Reference values for heart rate frequency and variability in premature neonates during the first week of life

Abstract Objectives This study aimed to establish reference values for heart rate frequency and variability indices in preterm neonates admitted to a neonatal intensive care unit of a tertiary care hospital during their first week of life. Methods In this retrospective cohort study, the Generalized Additive Models for Location Scale and Shape framework was employed to establish reference values for heart rate indices across time-domain, frequency-domain and nonlinear-domain in neonates considering gestational age, postnatal age, sex and birth weight. Results Heart rate tracings of 594 neonates (45 % female; median gestational age at birth 29 0 (IQR 26 6 –30 5 ); 38 % birth weight p90) were analyzed. Reference values were established for 25 heart rate indices. Nearly all heart rate indices were significantly influenced by gestational age, postnatal age and sex. Baseline heart rate decreased with gestational age, increased with postnatal age and was higher in females. Heart rate standard deviation increased with gestational age and postnatal age and was lower in female. Inclusion of birth weight significantly improved model fit for all HRV indices. Conclusions This study highlights the importance of considering gestational and postnatal age, sex and birth weight when interpreting neonatal heart rate frequency and variability in preterm neonates. These findings support the need for personalized approaches for neonatal monitoring and interpretation. Future research should validate these values in larger, more diverse populations, including additional clinical factors such as neonatal complications and medication administration, to determine their clinical relevance.