1043-3155 Pediatr Neurol Briefs pedneurbriefs Pediatr Neurol Briefs Pediatric Neurology Briefs Pediatr Neurol Briefs 2166-6482 1043-3155 2166-3155 Pediatric Neurology Briefs Publishers Chicago, IL, USA PNB-1-42 10.15844/pedneurbriefs-1-6-5 CNS Developmental Disorders Neurology Pediatrics Nervous System Diseases Child Development Brain Diseases Neurosurgery Child Infant Congenital Malformation and Maternal Phenylketonuria http://orcid.org/0000-0002-0173-7931 Millichap J. Gordon MD 1 2 * Division of Neurology, Children's Memorial Hospital, Chicago, IL Departments of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL Correspondence: Dr. J. Gordon Millichap, E-mail: jgmillichap@northwestern.edu 11 1987 01 08 2016 1 6 42 43 Copyright: © 1987 The Author(s) 1987 This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Timing of strict diet in relation to fetal damage in maternal phenylketonuria. An international collaborative study by the MRC/DHSS Phenylketonuria Register

Infants born to women with PKU are frequently mentally retarded, microcephalic, of low birthweight, and have various malformations.

 Phenylalanine Diet Maternal Phenylalanine Substantial Number

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.

 Drogari E Smith I Beasley M Lloyd JK Timing of strict diet in relation to fetal damage in maternal phenylketonuria. An international collaborative study by the MRC/DHSS Phenylketonuria Register Lancet 1987 Oct 24 2 8565 927 30 2889860 10.1016/S0140-6736(87)91418-8 Levy HL Waisbren SE Effects of untreated maternal phenylketonuria and hyperphenylalaninemia on the fetus N Engl J Med 1983 Nov 24 309 21 1269 74 6633585 10.1056/NEJM198311243092101