Background: The effects of maternal phenylalanine on the fetus include facial dysmorphism, microcephaly, intrauterine growth retardation, developmental delay, and congenital heart disease. Aims: To evaluate the impact of phenylalanine restricted diet in pregnant women with phenylketonuria (PKU) on their offspring. Methods: Data on virtually all pregnancies of women with PKU in the United Kingdom between 1978 and 1997 were reported to the United Kingdom PKU Registry. The effect of the use and timing in relation to pregnancy of a phenylalanine restricted diet on birth weight, birth head circumference, the presence or absence of congenital heart disease (CHD), 4 year developmental quotient, and 8 year intelligence quotient were examined. Results: A total of 228 pregnancies resulted in live births (seven twin pregnancies were excluded). In 110 (50%), diet started before conception. For this group mean (SD) birth weight was 3160 (612) g, birth head circumference 33.6 (1.9) cm, 4 year DQ 108.9 (13.2), 8 year IQ 103.4 (15.6), and incidence of CHD was 2.4%. In comparison, for those born where treatment was started during pregnancy (n=91), birth weight was 2818 (711) g, birth head circumference 32.7 (2.0) cm, 4 year DQ 96.8 (15.0), 8 year IQ 86.5 (13.0), and incidence of CHD was 17%. Month-by- month regression analyses suggested that metabolic control by 12-16 weeks gestation had most influence on outcome. Conclusions: Many features of the maternal PKU syndrome are preventable by starting a phenylalanine restricted diet. Women with PKU and their carers must be aware of the risks and should start the diet before conception, or as soon after as possible. Background: The effects of maternal phenylalanine on the fetus include facial dysmorphism, microcephaly, intrauterine growth retardation, developmental delay, and congenital heart disease. Aims: To evaluate the impact of phenylalanine restricted diet in pregnant women with phenylketonuria (PKU) on their offspring. Methods: Data on virtually all pregnancies of women with PKU in the United Kingdom between 1978 and 1997 were reported to the United Kingdom PKU Registry. The effect of the use and timing in relation to pregnancy of a phenylalanine restricted diet on birth weight, birth head circumference: the presence or absence of congenital heart disease (CHD), 4 year developmental quotient, and 8 year intelligence quotient were examined. Results: A total of 228 pregnancies resulted in live births (seven twin pregnancies were excluded). In 110 (50 For this group mean (SD) birth weight was 3160 (612) g, birth head circumference 33.6 (1.9) cm, 4 year DQ 108 9 years old (13.2), 8 year IQ 103.4 (15.6), and incidence of CHD was 2.4%. Intended for those born where treatment was started during pregnancy (n = 91), birth weight was 2818 (711) g, birth months-by-month regression analyzes suggested that metabolic control by 12-16 weeks gestation had (8) most influences on outcome. Conclusions: Many features of the maternal PKU syndrome are preventable by starting a phenylalanine restricted diet. Women with PKU and their carers be be aware of the risks and should start the diet before conception, or as soon after as possible.