Age-adjusted eosinophilia in preterm infants with feeding intolerance: a retrospective cohort study.

PURPOSE: Feeding intolerance (FI) remains diagnostically challenging because of nonspecific symptoms and overlap with multiple gastrointestinal conditions. This study investigated the association between peripheral eosinophilia and FI in preterm infants with exploratory evaluation of necrotizing enterocolitis (NEC) and cow's milk protein-related gastrointestinal disease in relation to eosinophilia.

METHODS

In this retrospective cohort study, 122 preterm infants (< 34 weeks' gestation, < 2000 g) with eosinophil counts ≥ 700/mm³ were included. Infants were subsequently reclassified according to gestational- and postnatal-age-adjusted eosinophil reference values. Clinical features of FI, NEC, and cow's milk protein-related gastrointestinal disease were compared between infants with and without age-adjusted eosinophilia. Multivariable logistic regression was used to explore clinical variables independently associated with feeding intolerance.

RESULTS

Age-adjusted eosinophilia was present in 100 infants. FI was more frequent in eosinophilic infants (86% vs. 63.6%, p = 0.027), with longer feeding interruption (median 2 vs. 0.5 days, p = 0.028), more abdominal distension (60% vs. 31.8%, p = 0.019), and prolonged hospitalization (60 vs. 41 days, p = 0.034). In the primary multivariable model, age-adjusted eosinophilia was independently associated with feeding intolerance (OR 6.00; 95% CI 1.32-27.26; p = 0.020), although the association was attenuated in sensitivity analysis (OR 2.87; 95% CI 0.86-9.58; p = 0.087). All 13 NEC cases occurred in eosinophilic infants, although the temporal relationship between eosinophilia and NEC varied. Suspected cow's milk protein-related gastrointestinal disease was identified in 11 infants, all of whom showed clinical improvement following dietary elimination.

CONCLUSIONS

Age-adjusted eosinophilia was frequently observed in preterm infants with FI and more severe gastrointestinal manifestations. While unlikely to be causally related to FI, it may reflect an accompanying immune or inflammatory response during gastrointestinal disease. Eosinophil counts may provide supportive information in selected infants with persistent FI or NEC-like presentations, particularly when alternative inflammatory gastrointestinal processes are being considered.