Supplementary Material for: Association of heart rate variability with postnatal maturation in preterm infants

Introduction
We assessed whether longitudinal measurements of sample entropy (SampEn) of heart rate time series reflect postnatal maturation in preterm infants and evaluated its predictive value at 32 weeks postmenstrual age (PMA) for estimating discharge home. We further compared SampEn of preterm infants at discharge with that of term infants.
Methods
We conducted a prospective study at the University Children's Hospital Basel, Switzerland from 2018 to 2022. We included preterm infants born before 32 weeks of gestation and a control group of term infants. Heart rate was recorded using the clinical monitoring system. We assessed preterm infants at 32 and 36 weeks PMA, and at discharge; term infants were evaluated between 3 to 28 days of life. SampEn was calculated from 90-min recordings using custom analytical software.
Results
We obtained valid data from 183/183 preterm infants (mean (range) 28.4 (23.3-31.7) weeks gestation) and from 80/104 (76%) term infants. In preterm infants, SampEn increased from 32 to 36 weeks PMA (0.35 vs. 0.40; p<0.01) without further increase to discharge. SampEn was positively associated with maturation and growth, and negatively with complications of prematurity, particularly with bronchopulmonary dysplasia. SampEn at 32 weeks PMA did not improve clinical predictions of PMA at discharge. At discharge, SampEn did not differ significantly between preterm and term infants.
Conclusion
SampEn of heart rate time series increased with postnatal maturation in preterm infants, reaching values of term infants at discharge. It was negatively associated with complications of prematurity but its prognostic value for discharge timing is limited.