Twenty-five years of research on neurocognitive outcomes in early-treated phenylketonuria: intelligence and executive function.

Studies published from 1980 through 2004, which explored intelligence and executive function outcomes in early-treated PKU, were included in the present meta-analysis. The objective of this study was to examine the degree of difference between early-treated PKU and unaffected control groups (primarily non-familial controls), known as effect size, for various components of measured intelligence (i.e., full-scale, verbal, performance, and "other") and executive function (i.e., planning, working memory, inhibition, flexibility, and "other"). Secondly, in the case of heterogeneity among observed effect sizes, the moderator variables of "years since publication" and "measurement tools" were examined for their potential contribution to this heterogeneity. Thirty-three primary studies, with a total 200 outcomes meeting our inclusionary and exclusionary criteria, were meta-analyzed using Hedges g for effect size to correct for small samples in primary studies. The effect sizes for intelligence outcomes were "small" to "moderate" falling in the range of .20 to .42, with no significant heterogeneity among outcomes. Effect sizes for executive function and its various component processes were in the "moderate" and "large range" falling between .591 (planning) and 1.15 (flexibility). Significant heterogeneity among the executive function effect sizes was identified, and both "years since publication" and "measurement tools" were found to be significant moderators. Studies published more recently exhibited larger effect sizes, and particular executive function tasks demonstrated larger effect sizes than other tests. The results are discussed in terms of the contributions this meta-analysis makes to our understanding of neurocognitive outcomes in early-treated PKU, as well as suggestions for the conduct and reporting of future research in this area.