Introduction

Human growth and development are two inseparable processes on the way towards adulthood. Despite being commonly associated with the musculoskeletal system, they take place simultaneously in all parts of the body, including the circulatory system. As the body grows, the left ventricular mass (LVM) increases to provide satisfactory cardiac output with lower resting heart rate (HR). As a consequence, important changes on the electrocardiogram (ECG) appear, including elongation of the mean RR interval and all its components (PR, QRS, QT) in various proportions, gradual left heart axis deviation, and changes in wave amplitudes.

A human’s individual growth curve is not linear in nature. Its shape in the first years of life is strongly dependent on genetic and environmental factors that can change it significantly [1]. The majority of pubescent children experience a growth spurt, which is a phase of intense somatic metamorphosis and subsequent physiological adaptations triggered by a rapid increase in GnRH secretion [2]. Both sexes undergo a series of transitions in a specific order. The intense growth phase in males begins approximately 2 years later than in females, is usually longer, and brings greater effects. The human heart’s growth has also been proven to be sex-dependent [3] as well as related to fat-free body mass [4]. These observations, however, have not been attributed to variations in ECG. Similarly to many other diagnostic tools, paediatric ECG has its age-dependent reference values [5, 6], however, wide normal ranges of the parameters are a source of doubt for health practitioners assessing the lengths and durations of distinct waveforms. This study was conducted to investigate the effect of growth on individual changes in resting ECG of healthy adolescents in 3-year observation.

Material and methods

The study was conducted as a part of a yearly program SOPKARD-Junior [7], which is aimed at the primary prevention of non-communicable diseases. It was originally addressed to 5th grade students (10–11 years of age) in September 2016 and repeated after 3 years, in September 2019. The program included all children studying in the town of Sopot (about 36 000 inhabitants) provided that written consent was given by their parents. In September 2016 164 students participated in the program, 131 of which were present again during the second edition (79.9%). 120 students with correct ECG recordings obtained in both editions were included in the study. We excluded 11 participants: 6 participants for heart rhythm disturbances on one of the recordings and 5 for school absence on the day of examination. None of the subjects had signs of a substantial heart defect or cardiomyopathy on transthoracic echocardiography. On the examination day the students’ height and weight were measured and standard 12-lead, 10-second electrocardiograms were recorded. We used the Mortara Eli 280 instrument at the chart speed of 25 mm/s and the standard calibration of 10 mm/mV. All tests for each year were performed by one physician. The technical quality of each recording was assessed straight away. In case it was not satisfactory, the ECG was repeated. All files were converted to digital format. Measurements of heart rate, PR, QRS, and QT were taken automatically and visually checked. In case the automatically taken measurement differed by ≥ 20 ms from the manually taken, it was replaced. Subsequently, R and S wave amplitudes were measured in each lead after magnifying the image by 200%. We used a digital measuring tool from Adobe Acrobat Reader DC software. The peak wave amplitude and the isoelectric line were indicated manually by the same investigator. For the R and S amplitudes, we took the mean of the two corresponding measurements (from the 1st and the 2nd QRS complex). The study conception was approved by the local Independent Bioethics Committee for Scientific Research.

A statistical comparison of each electrocardiographic variable was performed as follows:

Finally, the analysis of correlations between changes in anthropometric parameters (height, weight, body mass index [BMI]) and changes in electrocardiographic variables throughout the follow-up period was performed.

The statistical analysis was made in TIBCO Software Inc. (2017). Statistica, version 13. We used the Shapiro-Wilk test to determine the normal distribution of data. Because most of the variables were not normally distributed, the Mann-Whitney U test was used for comparative analysis of groups, and the Wilcoxon test was used for dependent samples. Spearman coefficients were calculated as determinants of correlations between variables.

Results

A total of 120 adolescents were examined, 62 (51.6%) of which were male. The mean age was 10.8 (0.49) years in 2016 and 13.8 (0.49) years in 2019 and was the same for both sexes. Average values of height, weight, and BMI were presented in Table 1. Height gain in 3-year time was greater in boys’ respect for girls (p < 0.001).

For each of the ECG variables, at least 94% of the scores were within the 2–98 percentile range in accordance with Rijnbeek’s tables. There were no significant differences between sexes in terms of the PR interval, QRS axis, QRS duration, QT, and QTc time neither in 2016, nor 2019 (p > 0.05). The PR (p < 0.001), QRS (p < 0.001) and QT (p < 0.001) durations changed significantly in three years time, while the QRS axis and QTc remained stable (p = 0.320 and 0.857 respectively). There were high positive correlation ratios between PR (r = 0.76), QRS duration (r = 0.78), and QRS axis (r = 0.90) measured in the 3-year interval. Correlations between QT and QTc measurements at the two visits were also statistically significant however of lower strength (r = 0.52 and r = 0.54 respectively) (Table 2).

In contrast to interval lengths, the QRS morphology was sex-dependent (Figure 1). At both visits, the R voltages in lead aVR and precordial leads were significantly greater in boys’ ECGs. There was a significant decline in R voltages through the follow-up period, regarding all leads except lead I in girls and some of the precordial leads in boys. As for the S waves, their amplitudes decreased in girls’ ECGs in all leads except lead I, whereas, in boys a decline in leads V1 and V6 and an increase in lead I, V3 and V4 were observed. Substantial correlations between measurements taken in 2016 and 2019 were reported for both sexes.

No significant correlations between changes in height and interval lengths were observed. Heart rate both in 2016 and 2019 was independent of anthropometric parameters. The same referred to heart rate change in relation to somatic growth. Neither PR and QRS lengths nor their changes in 3 years were related to students’ somatic growth. In male students, we observed a moderate positive correlation (r = 0.45) of QRS axis deviation towards the right with height change (Figure 2). QT elongation in boys corresponded negatively with BMI increase, but the coefficient was low (r = –0.26). No significant correlations were observed after QT correction (QTc).

Figure 2. A scatter chart showing the relationship between the change of the QRS axis and height. A positive correlation (r = 0.45) is only present in boys

The analysis of correlations between wave amplitudes and indices of somatic growth revealed important discrepancies between sexes (Table 3). In boys, height gain had no substantial impact on R and S voltages, while weight gain correlated with higher R (r = 0.27) and S (r = 0.47) voltages in lead I, and higher R voltages in lead V6 (r = 0.31). Similarly, increase in BMI during the follow-up period was associated with an increase in R amplitudes in lead I (r = 0.36) and V6 (r = 0.38), as well as S amplitudes in lead I (r = 0.38) and aVR (r = 0.40). In girls, height gain correlated with a decline in S amplitudes in lead I (r = 0.35) and aVR (r = 0.32), while an increase in BMI was associated with R voltage gain in lead I (r = 0.28).

Importantly, in girls, there were negative correlations between indices of growth and changes in wave amplitudes regarding leads V2–V6. The Spearman coefficients for the aforementioned analysis were collected in Table 3.

Discussion

The study proved that the physiological elongation of ECG intervals is independent from height, weight, and BMI change in early adolescents. Additionally, it showed that there is no significant difference between adolescent boys’ and girls’ ECGs in terms of PQ, QRS, and QT durations. An interesting part of the analysis is the observations regarding R and S wave amplitudes. Not only were they higher in boys’ respect for girls, but also the decline in R and S voltages correlated with somatic growth in pubescent girls. This finding is probably due to breast development in the female subject throughout the follow-up period.

Our results are consistent with previous studies where a significant sex-dependent variation of interval lengths was not observed [5, 8–11]. In Rijnbeek’s study [6] the QRS duration was longer in adolescent boys than in girls, with median values and upper limits (98 pc) differing by 3–5 ms. In our study a similar difference regarding the mean values was not statistically significant, which might be the result of a smaller sample number. As for the QTc, upper limits are higher for adolescent girls by about 10 ms [6, 8, 10], however, the differences reported in cross-sectional studies are not always remarkable. A significant difference in QTc in children aged 13–18 was observed by Lue [8], in contrast to Rijnbeek’s study [6]. We did not detect a significant change in QTc over time, which is consistent with previous reports.

Even though, electrocardiography has a limited role in screening for structural heart disease, high QRS amplitudes in precordial leads are commonly being associated with ventricular hypertrophy. Noticeably, left ventricular mass (LVM) is not the only predictor of R and S voltage; other factors include the heart’s distance from the chest wall [12], the composition of tissues surrounding the heart, and their inhomogeneities [13–15]. Importantly, an increase in LVM in children was proven to be confluent with somatic growth and related to sex, aerobic fitness, and family history of cardiovascular disease [3, 4]. Thus, in a healthy population, boys have greater LVM at any age and undergo an additional considerable increase during adolescence, while in females LVM increases more steadily [16]. Normal values of R and S wave amplitudes are, therefore, sex-dependent [6, 8, 10], which was additionally confirmed in our study. The discrepancy in R waves in left precordial leads was observed by Rijnbeek [6] from the 1st month of life onwards, and appeared in the other leads in early adolescence, while Lue [8] reported significant differences between males and females starting from the age of 9. Similarly, in our study R waves in boys and girls differed significantly at both visits. Apart from greater LMV increase in boys, the difference may be attributed to breast development, which normally takes place at the age of 10–14. These two phenomena can explain opposite coefficient signs in correlations (positive in boys, negative in girls) between changes of wave amplitudes in precordial leads and an increase in BMI and weight.

To our knowledge, height gain has not been evaluated in terms of electrocardiographic variables in previous studies. In the present analysis, height was not an independent predictor for any of the analyzed parameters except for QRS axis in boys. Right axis deviation following a rapid growth can be explained by the vertical orientation of the heart in the elongated chest. Noticeably, in girls, whose growth is more steady, such a relationship did not occur. A low degree of correlation of height gain with some of the R and S waves was secondary to a positive relationship between changes in height and weight throughout the observation period.

Another factor declared to influence the shape of the electrocardiogram is body stature. In our study population the change in body weight and BMI was not only due to linear growth but in some cases a sign of developing obesity. In fact, 10 students (6 boys and 4 girls), were placed above the 95th percentile for BMI at the age of 14 with 8 of them not being obese 3 years before. The effect of excess weight on ECG was discussed in several studies regarding both adults [17, 18] and children [11, 19]. Simple obesity is not related to pathological left axis deviation as is commonly thought but to low QRS voltage [17]. Additionally, in their cross-sectional study on obese and normal-weight adolescents, Sun and colleagues observed positive correlations of the PR interval and QRS duration with BMI [19]. The effect of obesity on QTc prolongation is debatable [20, 21]. As in the case of Sun’s study [19], we observed no relationship between BMI increase and QT.

Our study has some limitations. First of all, we used different precordial electrodes than the authors of ECG percentile charts. We found the standard V1–V6 set more appropriate for our study population than the one including V3R and V7 electrodes instead of V5. Secondly, QRS amplitudes measurements in the present study were not made from, so-called, mean beats, applied by previous researchers. Even though the method differed, our measurements did not diverge substantially from Rijnbeek’s normal limits [6]. Additionally, the use of nonparametric statistics might have limited accuracy of our estimations. Finally, we did not take daily physical activity into consideration in our analysis regarding QRS voltage, which might be subject to further evaluation. Repetition of the analysis in another 3 years’ time could also give better insight into the subject.

In conclusion, sex and body stature are considerable determinants of electrocardiographic variables in early
adolescents, predominantly regarding QRS amplitudes. We suggest using sex-dependent reference values for ECG evaluation in this group. In paediatric patients with no underlying heart defect, the process of their somatic growth should be taken into consideration when interpreting an ECG.

Conflict of interest

The authors have stated that there are no conflicts of interest in connection with this article.

Written informed consent was obtained from legal guardians of the study participants.

Funding

Paulina Figarska received funds from EU project “Integrated Development Program of the Medical University of Gdańsk POWER 3.5” to cover the costs of article preparation and processing.