Outcome at Age 4 Years in Offspring of Women With Maternal Phenylketonuria: The Maternal PKU Collaborative Study

CONTEXT Untreated maternal phenylketonuria (PKU) increases risk for developmental problems in offspring. The extent to which this risk is reduced by maternal dietary therapy at various stages of pregnancy is not known. OBJECTIVE To determine whether dietary treatment during pregnancy of women with PKU affects developmental outcomes of offspring. DESIGN The Maternal PKU Collaborative Study, an ongoing, longitudinal prospective study begun in 1984. SETTING A total of 78 metabolic clinics and obstetrical offices in the United States, Canada, and Germany. PARTICIPANTS A total of 253 children of women with PKU (n=149), with untreated mild hyperphenylalaninemia (n=33), or without known metabolic problems (comparison group; n=71) were followed up to age 4 years. INTERVENTION Women with PKU were offered a low-phenylalanine diet prior to or during pregnancy with the aim of maintaining metabolic control (plasma phenylalanine ≤10 mg/dL [≤605 µmol/L]). Women with mild hyperphenylalaninemia, who had plasma phenylalanine levels of no more than 10 mg/dL (605 µmol/L) on a normal diet, were not treated. MAIN OUTCOME MEASURES Children's scores on cognitive and behavioral assessments (McCarthy Scales of Children's Abilities, Test of Language Development, Achenbach Child Behavior Checklist, Vineland Adaptive Behavior Scales, and Home Observation for Measurement of the Environment), compared by maternal metabolic status at 0 to 10 weeks', 10 to 20 weeks', and after 20 weeks' gestation. RESULTS Scores on the McCarthy General Cognitive Index decreased as weeks to metabolic control increased (r = −0.58; P