin may be elevated early in life for many infants, but rapidly decline with time. Ordering trends show that, for infants/toddlers age 0 to 2 years, fecal calprotectin ordering has grown rapidly, whereas fecal lactoferrin has remained stable. In conclusion, while fecal calprotectin and lactoferrin are widely used markers of pathologic intestinal inflammation in adults, results in infants must be interpreted with great care. An elevated calprotectin or lactoferrin concentration in infant stool may be pathological, perhaps due to necrotizing enterocolitis or food-associated enteropathy, but is also associated with nonpathological reasons such as intestinal exposure to food antigens or commensal bacteria. Literature studies have shown associations of elevated calprotectin or lactoferrin with diet, gestational age at birth, and even mode of delivery. Thus, it is essential that clinicians interpret calprotectin levels or the presence of elevated lactoferrin in the context of the entire clinical picture and understand the lack of specificity of these markers for pathological conditions in infants.