Official Journal of NASPEM and the European Group of PWP

Pediatric Exercise Science, 2014, 26, 147-158 http://dx.doi.org/10.1123/pes.2013-0063 © 2014 Human Kinetics, Inc.

www.PES-Journal.com REVIEWS

The Effect of Physical Training on Heart Rate Variability in Healthy Children: A Systematic Review With Meta-Analysis Carla Cristiane da Silva GEAFIT

Ligia Maxwell Pereira and Jefferson Rosa Cardoso PAIFIT

Jonathan Patrick Moore Bangor University

Fábio Yuzo Nakamura GEAFIT The positive effects of physical training on heart rate variability (HRV) in healthy adults are widely recognized; however, the responsiveness to training in healthy children has not yet been established. The aim of this study was to determine the influence of physical training on HRV in prepubertal healthy children. Systematic computerized searches were performed from 1950 to 2012 in the following databases: Medline, Embase, Cinahl, Lilacs, Scielo, SportDiscus, ProQuest; Web of Science; PEDro; Academic Search Premier and the Cochrane Library. The key words used were: heart rate variability, autonomic nervous system, exercise training, physical activity, continuous exercise, intermittent exercise, children, prepubescent, adolescents, and healthy. Although the database search initially identified 6,164 studies, after removing duplicates and excluding by title the number was 148, however, only 2 studies were included in this systematic review. The meta-analysis compared the experimental group (n = 29) with the control group (n = 28) for the HRV parameters: RR intervals, SDNN, RMSSD, pNN50, LF (log), HF (log), LF/HF and Total Power (log). The meta-analysis demonstrated similar HRV indices between both the experimental and control groups. In conclusion, the available results from randomized controlled trials do not support the hypothesis that physical training improves HRV in healthy children[AUQ2]. Keywords: autonomic nervous system, prepubertal, exercise High levels of habitual physical activity and endurance training are associated with resting bradycardia in young, healthy adults (24,31,51), this is due primarily to the alteration of cardiovascular autonomic control (10,46). Furthermore, given that autonomic imbalance may be a final common pathway to increased morbidity and mortality from a host of conditions and diseases, da Silva and Nakamura are with the Physiological Adaptations to Training Research Group- GEAFIT, Londrina, Brazil. Pereira and Cardoso are with the Research Group in Physical Therapy Assessment and Intervention- PAIFIT, Londrina, Brazil. Moore is with the School of Sport, Health and Exercise Sciences, Bangor University, Wales, UK. Address author correspondence to Fábio Yuzo Nakamura at [email protected].

including cardiovascular disease, the clinical relevance of physical training on cardiovascular health is recognized as an important intervention in minimizing the incidences of cardiovascular disease, the main cause of death among adults worldwide (62). Furthermore, although the more severe complications of cardiovascular diseases occur in adulthood, the preventive strategies should begin in childhood and adolescence (1,38,58). These early preventive strategies have been receiving prominent attention in the recommendations for cardiovascular health promotion (52). Autonomic regulation of the cardiovascular system is affected by the sympathetic and parasympathetic pathways. Heart rate variability (HRV)—i.e., beat-to-beat variation in the duration of the R-R intervals—is considered an easy and noninvasive method of providing indirect 147

148  da Silva et al.

assessment of the balance between the sympathetic and parasympathetic branches on the sinoatrial node’s intrinsic rhythm (55). This analysis has been previously validated in children and adolescents at rest (18,19,32,41,59,60), and in situations that involve stress, such as physical exercise (8,29,36,44,56,57). From a clinical and functional standpoint, previous studies in adults have demonstrated that a reduction in HRV is associated with an increased risk of cardiac events and premature death (34,35). This also holds true for children with cardiac diseases (25,40). Sandercock et al. (50) performed a meta-analysis with 22 studies (298 cases) and concluded that aerobic exercise significantly increases the R-R interval length and parasympathetic activity as assessed by the high frequency band (HF) of spectral analyses in adults. Furthermore, it was noted that older subjects presented lower responsiveness to aerobic training when compared with younger adults. However, there is no strong evidence regarding the effect of physical training on HRV in children. Therefore, whether exercise training improves cardiac autonomic activity throughout life remains unknown. Although the literature reports studies involving children (36,45,60) and adolescent athletes practicing different sports (8,29,56,57), it is difficult to reach a conclusion on the real impact of exercise training on HRV in these groups, especially as higher levels of HRV in youth are reported to be resistant to change with regular exercise training (36). Furthermore; methodological differences in HRV assessment, different physical training protocols, initial training status and maturational stages (61), the cross-sectional design of most studies and a lack of control groups in the few longitudinal ones available, make it difficult to elucidate the role of regular exercise on HRV in children. Thus, the aim of this systematic review was to determine the influence of physical training on HRV in healthy, prepubertal children.

Methods Systematic computerized searches were performed in the following databases: Medline (1950—December 2012), Embase (1980—December 2012), CINAHL (Cumulative Index to Nursing and Allied Health Literature—1982— December 2012), Lilacs (Latin American and Caribbean Health Science Literature Database- 1982—December 2012), Scielo (Scientific Electronic Library Online1998), SportDiscus (1975—December 2012), ProQuest (1980—December 2012); Web of Science; PEDro; Academic Search Premier and the Cochrane Controlled Trials Register Library (Issue 10, 2012). The search strategy was formulated by a specialist librarian and included the following keywords both in isolation and combined: heart rate variability, autonomic nervous system, exercise training, physical activity, continuous exercise, intermittent exercise, children, prepubescent, adolescents and healthy. The references of identified studies were also searched to obtain further randomized controlled trials (RCTs) which had not been identified by the electronic searches. There were no language restrictions. For inclusion in the current study, 2

authors screened the search results for potentially eligible studies. When titles and abstracts suggested that a study was potentially eligible for inclusion, a copy of the full text of the manuscript was obtained. Disagreements between the 2 authors regarding a study’s eligibility were resolved by discussion or, when necessary, by a third author. This systematic review followed the recommendations of the PRISMA Statement (37). According to the recommendations proposed by the Cochrane Collaboration Handbook (30), only randomized controlled trials, published or not, that assessed the effect of physical training on heart rate variability in children were included in this review. Clinical trials that were not randomized or quasi-random were excluded. Included participants from eligible studies were healthy, of both sexes, prepubertal (Tanner stage 1) with no clinical or historical evidence of cardiovascular disease, hypertension, insulin-dependent diabetes mellitus or obesity, and were not taking any medication. With respect to training, eligible studies included a minimum of anaerobic and/or aerobic training for 4 weeks. Studies were only included if they provided assurance of valid and standardized processing of the RR interval data that had been recorded using a Holter or heart rate monitor (Polar S810) with a sampling frequency of at least 1,000 Hz. In addition, studies were only included if the authors had made a clear statement of the data treatment for abnormal or ectopic beats. No restriction was made concerning the recording position of children during the evaluation of HRV (sitting, standing or lying) and both short-term (10 min) and long-term (24 hr) studies were included. The control of respiratory rate during data collection was not a necessary inclusion criterion; however, all HRV results were required to be presented numerically in the time and/or frequency domain. With respect to the training program of studies included in the systematic review, they were all required to document the volume, intensity and duration of the training program including the recovery intervals between bouts (in the case of interval training) and sessions. The control group was categorized as those participants who did not practice any kind of exercise training over the duration of the study. The risk of bias was assessed according to the recommendations of The Cochrane Collaboration’s Handbook (30) involving random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting and other bias. The risk of bias for each of the studies was evaluated by two independent authors and each assigned a score according to the criteria (eg, high risk, unclear or low risk of bias). Where there was disagreement between the two authors, a third experienced reviewer assisted with the final decision. Pertinent information missing from any of the studies, which could have negatively affected its score, was obtained by contacting the lead author of the study. Descriptive results were presented with the data pooled to compare HRV outcomes between experimental and control groups. The standardized mean difference (SMD) with a 95% confidence interval was calculated and

Training on Heart Rate Variability  149

the random effect was used to identify differences due to the intervention via Review Manager 5.1.7 software (49). The Kappa coefficient was calculated using SPSS 20 (Chicago, IL, USA) to assess the agreement among judges for risk of bias of the randomized controlled trials. Statistical significance was set at 5%.

Results The database search initially identified 6,164 studies. After preliminary screening, 32 full texts were assessed for eligibility based on their titles; however, thirty were excluded due to other eligibility criteria (Table 1) Nev-

ertheless, we have analyzed the outcomes of the longitudinal noncontrolled studies which were excluded from the analysis. Ultimately, only two studies were able to be included in the meta-analysis (Table 2). The flow of information across the different phases of this systematic review is presented in Figure 1. The majority of published studies examined the effects of physical training on HRV in children with obesity (27,28,53), diabetes (11), congenital heart disease/cardiomyopathies (25,40), or athletes (eg, swimming (56,57), soccer players (8), and cross-country skiers (29). All studies with acute exercise responses or post-exercise parasympathetic reactivation in children were also excluded (23,45,59).

Table 1  Characteristics of Excluded Studies and the Outcomes of Longitudinal Studies Groups

Author

Reason for Exclusion

Reproducibility

Leich et al. (2008)

These 2 studies only tested the reproducibility of HRV in children, and did not involve training.

Wisley et al. (2003) Adolescents

Goulopoulou et al. (2010) Henje Blom et al. (2009) Longin et al. (2009)

Athletes

Buchheit et al. (2010) Buchheit et al. (2011) Carrillo et al. (2011)

Participants included from eligible studies in this systematic review were prepubertal (Tanner stage 1). The studies in this group investigated HRV in adolescents. Participants included from eligible studies in this systematic review were healthy, nonathlete subjects. Excessive training loads potentially experienced by athletes may reduce HRV in children, biasing interpretation of training effects in response to nonsports activities.

Hedelin et al. (2000) Triposkiadis et al. (2002) Vinet et al. (2005) Perini et al. 2006 V.-A. Bricout et al. (2010) Diseases

Chen et al. (2008) Gutin et al. (1997) Gutin et al. (2000) Gutin et al. (2005) Nagai & Moritani. (2004) Prado et al. (2010)

Participants included from eligible studies in this systematic review were healthy, of both sexes, prepubertal (Tanner stage 1) with no clinical or historical evidence of cardiovascular disease or hypertension, insulindependent diabetes mellitus, obesity, and not taking any medication. The studies in this group included children with type 1 diabetes; lean and obese children; children with exercise-induced idiopathic ventricular arrhythmias, boys who had suffered a severe traumatic brain injury and asthmatic children.

Bjelakovic et al. (2010) Katz-Leurer et al. (2010) Fujii et al. (2000) Children

Iwasa et al. (2005) Gamelin et al. (2004)

Acute

Buchheit et al. (2007) Buchheit et al. (2008) Buchheit et al. (2010; B)

The first study in this group investigated heart rate variability and its association with physical activity levels, while the second observed the effect of physical training on children with low HRV. The studies in this group investigated heart rate and heart rate variability during post-exercise recovery. This systematic review comprised only studies with resting HRV measurements.

Goulopolou et al. (2006) Ohuchi et al. (2000) Preadolescents

Buchheit et al. (2007; B)

This is a cross-sectional study.

Longitudinal studies (no control group)

Bricout et al. (2010)

Significant positive effect of soccer training on HRV

Hedelin et al. (2000)

Significant positive effect of cross-country skiing on HRV

Perini et al. (2006)

Significant positive effect of swimming on HRV

Gutin et al. (1997; 2000; 2005).

Significant positive effect of physical training on HRV in obese children.

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Figure 1 — Diagram of the selection of eligible randomized controlled trials (RCTs) from all identified citations.

The agreement between reviewers regarding the assessment of risk of bias for the twoincluded studies was considered high (Kappa = 0.88). The authors did not describe the randomization process or the allocation concealment. The blinding of the outcome assessment was not cited in one study (20). Neither study presented follow-up or intention to treat analysis. The 2 randomized controlled trials included in the systematic review are described in Table 2. Gamelin et al. (20) compared the effects of 7 weeks of intermittent training on supine, 5-min HRV measures. The intermittent training group (n = 7 boys and 10 girls) performed runs at velocities ranging from 100% to 190% of maximal aerobic velocity (MAV), 3 times per week, comprising 30-min sessions, while the control group (n = 12 boys and 9 girls) did not receive any systematic training. The authors concluded that 7 weeks of high-intensity intermittent training improved aerobic performance of MAV, which was not accompanied by significant improvements in cardiac autonomic activity in prepubescent children.

Mandigout et al. (39) examined 19 children (6 boys and 6 girls in the experimental group, and 3 boys and 4 girls in the control group), all of whom were classified as within Tanner stage 1. The training intervention program consisted of three different sessions: one interval training session with repeated work-recovery bouts over short distances, one continuous long distance running session, and one session with other aerobic activities (swimming, soccer, and basketball), with children spending on average 25 to 35 min per hour within the target HR zone (> 80% HRmax). Similar to the study of Gamelin et al. (20), this study protocol consisted of high-intensity intermittent sessions. HRV was recorded 5 days before and after training, using 24-hr Holter recordings. Following 13 weeks of training, an improvement in nocturnal global HRV was reported in healthy prepubertal children, except for the sympathetic/parasympathetic balance variable. Therefore, Mandigout et al. (39) and Gamelin et al. (20) were the only RCTs that met the inclusion criteria of examining healthy children and the effects of regular

Training on Heart Rate Variability  151

training on HRV. Results from these two studies were pooled in the meta-analysis (20,39 Figures 2–4). The meta-analysis compared the experimental group to the control group for the following parameters of HRV: R-R intervals, standard deviation of normal RR intervals (SDNN), square root of the mean differences in successive normal beat to normal beat intervals (RMSSD), number of pairs of adjacent R-R intervals differing by more than 50 ms (pNN50), low frequency band (LF, log transformed, 0.03–0.15Hz), high frequency band (HF, log transformed, 0.15–0.5Hz), LF/HF and total power (log transformed, 0.03–0.5Hz). The total number of children in the intervention group was 29, while 28 were included in the control group. Figure 2 shows the effects of training on R-R intervals with no significant difference in R-R intervals between the experimental and control group (SMD = 0.36; 95% CI –17.0;0.90; P = .77). Similarly, SDNN (SMD = 0.14; 95%CI –0.55;0.83; P = .21, Figure 3A), RMSSD (SMD = –0.04; 95%CI –0.57;0.49; P = .35, Figure 3B) and pNN50 (SMD = –0.11; 95%CI 0.64;0.42; P = .71, Figure 3C) were not different between the experimental and control groups. Likewise, LF (SMD = 0.09; 95%CI –0.43;0.62; P = .52, Figure 4A), HF (SMD = 0.03; 95% CI –0.50;0.55; P = .65, Figure 4B), LF/HF (SMD = 0.37; 95%CI –0.16;0.90; P = .73, Figure 4C), and total power (SMD = –0.05; 95%CI –0.58;0.48; P = .96, Figure 4D) were not significantly different between the groups.

Discussion This review did not reveal any significant effect of exercise training on HRV indices in healthy prepubescent children. The studies included in this systematic review showed a high risk of bias due to the authors’ failure to adequately describe the randomization process or the allocation concealment. No study presented the follow-up or intention to treat analysis. Furthermore, the sample sizes were small in both included studies and neither described the a priori calculation of the sample size, the blinding of participants and researchers or the outcome assessments. Therefore, the absence of significant training effects on HRV in healthy prepubescents may be due to the inherent physiological characteristics of the population or to the limitations in the study design of the few available studies matching the criteria for inclusion in the meta-analysis. The exact mechanisms for HRV alterations, after chronic physical training, in healthy children and adolescents are not known. In addition, some biases inherent to the assessment of HRV must be highlighted, such as the use of different time windows for RR recordings and the different recording devices used. Two other factors should be considered: 1) the effects of various respiratory patterns (59), and 2) the influence of taking measurements in different body positions (12,13). Furthermore, the effects of age, sex, and biological maturation during childhood and adolescence have been controversial in previous literature (7,14,16,41,42,54).

Massin and Bernuth (41) investigated 24-hr HRV in 210 individuals, aged 3 days to 14 years old (108 females and 102 males), noting a significant influence of age, which is consistent with previous findings (14). Similarly, Goto et al. (21) demonstrated an increase in cholinergic and a decrease in adrenergic modulation of HRV with age, confirming the progressive maturation of the autonomic nervous system throughout childhood and adolescence (aged 3 to 15 years). The sex effect was recently demonstrated in a crosssectional study (n = 460) involving prepubertal children (5–10 years old). The results confirmed the effect of age as well as a higher HRV in boys compared with girls (42). Silvetti et al. (54) found similar results with 103 healthy children and adolescents (ages 1–5, 6–10, 11–15, 16–20 years). In contrast, Fukuba et al. (16) and Longin et al. (38) did not report significant differences between the sexes. Therefore, the effect of sex on HRV, which is well described in adults (17), remains uncertain in children and adolescents. Currently, many studies have investigated the impact of physical training on children and adolescents which indicated positive effects on cardiac autonomic modulation (Table 1). There have been some longitudinal studies that have demonstrated improvements in HRV after physical training in different sports, such as soccer, cross-country skiing and swimming (2,29,47). In addition, two different cross-sectional studies have shown controversial results regarding HRV indices for swimmers compared with their nonphysically active counterparts (Table 1). In one study, Triposkiadis et al. (56) observed higher HRV indices for swimmers compared with a control group, while in the other, Vinet et al. (57) did not find positive effects of swimming on HRV indices. Regarding the effects of training on a prepubertal group, we found one study conducted with a group of 305 children intentionally selected as having a low HRV (6–11 years), and a randomly selected control group matched by age, height, and weight. This study showed that 12 months of 20 min of moderate aerobic training had a positive effect on the cardiac autonomic nervous system in the children who had initially had low heart rate variability (44). In addition, previous studies have shown positive cardiac vagal modulation adaptations in overweight/ obese children and adolescents submitted to aerobic physical training. Among these studies with physical training intervention, the studies of Gutin et al. (27,28) are highlighted. These authors demonstrated that 4 months of physical training in 7- to 11-year-old obese children, led to improvements in the RMSSD and LF/HF. This result reflects an increase in parasympathetic activity. In addition, the authors followed-up the children during a 4-month period after the end of the training protocol aiming to determine the effects of detraining on HRV indices. In this follow-up they found that after the cessation of training there were decreases in the parasympathetic indices.

152

Gamelin et al. (2009)

Authors

-Log transformation (ln)

(RMSSD: 54 ± 25 ms- NS);

(SDNN: 58 ± 20 ms- NS);

Frequency Domain

(LF/HF: –0.1 ± 0.6). NS

(HF: 5.7 ± 1.1 ln m2).

-CG (LF: 5.8 ± 0.8 ln m2).

(LF/HF: 0.2 ± 0.8). NS

(HF: 5.4 ± 1.3 ln m2).

-TG (LF: 5.5 ± 0.7 n m2).

(pNN50: 101 ± 69 ms- NS).

-30 s running/30 s pause -Control Group: absence of any training

(SDNN: 61 ± 28 ms- NS); (RMSSD: 61 ± 38 ms- NS);

-15 s running/10 s pause; -20 s running/20 s pause;

(pNN50: 97 ± 61 ms- NS).

Intermittent training with different ratios of effort/pause over the weeks:

-Control Group (CG; n = 12 boys, and n = 9 girls)

-Signals were continuously recorded for 5 min

-TG (R-R: 765 ± 76 ms- NS).

-GC (R-R: 740 ± 80 ms- NS).

3 times per week for 30 min per session

-Training (IT; n = 7 boys, and n = 10 girls)

-Heart rate variability -S810 Polar in supine position

Results Time Domain

-5 s running/15 s pause;

-7 weeks of short intermittent runs at velocities ranging from 100% to 190% of maximal aerobic velocity (MAV)

-Randomized in two groups (intermittent training and control group)

Outcome Main outcome

-10 s running/10 s pause;

Training

Intervention

-n = 38 in Tanner stage 1 under 10 years old.

Subjects

Table 2  Characteristics of Included Studies Conclusions

(continued)

- 7 weeks of high intensity intermittent training was not enough to establish a possible effect on heart rate autonomic regulation in children.

153

Mandigout et al. (2002)

Authors

- 13 week training program

- 1 hr per session

- 3 sessions/week

-Randomized in two groups: training group, with a program based on interval and continuous running, and control group)

Training Group (TG)= (n = 6 boys and n = 6 girls)

Control Group (CG; n = 3 boys and n = 4 girls)

Outcome

Results

(TP: 3.8 ± 0.2 m2 - NS)

(LF/HF: 0.12 ± 0.23- NS)

(HF: 3.9 ± 0.3 ln m2- NS)

-CG (LF: 3.1 ± 0.2 log m2 - NS)

(TP: 3.7 ± 0.3 m2 P < .01).

(LF/HF: 0.17 ±0.19- NS)

(HF: 3.1 ± 0.3 log m2 P < .05)

-TG (LF: 3.3 ± 0.3 log m2 P < .01)

Frequency Domain

(RMSSD: 71 ± 19 ms- NS)

-Control Group: absence of any training

-CG (R-R: 836 ± 59 ms- NS)

(RMSSD: 82 ± 38 ms- NS)

(SDNN:120 ± 35 ms- P < .05)

-TG (R-R: 887 ± 118 ms-P < .05)

Time Domain

(SDNN:101 ± 20 ms- NS)

- Logarithmic Transformation (Log)

- Signals were continuously recorded for 5 hr (00:00– 05:00) during the night

- Holter analysis system in supine position

-Heart rate variability

Main outcome

The program consisted of three different sessions: one interval training session with repeated work-recovery bouts over short distances (for example, 10 × 100 m, 6 × 200 m, 4 × 600 m), one continuous long distance running session (around 15–35 min, 1,500–4,500 m), and one session with another aerobic activity (swimming, soccer, basketball). The recording of the heart rate monitor indicated that during one hour of training, children spent on average around 25–35 min in the target zone (> 80% HRmax).

-Activity Training:

Training

Intervention

-n = 19 in Tanner stage 1 aged between 10 and 11.

Subjects

Table 2  (continued) Conclusions -The results of 13 weeks of training indicated an improvement in nocturnal global heart rate variability in healthy prepubertal children.

154  da Silva et al.

Figure 2 — Meta-analysis of studies showing change in R-R intervals due to training.

Figure 3 — Meta-analysis of change in indexes of Time Domain due to training: SDNN (A), RMSSD (B), pNN50 (C).

Although the noncontrolled studies suggest the trainability of the cardiac autonomic system in children, the pooled results of the only two randomized controlled trials do not provide support to this finding. The responsiveness of HRV in healthy children to physical training cannot be guaranteed unless randomized controlled trials are conducted with a low risk of bias. Hence, the issue of HRV trainability in children remains to be elucidated in future studies.

Implications for Practice This systematic review with meta-analysis highlighted many limitations within the studies on HRV and exercise training in children, with no evidence of a significant

effect of physical training on HRV in healthy children. One positive aspect was that the Polar S810 was validated to measure R-R intervals in children (19) and therefore provides a simple noninvasive tool for easy applicability in pediatric populations in future studies.

Implications for Future Research The influence of ethnicity, sex, and biological maturation on HRV is not fully understood. Standardization of HRV measurement is required across studies to minimize possible confounding factors such as posture and ventilation. With improved standardization, it may be possible to highlight the real impact of physical training on HRV in healthy children.

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Figure 4 — Meta-analysis of change in Frequency Domain due to training: LF (log; A), HF (Log; B), balance LF/HF (C) and Total Power (Log; D)

Given that there is not enough evidence to determine whether exercise training impacts on HRV in healthy children, we recommend that further research be conducted. In particular, an RCT following the guidelines of the Consort-Statement (43) would be beneficial. The key feature of the RCTs is that study participants, after assessment of eligibility and recruitment, are randomly allocated to receive (or not receive) the intervention. This design permits elimination of biases such as selection and confusion factors, since treatment and control groups are allocated using appropriate randomization techniques. Special attention should be given to the eligibility criteria to ensure that all participants included in the study are prepubertal. In addition, care should be taken to perform studies separating participants by sex, as its influence on the outcomes still remains controversial. Other important aspects that were not performed in the studies included in this systematic review are: the

intention-to-treat analysis and the follow-up. The intention to treat analysis includes all participants involved in the randomized controlled trial in the statistical analysis, even those who did not complete the intervention. This strategy preserves the benefit of randomization, allowing for the balanced distribution of prognostic factors in the groups compared with the observed effect resulting from the assigned treatment. A follow-up on studies with physical training would allow the establishment of any sustained effects of physical training on HRV in healthy children, including the time course of any detraining effects.

Conclusion No significant differences for any of the HRV indices (R-R interval, SDNN, RMSSD, pNN50, LF, HF, balance LF/HF or total power) were found between the experi-

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mental and control groups. Available evidence from RCTs was not strong enough to confirm physical training as an intervention strategy to improve HRV in healthy children. Acknowledgments No funding was provided for the preparation of this study. There are no relevant conflicts of interest for any of the authors. The authors would like to thank Anthony Scott Leicht for the careful review of this manuscript. Fábio Yuzo Nakamura and Jefferson Rosa Cardoso wish to thank CNPq, a Brazilian research agency part of the Ministry of Science and Technology, for the productivity scholarships.

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The effect of physical training on heart rate variability in healthy children: a systematic review with meta-analysis.

The positive effects of physical training on heart rate variability (HRV) in healthy adults are widely recognized; however, the responsiveness to trai...
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