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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.