Outcome at age 4 years in offspring of women with maternal phenylketonuria: the Maternal PKU Collaborative Study. 2000

S E Waisbren, and W Hanley, and H L Levy, and H Shifrin, and E Allred, and C Azen, and P N Chang, and S Cipcic-Schmidt, and F de la Cruz, and R Hall, and R Matalon, and J Nanson, and B Rouse, and F Trefz, and R Koch
Genetic Service, Children's Hospital, Boston, Mass 02115, USA. waisbren@al.tch.harvard.edu

BACKGROUND 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. METHODS The Maternal PKU Collaborative Study, an ongoing, longitudinal prospective study begun in 1984. METHODS A total of 78 metabolic clinics and obstetrical offices in the United States, Canada, and Germany. METHODS 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. METHODS Women with PKU were offered a low-phenylalanine diet prior to or during pregnancy with the aim of maintaining metabolic control (plasma phenylalanine < or =10 mg/dL [< or =605 micromol/L]). Women with mild hyperphenylalaninemia, who had plasma phenylalanine levels of no more than 10 mg/dL (605 micromol/L) on a normal diet, were not treated. METHODS 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<.001). Offspring of women who had metabolic control prior to pregnancy had a mean (SD) score of 99 (13). Forty-seven percent of offspring whose mothers did not have metabolic control by 20 weeks' gestation had a General Cognitive Index score 2 SDs below the norm. Overall, 30% of children born to mothers with PKU had social and behavioral problems. CONCLUSIONS Our data suggest that delayed development in offspring of women with PKU is associated with lack of maternal metabolic control prior to or early in pregnancy. Treatment at any time during pregnancy may reduce the severity of delay.

UI MeSH Term Description Entries
D008137 Longitudinal Studies Studies in which variables relating to an individual or group of individuals are assessed over a period of time. Bogalusa Heart Study,California Teachers Study,Framingham Heart Study,Jackson Heart Study,Longitudinal Survey,Tuskegee Syphilis Study,Bogalusa Heart Studies,California Teachers Studies,Framingham Heart Studies,Heart Studies, Bogalusa,Heart Studies, Framingham,Heart Studies, Jackson,Heart Study, Bogalusa,Heart Study, Framingham,Heart Study, Jackson,Jackson Heart Studies,Longitudinal Study,Longitudinal Surveys,Studies, Bogalusa Heart,Studies, California Teachers,Studies, Jackson Heart,Studies, Longitudinal,Study, Bogalusa Heart,Study, California Teachers,Study, Longitudinal,Survey, Longitudinal,Surveys, Longitudinal,Syphilis Studies, Tuskegee,Syphilis Study, Tuskegee,Teachers Studies, California,Teachers Study, California,Tuskegee Syphilis Studies
D008297 Male Males
D010661 Phenylketonurias A group of autosomal recessive disorders marked by a deficiency of the hepatic enzyme PHENYLALANINE HYDROXYLASE or less frequently by reduced activity of DIHYDROPTERIDINE REDUCTASE (i.e., atypical phenylketonuria). Classical phenylketonuria is caused by a severe deficiency of phenylalanine hydroxylase and presents in infancy with developmental delay; SEIZURES; skin HYPOPIGMENTATION; ECZEMA; and demyelination in the central nervous system. (From Adams et al., Principles of Neurology, 6th ed, p952). Biopterin Deficiency,Dihydropteridine Reductase Deficiency Disease,Hyperphenylalaninemia, Non-Phenylketonuric,Phenylalanine Hydroxylase Deficiency Disease,BH4 Deficiency,DHPR Deficiency,Deficiency Disease, Dihydropteridine Reductase,Deficiency Disease, Phenylalanine Hydroxylase,Deficiency Disease, Phenylalanine Hydroxylase, Severe,Dihydropteridine Reductase Deficiency,Folling Disease,Folling's Disease,HPABH4C,Hyperphenylalaninaemia,Hyperphenylalaninemia Caused by a Defect in Biopterin Metabolism,Hyperphenylalaninemia, BH4-Deficient, C,Hyperphenylalaninemia, Tetrahydrobiopterin-Deficient, Due To DHPR Deficiency,Non-Phenylketonuric Hyperphenylalaninemia,Oligophrenia Phenylpyruvica,PAH Deficiency,PKU, Atypical,Phenylalanine Hydroxylase Deficiency,Phenylalanine Hydroxylase Deficiency Disease, Severe,Phenylketonuria,Phenylketonuria I,Phenylketonuria II,Phenylketonuria Type 2,Phenylketonuria, Atypical,Phenylketonuria, Classical,QDPR Deficiency,Quinoid Dihydropteridine Reductase Deficiency,Tetrahydrobiopterin Deficiency,Atypical PKU,Atypical Phenylketonuria,Biopterin Deficiencies,Classical Phenylketonuria,Deficiency, BH4,Deficiency, Biopterin,Deficiency, DHPR,Deficiency, Dihydropteridine Reductase,Deficiency, PAH,Deficiency, Phenylalanine Hydroxylase,Deficiency, QDPR,Deficiency, Tetrahydrobiopterin,Disease, Folling,Disease, Folling's,Hyperphenylalaninemia, Non Phenylketonuric,Non Phenylketonuric Hyperphenylalaninemia,Non-Phenylketonuric Hyperphenylalaninemias
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011248 Pregnancy Complications Conditions or pathological processes associated with pregnancy. They can occur during or after pregnancy, and range from minor discomforts to serious diseases that require medical interventions. They include diseases in pregnant females, and pregnancies in females with diseases. Adverse Birth Outcomes,Complications, Pregnancy,Adverse Birth Outcome,Birth Outcome, Adverse,Complication, Pregnancy,Outcome, Adverse Birth,Pregnancy Complication
D011256 Pregnancy Outcome Results of conception and ensuing pregnancy, including LIVE BIRTH; STILLBIRTH; or SPONTANEOUS ABORTION. The outcome may follow natural or artificial insemination or any of the various ASSISTED REPRODUCTIVE TECHNIQUES, such as EMBRYO TRANSFER or FERTILIZATION IN VITRO. Outcome, Pregnancy,Outcomes, Pregnancy,Pregnancy Outcomes
D011581 Psychological Tests Standardized tests designed to measure abilities (as in intelligence, aptitude, and achievement tests) or to evaluate personality traits. Parenting Stress Index,Trier Social Stress Test,Trier Stress Test,Psychologic Tests,Psychological Test,Test, Psychological,Tests, Psychological,Index, Parenting Stress,Psychologic Test,Stress Index, Parenting,Stress Test, Trier,Test, Psychologic,Test, Trier Stress,Trier Stress Tests
D002652 Child Behavior Any observable response or action of a child from 24 months through 12 years of age. For neonates or children younger than 24 months, INFANT BEHAVIOR is available. Behavior, Child
D002658 Developmental Disabilities Disorders in which there is a delay in development based on that expected for a given age level or stage of development. These impairments or disabilities originate before age 18, may be expected to continue indefinitely, and constitute a substantial impairment. Biological and nonbiological factors are involved in these disorders. (From American Psychiatric Glossary, 6th ed) Child Development Deviations,Child Development Disorders,Child Development Disorders, Specific,Developmental Delay Disorders,Disabilities, Developmental,Development Disorders, Child,Child Development Deviation,Child Development Disorder,Development Deviation, Child,Development Deviations, Child,Development Disorder, Child,Developmental Delay Disorder,Developmental Disability,Deviation, Child Development,Disability, Developmental
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children

Related Publications

S E Waisbren, and W Hanley, and H L Levy, and H Shifrin, and E Allred, and C Azen, and P N Chang, and S Cipcic-Schmidt, and F de la Cruz, and R Hall, and R Matalon, and J Nanson, and B Rouse, and F Trefz, and R Koch
May 2001, Pediatric research,
S E Waisbren, and W Hanley, and H L Levy, and H Shifrin, and E Allred, and C Azen, and P N Chang, and S Cipcic-Schmidt, and F de la Cruz, and R Hall, and R Matalon, and J Nanson, and B Rouse, and F Trefz, and R Koch
May 1979, Pediatrics,
S E Waisbren, and W Hanley, and H L Levy, and H Shifrin, and E Allred, and C Azen, and P N Chang, and S Cipcic-Schmidt, and F de la Cruz, and R Hall, and R Matalon, and J Nanson, and B Rouse, and F Trefz, and R Koch
April 1992, American journal of obstetrics and gynecology,
S E Waisbren, and W Hanley, and H L Levy, and H Shifrin, and E Allred, and C Azen, and P N Chang, and S Cipcic-Schmidt, and F de la Cruz, and R Hall, and R Matalon, and J Nanson, and B Rouse, and F Trefz, and R Koch
January 1987, Research in developmental disabilities,
S E Waisbren, and W Hanley, and H L Levy, and H Shifrin, and E Allred, and C Azen, and P N Chang, and S Cipcic-Schmidt, and F de la Cruz, and R Hall, and R Matalon, and J Nanson, and B Rouse, and F Trefz, and R Koch
January 1994, Journal of inherited metabolic disease,
S E Waisbren, and W Hanley, and H L Levy, and H Shifrin, and E Allred, and C Azen, and P N Chang, and S Cipcic-Schmidt, and F de la Cruz, and R Hall, and R Matalon, and J Nanson, and B Rouse, and F Trefz, and R Koch
January 1991, Journal of inherited metabolic disease,
S E Waisbren, and W Hanley, and H L Levy, and H Shifrin, and E Allred, and C Azen, and P N Chang, and S Cipcic-Schmidt, and F de la Cruz, and R Hall, and R Matalon, and J Nanson, and B Rouse, and F Trefz, and R Koch
January 1993, Journal of inherited metabolic disease,
S E Waisbren, and W Hanley, and H L Levy, and H Shifrin, and E Allred, and C Azen, and P N Chang, and S Cipcic-Schmidt, and F de la Cruz, and R Hall, and R Matalon, and J Nanson, and B Rouse, and F Trefz, and R Koch
July 1996, European journal of pediatrics,
S E Waisbren, and W Hanley, and H L Levy, and H Shifrin, and E Allred, and C Azen, and P N Chang, and S Cipcic-Schmidt, and F de la Cruz, and R Hall, and R Matalon, and J Nanson, and B Rouse, and F Trefz, and R Koch
July 1996, European journal of pediatrics,
S E Waisbren, and W Hanley, and H L Levy, and H Shifrin, and E Allred, and C Azen, and P N Chang, and S Cipcic-Schmidt, and F de la Cruz, and R Hall, and R Matalon, and J Nanson, and B Rouse, and F Trefz, and R Koch
September 2023, JIMD reports,
Copied contents to your clipboard!