Objective: To determine the relationships among serum leptin, insulin-like growth factor-I, and insulin levels in large for gestational age (LGA) infants. Methods: Serum samples were collected from maternal veins and umbilical arteries of 52 consecutive, term, LGA neonates of nondiabetic mothers. Maternal and neonatal serum samples were analyzed for levels of leptin, insulin-like growth factor-I, and insulin by specific radioimmunoassays. Multiple regression analysis was used to determine independent risk factors for fetal macrosomia. Results: The independent risk factor significantly associated with fetal macrosomia was umbilical cord leptin concentration (P < .01, β = 0.59). There was a statistically significant correlation between umbilical cord leptin and insulin-like growth factor-I levels and birth weight (r = 0.51, P < .01; r = 0.37, P < .01; respectively). The correlation between umbilical cord insulin levels and birth weight was not statistically significant (r = 0.06, P = .63), nor was that between maternal body mass index and birth weight (r = 0.09, P = .50). Conclusion: Our data showed that umbilical cord leptin concentration was an independent risk factor for fetal macrosomia. (C) 2000 by The American College of Obstetricians and Gynecologists.