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PEDIATRICS Vol. 112 No. 6 December 2003, pp. 1537-1543

SUPPLEMENT ARTICLE

Relation of Prenatal Phenylalanine Exposure to Infant and Childhood Cognitive Outcomes: Results From the International Maternal PKU Collaborative Study

Keith F. Widaman, PhD* and Colleen Azen, MS{ddagger}

* Department of Psychology, University of California at Davis, Davis, California
{ddagger} Children’s Hospital Los Angeles, Los Angeles, California

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.

Key Words: prenatal effects • phenylalanine • PKU • maternal PKU • intelligence • teratogenic effects • socioeconomic status • maternal intelligence • maternal age • pregnancy • birth outcomes • infancy • childhood • regression • spline models • structural equation models • longitudinal study

Abbreviations: Phe, phenylalanine • SES, socioeconomic status • PKU, phenylketonuria • SD, standard deviation • PAH, phenylalanine hydroxylase • MDI, Mental Development Index • PDI, Psychomotor Development Index • GCI, General Cognitive Index • WISC-R, Wechsler Intelligence Scale for Children–Revised