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This article presents a Norwegian prospective, longitudinal study of children prenatally exposed to opiates and other substances under conditions of minimal postnatal social risk. Outcome at 4½ years of age is presented. The study reports on the prediction of later intellectual performance, on the basis of the children’s prenatal, perinatal, and early developmental status, as well as the foster or adoptive parents’ socioeconomic level. Significant differences were found between the substance-exposed group and the comparison group on the Bayley Scales at age 1 year and on the McCarthy Scales at age 4½ years. The findings showed that although the mean cognitive scores were within normal limits at age 4½ years, a special weakness in the area of visual-motor and perceptual abilities was detected among the substance-exposed children. It is indicated that these areas of performance are especially sensitive to the effect of prenatal adversity. A special vulnerability among the substance-exposed boys, detected at an earlier age, persisted at 4½ years. The study indicates that even if children experience adequate caregiving, the accumulation of biomedical risk factors associated with prenatal substance exposure is still a potential determinant of developmental problems, especially in the area of perceptual-performance functions. The study also hints at differential influences of biomedical and environmental variables on outcome at age 4½ years.