Background : The roles of antioxidants in the placenta and genetic susceptibility to oxidant chemicals in relation to neonatal birth weight have not been elucidated. We determined whether the level of placental manganese superoxide dismutase (MnSOD) and its genetic polymorphism plays any role in oxidative stress and neonatal birth weight. Methods : We measured placental MnSOD and determined MnSOD genetic polymorphism among 108 pregnant women who were hospitalized for delivery and their singleton live births in Korea. Main outcome measurements are maternal urinary malondialdehyde (MDA) and birth weight. Results : Maternal urinary concentrations of MDA were significantly associated with neonatal birth weight (P=0.04). The enzyme level of placental MnSOD was also significantly associated with MDA concentration (P=0.04) and neonatal birth weight (p<0.01). We observed dose-response relationships between placental MnSOD and maternal urinary MDA, and neonatal birth weight after adjusting for maternal weight, height, age, and neonatal sex. After controlling for covariates, MnSOD variant genotype increased maternal urinary MDA concentrations (p<0.01) and reduced birth weight by 149 gm (P=0.08). Conclusions : This study demonstrates that the placental level of MnSOD during pregnancy significantly affects fetal growth by reducing oxidative stress, and that genetic polymorphism of MnSOD probably modulate the effects of oxidants on fetal growth.