Season of birth and primary central nervous system tumors: a systematic review of the literature with critical appraisal of underlying mechanisms

Abstract Purpose Season of birth has been considered a proxy of seasonally varying exposures around perinatal period, potentially implicated in the etiology of several health outcomes, including malignancies. Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we have systematically reviewed published literature on the association of birth seasonality with risk of central nervous system tumors in children and adults. Results Seventeen eligible studies using various methodologies were identified, encompassing 20,523 cases. Eight of 10 studies in children versus four of eight in adults showed some statistically significant associations between birth seasonality and central nervous system tumor or tumor subtype occurrence, pointing to a clustering of births mostly in fall and winter months, albeit no consistent pattern was identified by histologic subtype. A plethora of perinatal factors might underlie or confound the associations, such as variations in birth weight, maternal diet during pregnancy, perinatal vitamin D levels, pesticides, infectious agents, immune system maturity, and epigenetic modifications. Conclusions Inherent methodological weaknesses of to-date published individual investigations, including mainly underpowered size to explore the hypothesis by histological subtype, call for more elegant concerted actions using primary data of large datasets taking also into account the interplay between the potential underlying etiologic factors.