Objectives: The Maternal Phenylketonuria Study was designed to determine the effect of a phenylalanine (Phe)-restricted diet in reducing the morbidity on the fetus. Congenital abnormalities were noted, with the focus on the effect of congenital heart defects (CHDs) and microcephaly (MICRO) on developmental outcome at 4 and 6 years of age.
Study design: Women with blood Phe levels >240 micromol/L (n=526; to convert micromol/L to mg/dL, divide by 60) were enrolled; 382 contributed 572 pregnancies. The women had 413 offspring examined at birth and annually. At 4 years, the McCarthy General Cognitive Index was administered, and at 6 years, the Wechsler Intelligence Scale for Children Revised was administered.
Results: Microcephaly was noted in 137 (33%) of the offspring, and 32 (7.7%) had CHD. Maternal blood Phe levels were higher for infants with CHD and MICRO than for infants with CHD only (P=.02). Mean Phe levels at 4 to 8 weeks gestation predicted CHD (P<.0001). The McCarthy General Cognitive Index score was lower with CHD (P=.005) and MICRO (P=.0017), as was the Wechsler Intelligence Scale for Children Revised full-scale IQ score (P=.0002 for CHD and P=.0001 for MICRO). None of the subjects who had offspring with CHD had Phe control between 120 and 360 micromol/L during the first 8 to 10 weeks of gestation.
Conclusions: Women with phenylketonuria need to be educated regarding diet for life. This should help improve diet control before conception and throughout pregnancy.