Low birth weight is a significant cause of morbidity and mortality among newborns, and may result from impaired placental function during the first trimester of pregnancy. Here we show that the risk of delivering a low-birth-weight baby at term after an uncomplicated pregnancy varies with maternal circulating concentrations of a placental protein, pregnancy-associated plasma protein-A (PAPP-A) in the first 10 weeks after conception. Poor fetal growth may therefore already have been determined by the time obstetric monitoring begins after completion of the first trimester.