Total parenteral nutrition exposure in neonates and the risk of long‐term food allergy: A retrospective cohort study

Background Total parenteral nutrition (TPN) is essential for critically ill neonates but bypasses enteral stimulation and may induce gut dysbiosis, raising concern about long‐term allergic outcomes. We hypothesized that neonatal TPN exposure is associated with an increased risk of food allergy in infants compared with the absence of TPN. Methods Using the South Korean National Health Insurance Service database, we followed 2,325,275 infants born between 2005 and 2010 from their first birthday until December 31, 2023. Our exposure of interest was TPN administered during the first 28 days of life; our primary outcome was the initial clinical diagnosis of food allergy after the first year of life. Propensity score overlap weighting, targeting the average treatment effect in the overlap population, constituted the primary analysis, with robust sandwich variance estimators. Results In total, 7661 infants (0.33%) received TPN. Food allergy occurred in 156 TPN‐exposed infants (1.33 per 1000 person‐years) and 45,608 unexposed infants (1.23 per 1000 person‐years). The unadjusted association (hazard ratio [HR], 1.42; 95% CI: 1.21–1.66) was fully attenuated after overlap weighting (HR, 1.00; 95% CI: 0.83–1.21; P = 0.99). Results were consistent in multivariable, pre‐exposure‐covariate‐only, and competing‐risks (Fine–Gray) analyses, across food allergy subtypes and high‐risk subgroups, and no association was observed per additional day of TPN administration. Conclusion Neonatal TPN exposure was not significantly associated with the long‐term risk of food allergy. The unadjusted association appears attributable to confounding by baseline clinical severity, although a modest increase in risk cannot be excluded.