BACKGROUND: Developmental delay in the offspring of women with phenylketonuria (PKU) can be prevented by maintaining maternal blood phenylalanine (Phe) within a target range (100-250 micromol/L). OBJECTIVE: We aimed to analyze outcomes in the offspring of women with PKU during pregnancy and to identify prognostic factors. DESIGN: Occipitofrontal circumference at birth (OFC-B); developmental scores [developmental quotient (DQ) and intelligence quotient (IQ)]at 1, 4, 8, and 14 y; and the time of starting a Phe-restricted diet (before or after conception) were collected. The influence of maternal Phe concentrations during pregnancy on offspring outcomes also was assessed. RESULTS: The study included 105 children born to 67 mothers with PKU. Mean (+/-SD) OFC-B z scores did not differ between the preconception and postconception diet groups (0.42 +/- 1.24 and -0.96 +/- 1.19, respectively). DQ at 1 y and IQ at 8 y were higher in offspring from the preconception diet group than in offspring from the postconception diet group [DQ: 107 +/- 13.8 and 99.3 +/- 13.3, respectively (P = 0.014); IQ: 110.6 +/- 14.8 and 91.2 +/- 23.9, respectively (P = 0.005)]. Maternal Phe concentrations correlated negatively with DQ and IQ scores, and variations (SD) in all maternal blood Phe correlated negatively with 4-, 8-, and 14-y IQ scores (r = -0.385, -0.433, and -0.712; P = 0.002, 0.008, and 0.031, respectively), even when concentrations were consistently within the target range. CONCLUSIONS: The study suggests that women with PKU should start a Phe-restricted diet before conception. Maintenance of maternal blood Phe within the target range predicts good offspring outcomes, but variations even within that range should be avoided.
BACKGROUND: Developmental delay in the offspring of women with phenylketonuria (PKU) can be prevented by maintaining maternal blood phenylalanine (Phe) within a target range (100-250 micromol/L). OBJECTIVE: We aimed to analyze outcomes in the offspring of women with PKU during pregnancy and to identify prognostic factors. DESIGN: Occipitofrontal circumference at birth (OFC-B); developmental scores [developmental quotient (DQ) and intelligence quotient (IQ)]at 1, 4, 8, and 14 y; and the time of starting a Phe-restricted diet (before or after conception) were collected. The influence of maternal Phe concentrations during pregnancy on offspring outcomes also was assessed. RESULTS: The study included 105 children born to 67 mothers with PKU. Mean (+/-SD) OFC-B z scores did not differ between the preconception and postconception diet groups (0.42 +/- 1.24 and -0.96 +/- 1.19, respectively). DQ at 1 y and IQ at 8 y were higher in offspring from the preconception diet group than in offspring from the postconception diet group [DQ: 107 +/- 13.8 and 99.3 +/- 13.3, respectively (P = 0.014); IQ: 110.6 +/- 14.8 and 91.2 +/- 23.9, respectively (P = 0.005)]. Maternal Phe concentrations correlated negatively with DQ and IQ scores, and variations (SD) in all maternal blood Phe correlated negatively with 4-, 8-, and 14-y IQ scores (r = -0.385, -0.433, and -0.712; P = 0.002, 0.008, and 0.031, respectively), even when concentrations were consistently within the target range. CONCLUSIONS: The study suggests that women with PKU should start a Phe-restricted diet before conception. Maintenance of maternal blood Phe within the target range predicts good offspring outcomes, but variations even within that range should be avoided.
Authors: Charlotte Dawson; Elaine Murphy; Charlé Maritz; Heidi Chan; Charlotte Ellerton; R H S Carpenter; Robin H Lachmann Journal: J Inherit Metab Dis Date: 2011-02-03 Impact factor: 4.982
Authors: A M J van Wegberg; A MacDonald; K Ahring; A Bélanger-Quintana; N Blau; A M Bosch; A Burlina; J Campistol; F Feillet; M Giżewska; S C Huijbregts; S Kearney; V Leuzzi; F Maillot; A C Muntau; M van Rijn; F Trefz; J H Walter; F J van Spronsen Journal: Orphanet J Rare Dis Date: 2017-10-12 Impact factor: 4.123
Authors: William L Zeile; Helen C McCune; Donald G Musson; Brian O'Donnell; Charles A O'Neill; Laurie S Tsuruda; Roberto T Zori; Philip J Laipis Journal: Pediatr Res Date: 2018-01-31 Impact factor: 3.756