Maternal phenylketonuria syndrome: Congenital heart defects, microcephaly,and developmental outcomes

Objective: A cohort of women with phenylketonuria (PKU) were selected to ex plore the impact of phenylalanine (Phe) levels and other factors on congeni tal heart defects (CHDs), microcephaly, and development of their offspring. Study design: Three hundred fifty-four women with PKU were followed up week ly with diet records, blood Phe levels, and sonograms obtained at 18 to 20 and 32 weeks' gestation. At birth, 413 offspring Lr ere examined and follow ed up at 6 months and annually by means of Bayley Mental Developmental Inde x and Psychomotor Developmental Index tests at 1 and 2 years. The women had Wechsler Adult Intelligence Scales and DNA testing. Results: Thirty-one offspring had CHDs; of these, 17 also had microcephaly Mean Phe levels at 4 to 8 weeks' gestation predicted CHDs (P < .0001), An i nfant with a CHD had a 3-fold risk of having microcephaly when the mother h ad higher Phe levels (P = .02). The Bayley Mental Developmental Index and P sychomotor Developmental Index scores correlated with both CHDs (P = .037 a nd .0015, respectively) and microcephaly (P = .0001 for both). No direct re lationship to the PKU mutation was found. Conclusion: None of the women whose offspring had CHDs had blood Phe levels in control during the brat 8 weeks of gestation. Women with PKU need to be well controlled on a low-phenylalanine diet before conception and througho ut pregnancy. (J Pediatr 2000;136:57-61).