Baseline NIPE^® index and heart rate variability in preterm infants: influence of maturity and clinical modulators

The NIPE^® monitor estimates parasympathetic tone as a measure of infant pain through heart rate variability analysis. However, reference values and influencing factors remain unclear in preterm neonates. This study aimed to describe baseline NIPE values and their association with sex, gestational age (GA), and clinical conditions in this population. Prospective observational study conducted in a III-C level neonatal unit. Preterm neonates born before 32 weeks of GA were monitored using the NIPE device at four time points: birth (T1), day 7 (T7), day 15 (T15), and 36 weeks postmenstrual age (T36). Clinical and demographic data were collected. Linear mixed-effects models were used to analyse changes in mean NIPE values over time and their association with sex and GA. Fifty-three subjects were analysed. The expected mean NIPE value at T1 was 57.6 (95% CI [55.9,59.4]). No significant differences were found by sex (β =  - 0.35, p = 0.85) or GA (β = 0.60, p = 0.11). A significant decrease was observed at T7 (β =  - 2.40, p < 0.001) and T15 (β =  - 3.60, p < 0.001), with partial recovery at T36 (β =  - 0.20, p < 0.001). Patients receiving invasive mechanical ventilation showed lower NIPE values (β =  - 1.33, p < 0.001). Sedative and/or analgesic treatment significantly reduced NIPE (β =  - 2.92, p < 0.001). A significant increase in NIPE was observed in patients with abnormal cerebral ultrasound (β = 2.52, p < 0.001). Baseline NIPE values in a cohort of preterm newborns were close to the manufacturer's proposed comfort threshold (above 50) but may be influenced by specific clinical conditions. Further research is needed to establish reference values and define its utility across different clinical scenarios. What is known • The NIPE monitor assesses parasympathetic activity as a proxy for neonatal comfort, but its validation in preterm infants remains uncertain. • Heart rate variability is influenced by gestational age and other clinical conditions. What is new • Baseline NIPE values in preterm neonates are close to the comfort threshold of 50 established by the manufacturer. • NIPE threshold for defining comfort in preterm infants may need to be redefined according to postmenstrual age and adapted to the clinical context.