Pregnancy experiences in the woman with mild hyperphenylalaninemia

Pediatrics. 2003 Dec;112(6 Pt 2):1548-52.


Objective: A major issue in maternal phenylketonuria (MPKU) has been whether maternal non-PKU mild hyperphenylalaninemia (MHP) is teratogenic. Such untreated pregnancies and their outcomes are presented on this report.

Methods: Enrolled pregnancies in which the untreated prepregnancy assigned phenylalanine level (APL) was no more than 600 micro mol/L were included in the Maternal PKU Collaborative Study and were followed according to protocol.

Results: Forty-eight enrolled women with non-PKU MHP had mean APL 408 +/- 114 micromol/L. They had a total of 58 pregnancies that resulted in live births. Fifty were untreated. Maternal phenylalanine (Phe) levels in the untreated pregnancies decreased during pregnancy for average Phe exposure of 270 +/- 84 micromol/L, virtually identical to the level of 269 +/- 136 micromol/L in the 8 treated pregnancies. Birth measurements in the 50 offspring from untreated pregnancies were within normal limits with z scores of -0.25 for weight, 0.28 for length, and -0.63 for head circumference, although birth head circumference was negatively correlated with maternal APL (r = -0.30). Only 1 offspring had congenital heart disease. Offspring IQ was 102 +/- 15 compared with 96 +/- 14 in the mothers with untreated pregnancies and with 109 +/- 21 in control offspring.

Conclusion: Maternal non-PKU MHP no more than 600 micromol/L does not require dietary therapy. The naturally lower Phe level during pregnancy seems to protect against teratogenesis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Birth Weight
  • Body Height
  • Case-Control Studies
  • Female
  • Head / anatomy & histology*
  • Humans
  • Infant
  • Infant, Newborn
  • Intelligence Tests
  • Intelligence*
  • Mutation
  • Phenylalanine / blood*
  • Phenylketonuria, Maternal / diet therapy
  • Phenylketonurias* / diet therapy
  • Phenylketonurias* / genetics
  • Pregnancy
  • Pregnancy Complications* / diet therapy
  • Reference Values


  • Phenylalanine