Pregnancy Experiences in the Woman with Mild Hyperphenylalaninemia

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 μmol/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 μmol/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 μmol/L, virtually identical to the level of 269 ± 136 μmol/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 μmol/L does not require dietary therapy. The naturally lower Phe level during pregnancy seems to protect against teratogenesis.