We aimed to describe if polymorphisms in xenobiotics-metabolizing genes modify the effect of maternal exposure to fine particulate matter (PM(2.5)) on offspring birth weight. Among newborns from LISA cohort, we tested if polymorphisms of GSTT1, GSTP1, GSTM1, and CYP2D6 genes modified the effect measure of PM(2.5) on term birth weight. Subsequently, we tested if polymorphisms modified the effect of other exposure factors with possibly similar pathways of action (active or passive smoking). PM (2.5) exposure above the median value (reference, below) was associated with birth weight changes by 76 g in the homozygous wild type genotype (n=161), -90 g in the heterozygous genotype (n=154) and -168 g in children with GSTP1 *1B/*1B mutant genotype (n=39, interaction test, p=0.05). No effect measure modification with PM(2.5) was detected for GSTT1, GSTM1 or CYP2D6 polymorphisms (p≥ 0.12). No effect measure modification with GSTP1 polymorphism was detected for active (p=0.71) nor for passive smoking effects on birth weight (p=0.13).