Association between sample entropy and cardiorespiratory events in preterm infants routinely immunized in the hospital

Abstract Timely vaccination of preterm infants < 32 weeks gestation is essential for protection against vaccine-preventable diseases. Vaccination may temporarily challenge autonomic regulation and trigger cardiorespiratory events (CRE), sometimes requiring interventions such as tactile stimulation or respiratory support. Concerns about post-vaccination CRE may lead to delayed vaccination. Objective markers identifying infants at risk for post-vaccination CRE are lacking. We therefore assessed whether sample entropy (SampEn) of heart rate time series, a-non-linear measure of heart rate variability, is associated with post-vaccination CRE and related interventions. In this prospective observational single-centre study, conducted from 2018 to 2022, we recorded heart rate and oxygen saturation using standard monitoring at vaccination timepoints. SampEn was calculated from 90-minute ECG recordings. Of 188 enrolled infants, 103 (56%) underwent SampEn analysis at first vaccination during their primary hospital stay. Mean gestational age was 27.3 weeks (range: 23.3 to 31.3 weeks). We found that CRE increased after vaccination, but SampEn was not associated with occurrence of CRE. Lower SampEn and lower gestational age were independently associated with the need for clinical intervention following vaccination. SampEn may help identify infants requiring clinical intervention after vaccination, but its lack of association with CRE limits broader clinical utility.