- With rising obesity rates among pregnant women, more children are exposed in utero to maternal obesity. In prior epidemiological studies, exposure to maternal obesity was associated with lower intelligence quotient (IQ) scores and worse cognitive abilities in offspring. Further studies have shown that offspring exposed to maternal obesity, exhibit differences in the white matter microstructure properties, fractional anisotropy (FA) and mean diffusivity (MD). In contrast, physical activity was shown to improve cognition and white matter microstructure during childhood. We examined if child physical activity levels modify the relationship between prenatal exposure to maternal obesity with IQ and white matter microstructure in offspring.One hundred children (59% girls) age 7-11 years underwent brain magnetic resonance imaging and IQ testing. Maternal pre-pregnancy BMI was abstracted from electronic medical records. White matter was assessed using diffusion tensor imaging with the measures, global FA, MD. The 3-day physical activity recall was used to measure moderate-to-vigorous physical activity and vigorous physical activity (VPA). Linear regression was used to test for interactions between prenatal exposure to maternal overweight/obesity and child PA levels on child IQ and global FA/MD.The relationship between prenatal exposure to maternal overweight/obesity and child IQ and global FA varied by child VPA levels. Children exposed to mothers with overweight/obesity who engaged in more VPA had higher IQ scores and global FA compared to exposed children who engaged in less VPA. Associations were independent of child age, sex, BMI Z-score and socioeconomic status. Children born to normal-weight mothers did not differ in either IQ or global FA by time in VPA.Our findings support findings in rodent models and suggest that VPA during childhood modifies the relationship between prenatal exposure to maternal obesity and child IQ and white matter microstructure.