Abstract
Background
The spectrum of cardiac diseases in children is distinct from that in adults, and changes with advances in medical care and socioeconomic conditions. Such data are important for the allocation of medical resources, but are unclear. Based on a longitudinal pediatric cardiac screening program, we sought to delineate the spectrum and the trends.
Methods
From 2002 to 2018, citywide screening programs of cardiac diseases for children were performed in Taipei, Taiwan. Participants, mainly students entering the first grade of elementary school, were evaluated using questionnaires, simplified 4-lead electrocardiography (EKG), phonocardiography, and physical examinations. Those suspected of having abnormal cardiac lesions received detailed evaluations by pediatric cardiologists for a final diagnosis.
Results
The median prevalence of cardiac lesions in the children was 19.60/1000 (range from 14.9 to 24.65/1000), including congenital heart disease (32.02%), EKG abnormalities (33.34%), mitral valve prolapse (15.17%), Kawasaki disease (6.89%), rheumatic heart disease (0.17%) and others (12.41%). A significant time trend was only observed in a trend of decline in rheumatic heart disease. The median prevalence rates of congenital heart disease, Kawasaki disease, rheumatic heart disease, mitral valve prolapse, and EKG abnormalities were 6.20, 1.37, 0, 3.12, and 6.46 per 1000 children, respectively.
Conclusions
This study, based on a citywide cardiac screening program, indicates that the spectrum of cardiac diseases in children has not changed in recent decades, except for a decline or disappearance of rheumatic heart disease in the Taipei metropolitan area. While congenital heart disease and EKG abnormalities were the most common, Kawasaki disease was the most commonly acquired heart disease in children.
Keywords: Cardiac screening, Congenital heart disease, Kawasaki disease, Rheumatic heart disease
INTRODUCTION
The spectrum of pediatric cardiac diseases is different from that in adults, and it changes with advances in perinatal and postnatal medical care as well as socioeconomic condition. The major cardiac disease in children is congenital heart disease (CHD), which is also the most common congenital anomaly.1,2 Rheumatic fever and rheumatic heart disease (RHD) were once an important acquired heart disease in children.3 However, with improvements in socioeconomic conditions and the implementation of primary and secondary prevention, there are few newly diagnosed patients in developed countries.3,4 Instead, Kawasaki disease (KD) has become the most common acquired heart disease in children.5-8 Patients with KD may have coronary sequelae which have distinct pathophysiological processes.9 Therefore, there may have been a marked change in the profile of cardiac diseases in children in the recent decade in most countries, and this warrants clarification for the allocation of medical resources. In Taiwan, the Cardiac Children’s Foundation Taiwan started a cardiac screening program for school children in the 1970s. The aim of this study was to use these data to investigate the trend and transition of the profile of cardiac diseases in children in Taiwan.
METHODS
Screening programs for cardiac disease in children were initiated by the Cardiac Children’s Foundation Taiwan in the 1970s, mainly for students in Taipei. Between 2002 and 2018, all students entering the first (all years) and fourth (selected years) grades of elementary school, and some students in other grades who transferred to the Taipei metropolitan area were evaluated using questionnaires, simplified 4-lead electrocardiography (EKG), and phonocardiography (level 1 screening). Questionnaire items included demographic data, symptoms of heart disease (including palpitation, chest pain, syncope, dyspnea), past history of cardiac diseases, any prolonged fever related to rheumatic disease, or a history of KD and any family history of cardiac disease (level 1 screening). The simplified 4-lead EKGs and phonocardiographs (Fukuda Denshi ECP-50C and ECP-50CT) were recorded with the subjects in the supine position. A simplified 4-lead EKG (leads I, aVF, V1, and V6) has been reported to be an efficient screening method in children. The phonocardiograph recorded acoustic signals from the apex, left second, and left fourth intercostal spaces.
Children who had either an abnormal EKG, abnormal phonocardiography (i.e. any non-noise signal other than S1 and S2, and widened S2 split), or a cardiac lesion reported on or suspected based on the questionnaire received a physical examination by a pediatric cardiologist (level 2 screening). A negative control group (designated ID1 and ID10 in each class) also underwent physical examinations. After the level 2 screening, those who were suspected of having abnormal cardiac lesions were invited back to pediatric cardiology clinics for detailed evaluation and final diagnosis.10,11
EKG abnormalities included atrial premature contraction (APC), ventricular premature contraction, variable degree of atrioventricular block, right and left bundle branch block (RBBB and LBBB), intraventricular conduction delay, sinus bradycardia, long QT syndrome (LQTS) and Wolff-Parkinson-White (WPW) syndrome. For detailed definitions, please refer to Chiu et al.10
Statistics
The prevalence is presented as a percentage of the total population receiving an evaluation. We used the Statistical Package for the Social Sciences (SPSS, Version 20.0, SPSS Inc., Chicago, IL, USA) or Statistics Analysis System (SAS, Version 9.4, SAS Institute Inc., Cary, NC, USA) for analysis. The trend with year was then examined using a Poisson regression model. All p values were 2-sided, and statistical significance was defined as p < 0.05.
RESULTS
Taipei metropolitan area screening
From 2002 to 2018, an average 45276 ± 6554 (mean ± standard deviation) students were screened annually (range from 38178 to 54438). The number of students who received screening decreased with each calendar year, compatible with the decreasing birth rate in Taiwan, as in other developed countries.12
The median prevalence of cardiac lesions was 19.60/1000 (range from 14.9 to 24.65/1000), including CHD (32.02%), EKG abnormalities (33.34%), mitral valve prolapse (MVP, 15.17%), KD (6.89%), RHD (0.17%) and others (12.41%) (Figure 1).
Figure 1.
Percent distribution of various cardiac diseases as the main diagnosis from cardiac children screening 2002-2018 (children aged 6-7 years). CHD, congenital heart disease; EKG, electrocardiography; KD, Kawasaki disease; MVP, mitral valve prolapse; RHD, rheumatic heart disease.
The prevalence data of various heart diseases detected in cardiac screening programs in each year are summarized in Table 1. The time trend of each type of cardiac disease is shown in Table 2. A significant time trend was only observed with a trend of decline in RHD (p < 0.001). The lower, median and upper quartiles of the prevalence of RHD were 0/1000, 0/1000 and 0.02/1000, respectively. No RHD patient has been detected in screening programs since 2008.
Table 1. The prevalence (‰) of various heart diseases in screened children by year from 2002 to 2018.
| Year (No. screened) | Congenital heart disease (95th CI) | Kawasaki disease (95th CI) | Rheumatic heart disease* (95th CI) | Mitral valve prolapse (95th CI) | EKG abnormality (95th CI) | Others (95th CI) | Total (95th CI) |
| 2002 (54, 438) | 5.90 (5.29, 6.58) | 1.80 (1.48, 2.19) | 0.10 (0.04, 0.23) | 2.20 (1.84, 2.63) | 6.80 (6.14, 7.53) | 3.80 (3.32, 4.35) | 20.60 (19.44, 21.83) |
| 2003 (52, 872) | 6.50 (5.85, 7.22) | 1.20 (0.94, 1.53) | 0.20 (0.11, 0.37) | 2.60 (2.20, 3.07) | 4.40 (3.87, 5.00) | 2.40 (2.02, 2.86) | 17.30 (16.22, 18.45) |
| 2004 (53, 086) | 5.90 (5.28, 6.59) | 1.40 (1.12, 1.76) | 0.02 (0.003, 0.13) | 2.20 (1.84, 2.64) | 5.60 (5.00, 6.27) | 2.10 (1.74, 2.53) | 17.22 (16.15, 18.36) |
| 2005 (51, 692) | 6.50 (5.84, 7.23) | 1.30 (1.02, 1.65) | 0.02 (0.003, 0.14) | 2.30 (1.92, 2.75) | 7.20 (6.51, 7.97) | 1.00 (0.76, 1.31) | 18.32 (17.20, 19.51) |
| 2006 (52, 740) | 6.10 (5.47, 6.80) | 1.20 (0.94, 1.54) | 0.13 (0.06, 0.27)0 | 2.90 (2.48, 3.40) | 7.30 (6.61, 8.06) | 1.97 (1.63, 2.39) | 19.60 (18.45, 20.82) |
| 2007 (51, 539) | 5.94 (5.31, 6.64) | 1.42 (1.13, 1.79) | 0.02 (0.003, 0.14) | 3.49 (3.02, 4.04) | 7.40 (6.70, 8.18) | 2.32 (1.94, 2.77) | 20.59 (19.40, 21.85) |
| 2008 (47, 772) | 6.85 (6.15, 7.63) | 1.37 (1.08, 1.75) | 0 | 3.15 (2.69, 3.69) | 6.83 (6.13, 7.61) | 2.99 (2.54, 3.52) | 21.24 (19.99, 22.57) |
| 2009 (46, 786) | 6.00 (5.34, 6.74) | 1.05 (0.79, 1.39) | 0 | 3.70 (3.19, 3.29) | 5.90 (5.25, 6.64) | 2.40 (2.00, 2.88) | 19.05 (17.85, 20.33) |
| 2010 (44, 155) | 6.50 (5.79, 7.29) | 0.98 (0.73, 1.32) | 0 | 3.75 (3.22, 4.37) | 6.46 (5.75, 7.25) | 1.78 (1.43, 2.22 | 19.47 (18.22, 20.80) |
| 2011 (44, 391) | 6.77 (6.05, 7.58) | 1.36 (1.06, 1.75) | 0 | 3.30 (2.81, 3.88) | 6.26 (5.57, 7.04) | 2.80 (2.35, 3.34) | 20.49 (19.21, 21.85) |
| 2012 (41, 901) | 7.30 (6.53, 8.16) | 1.40 (1.08, 1.81) | 0 | 4.43 (3.84, 5.11) | 7.94 (7.13, 8.84) | 2.82 (2.36, 3.38) | 23.89 (22.47, 25.40) |
| 2013 (40, 683) | 7.30 (6.52, 8.18) | 1.50 (1.17, 1.93) | 0 | 4.45 (3.85, 5.15) | 8.90 (8.03, 9.86) | 2.50 (2.06, 3.04) | 24.65 (23.19, 26.20) |
| 2014 (38, 721) | 6.90 (6.12, 7.78) | 1.47 (1.13, 1.91) | 0 | 3.12 (2.61, 3.73) | 7.94 (7.10, 8.88) | 1.59 (1.24, 2.04) | 21.02 (19.64, 22.50) |
| 2015 (37, 737) | 6.09 (5.35, 6.93) | 1.70 (1.33, 2.17) | 0 | 3.30 (2.77, 3.93) | 6.20 (5.46, 7.04) | 3.60 (3.04, 4.26) | 20.89 (19.50,22.38) |
| 2016 (37, 282) | 5.10 (4.43, 5.88) | 1.59 (1.23, 2.05) | 0 | 2.80 (2.31, 3.39) | 5.70 (4.98, 6.52) | 2.70 (2.22, 3.28) | 17.89 (16.59, 19.29) |
| 2017 (35, 714) | 6.20 (5.44, 7.07) | 1.00 (0.72, 1.39) | 0 | 2.00 (1.59, 2.52) | 5.80 (5.06, 6.64) | 3.00 (2.48 ,3.62) | 18.00 (16.67, 19.43) |
| 2018 (38, 178) | 5.30 (4.62, 6.08) | 1.30 (0.98, 1.72) | 0 | 1.30 (0.98, 1.72) | 5.00 (4.34, 5.76) | 2.00 (1.60, 2.50) | 14.90 (13.73, 16.17) |
CI, confidence interval; EKG, electrocardiography.
* Including rheumatic fever.
Table 2. The prevalence and the trend of various heart diseases in screened children from 2002 to 2018.
| Prevalence 2002-2018 | Congenital heart disease (‰) | Kawasaki disease (‰) | Rheumatic heart disease (‰)* | Mitral valve prolapse (‰) | EKG abnormality (‰) | Others (‰) | Total (‰) |
| Lower quartile | 5.94 | 1.20 | 0.00 | 2.30 | 5.80 | 2.00 | 18.00 |
| Median | 6.20 | 1.37 | 0.00 | 3.12 | 6.46 | 2.40 | 19.60 |
| Upper quartile | 6.77 | 1.47 | 0.02 | 3.49 | 7.30 | 2.82 | 20.89 |
| Year trend 2002-2018 | p = 0.801 | p = 0.753 | p < 0.001, Decrease trend | p = 0.090 | p = 0.504 | p = 0.340 | p = 0.376 |
The prevalence of rheumatic heart disease showed significant decreasing trend, while the prevalence of congenital heart disease, Kawasaki disease, mitral valve prolapse, and EKG abnormality showed no significant trends. EKG, electrocardiography.
* Including rheumatic fever.
The prevalence of CHD ranged from 5.1/1000 to 7.3/1000, with the lower, median and upper quartiles being 5.94/1000, 6.20/1000 and 6.77/1000, respectively. EKG abnormalities were similarly common in the children, with the prevalence ranging from 4.4/1000 to 8.9/1000, with the lower, median and upper quartiles being 5.80, 6.46, and 7.30 per 1000 children, respectively.
The prevalence of MVP ranged from 1.3/1000 to 4.45/1000, with lower, median and upper quartiles of 2.30, 3.12, and 3.49 per 1000 children, respectively. The general trend was stationary. In addition, the prevalence of KD ranged from 0.98/1000 to 1.8/1000, with lower, median and upper quartiles of 1.20/1000, 1.37/1000 and 1.47/1000, respectively.
Extended observation of cardiac screening programs
To delineate the trends of CHD, RHD and KD, we included prevalence data from earlier screening (Figure 2). The incidence of CHD increased gradually from 1993 to 2002 and then remained stationary. The National Health Insurance program in Taiwan was implemented in 1995, and the program waived copayments for CHD patients. This national health care policy may explain at least in part the increase in CHD prevalence during the period from 1993 to 2002. The prevalence of KD also increased over time until 2002.
Figure 2.
The prevalence trends of CHD, RHD, and KD, presented with prevalence (1/1000) by year of screening, with the prevalence data included in the bottom. The trend of CHD increased from 1993 to 2002, and kept stationary, while the trend of RHD decreased significantly since 1970 and down to zero after 2009. CHD, congenital heart disease; KD, Kawasaki disease; RHD, rheumatic heart disease.
In contrast, the prevalence of RHD decreased significantly from 1.42/1000 in 1970 to 0.39/1000 in 1987, and further to 0.1/1000 in 1999. Since 2008, no patient has been diagnosed with RHD through the screening program.
DISCUSSION
Longitudinal citywide school surveys in the Taipei metropolitan area in children aged 6-7 years revealed a change in the spectrum of cardiac diseases in children in recent decades, reflecting the impact of advanced health care and a rapidly developing socioeconomic condition. A significant time trend of a decline in RHD was noted, with no new cases identified since 2008 in the Taipei metropolitan area. CHD and EKG abnormalities were the most common cardiac diseases, and KD was the most common acquired heart disease. To the best of our knowledge, this is the first report regarding the prevalence and time trends of different types of pediatric cardiac diseases based on cardiac screening programs.
As shown in the current study, CHD was the most common heart disease in children. The prevalence of CHD ranged from 5.1/1000 to 7.3/1000, without significant changes over time, which is consistent with previous reports.11 A previous study in Taitung City in 2005-2007 reported a lower prevalence of CHD of 2.91/1000, compared to 6.04/1000 in the Taipei metropolitan area. However, the proportion of previously undiagnosed disease that was discovered only on screening was significantly higher in Taitung than in Taipei.11 According to the National Health Insurance Database 2000-2010 in Taiwan, the prevalence of CHD in newborns was 13.08 per 1000 live births, and the overall prevalence of pediatric CHD was 9.18 per 1000 children.13,14 These data are higher than the estimation from this screening program. The discrepancy may be attributed to the detection rate of clinically insignificant lesions in the screening program or the spontaneous resolution of simple CHD, and early deaths from severe CHD. Variations in the prevalence of CHD depend on the inclusion of trivial to small lesions (e.g. small ventricular septal defects or atrial septal defects), which may not be comprehensively detected in screening programs.1 Regional difference may also be present, but remain still unclear. The leading diagnoses in this screening program of CHD were ventricular septal defects, atrial septal defects, pulmonary stenosis, and patent ductus arteriosus, as reported by Yu et al.,11 which is also compatible with the results from National Health Insurance Database.14
Rheumatic heart disease remains an important cardiovascular disease in under-developed and developing countries.15,16 It is still a great burden in some regions, such as Africa, South Asia, and Pacific Islands.16-18 With advances in socioeconomic conditions and the application of primary and secondary prevention for group A streptococcal pharyngitis, the occurrence of RHD has declined dramatically globally in both developing and developed countries.15-18 The first pediatric patient with RHD in Taiwan was reported in 1946. Since then, the number of pediatric RHD patients increased gradually and reached a peak between 1964 and 1980, followed by a steady decline. The prevalence rates of RHD were highest in 1970 (1.42/1000) and 1971 (1.26/1000), and fell to 0.39/1000 in 1987.18 As shown in Figure 2, the prevalence of RHD was 0.43/1000 in 1993, then fell to zero and has remained at zero since 2008. This trend may reflect the improvement in public health and socioeconomic conditions in Taiwan during the recent decades. Efforts to improve the efficacy of secondary prophylaxis to prevent recurrence of rheumatic fever are also key to the successful elimination of RHD.19,20
In contrast to RHD, KD has become the most important acquired heart disease in Taiwan.5 Children aged less than 5 years are the most vulnerable age group to the occurrence of KD, and the incidence and prevalence are higher in Asian countries than in Western countries.21 The first KD patient in Taiwan was reported in 1976.8 The annual incidence has increased gradually and reached 69/100,000 children < 5 years old between 2003 and 2006, being the third highest globally, just behind Japan and Korea.6,22 According to the Taiwan National Health Insurance Database, the postnatal cumulative incidence by 5 years of age for each neonate was 2.28/1000 in 2000 and 3.67/1000 children in 2009, with a significant increasing trend with birth year.23 Our data showed a lower prevalence (median 1.37 per 1000 children) in children aged 6-7 years (first year of elementary school). Since the diagnosis of KD in the cardiac screening program largely depends on self-reported history, some families may not report uncomplicated KD, which may have resulted in the prevalence being underestimated.
The median prevalence of EKG abnormalities was 6.46 per 1000 children with no significant change over time. The most common diagnoses were incomplete RBBB, complete RBBB, ventricular premature contraction, and pre-excitation syndrome (WPW syndrome).10 Other EKG abnormalities included AV block with variable degrees, APCs, sinus bradycardia, and LQTS. Some CHDs or high risk conditions were diagnosed after the EKG abnormalities had been identified, implying the value of EKG screening in the diagnosis of CHD and potentially life-threatening arrhythmia.10,11,24 There is general consensus about pre-participation cardiac evaluation in athletes, while screening for the general pediatric population is still controversial, and the policy varies between countries.24,25
In the current study, MVP was also relatively common in school children, with a median prevalence of 3.12/1000. Mitral valve prolapse refers to when the flap of the mitral valve swings back into the left atrium during systolic phase. While some children with MVP had associated syndromes or specific cardiac diseases, such as Marfan syndrome or Ehlers-Danlos syndrome,26 most children with this diagnosis had only isolated MVP without significant clinical manifestations. Evidence of MVP has be reported in 30% of those with rheumatic mitral regurgitation, and these children have less favorable outcome.27 However, such clinical associations are very rare in the current decade. In adults, the Framingham study reported a prevalence of MVP of 2.4%.28 Data on pediatric populations are still limited. In an institutional study from Japan, the incidence of MVP in children aged 6-7 years was 2.1%.29 The difference between these data and the data from the current study may be attributed to bias in study cohorts. No population studies had ever described the incidence of MVP in children, and this study provides a preliminary estimation of MVP in childhood. The prevalence in this study was much less than that in adults in the Framingham study, implying that MVP may become more prominent with age.
Limitations
Since we did not perform comprehensive chart reviews, the details of disease patterns in all categories were not available. The clinical significance and severity in different cardiac disease categories (e.g. critical congenital heart disease in the CHD category, coronary artery aneurysm in the KD category) could not be delineated. In addition, although the pediatric cardiac screening process has been standardized, there may still be some individual differences in the cardiac diagnosis. Nevertheless, the Cardiac Children’s Foundation Taiwan screening team would review the final diagnosis if variations are noted. For example, the diagnostic criteria for MVP are subject to echocardiographers’ interpretation, and the incidence showed some variation between different years. Also, under the screening-based protocol, the detected MVP may reflect symptomatic and clinically significant MVP, rather than all MVP.
CONCLUSIONS
This study provides data on the contemporary spectrum of cardiac diseases in school children as well as the trend over time. With improved public health policy and socioeconomic conditions, RHD has almost disappeared, while CHD and EKG abnormalities remain the most common diseases. Kawasaki disease has become the most common acquired heart disease in children. The clinical implications of MVP needs to be clarified in future studies.
Acknowledgments
We would like to express our gratitude to the Department of Education, Taipei City Government and the Cardiac Children’s Foundation Taiwan for their support in the screening program. We would also like to thank all 55 pediatric cardiologists who participated in the screening program.
CONFLICT OF INTEREST
All the authors declare no conflict of interest.
REFERENCES
- 1.Hoffman JIE, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002;39:1890–1900. doi: 10.1016/s0735-1097(02)01886-7. [DOI] [PubMed] [Google Scholar]
- 2.Dolk H, Loane M, Garne E. The prevalence of congenital anomalies in Europe. Adv Exp Med Biol. 2010;686:349–364. doi: 10.1007/978-90-481-9485-8_20. [DOI] [PubMed] [Google Scholar]
- 3.Carapetis JR, McDonald M, Wilson NJ. Acute rheumatic fever. Lancet. 2005;366:155–168. doi: 10.1016/S0140-6736(05)66874-2. [DOI] [PubMed] [Google Scholar]
- 4.Lue HC, Chen CL, Wei H, et al. The natural history of rheumatic fever and rheumatic heart disease in the orient. Jpn Heart J. 1979;20:237–252. doi: 10.1536/ihj.20.237. [DOI] [PubMed] [Google Scholar]
- 5.Wu MH, Chen HC, Yeh SJ, et al. Prevalence and the long-term coronary risks of patients with Kawasaki disease in a general population < 40 years. Circ Cardiovasc Qual Outcomes. 2012;5:566–570. doi: 10.1161/CIRCOUTCOMES.112.965194. [DOI] [PubMed] [Google Scholar]
- 6.Lin MT, Wu MH. The global epidemiology of Kawasaki disease: review and future perspectives. Glob Cardiol Sci Pract. 2017;2017:e201720. doi: 10.21542/gcsp.2017.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Lue HC, Chen LR, Lin MT, et al. Epidemiological features of Kawasaki disease in Taiwan, 1976-2007: results of five nationwide questionnaire hospital surveys. Pediatr Neonatol. 2014;55:92–96. doi: 10.1016/j.pedneo.2013.07.010. [DOI] [PubMed] [Google Scholar]
- 8.Lue HC, Philip S, Chen MR, et al. Surveillance of Kawasaki disease in Taiwan and review of the literature. Acta Paediatr Taiwan. 2004;45:8–14. [PubMed] [Google Scholar]
- 9.Lin MT, Sun LC, Wu ET, et al. Acute and late coronary outcomes in 1073 patients with Kawasaki disease with and without intravenous γ-immunoglobulin therapy. Arch Dis Child. 2015;100:542–547. doi: 10.1136/archdischild-2014-306427. [DOI] [PubMed] [Google Scholar]
- 10.Chiu SN, Wang JK, Wu MH, et al. Cardiac conduction disturbance detected in a pediatric population. J Pediatr. 2008;152:85–89. doi: 10.1016/j.jpeds.2007.05.044. [DOI] [PubMed] [Google Scholar]
- 11.Yu CH, Lue HC, Wu SJ, Chen MR. Heart disease screening of schoolchildren in Taiwan. Arch Pediatr Adolesc Med. 2009;163:233–237. doi: 10.1001/archpediatrics.2008.562. [DOI] [PubMed] [Google Scholar]
- 12.Basten S, Verropoulou G. A re-interpretation of the ‘two-child norm’ in post-transitional demographic systems: fertility intentions in Taiwan. PLoS One. 2015;10:e0135105. doi: 10.1371/journal.pone.0135105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Wu MH, Chen HC, Lu CW, et al. Prevalence of congenital heart disease at live birth in Taiwan. J Pediatr. 2010;156:782–785. doi: 10.1016/j.jpeds.2009.11.062. [DOI] [PubMed] [Google Scholar]
- 14.Yeh SJ, Chen HC, Lu CW, et al. Prevalence, mortality, and the disease burden of pediatric congenital heart disease in Taiwan. Pediatr Neonatol. 2013;54:113–118. doi: 10.1016/j.pedneo.2012.11.010. [DOI] [PubMed] [Google Scholar]
- 15.Hwang JJ, Lai YC, Tsai CH, et al. Rheumatic heart disease in Taiwan. J Formos Med Assoc. 1993;92 Suppl 4:S200–S216. [PubMed] [Google Scholar]
- 16.Watkins DA, Johnson CO, Colquhoun SM, et al. Global, regional, and national burden of rheumatic heart disease, 1990-2015. N Engl J Med. 2017;377:713–722. doi: 10.1056/NEJMoa1603693. [DOI] [PubMed] [Google Scholar]
- 17.Murray CJL, Vos T, Lozano R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2197–2223. doi: 10.1016/S0140-6736(12)61689-4. [DOI] [PubMed] [Google Scholar]
- 18.Lue HC. Rheumatic fever and rheumatic heart disease in Taiwan. Formos J Med. 1998;2:261–274. [Google Scholar]
- 19.Lue HC, Wu MH, Hsieh KH, et al. Rheumatic fever recurrences: controlled study of 3-week versus 4-week benzathine penicillin prevention programs. J Pediatr. 1986;108:299–304. doi: 10.1016/s0022-3476(86)81009-5. [DOI] [PubMed] [Google Scholar]
- 20.Lue HC, Wu MH, Wang JK, et al. Long-term outcome of patients with rheumatic fever receiving benzathine penicillin G prophylaxis every three weeks versus every four weeks. J Pediatr. 1994;125:812–816. doi: 10.1016/s0022-3476(94)70082-6. [DOI] [PubMed] [Google Scholar]
- 21.McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135:e927–e999. doi: 10.1161/CIR.0000000000000484. [DOI] [PubMed] [Google Scholar]
- 22.Huang WC, Huang LM, Chang IS, et al. Epidemiologic features of Kawasaki disease in Taiwan, 2003-2006. Pediatrics. 2009;123:e401–e405. doi: 10.1542/peds.2008-2187. [DOI] [PubMed] [Google Scholar]
- 23.Wu MH, Lin MT, Chen HC, et al. Postnatal risk of acquiring Kawasaki disease: a nationwide Birth Cohort Database Study. J Pediatr. 2017;180:80–86. doi: 10.1016/j.jpeds.2016.09.052. [DOI] [PubMed] [Google Scholar]
- 24.Vetter VL. Best practices for ECG screening in children. J Electrocardiol. 2015;48:316–323. doi: 10.1016/j.jelectrocard.2015.03.004. [DOI] [PubMed] [Google Scholar]
- 25.Asif IM, Drezner JA. Sudden cardiac death and preparticipation screening: the debate continues-in support of electrocardiogram-inclusive preparticipation screening. Prog Cardiovasc Dis. 2012;54:445–450. doi: 10.1016/j.pcad.2012.01.001. [DOI] [PubMed] [Google Scholar]
- 26.Tourneau TL, Mérot J, Rimbert A, et al. Genetics of syndromic and non-syndromic mitral valve prolapse. Heart. 2018;104:978–984. doi: 10.1136/heartjnl-2017-312420. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Wu MH, Lue HC, Wang JK, Wu JM. Implications of mitral valve prolapse in children with rheumatic mitral regurgitation. J Am Coll Cardiol. 1994;23:1199–1203. doi: 10.1016/0735-1097(94)90611-4. [DOI] [PubMed] [Google Scholar]
- 28.Freed LA, Levy D, Levine RA, et al. Prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med. 1999;341:1–7. doi: 10.1056/NEJM199907013410101. [DOI] [PubMed] [Google Scholar]
- 29.Ohara N, Mikajima T, Takagi J, Kato H. Mitral valve prolapse in childhood: the incidence and clinical presentations in different age groups. Acta Paediatr Jpn Overseas Ed. 1991;33:467–475. doi: 10.1111/j.1442-200x.1991.tb02573.x. [DOI] [PubMed] [Google Scholar]