Genes, Environments, and the Development of Intelligence in Children of Mothers With Phenylketonuria

This study modeled relations among maternal background variables, pregnancy-related variables, and physical indicators at birth with later offspring cognitive outcomes during infancy and childhood in a sample of children of mothers with phenylketonuria (PKU). Participants were the 413 children and their mothers from the International Maternal PKU Collaborative Study. We used structural equation modeling to estimate effects of background variables and sets of mediator variables on offspring mental ability measures at 1, 2, 4 and 7 years of offspring age. Mothers had a mean IQ of 85.9, about one SD below the population mean, and average education of completion of high school. Maternal background variables had hypothesized correlations with pregnancy-related variables, but only severity of the mother’s PKU genetic defect had a large effect (β = 0.50) on the key pregnancy variable, average phenylalanine (PHE) in mother’s blood during pregnancy. In turn, average PHE in mother’s blood during pregnancy had large direct effects on birth size (length and weight) (β = ‒0.37), birth head circumference (β = ‒0.54), and child IQ at 1 year (β = ‒0.51), and substantial lagged effects on child IQ at 2 and 4 years of age (βs = ‒0.32 and ‒0.38, respectively). Average PHE in mother’s blood during pregnancy largely mediated effects of maternal background variables on infant and childhood cognitive outcomes. The results have implications for our understanding of early development of intelligence and for the interplay of genetic and environmental factors that influence development.