Abstract Background: Central nervous system (CNS) tumors are the most common solid tumors in children and remain a significant contributor to death by disease in this population. While there is evidence that pediatric CNS tumors arise in early-life, limited knowledge is available on the role of maternal and perinatal factors in the etiology of these malignancies, which hampers prevention efforts. Therefore, we investigated the association between these early-life factors and risk of CNS tumors in children using data from Texas Cancer Registry, which is one of the world's largest and most diverse cancer registries, which may lead to the identification of modifiable risk factors. Methods: Information on pediatric CNS tumor cases (N=1950) for the period 1995-2011 was obtained from the Texas Cancer Registry. Birth certificate controls were frequency-matched on year of birth at a ratio of 10:1 for the same period. Variables evaluated were obtained from birth records and included maternal race/ethnicity, maternal age, maternal education, maternal nativity, maternal residency (urban vs rural), residency on Mexican border, plurality and birth order of child, size for gestational age, term of birth, and mode of delivery. Unconditional logistic regression was used to generate an adjusted odds ratio (OR) and 95% confidence interval (CI) testing the association between each factor and CNS tumors overall, as well as astrocytoma (N=978) and ependymoma (N=157) subtypes individually. Results: Hispanic and non-Hispanic black mothers were less likely to have children who developed CNS tumors compared to non-Hispanic white mothers (OR: 0.88 [95%CI: 0.79-0.98]; OR: 0.78 [95%CI: 0.66-0.91], respectively). Conversely, infants born large for gestational age (OR: 1.26 [95%CI: 1.08-1.48]) as well as those delivered pre-term (<37 weeks) (OR: 1.18 [95%CI: 1.03-1.36]) showed an increased risk of CNS tumors compared to the respective reference groups. Compared to women with spontaneous vaginal delivery, those with vaginal forceps or vacuum delivery were more likely to have children that developed CNS tumors (OR: 1.35 [95%CI: 1.12-1.62]). This was also true for cesarean delivery, but the confidence interval included the null (OR: 1.10 [95%CI: 0.99-1.22]). Effect estimates for pre-term birth as well as vaginal forceps or vacuum delivery were stronger for astrocytomas. An increased risk of ependymoma subtype was found for offspring of native-born Mexican mothers compared to mothers born in the United States (OR: 1.67 [95%CI: 1.03-2.71]), while a decreased risk of this subtype was detected for children of mothers with education greater than high school (OR: 0.54 [95%CI: 0.35-0.82]). Conclusions: Overall, several maternal and perinatal factors were associated with pediatric CNS tumors, indicating the important role of these characteristics in the etiology of these clinically significant malignancies. Citation Format: Maral Adel Fahmideh, Erin C. Peckham-Gregory, Jeremy M. Schraw, Murali Chintagumpala, Stephen C. Mack, Philip J. Lupo, Michael E. Scheurer. Evaluating the role of early-life factors on the risk of pediatric central nervous system tumors: A registry-linkage study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4656.