European Journal of Pediatrics

, Volume 155, Supplement 1, pp S169–S172 | Cite as

The North American Maternal Phenylketonuria Collaborative Study, developmental assessment of the offspring: preliminary report

  • W. B. Hanley
  • R. Koch
  • H. L. Levy
  • R. Matalon
  • B. Rouse
  • C. Azen
  • F. de la Cruz


Preliminary results of 2-year Bay ley and 4-year McCarthy test scores are presented. To date numbers are too small to statistically correlate: — offspring from pregnancies in which diet was started prior to conception, offspring from pregnancies with phenylalanine (Phe) levels of 120–360 µmol/l versus 360–600 µmol/l, influence of home environment, influence of maternal nutrition, language development, behaviour/hyperactivity, Revised Wechsler Intelligence Score, school performance and learning disabilities. Two-year Bayley scores (mental and motor) revealed a median developmental quotient of 113 in 58 offspring from control pregnancies, 104 in 19 offspring from untreated “non-phenylketonuria (PKU) mild hyper-phenylalaninaemia” (natural Phe levels <600 µmol/1) pregnancies, 104 in 32 offspring from pregnancies whose Phe levels decreased on treatment to <600 µmol/1 by 10 weeks gestation and remained in that range for the remainder of the pregnancy, 98 in offspring from 32 pregnancies where permanent control was not achieved until 10–20 weeks and 72 in offspring from 51 pregnancies where control was not attained until after 20 weeks gestation. IQ scores determined by the McCarthy test at age 4–5 years revealed a mean of 112 in 43 offspring of control mothers, 99 in 12 offspring of “non PKU mild hyperphenylalaninaemia” women, 93 in 14 offspring whose mother’s Phe levels were continuously under 600 µmol/1 by 10 weeks gestation, 88 in 24 offspring from pregnancies in metabolic control by 10–20 weeks and 73 in 28 offspring of pregnancies not in metabolic control until after 20 weeks gestation. These preliminary results suggest that early and adequate dietary treatment during pregnancy in maternal PKU may provide some protection to the fetus for later intellectual development but much more data is required before definitive statements about cognition can be made.

Key words

Phenylketonuria Maternal phenylketonuria 



development quotient


Maternal phenylketonuria


Maternal PKU Collaborative Study






  1. 1.
    Acosta PB, Blascovics M, Cloud H, Lis E, Stroud E, Wenz E (1982) Nutrition in pregnancy in women with hyperphenylalaninemia. J Am Diet Assoc 80:443–450PubMedGoogle Scholar
  2. 2.
    Autti-Ramo I, Gaily E, Granstrom M-L (1992) Dysmorphic features in offspring of alcoholic mothers. Arch Dis Child 67:712–716PubMedCrossRefGoogle Scholar
  3. 3.
    Autti-Ramo I, Korkman M, Hilakivi-Clarke L, Lehtoten M, Halmesmaki E, Granstrom M-L (1992) Mental development of 2-year-old children exposed to alcohol in utero. J Pediatr 120: 740–746PubMedCrossRefGoogle Scholar
  4. 4.
    Brenton DP, Lorek A, Baudin J, Stewart A (1994) Maternal phenylketonuria: preconception dietary control and outcome. Int Pediatr 9 [Suppl 2]: 5–10Google Scholar
  5. 5.
    Fuggle PW, Tokar S, Grant DB, Smith I (1992) Rising IQ scores in British children: recent evidence. J Child Psychol Psychiatry 33:1241–1247PubMedCrossRefGoogle Scholar
  6. 6.
    Flynn J (1987) Massive IQ gains in 14 nations: what IQ tests really measure. Psycholog Bull 101:171–191CrossRefGoogle Scholar
  7. 7.
    Hanley WB, Clarke JTR, Schoonheyt WE (1987) Maternal phenylketonuria (PKU) – a review. Clin Biochem 20: 149–156PubMedCrossRefGoogle Scholar
  8. 8.
    Jones KL (1986) Fetal alcohol syndrome. Pediatr Rev 8:122–126PubMedCrossRefGoogle Scholar
  9. 9.
    Koch R, Levy H, Matalon R, Rouse B, Hanley W, Azen C (1993) The North American collaborative study of maternal phenylketonuria. Status report 1993. Am J Dis Child 147:1224–1230PubMedGoogle Scholar
  10. 10.
    Lacey DJ, Terplan K (1987) Abnormal cerebral cortical neurons in a child with maternal PKU syndrome. J Child Neurol 2:201–204PubMedCrossRefGoogle Scholar
  11. 11.
    Lenke RR, Levy HL (1980) Maternal phenylketonuria and hyperphenylalaninemia — an international study of outcome of treated and untreated pregnancies. N Engl J Med 303:1202–1208PubMedGoogle Scholar
  12. 12.
    Levy HL, Waisbren SE (1983) Effect of untreated maternal phenylketonuria and hyperphenylalaninema on the fetus. N Engl J Med 309:1269–1274PubMedGoogle Scholar
  13. 13.
    Levy HL, Shih VE, Karolkewicz, et al (1971) Persistent mild hyperphenylalaninemia in the untreated state. A prospective study. N Engl J Med 285: 424–429PubMedCrossRefGoogle Scholar
  14. 14.
    Levy HL, Lobbregt D, Waisbren SE, et al (1994) Maternal mild hyperphenylalaninemia (abstract). VI Int Congress Inborn Errors of Metabolism. Milano, Italy, 27–30 MayGoogle Scholar
  15. 15.
    Lipson A, Beuhler B, Bartley J, et al (1984) Maternal hyperphenylalaninemia fetal effects. J Pediatr 104:216–220PubMedCrossRefGoogle Scholar
  16. 16.
    Matalon R, Michals K, Azen C, Friedman E, Koch R, Rouse B, Hanley W, Cruz F de la (1994) Maternal PKU collaborative study: pregnancy outcome and postnatal head growth. J Inherited Metab Dis 17:353–355PubMedCrossRefGoogle Scholar
  17. 17.
    Medical Research Council Working party on Phenylketonuria (1993) Phenylketonuria due to phenylalanine hydroxylase deficiency: an unfolding story. BMJ 306:115–119CrossRefGoogle Scholar
  18. 18.
    Robinson BH, MacMillan H, Petrova-Benedict R, Sherwood WG (1987) Variable clinical presentation in patients with defective El component of pyruvate dehydrogenase complex. J Pediatr 111: 525–533PubMedCrossRefGoogle Scholar
  19. 19.
    Rouse B, Lockhart L, Matalon R, Azen C, et al (1990) Maternal phenylketonuria pregnancy outcome: a preliminary report of facial dysmorphology and major malformations. J Inherited Metab Dis 13:289–291PubMedCrossRefGoogle Scholar
  20. 20.
    Schoonheyt WE, Clarke JTR, Hanley WB, Johnson LM, Lehotay DC (1994) Feto-maternal plasma phenylalanine concentration gradient from 19 weeks gestation to term. Clin Chim Acta 225: 165–169PubMedCrossRefGoogle Scholar
  21. 21.
    Weisbren SE, Levy HL (1990) Effects of untreated hyperphenylalaninemia on the fetus: further studies of families identified by routine cord blood screening. J Pediatr 116:926–929CrossRefGoogle Scholar
  22. 22.
    Waisbren SE, Schnell R, Levy HL (1984) Intelligence and personality characteristics in adults with untreated atypical phenylketonuria and mild hyperphenylalaninemia. J Pediatr 105: 955–958PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • W. B. Hanley
    • 1
  • R. Koch
    • 2
  • H. L. Levy
    • 3
  • R. Matalon
    • 4
  • B. Rouse
    • 5
  • C. Azen
    • 2
  • F. de la Cruz
    • 6
  1. 1.Division of Clinical GeneticsThe Hospital for Sick ChildrenTorontoCanada
  2. 2.Children’s Hospital of Los AngelesLos AngelesUSA
  3. 3.Children’s HospitalBostonUSA
  4. 4.Miami Children’s HospitalMiamiUSA
  5. 5.University of Texas Medical BranchGalvestonUSA
  6. 6.National Institute of Child Health and Human DevelopmentBethesdaUSA

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