Pediatric Reference Limits for Holter Monitor Heart Rate Variability Parameters: Defined Using Meta-Analysis
摘要
Low heart rate variability (HRV) has been associated with increased risk of morbidity and mortality. While HRV measurements from Holter monitoring have been available for over 3 decades, pediatric reference limits have not been adequately defined. We sought to determine these limits using meta-analysis. Multiple databases were searched through 2024 for relevant studies. Data extraction with meta-analysis and estimation of 95% reference ranges were performed. Linear time- and frequency-domain HRV variables were grouped by the following age ranges: infants (birth-11 months), younger children (1–6 years), older children (7–12 years), and adolescents (13–18 years). Forty-nine studies including 2993 participants were analyzed. SDNN (standard deviation of all sinus NN intervals), SDANN (standard deviation of averages of NN intervals in all 5 min segments), SDNNi (mean of standard deviations of NN intervals for all 5 min segments), rMSSD (root mean square of differences between adjacent NN intervals), and pNN50 (percentage of adjacent NN intervals that varied by more than 50ms) all demonstrated a progressive increase in younger children that required subdivision of that reference range. SDNN and SDANN exhibited further milder increases into adolescence, while SDNNi, rMSSD, and pNN50 remained relatively stable after age 4 years. LF (low frequency) and HF (high frequency) parameters increased abruptly from infancy to early childhood with minimal change thereafter. Remarkably, pediatric age-group lower limits for rMSSD, pNN50, and LF/HF were frequently at or near zero, limiting their utility for detecting decreased HRV. Age-stratified Holter monitor reference limits for HRV parameters in infants, children and adolescents are proposed.