Pediatric Reference Limits for Holter Monitor Heart Rate Variability Parameters: Defined Using Meta-Analysis

Q: What are the key findings of this study?

Reference limits for SDNN, SDANN, SDNNi, LF, and HF are proposed for pediatric patients, with lower limits indicative of decreased HRV identified for each age group, but measures such as rMSSD and pNN50 are unreliable for this purpose due to many lower limits at or near zero.

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Heart Rate Variability (n=2993). Intervention: Holter Monitor Heart Rate Variability Analysis. Primary outcome: Age-stratified reference limits for Holter monitor HRV parameters in healthy infants, children, and adolescents.

Q: What does this research mean for the field?

Age-stratified pediatric reference limits for Holter monitor heart rate variability parameters (SDNN, SDANN, SDNNi, LF, HF) can effectively identify decreased HRV, whereas rMSSD and pNN50 are unreliable for this purpose because their lower limits are frequently at or near zero. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

James J. Joyce; Collins Odhiambo; Soujanya Bogarapu; Pavana Sreenivasan; Harold L. Kennedy; Sunita J. Ferns

doi:10.1007/s00246-026-04219-x

March 10, 2026Pediatric CardiologyOpen Access

Pediatric Reference Limits for Holter Monitor Heart Rate Variability Parameters: Defined Using Meta-Analysis

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Key result

Pediatric HRV reference limits define thresholds for decreased SDNN while finding rMSSD and pNN50 unreliable.

n=2,993

Why the study?

Low heart rate variability is associated with increased morbidity and mortality, but pediatric reference limits for Holter monitor heart rate variability parameters have not been adequately defined.

Key Points

To establish age-stratified normative reference limits for linear time- and frequency-domain Holter monitor heart rate variability parameters in healthy infants, children, and adolescents.
Conducted a systematic search through 2024, analyzing 49 studies comprising 2993 healthy participants across 20 countries.
Extracted continuous time- and frequency-domain heart rate variability parameters and calculated pooled means with 95% reference intervals using random-effects meta-analysis models.
Stratified subjects into four primary developmental age groups: birth to 11 months, 1 to 6 years (subdivided into 1–3 and 4–6 years for time-domain metrics), 7 to 12 years, and 13 to 18 years.
Time-domain parameters SDNN and SDANN increased progressively across childhood, with SDNN mean values rising from 54 ms (95% reference interval: 22–85 ms) in infants to 88 ms (23–151 ms) at 1–3 years, 132 ms (68–197 ms) at 4–6 years, 139 ms (66–221 ms) at 7–12 years, and 167 ms (78–252 ms) in adolescents.
Frequency-domain indices ln LF and ln HF increased sharply after infancy with minimal change thereafter, as mean ln LF rose from 4.6 ms2 (95% reference interval: 2.3–6.8 ms2) in infants to 6.6 ms2 (5.5–7.6 ms2) at 1–6 years and 7.1 ms2 (5.9–8.4 ms2) in adolescents.
Lower reference limits for rMSSD, pNN50, and LF/HF frequently approached or reached zero across pediatric cohorts (e.g., pNN50 95% reference intervals of 0–22% at 1–3 years and 0–48% at 4–6 years and in adolescents), limiting their clinical utility for identifying depressed heart rate variability.

Study Design

Type

Meta-Analysis (n=2,993)

Multicenter

Yes

Structured PICO

P

Population

2,993 healthy pediatric subjects (aged <19 years) pooled from 49 studies. Key inclusion: clinically healthy without disease as assessed by normal screening history and physical examination, not on any prescription medication, and not known to be involved in endurance sports training. Key exclusion: preterm infants.

I

Intervention

24-hour ambulatory electrocardiography (Holter monitoring) for heart rate variability (HRV) analysis

O

Outcome

Age-stratified 95% reference intervals for linear time-domain (SDNN, SDANN, SDNNi, rMSSD, pNN50) and frequency-domain (LF, HF, LF/HF ratio) HRV parameterssurrogate

This meta-analysis establishes the first comprehensive, age-stratified reference limits for 24-hour Holter monitor heart rate variability parameters in healthy pediatric patients.

Limitations

Variability in sample sizes across studies
Proprietary devices and parameters reported varied
Non-universal screening methods for health status
Inadequate number of sex-specific studies and participants to complete a thorough age level male-female comparison meta-analysis
Possible inadvertent inclusion of subjects with subclinical heart disease since screening with 12-lead electrocardiogram and echocardiogram was not universal
Subdivision of the 1-6 year age group led to a reduction in the total number of subjects in the reference ranges

Discussion

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Implication

Enables clinicians to identify low HRV in children by age group; extends literature with first comprehensive Holter reference limits.

Abstract

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.

Cite This Study

Joyce et al. (2026) conducted a meta-analysis in Heart Rate Variability (n=2,993). Holter Monitor Heart Rate Variability Analysis was evaluated on Age-stratified reference limits for Holter monitor HRV parameters in healthy infants, children, and adolescents. Reference limits for SDNN, SDANN, SDNNi, LF, and HF are proposed for pediatric patients, with lower limits indicative of decreased HRV identified for each age group, but measures such as rMSSD and pNN50 are unreliable for this purpose due to many lower limits at or near zero.

synapsesocial.com/papers/69b3ab9102a1e69014ccc92a https://doi.org/10.1007/s00246-026-04219-x

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Pediatric Reference Limits for Holter Monitor Heart Rate Variability Parameters: Defined Using Meta-Analysis

Key Points

Study Design

Structured PICO

Limitations

Discussion

Implication

Abstract

Cite This Study

Pediatric Reference Limits for Holter Monitor Heart Rate Variability Parameters: Defined Using Meta-Analysis

Key Points

Study Design

Structured PICO

Limitations

Discussion

Implication

Abstract

Cite This Study

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