Prenatal supplementation of folic acid has been shown to decrease the risk of several congenital malformations. Several studies have recently suggested a potential protective effect of folic acid on certain pediatric cancers. The protective role of prenatal multivitamins has not been elucidated. We conducted a systematic review and meta-analysis to assess the potential protective effect of prenatal multivitamins on several pediatric cancers. Medline, PubMed, EMBASE, Toxline, Healthstar, and Cochrane databases were searched for studies published in all languages from 1960 to July 2005 on multivitamin supplementation and pediatric cancers. References from all articles collected were reviewed for additional articles. Two blinded independent reviewers assessed the articles for inclusion and exclusion. Rates of cancers in women supplemented with multivitamins were compared with unsupplemented women using a random effects model. Sixty-one articles were identified in the initial search, of which, seven articles met the inclusion criteria. There was an apparent protective effect for leukemia (odds ratio (OR)=0.61, 95% confidence interval (CI)=0.50-0.74), pediatric brain tumors (OR=0.73, 95% CI=0.60-0.88) and neuroblastoma (OR=0.53, 95% CI=0.42-0.68). In conclusion, maternal ingestion of prenatal multivitamins is associated with a decreased risk for pediatric brain tumors, neuroblastoma, and leukemia. Presently, it is not known which constituent(s) among the multivitamins confer this protective effect.