Objective. The primary aims of this study were to model the form of the relation between prenatal exposure to phenylalanine (Phe) and measures of offspring intellectual development and to estimate the developmental relations of maternal demographic, pregnancy-related, and perinatal variables on offspring intelligence during infancy and childhood. Methods. The participants were the 413 children and their mothers from the International Maternal PKU Collaborative Study. Results. Results supported a nonlinear relation between prenatal Phe exposure and offspring cognitive outcomes, with damage to the developing fetus if average Phe levels are above approximately 360 μmol/L. Moreover, prenatal Phe exposure had a strong effect on offspring outcomes at 1 year of age and was the only one of the background, pregnancy-related, or perinatal variables to influence directly offspring outcomes at 2, 4, and 7 years of age. Conclusion. The present study was able to document the importance of prenatal exposure to Phe for predicting offspring cognitive outcomes in the presence of other predictors of these outcomes.