Outcome at age 4 years in offspring of women with maternal phenylketonuria

The Maternal PKU Collaborative Study

Susan E. Waisbren, William Hanley, Harvey L. Levy, Harvey Shifrin, Elizabeth Allred, Colleen Azen, Pi Nian Chang, Sanja Cipeic-Schmidt, Felix De La Cruz, Ramona Hall, Reuben Matalon, Jo Nanson, Bobbye Rouse, Fritz Trefz, Richard Koch

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

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<.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.

Original languageEnglish (US)
Pages (from-to)756-762
Number of pages7
JournalJournal of the American Medical Association
Volume283
Issue number6
StatePublished - Feb 9 2000

Fingerprint

Maternal Phenylketonuria
Phenylketonurias
Pregnancy
Mothers
Phenylalanine
Diet
Language Development
Aptitude
Social Problems
Psychological Adaptation
Child Behavior
Checklist
Canada
Germany
Longitudinal Studies
Therapeutics
Observation
Outcome Assessment (Health Care)
Prospective Studies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Waisbren, S. E., Hanley, W., Levy, H. L., Shifrin, H., Allred, E., Azen, C., ... Koch, R. (2000). Outcome at age 4 years in offspring of women with maternal phenylketonuria: The Maternal PKU Collaborative Study. Journal of the American Medical Association, 283(6), 756-762.

Outcome at age 4 years in offspring of women with maternal phenylketonuria : The Maternal PKU Collaborative Study. / Waisbren, Susan E.; Hanley, William; Levy, Harvey L.; Shifrin, Harvey; Allred, Elizabeth; Azen, Colleen; Chang, Pi Nian; Cipeic-Schmidt, Sanja; De La Cruz, Felix; Hall, Ramona; Matalon, Reuben; Nanson, Jo; Rouse, Bobbye; Trefz, Fritz; Koch, Richard.

In: Journal of the American Medical Association, Vol. 283, No. 6, 09.02.2000, p. 756-762.

Research output: Contribution to journalArticle

Waisbren, SE, Hanley, W, Levy, HL, Shifrin, H, Allred, E, Azen, C, Chang, PN, Cipeic-Schmidt, S, De La Cruz, F, Hall, R, Matalon, R, Nanson, J, Rouse, B, Trefz, F & Koch, R 2000, 'Outcome at age 4 years in offspring of women with maternal phenylketonuria: The Maternal PKU Collaborative Study', Journal of the American Medical Association, vol. 283, no. 6, pp. 756-762.
Waisbren, Susan E. ; Hanley, William ; Levy, Harvey L. ; Shifrin, Harvey ; Allred, Elizabeth ; Azen, Colleen ; Chang, Pi Nian ; Cipeic-Schmidt, Sanja ; De La Cruz, Felix ; Hall, Ramona ; Matalon, Reuben ; Nanson, Jo ; Rouse, Bobbye ; Trefz, Fritz ; Koch, Richard. / Outcome at age 4 years in offspring of women with maternal phenylketonuria : The Maternal PKU Collaborative Study. In: Journal of the American Medical Association. 2000 ; Vol. 283, No. 6. pp. 756-762.
@article{fb465f80c91b4d68aa5d35588155ecda,
title = "Outcome at age 4 years in offspring of women with maternal phenylketonuria: The Maternal PKU Collaborative Study",
abstract = "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<.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.",
author = "Waisbren, {Susan E.} and William Hanley and Levy, {Harvey L.} and Harvey Shifrin and Elizabeth Allred and Colleen Azen and Chang, {Pi Nian} and Sanja Cipeic-Schmidt and {De La Cruz}, Felix and Ramona Hall and Reuben Matalon and Jo Nanson and Bobbye Rouse and Fritz Trefz and Richard Koch",
year = "2000",
month = "2",
day = "9",
language = "English (US)",
volume = "283",
pages = "756--762",
journal = "JAMA - Journal of the American Medical Association",
issn = "0002-9955",
publisher = "American Medical Association",
number = "6",

}

TY - JOUR

T1 - Outcome at age 4 years in offspring of women with maternal phenylketonuria

T2 - The Maternal PKU Collaborative Study

AU - Waisbren, Susan E.

AU - Hanley, William

AU - Levy, Harvey L.

AU - Shifrin, Harvey

AU - Allred, Elizabeth

AU - Azen, Colleen

AU - Chang, Pi Nian

AU - Cipeic-Schmidt, Sanja

AU - De La Cruz, Felix

AU - Hall, Ramona

AU - Matalon, Reuben

AU - Nanson, Jo

AU - Rouse, Bobbye

AU - Trefz, Fritz

AU - Koch, Richard

PY - 2000/2/9

Y1 - 2000/2/9

N2 - 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<.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.

AB - 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<.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.

UR - http://www.scopus.com/inward/record.url?scp=0033950629&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033950629&partnerID=8YFLogxK

M3 - Article

VL - 283

SP - 756

EP - 762

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0002-9955

IS - 6

ER -