Tobacco, alcohol and illicit drugs during pregnancy and risk of neuroblastoma: systematic review

OBJECTIVE: To determine whether prenatal and perinatal maternal consumption of alcohol, tobacco and/or illicit drugs is associated with risk of neuroblastoma. DATA SOURCES: Medline and Embase (both from inception to February 2017), and reference lists of included studies. STUDY SELECTION: To be eligible, a study had to be an original report including data on intake of alcohol, tobacco smoking and/or consumption of illicit drugs during pregnancy and risk of neuroblastoma in the child. DATA EXTRACTION: From eligible studies, data study characteristics as well as effect measures and confounders were extracted. We assessed unadjusted and confounder-adjusted estimates, performed risk of bias analysis, constructed random-effects models and assessed heterogeneity. RESULTS: We identified 14 case-control studies (1987-2016) involving a total of 3114 children with neuroblastoma. Meta-analysis of unadjusted estimates showed an association between alcohol (OR 1.26; 95% CI 1.07 to 1.49), tobacco (OR 1.22; 95% CI 1.04 to 1.44) and illicit drug consumption during pregnancy and risk of neuroblastoma during childhood, with illicit drug consumption showing the strongest association (OR 3.26; 95% CI 1.36 to 7.86). However, adjusted estimates were highly heterogeneous. LIMITATIONS: All studies were at high risk of bias. CONCLUSIONS: Smoking, alcohol or illicit drugs during pregnancy might play a role in the development of neuroblastoma. However, well-designed studies are needed to assess whether these exposures are causal and whether time period during pregnancy, dose or co-consumption of substances is critical. TRIAL REGISTRATION NUMBER: Registration number CRD42016036165.