Maternal immune activation (MIA) has been implicated in offspring neurodevelopmental and psychiatric disorders, although it is unknown to what extent MIA affects neurodevelopment in the general population, and whether effects differ by sex. The current study was set within FinnBrain, a prospective birth cohort study based in Turku, Finland. We examined the association between maternal prenatal C-reactive protein (CRP), a commonly used systemic inflammatory marker, and white matter fractional anisotropy (FA) and mean diffusivity (MD) in infant and 5-year-old offspring, using voxel-wise statistics. In a related in vitro study, developing human neurons were exposed to low- or high-CRP maternal serum to determine whether there were effects on neuronal differentiation and morphology (Fig. 1C). All analyses were carried out across the whole sample and stratified by sex.Maternal CRP within a normal physiological range (< 10 mg/L) associated positively with FA values and negatively with MD values in 5-year-old females (Fig. 1B). Hyperphysiological maternal CRP (> 10 mg/L) was associated with increased FA and decreased MD in female infants, particularly in the left external capsule and body of corpus callosum (Fig. 1A). At both ages, there was no significant association in males. Furthermore, high-CRP maternal serum induced increased growth-associated protein 43 (GAP43)+ neurite length in vitro, particularly from mothers with female offspring (Fig. 1D-E). Overall, these data demonstrate that CRP, as a proxy measure of MIA, is associated with white matter development in typically developing female children.