Infants born to women with PKU are frequently mentally retarded, microcephalic, of low birthweight, and have various malformations. The results of an international collaborative study (in UK, Europe, Australia) by the MRC/DHSS Phenylketonuria Register concerning the diet of pregnant women with PKU are reported from the Institute of Child Health, London: (1) Normal birth weights and head circumferences and no malformations in 17 infants whose mothers received a strict low phenylalanine diet at conception; (2) below average birthweights and head circumferences and excess malformations a) in 29 infants whose mothers were on a relaxed or normal diet at conception and a strict diet during pregnancy, and b) in 18 infants whose mothers received no dietary treatment during pregnancy. Birth weights and head circumferences of the 64 infants were inversely related to the maternal phenylalanine concentrations at conception, and hyperphenylalaninemia in early gestation had a dose-dependent effect on the fetus. The authors estimate 2000 women with PKU of fertile age by 1990 in the UK and unless monitored closely through their reproductive lives, a substantial number of microcephalic and mentally retarded children will be expected. [1]

COMMENT. A National Collaborative Study of Maternal PKU was initiated in the US in 1984 and initial findings will be evaluated in 1991. Female PKU patients of fertile age receive education concerning risks to offspring and need for dietary and blood phenylalanine monitoring during pregnancies (O’Flynn M, Director PKU Clinic, Children’s Memorial Hospital, Chicago, personal communication).

Levy HL and Waisbren SE [2] studied the effects of maternal PKU and hyperphenylalaninemia on 53 offspring from untreated pregnancies. Decreases in IQ, head circumference, and birth weight of the infants were correlated directly with the maternal IQ and inversely with maternal blood phenylalanine level. These authors concluded that maternal PKU has a substantial adverse effect on the fetus, and less severe maternal PKU may have subtle effects, resulting in slight reduction in IQ and intrauterine head growth. The UK report demonstrates that mothers with PKU who start a low phenylalanine diet before conception can give birth to normal infants despite variable phenylalanine blood levels during pregnancy. Congenital malformations and irreversible impairment of brain and body growth are determined within the first trimester of pregnancy.