Maternal hyperphenylalaninaemia in the normal and phenylketonuric mother and its influence on maternal plasma and fetal fluid amino acid concentrations.

Abstract

SummaryAn oral load of L‐phenylalanine (150 mg. per kg. body weight) was given to five women three hours before delivery by hysterotomy of their 16–18 week conceptuses. A sixth woman was delivered of a 16‐week conceptus after two hours continuous intravenous infusion of L‐phenylalanine (75 mg. per kg. body weight per hour).Concentrations of free amino acids were measured in maternal venous plasma, umbilical arterial plasma, fetal urine, amniotic fluid and cerebrospinal fluid. Free amino acid concentrations were also measured in maternal and umbilical vein plasma and amniotic fluid of a treated phenylketonuric mother delivered spontaneously at 36 weeks gestation of a non‐phenylketonuric infant.Increased concentrations of phenylalanine were measured in all maternal plasma samples obtained one, two and three hours after ingestion of L‐phenylalanine and during intravenous infusion. There were correspondingly high concentrations of phenylalanine in fetal plasma, fetal urine, amniotic fluid and fetal cerebrospinal fluid at delivery.Tyrosine concentrations were also increased in maternal and fetal plasma, fetal urine, amniotic fluid and fetal cerebrospinal fluid of mothers given phenylalanine. Although maternal plasma, fetal plasma and amniotic fluid from the phenylketonuric mother contained increased concentrations of phenylalanine, there was no increase in the tyrosine concentrations in these fluids.The mean umbilical artery plasma‐maternal vein plasma ratios for phenylalanine was 2·35 in normal 15‐ to 20‐week pregnancies, 2·26 three hours after oral L‐phenylalanine, 1·29 after intravenous infusion of L‐phenylalanine and 1·45 in the phenylketonuric pregnancy. Corresponding ratios for tyrosine were 2·52, 2·30, 2·15 and 2·90. In the acute tolerance studies the mean fetal plasma phenylalanine‐tyrosine ratio was 2·47 and in the phenylketonuric fetus 8·16.There were reductions in maternal plasma concentrations of most amino acids three hours after the oral phenylalanine and these reductions were significant for methionine, lysine, histidine and arginine. These changes were not reflected in the amniotic fluid but there were significant reductions in fetal plasma threonine and arginine and in fetal urine threonine and taurine. Methionine concentrations were increased in the maternal plasma, fetal plasma and amniotic fluid of the treated phenylketonuric mother.The human placenta does not “protect” the fetus from increased maternal plasma concentrations of phenylalanine in the normal or phenylketonuric mother.