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

Abstract

The offspring of women with untreated phenylketonuria(PKU) are at very high risk of being mentally retarded and microcephalic. Low birth weight and congenital heart disease also may occur. Whether dietary management during pregnancy improves developmental outcomes was examined in the Maternal PKU Collaborative Study, a longitudinal prospective trial started in 1984 at 78 metabolic clinics and obstetrical offices in the United States, Canada, and Germany. The 149 children whose mothers had PKU were followed to age 4 years, as were 33 children whose mothers had mild, untreated hyperphenylalaninemia and 71 children whose mothers had no metabolic disorders. The women with PKU were offered a low-phenylalanine diet intended to maintain the plasma phenylalanine concentration at 10 mg/dl or less. The McCarthy Scales of Children’s Abilities was the primary instrument used for assessment; this instrument was supplemented by the Test of Language Development– Primary, the Achenbach Child Behavior Checklist, and the Vineland Adaptive Behavior Scales. The Home Observation for Measurement of the Environment scale provided a measure of the physical features of the home and the experiences available to the child. McCarthy Scale scores dropped as the time to metabolic control increased, suggesting a dose-response relationship. Language dysfunction and abnormal perceptual performance/motor scores were especially evident. Children whose mothers achieved metabolic control after pregnancy began but within 6 weeks of birth did less well overall than those treated before conception. Language testing pointed to specific effects on expressive language and memory. In the behavioral realm, 30 percent of children received total behavior problem ratings in the clinical range, with an expected frequency of 18 percent. Few children had somatic problems, anxiety, or delinquency. Social skills seemed to develop more slowly than usual. The children whose mothers had PKU had significantly lower McCarthy Scale scores at age 4 than Bayley Scale scores at age 2 years. The best way to protect children of mothers with PKU is to ensure that women gain metabolic control before conception Maternal phenylalanine levels higher than 10 mg/dl during pregnancy clearly affect the fetus adversely. Children born to women with PKU closely resemble those whose mothers consume large amounts of alcohol. It is possible that, after birth, the home environment could moderate the negative effects of maternal PKU. JAMA 2000;283:756–762