Eur J Pediatr (2009) 168:1081–1090 1087 Table 2 (continued) Menegaux et al. [18] USA/Canada, 1992–1994 Multicentre (139 hospitals) retrospective cohort study Patients and methods Patients (<19 years) newly diagnosed with NB (n=741) 538 (73) nm Age matched controls selected through a random digit dialling method (n=504) Standardised telephone interview with mother Results 15 (2.0) 3 (0.6) Odds ratio 4.27 (95% CI 1.22–15.0)d Yanai et al. [29] Chow et al. [5] Munzer et al. [22] Current study Japan, 1990–2002 Two-centre retrospective patient series Patients newly diagnosed with NB (n=nm)c 156 (% unclear) nm Review of charts – – – 4 (2.6) USA, 1980–2004 Multicentre (national cancer registry) retrospective cohort study Patients (<20 yrs) newly diagnosed with NB and born in Washington (n=240) 240 (100) Localised, 12.9%; regional, 20%; distant metastatic, 40.8%; unspecified, 26.3% Birth certificates of age matched controls from the same area (n=2,400) Review of birth certificates and hospital discharge records database after linkage with cancer registry 5 (2.1) 9 (0.4) Odds ratio 5.84 (95% CI 1.93–17.66)d France, 2003–2004 Multi-centre (National Registry of childhood solid tumours) retrospective cohort study Patients (<15 years) newly diagnosed with NB, surviving and not terminally ill (n=235) 191 (75) nm Age and sex matched controls selected through a random digit dialing method (n=1,681) Standardised telephone interview with mother 0 (0) 5 (0.3) Odds ratio 0d Netherlands, 1966–2006 Single centre retrospective/ prospective cohort study Patients newly diagnosed with NB, alive at time of study (n=133) 119 (89.5) INSS stage I–3, 62.2%; stage 4, 37.8% Consecutive patients with acute lymphoblastic leukaemia ontrol group presented by George et al. [11] (n=192) Prospective echocardiography in 102 patients; review of echocardiography images in 17 patients 2 (1.68) 7 (3.6) P=0.49 NB neuroblastoma, CHD congenital heart defects, nm not mentioned a Neuroblastoma was detected incidentally at autopsy in all patients with CHD b In six patients neuroblastoma was detected incidentally in three cases during evaluation of CHD Systematic review of literature, methods and results To evaluate the existing evidence regarding the prevalence of CHD in neuroblastoma patients, we searched the electronic databases of PubMed (January 1966 to Decem- ber 2007) and Embase (1980 to December 2007), as well as references of eligible papers. The main search terms were neuroblastoma and congenital heart defects. We collected all studies of neuroblastoma patient series that reported on the proportion of CHD. The study cohort should at least include 20 neuroblastoma patients. The number of 20 was arbitrarily chosen, as we estimated that smaller cohorts or case series might introduce uncontrollable bias. Information about study design, study group and results were abstracted by two independent reviewers (KVE and JHM). The two independent reviewers also critically appraised internal and external validity of each study. The validity assessment was based on the guidelines proposed by Hayden et al. [12]. Details about the search strategy and validity assessment can be obtained from the authors.