AbstractBackgroundOsteosarcoma typically develops during puberty with tumors arising at sites of rapid bone growth, suggesting a role for growth‐regulating pathways in tumor etiology. Birthweight is one measure of perinatal growth that has been investigated as an osteosarcoma risk factor. Whether birthweight affects clinical features of osteosarcoma remains unexplored.MethodSix hundred seventy patients with osteosarcoma, aged 0–19 years, were identified through the California Cancer Registry. We analyzed birth certificate data from the California Department of Public Health vital statistics unit for these patients and 2,860 controls, matched by sex, birth‐year, and race/ethnicity. We examined the impact of birthweight on the risk, timing, and clinical presentation of pediatric osteosarcoma including tumor location, size, extension, differentiation, presence of metastasis, and age at onset. Regression models were adjusted for race, sex, gestational age, socioeconomic status, and tumor site.ResultsHigher birthweight was associated with more advanced tumor stage (P = 0.017), a trend toward greater tumor extension into surrounding tissues (P = 0.083), and with occurrence of tumors in sites other than the long bones of the arms/legs (P = 9.7 × 10⁻³). Higher birthweight was also associated with an increased likelihood of metastases present at diagnosis (P = 0.047), with each 200 g increase in birthweight associated with a 1.11‐fold increase in the odds of having metastatic disease (95% confidence interval: 1.01–1.22).ConclusionsThe association between higher birthweight and more aggressive osteosarcoma, frequently occurring at sites other than the long bones, suggests that growth pathways active during gestation may play an important role in future osteosarcoma progression, especially at anatomic sites with diminished rates of osteoblastic proliferation.