Eur J Pediatr (2009) 168:1081–1090 Table 1 Characteristics of the study group (n=119) Male (%) Median age at diagnosis of neuroblastoma in years (range) Tumour stage (INSS) I–III (%) IV (%) Tumour MYCN amplification Yes (%) Unknown (%) Median age at echocardiography in years (range) 51 (42.9) 0.8 (0.0–10.5) 74 (62.2) 45 (37.8) 4 (3.4) 49 (41.2) 15.7 (0.8–41.4) bias by selective follow-up. Patients who were deceased were not included in the echocardiography study; however, we reviewed medical charts of these patients to look for CHD. Methods One experienced paediatric cardiologist (JL) reviewed and performed all echocardiograms at the same laboratory in the AMC. First, we retrospectively analysed the echocardio- graphic images of patients who underwent echocardiogra- phy in the past before the start of this study. If the images were extensive enough to diagnose or exclude CHD, we used these in this study. If the images were not sufficient, or if echocardiographic data were not available, patients were invited to participate in this study. In the vast majority of patients, echocardiography was prospectively performed especially for this study. In those patients in whom accurate echocardiography could not be obtained we reviewed medical charts for evidence of CHD. Standard diagnostic definitions were used for CHD. Patent foramen ovale (PFO) at any age and atrial septal defect (ASD) or patent ductus arteriosus (PDA) at less than 2 months of age were regarded to be normal stages of cardiovascular development and therefore where not considered to be CHD. Fig. 2 Publications identified for study and exclusions Potentially relevant publications identified and screened for retrieval (n = 515) Publications retrieved for more detailed evaluation (n = 78) Publications included (n = 17) 1083 Neuroblastoma staging was performed according to the International Neuroblastoma Staging System (INSS) criteria [4]. In patients who had been diagnosed with neuroblasto- ma before the introduction of the INSS, we converted the staging system that had been used into the INSS. MYCN oncogene amplification was analysed by southern blot analysis of tumour cells. Data analysis We compared the prevalence of CHD in our cohort of neuroblastoma patients who had echocardiography with the prevalence of CHD in the acute lymphoblastic leukaemia (ALL) cohort as presented by George et al. [11]. This cohort consisted of 192 children diagnosed with ALL in one hospital in Boston, USA, between 1990 and 2000, who all have had echocardiography screening. We also com- pared the prevalence of CHD in our cohort to data from EUROCAT Northern Netherlands (1981–2005), a network for the registration of congenital anomalies (European Registration Of Congenital Anomalies) [7]. Children with congenital anomalies are registered in EUROCAT since 1981, after report by midwives, general practitioners and specialists. We estimated prevalence of CHD in patients as a proportion. Significance of our findings was determined by use of two-tailed P-values calculated by comparing the proportion of patients with CHD in our cohort to the proportion of patients with CHD in the control group (Fisher exact test). Results Between June 1966 and September 2006, 385 patients had been diagnosed with (ganglio)neuroblastoma at the Emma Excluded (n = 437) Not meeting inclusion criteria Excluded (n = 61) due to: Case report: 37 No neuroblastoma: 8 No CHD: 12 Not about prevalence: 2 Data reported elsewhere: 2