A Higher Incidence of Isolated Biliary Atresia in Rural Areas: Results From an Epidemiological Study in The Netherlands.

OBJECTIVES: Environmental factors may be involved in the pathogenesis of biliary atresia (BA). This epidemiological study aimed to analyze the relationships between the incidence of BA, the incidence of confirmed viral or bacterial infections and population density, and geographical and temporal clustering of BA in the Netherlands. STUDY DESIGN: Correlations between the monthly incidence of BA and the number of confirmed infections were assessed. BA incidence per province was calculated and compared to the province with highest population density. Birthplaces were classified as rural or urban. Temporal clustering of month of birth and month of conception were analyzed. We performed analyses for isolated BA (IBA) and syndromic BA (SBA) separately. Chi2, logistic regression, and Walter and Elwood test were used. RESULTS: A total of 262 IBA and 49 SBA patients, born between 1987 and 2018, were included. IBA incidence correlated to the number of confirmed infections of, for example, Chlamydia trachomatis (R = 0.14; P = 0.02) and adenovirus (R = 0.22; P = 0.005). We observed a higher incidence of IBA (0.75/10,000; odds ratio [OR] = 1.86; P = 0.04) and SBA (0.27/10,000; OR = 6.91; P = 0.001) in Groningen and a higher incidence of SBA in Gelderland (0.13/10,000; OR = 3.35; P = 0.03). IBA incidence was 68% higher in rural (0.67/10,000) versus urban areas (0.40/10,000) (P = 0.02). The estimated month of conception of patients with SBA clustered in November (85% increase compared to average SBA incidence [0.09/10,000; P = 0.04]). CONCLUSIONS: IBA incidence correlated weakly with national confirmed infections. IBA and SBA incidence varied geographically in the Netherlands. IBA incidence was higher in rural than in urban areas, which may be explained decreased exposure to pathogens. Our results provide support for a role of environmental factors in the pathogenesis of IBA.

Test Strategies to Predict Inflammatory Bowel Disease Among Children With Nonbloody Diarrhea.

OBJECTIVES: We evaluated 4 diagnostic strategies to predict the presence of inflammatory bowel disease (IBD) in children who present with chronic nonbloody diarrhea and abdominal pain. METHODS: We conducted a prospective cohort study including 193 patients aged 6 to 18 years who underwent a standardized diagnostic workup in secondary or tertiary care hospitals. Each patient was assessed for symptoms, C-reactive protein (>10 mg/L), hemoglobin (<-2 SD for age and sex), and fecal calprotectin (≥250 µg/g). Patients with rectal bleeding or perianal disease were excluded because the presence of these findings prompted endoscopy regardless of their biomarkers. Primary outcome was IBD confirmed by endoscopy or IBD ruled out by endoscopy or uneventful clinical follow-up for 6 months. RESULTS: Twenty-two of 193 (11%) children had IBD. The basic prediction model was based on symptoms only. Adding blood or stool markers increased the AUC from 0.718 (95% confidence interval [CI]: 0.604-0.832) to 0.930 (95% CI: 0.884-0.977) and 0.967 (95% CI: 0.945-0.990). Combining symptoms with blood and stool markers outperformed all other strategies (AUC 0.997 [95% CI: 0.993-1.000]). Triaging with a strategy that involves symptoms, blood markers, and calprotectin will result in 14 of 100 patients being exposed to endoscopy. Three of them will not have IBD, and no IBD-affected child will be missed. CONCLUSIONS: Evaluating symptoms plus blood and stool markers in patients with nonbloody diarrhea is the optimal test strategy that allows pediatricians to reserve a diagnostic endoscopy for children at high risk for IBD.