1088 Fig. 3 Overview of prevalence rates (%) of CHD in the selected studies with 95% Confidence Interval. The prevalence rate in the control group (George et al.) is also shown Eur J Pediatr (2009) 168:1081–1090 The literature search identified 515 unique articles. Reasons for exclusion are detailed in Fig. 2. Seventeen articles were eligible for our review. Table 2 presents descriptive characteristics and results of all studies, including the present one. The studies differed largely in terms of patient characteristics and methodology. The study of George et al. [11] was the only study in which patients had undergone echocardiography; the authors reviewed the echocardiographic images that had been recorded previously. In all other articles, it was not mentioned which cardiac assessment was used. The reported prevalence rates of CHD in neuroblastoma patients ranged from 0 to 20%, although the majority of the studies (14 out of 17) found a prevalence of less than 3.6% [2, 5, 10, 16, 18–26, 29]. In the echocardiographic review study, the prevalence was 20%. Figure 3 is an illustration of the prevalence rates of CHD with 95% confidence interval of proportion as calculated by us. A statistically higher prevalence of CHD in patients as compared to controls was present in six of eight studies that included a control group [5, 6, 9, 11, 16, 18]. However, all studies lacked information on different items of validity. In conclusion, several studies have evaluated the prevalence of CHD in neuroblastoma patients, with little information on validity. Echocardiography had been per- formed in only one study. The majority of the studies reported a prevalence of less than 3.6%, however, a prevalence of 20% was found in the echocardiographic review study. Discussion In this single centre cohort of consecutive neuroblastoma patients, the prevalence of CHD was 1.7%, which was not significantly different from two control groups [11]. The prevalence of CHD found in our study was much lower than the prevalence of 20% reported in the only other study in which echocardiography was used for detection of CHD, the study by George et al. [11]. Both studies have some limitations, however. In both studies it was not possible to evaluate the patients who died before echocar- diographic assessment and this might have led to under- estimation of prevalence of CHD in both studies. George et al. [11] did not perform echocardiography in all surviving neuroblastoma patients. Instead, the authors retrospectively analysed echocardiographic records and echocardiography was available in only 43% of neuroblastoma patients. This might have led to an over-estimation of the prevalence of CHD, since patients with CHD are more likely to have had echocardiography. In our study, we prospectively per- formed echocardiography in almost all eligible patients, regardless of symptoms or need for specific treatment. Another explanation for the difference in outcome of our study and the study by George et al. might be that patients in our study were older at time of echocardiography. Because some types of CHD can resolve spontaneously over time, such as spontaneous closure of septal defects [27], CHD might have been missed in our study. One patient in our study indeed had a VSD that had spontane- ously closed. However, most CHD do not disappear over time and would have been detected if present. An additional explanation for the high prevalence rate found by George et al. as compared to our study could be referral bias in their tertiary care centre study [11]. An important potential source of bias that may have led to overestimation of CHD in the study of George et al. as well as in other studies and case reports, is surveillance bias: patients with neuroblastoma are investigated thoroughly, during which (asymptomatic) CHD might be detected. Likewise, neuro- blastoma can be detected during workup of CHD patients.