Background: The aim of this study was to identify possible risk factors associated with term-born newborns with cerebral palsy and PWMI on imaging. Methods: This is a case-controlled study with cases from the Canadian Cerebral Palsy Registry and controls from Alberta Pregnancy Outcomes and Nutrition Study. PWMI was diagnosed based on MRI reports and 160 cases were compared to 1950 controls. Risk factor were selected a priori; including pregnancy complications, toxin exposure, perinatal infection, sex, small for gestational age, and perinatal adversity. Multivariate regression binomial model was used to calculate odds ratios(OR) and 95% confidence intervals(CI). Results: Multivariable analyses suggested PWMI was associated with pregnancy complications(OR=3.35; 95% CI=2.23-4.94), antenatal toxin exposure(OR=2.45; 95% CI=1.67-3.55), perinatal infection(OR=3.61; 95% CI=1.96-6.29) and perinatal adversity(OR=2.03; 95% CI=1.42-2.94). Term born males were not more likely to have PWMI compared to females(OR=1.37; 95% CI=0.98-1.93). Multiple regression analyses suggested independent associations between PWMI and pregnancy complications(OR=3.63; 95% CI 2.40-5.40), antenatal toxin exposure(OR=2.62; 95% CI 1.77-3.84), perinatal infection(OR=3.42; 95% CI 1.83-6.05) and perinatal adversity(OR=2.49; 95% CI= 1.71-3.69). Conclusions: Risk factors such as pregnancy complications, toxin exposure, perinatal infection and perinatal adversity are associated with PWMI in term-borns, suggesting a ‘two-hit’ model that could involve an interaction among both antenatal and perinatal variables.