POSTNATAL CLEARANCE OF MATERNALLY DERIVED PHENYLALANINE IN OFFSPRING OF MATERNAL PHENYLKETONURIA - IMPLICATIONS FOR NEWBORN SCREENING

Introduction: In maternal phenylketonuria (PKU), phenylalanine transverses the placenta, producing hyperphenylalaninemia in the fetus. This hyperphenylalaninemia is present in the offspring at birth and could produce false positive newborn PKU screening results unless rapidly cleared. Consequently, we determined the duration of postnatal hyperphenylalaninemia among offspring of maternal PKU/mild hyperphenylalaninemia. Methods: Capillary blood specimens were collected from offspring of maternal PKU/hyperphenylalaninemia pregnancies within the first 24 h of life. These specimens were analyzed by Guthrie bacterial assay for phenylalanine, Umbilical cord blood specimens were collected and analyzed for amino acids by the amino acid analyzer. Results: The mean blood phenylalanine levels in 51 unaffected offspring decreased from 8.2 +/- 6.1 mg/dl (497 +/- 370 mu mol/l) at age 4 h to 1.8 +/- 0.5 mg/dl (110 +/- 30 mu mol/l) at age 24 h. At 12 h of age, however, the phenylalanine level was still > 2 mg/dl (120 mu mol/l) in 59% and > 4 mg/dl (240 mu mol/l) in 37% of these infants. Based on umbilical cord blood valves, 74 +/- 22% of transferred phenylalanine remained in the offspring at 4 h of age, but the range was 32-100%, indicating wide variation in the initial clearance abilities of these infants, Two infants with mild hyperphenylalaninemia had persisting high blood phenylalanine at 24 h of age. Discussion: Most infants from maternal PKU pregnancies clear the maternally derived phenylalanine by 24 h of age. Thus, there is only a very short exposure to hyperphenylalaninemia postnatally in the infants from maternal PKU/mild hyperphenylalaninemia pregnancies. In addition, they are not likely to be designated as false positive in newborn screening, although they may be so designated in specimens collected before 24 h of age.