Perinatal and Familial Risk Factors for Brain Tumors in Childhood through Young Adulthood

Abstract

Perinatal factors including high birth weight have been associated with childhood brain tumors in case-control studies. However, the specific contributions of gestational age and fetal growth remain unknown, and these issues have never been examined in large cohort studies with follow-up into adulthood. We conducted a national cohort study of 3,571,574 persons born in Sweden in 1973–2008, followed up for brain tumor incidence through 2010 (maximum age 38 years) to examine perinatal and familial risk factors. There were 2,809 brain tumors in 69.7 million person-years of follow-up. After adjusting for potential confounders, significant risk factors for brain tumors included high fetal growth (incidence rate ratio [IRR] per additional 1 standard deviation, 1.04; 95% CI, 1.01–1.08, P=0.02), first-degree family history of a brain tumor (IRR, 2.43; 95% CI, 1.86–3.18, P<0.001), parental country of birth (IRR for both parents born in Sweden vs. other countries, 1.21; 95% CI, 1.09–1.35, P<0.001), and high maternal education level (Ptrend=0.01). These risk factors did not vary by age at diagnosis. The association with high fetal growth appeared to involve pilocytic astrocytomas, but not other astrocytomas, medulloblastomas, or ependymomas. Gestational age at birth, birth order, multiple birth, and parental age were not associated with brain tumors. In this large cohort study, high fetal growth was associated with an increased risk of brain tumors (particularly pilocytic astrocytomas) independently of gestational age, not only in childhood but also into young adulthood, suggesting that growth factor pathways may play an important long-term role in the etiology of certain brain tumor subtypes.

Factors related to pregnancy and birth and the risk of childhood brain tumours: The ESTELLE and ESCALE studies (SFCE, France)

“…Unlike previous recent studies conducted in the United States, Scandinavia and United Kingdom 5 which all used data linkage and an earlier meta‐analysis of eight studies (five of which used data linkage), we found no evidence to support our first hypothesis that the risk of CBT or any of its subtypes would be increased by high fetal growth or high birth weight. Nevertheless, our findings were similar to two case‐control studies, that is, a multinational study for birth weight and an Australian study for birth weight, appropriateness of birth weight and POBW.…”

“…The association between extremes of birth weight and CBT has been frequently investigated. Of nine papers published since 2010, the majority reported a positive association with higher birth weight, for either all CBT combined or at least one subtype, most commonly astrocytoma and one with lower birth weight . However, this apparent weight of evidence includes case populations from similar geographical areas with at least some overlapping diagnosis years with three from Scandinivia, three from California, and two from Texas …”

“…The findings in relation to fetal growth (rather than birth weight per se) are more heterogeneous, with only three of these studies reporting an association with being large‐for‐gestational age (LGA) and two with being small‐for‐gestational age (SGA) . By contrast an Australian study found no association with either birth weight per se , or with another measure of fetal growth, the percentage of optimum birth weight (POBW), which in addition to sex, birth weight and gestational age, also took into account maternal parity and height .…”

Peri-gestational risk factors for pediatric brain tumors in Neurofibromatosis Type 1

“…The authors reported a summary OR of 1.38 (95% CI 1.07–1.79) for individuals with birth weights >4000 versus ≤4000 g [13]. A population-based Swedish registry linkage study also examined associations between birth weight and astrocytoma subtypes in individuals whose brain tumors were diagnosed in childhood through younger adulthood (≤38 years), finding that individuals with birth weights >4000 versus 2500–3999 g had a significant increased risk for pilocytic astrocytomas specifically, but not for other astrocytomas, medulloblastomas, or ependymomas [19]. These results are consistent with our findings for NF1-OPGs, a glial neoplasm classified as a pilocytic astrocytoma of the optic nerve, chiasm, or tract [20].…”

Is Month of Birth a Risk Factor for Colorectal Cancer?

“…Epidemiological studies have linked season of birth with a wide variety of conditions including lifespan and mortality risk [3–5], cardiovascular events [2, 6], type II diabetes [7], hypertension [8], mental health conditions [9], and suicide risk [10]. An association with season of birth has also been identified in malignant conditions such as childhood and adolescent haematological [11–13] and central nervous system cancers [14]. …”