Longitudinal Variability of Fecal Calprotectin in Preterm Newborns: A Prospective Cohort Study

Fecal calprotectin (FC) is a potential biomarker of gastrointestinal inflammation; however, its physiological behavior in preterm newborns remains poorly understood. This prospective cohort study aimed to characterize the longitudinal variability of FC concentrations during the first month of life in preterm newborns of ≤34 weeks of gestational age admitted to a neonatal intensive care unit. Altogether, 48 preterm newborns and 42 mothers were examined, with 124 fecal samples collected weekly. The median FC levels exhibited wide interindividual and intraindividual variations, ranging from 56 µg/g in the first week to 65 µg/g in the third week, with no significant association with clinical or laboratory variables. No confirmed cases of NEC occurred during follow-up. Among the five preterm newborns with clinical suspicion of NEC, FC levels fluctuated without a consistent temporal pattern or discriminatory profile. Because stool samples were collected according to a predefined weekly schedule rather than at symptom onset, transient FC changes associated with acute gastrointestinal events may not have been captured. The very small number of newborns with clinically suspected NEC, particularly during later follow-up, substantially limited the statistical power of subgroup analyses. Therefore, statistical comparisons involving this subgroup should be interpreted as exploratory and hypothesis-generating rather than confirmatory. Therefore, FC levels may vary substantially in preterm newborns and, within the limitations of this study, these findings primarily characterize the baseline longitudinal variability of FC rather than its diagnostic value for NEC and support cautious interpretation of isolated FC measurements in this population.