1082 Several case reports have been published of patients with coexisting neuroblastoma and congenital heart defects (CHD) [1, 8, 10, 17, 28]. Some studies of patients with neuroblastoma suggest a higher prevalence of CHD in neuroblastoma patients than in the general population [5, 6, 9, 11, 18], however, others did not find an association between neuroblastoma and CHD [2, 20–25]. An associa- tion between neuroblastoma and CHD is considered to be plausible as neuroblastoma originates from embryonal neural crest-derived cells [3], and neural crest-derived cells are essential in cardiogenesis as well [14]. Neural crest cells play an important role in the septation of the outflow tract of the heart and in the formation of the conotruncal part of the ventricular septum [14]. Abnormal development or migration of neural crest cells, possibly due to an underlying genetic defect, has been postulated as a mechanism that could contribute to both conditions [1, 11, 13, 28]. Indeed, neural crest-derived CHD have been reported to be more frequent in neuroblastoma patients than is expected when considering the normal distribution of subtypes of CHD [11, 13]. An association between neuroblastoma and CHD might have clinical consequences: if neuroblastoma patients have a higher risk of CHD, cardiac screening might be indicated for all neuroblastoma patients. Early detection of CHD could be important for the patient, in terms of bacterial endocarditis prophylaxis, choice of anti-cancer treatment and possible need for treatment of the CHD. Fig. 1 Flow chart of inclusion and exclusion of patients Accurate echocardiography performed previously (n = 17) No accurate echocardiography performed previously (n = 116) Echocardiography newly performed (n = 104) Patients with accurate echocardiography (n = 119) Eur J Pediatr (2009) 168:1081–1090 To assess the prevalence of CHD in neuroblastoma patients we conducted an echocardiographic study in a large single centre cohort of consecutive neuroblastoma patients. In addition, we systematically searched and critically appraised the literature to evaluate the existing evidence regarding the prevalence of CHD in neuroblasto- ma patients. Materials and methods Patients The study group consisted of all patients diagnosed with neuroblastoma or ganglioneuroblastoma at the Emma Children’s Hospital, Academic Medical Centre (AMC), the Netherlands, between June 1966 and September 2006, who were eligible for echocardiography, i.e. all living patients (surviving patients and patients more recently diagnosed with neuroblastoma). The Emma Children’s Hospital-AMC is one of the five paediatric oncology centres in the Netherlands with a constant referral region. To minimise referral bias, we did not include patients who had been referred from another Dutch paediatric oncology centre to the Emma Children’s Hospital-AMC for specialised cancer treatment. Patients referred from other countries were also excluded. We placed special emphasis on making the cohort as complete as possible to minimise Neuroblastoma patients with (ganglio)neuroblastoma diagnosed in AMC 1966-2006 (n = 385) Patients originally from AMC (n = 318) Patients eligible for echocardiography (n = 133) Patients referred from other centers (n = 67) Patients deceased at time of study (n = 185) Patients lost to follow up (n = 12) Moved abroad: n = 3 No consent: n = 7 Not traceable: n = 2 Echocardiography of insufficient quality (n = 2)