Maternal phenylketonuria and hyperphenylalaninemia. An international survey of the outcome of untreated and treated pregnancies

N Engl J Med. 1980 Nov 20;303(21):1202-8. doi: 10.1056/NEJM198011203032104.


Since many women with phenylketonuria (PKU) will have children of their own, we were interested in ascertaining the effect of maternal PKU and hyperphenylalaninemia on the offspring of such women. We reviewed the literature on this subject and obtained additional unpublished data through an international survey. Data were collected on 524 pregnancies in 155 women; in 34 pregnancies a low-phenylalanine diet was begun after or shortly before pregnancy was established. Among untreated pregnancies, the frequencies of mental retardation, microcephaly, and congenital heart disease were greatly increased over those in the normal population, and these increases correlated with the mother's blood levels of phenylalanine. Ninety-five per cent of mothers with blood phenylalanine concentrations of 20 mg per deciliter or higher had at least one mentally retarded child. Bias introduced by case-finding methods cannot explain these results. It is not clear from our review whether dietary treatment begun after conception is helpful, but treatment begun before conception should be evaluated.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abortion, Spontaneous / etiology
  • Birth Weight
  • Female
  • Heart Defects, Congenital / etiology
  • Humans
  • Infant, Newborn
  • Intellectual Disability / etiology
  • Intelligence
  • Microcephaly / etiology
  • Phenylalanine / blood*
  • Phenylketonurias / diet therapy*
  • Phenylketonurias / prevention & control
  • Pregnancy
  • Pregnancy Complications / diet therapy*
  • Tyrosine / blood


  • Tyrosine
  • Phenylalanine