**Background:** Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gastrointestinal tract. Treatment goals have shifted from clinical remission to endoscopic and histologic remission, as these are associated with better long-term outcomes. Fecal calprotectin (FC) is a noninvasive biomarker of intestinal inflammation, but its correlation with endoscopic and histologic severity in pediatric IBD is not well established. This study aimed to examine the association of quantitative FC levels with endoscopic and histologic disease severity in pediatric IBD patients and to compare FC levels in IBD patients with endoscopic remission to those in non-IBD controls.
**Methods:** A retrospective chart review was conducted at a tertiary academic center, including patients who had FC measured between 30 days and 1 day prior to colonoscopy from January 1, 2014, to May 30, 2018. IBD patients were identified from a local database, and controls were patients without IBD. Endoscopic disease activity was scored by a single pediatric gastroenterologist using the Simple Endoscopic Score for Crohn's Disease (SES-CD) for CD and the Mayo endoscopic score for UC. Histologic activity was scored by a pathologist-in-training and a board-certified pediatric pathologist using the Geboes method. FC levels were measured by a quantitative enzyme-linked immunosorbent assay. Statistical analyses included descriptive statistics, boxplots with pairwise comparisons, and sensitivity analysis. Non-IBD controls were matched to IBD patients by age and gender using nearest neighbor matching with a 2:1 ratio.
**Key Results:** A total of 331 patients were included: 107 IBD patients (63 CD, 44 UC) and 224 controls. The median age of IBD patients was 14 years (IQR 11–16), 55.1% were male. In the overall IBD cohort, median FC levels increased with endoscopic disease severity: no disease 181 μg/g (IQR 445–749), mild 499 μg/g (IQR 42–779), moderate 599 μg/g (IQR 244–1071), severe 921 μg/g (IQR 462–1422). Significant differences were found between no disease vs. moderate (P=0.019) and severe (P=0.003), and between mild vs. severe (P=0.012). For histologic severity, median FC levels were: no disease 328 μg/g (IQR 116–833), mild 399 μg/g (IQR 235–1064), moderate 674 μg/g (IQR 325–1250), severe 895 μg/g (IQR 504–1434), with significant differences between no disease vs. moderate (P=0.021) and severe (P=0.018). In CD patients, median FC was significantly different between no disease and moderate (P=0.047) and severe (P=0.0047) endoscopic disease, and between moderate and severe (P=0.044). In UC patients, a clear linear increase was not observed endoscopically, but histologically, median FC differed significantly between no disease and moderate disease (P=0.023). Sensitivity analysis showed that FC >50 μg/g and >100 μg/g had 95% sensitivity and 23% and 38% specificity, respectively, for predicting any endoscopic inflammation. IBD patients in endoscopic remission had significantly higher median FC (181 μg/g) compared to matched non-IBD controls (35.5 μg/g; P=0.041).
**Clinical Implications:** This study demonstrates that FC levels correlate with both endoscopic and histologic disease severity in pediatric IBD, supporting its use as a noninvasive biomarker for monitoring disease activity. However, the finding that IBD patients in endoscopic remission have higher FC levels than non-IBD controls suggests that the threshold for defining remission in pediatric IBD may need to be higher than the standard cutoff used for screening. The study highlights the need for larger, prospective studies to establish standardized FC cutoff values for different disease severities and to account for disease type and location. Despite limitations including a small sample size, retrospective design, and variability in endoscopic media, the results provide valuable pediatric-specific data that can guide clinical use of FC in monitoring IBD activity and potentially reduce the need for invasive procedures.