Maternal phenylketonuria collaborative study (MPKUCS) offspring: Facial anomalies, malformations, and early neurological sequelae

Bobbye Rouse, Colleen Azen, Richard Koch, Reuben Matalon, William Hanley, Felix De La Cruz, Friedrich Trefz, Eva Friedman, Harvey Shifrin

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


Maternal phenylketonuria (PKU) in untreated women has resulted in offspring with microcephaly, mental retardation, congenital heart disease (CHD), and intrauterine growth retardation. The Maternal Phenylketonuria Collaborative Study (MPKUCS) was designed to determine the effect of dietary control of blood phenylalanine (Phe) during pregnancy in preventing damage to the fetus associated with untreated Maternal PKU. A cohort of offspring from MPKUS pregnancies was ascertained and examined to evaluate malformations, including CHD, craniofacial abnormalities, microcephaly, intrauterine and postnatal growth retardation, other major and minor defects, and early abnormal neurological signs. For analysis, the women were grouped according to their mean Phe levels in μmol/liter, ±360, 361-600, 601-900, or >900, during critical gestational weeks of 0-8 (N = 203) and 8-12 (N = 190), and average for Phe exposure throughout pregnancy (N = 183). Frequencies of congenital abnormalities increased with increasing maternal Phe levels. Significant relationships included average Phe 0-8 weeks and CHD (P = 0.001); average Phe 8-12 weeks and brain, fetal, and postnatal growth retardation (P < 0.0005 for all), wide nasal bridge (P < 0.0005), and anteverted nares (P = 0.001); and average Phe exposure during the entire pregnancy and neurological signs (P < 0.0005). Although 14% of infants had CHD, none of the CHD occurred at 120-360 μmol/liter and only one (3%) at 361600 μmol/liter. At levels of 120-360 μmol/liter, there were three infants (6%) with microcephaly, two (4%) with post-natal growth, and none with intrauterine growth retardation, in contrast to 85%, 51%, and 26%, respectively, with Phe above 900 μmol/liter. These data support the concept that women with PKU should begin a low-phenylalanine diet to achieve Phe levels of <360 μmol/liter prior to conception and should maintain this throughout pregnancy.

Original languageEnglish (US)
Pages (from-to)89-95
Number of pages7
JournalAmerican Journal of Medical Genetics
Issue number1
StatePublished - Mar 3 1997
Externally publishedYes


  • MPKU
  • congenital heart disease
  • facial dysmorphology
  • maternal phenylketonuria
  • microcephaly

ASJC Scopus subject areas

  • Genetics(clinical)


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