Temporal trends in heart rate characteristic index preceding necrotizing enterocolitis in preterm infants

Objective To evaluate temporal trends in heart rate variability as defined by the Heart Rate Characteristic index (HRCi) preceding necrotizing enterocolitis (NEC) in preterm infants. Study Design Retrospective cohort study of neonates with NEC (Bell Stage II/III) at a tertiary NICU from 2020 to 2024. Continuous HRCi data were extracted for 15 days before and 4 days after NEC diagnosis. HRCi trajectories were analyzed using generalized additive models, Wilcoxon signed-rank tests, and linear regression. Logistic regression models were fit to daily HRCi with NEC diagnosis day (Day 0) as the binary outcome, adjusting for gestational age, small for gestational age (SGA) status, and birth weight Z-scores. Model discrimination was assessed using receiver operating characteristic curves and area under the curve (AUC). Results Among 51 infants with NEC, median birth weight was 900 g and gestational age 27.7 weeks. HRCi rose progressively 2 weeks before onset of NEC, with a significant increase 3 days before diagnosis (median difference 0.31; p = 0.031). Logistic regression showed HRCi remained independently associated with NEC diagnosis day (OR = 1.28; 95% CI: 1.12–1.45; p < 0.001), while gestational age and birth weight Z-score were not. Within-patient AUCs were modest (0.65–0.66); exploratory comparison to the broader NICU population yielded higher discrimination (AUC = 0.84). Conclusion Rising HRCi preceded NEC diagnosis, with significant elevation 3 days before onset. HRCi demonstrated independent temporal association with NEC, though modest discrimination reflects the exploratory design. Prospective validation with matched controls and confounder adjustment is required to establish clinical utility.