title: Maternal phenylketonuria syndrome: congenital heart defects, microcephaly, and developmental outcomes.
abstract: OBJECTIVE
  A cohort of women with phenylketonuria (PKU) were selected to explore the impact of phenylalanine (Phe) levels and other factors on congenital heart defects (CHDs), microcephaly, and development of their offspring.
  
  
  METHODS
  Three hundred fifty-four women with PKU were followed up weekly with diet records, blood Phe levels, and sonograms obtained at 18 to 20 and 32 weeks' gestation. At birth, 413 offspring were examined and followed up at 6 months and annually by means of Bayley Mental Developmental Index and Psychomotor Developmental Index tests at 1 and 2 years. The women had Wechsler Adult Intelligence Scales and DNA testing.
  
  
  RESULTS
  Thirty-one offspring had CHDs; of these, 17 also had microcephaly. Mean Phe levels at 4 to 8 weeks' gestation predicted CHDs (P <.0001). An infant with a CHD had a 3-fold risk of having microcephaly when the mother had higher Phe levels (P =.02). The Bayley Mental Developmental Index and Psychomotor Developmental Index scores correlated with both CHDs (P =.037 and.0015, respectively) and microcephaly (P =.0001 for both). No direct relationship to the PKU mutation was found.
  
  
  CONCLUSIONS
  None of the women whose offspring had CHDs had blood Phe levels in control during the first 8 weeks of gestation. Women with PKU need to be well controlled on a low-phenylalanine diet before conception and throughout pregnancy.
authors.affiliation: Children's Hospital, University of Texas Medical Branch, Galveston, TX 77555-0319, USA.
authors.forename: B
authors.initials: B
authors.lastname: Rouse
authors.forename: R
authors.initials: R
authors.lastname: Matalon
authors.forename: R
authors.initials: R
authors.lastname: Koch
authors.forename: C
authors.initials: C
authors.lastname: Azen
authors.forename: H
authors.initials: H
authors.lastname: Levy
authors.forename: W
authors.initials: W
authors.lastname: Hanley
authors.forename: F
authors.initials: F
authors.lastname: Trefz
authors.forename: F
authors.initials: F
authors.lastname: de la Cruz
mesh_terms: D000328:Adult; D002657:Child Development / Q000502:physiology; D015331:Cohort Studies; D002658:Developmental Disabilities / Q000209:etiology*; D004032:Diet; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D005865:Gestational Age; D006330:Heart Defects, Congenital / Q000209:etiology*; D006801:Humans; D007231:Infant, Newborn; D007360:Intelligence / Q000502:physiology; D008499:Medical Records; D008831:Microcephaly / Q000209:etiology*; D009154:Mutation / Q000235:genetics; D010649:Phenylalanine / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D010661:Phenylketonurias / Q000150:complications* / Q000235:genetics / Q000517:prevention & control; D016742:Preconception Care; D011247:Pregnancy; D011248:Pregnancy Complications / Q000517:prevention & control; D011597:Psychomotor Performance / Q000502:physiology; D012307:Risk Factors; D016216:Ultrasonography, Prenatal
chemical_list: D010649:Phenylalanine