Effects Of Maternal Hyperphenylalaninemia Research Articles

Biochemical Studies on the Effect of Maternal Hyperphenyl‐alaninemia on Fetal Brain Maturation of Mice

Abstract The effects of maternal hyperphenylalaninemia during pregnancy on the biochemical maturation of neonatal mice brains were examined, thus establishing the critical concentration of phenylalanine in maternal blood and the critical period of maternal hyperphenylalaninemia during pregnancy. Hyperphenylalaninemia was induced by giving chow supplemented with 3%, 4%, 5%, or 6% phenylalanine (Phe.) and 0.12% p‐chlorophenylalanine (PCPA) for at least one month and then throughout pregnancy. Some of the pregnant mice fed the 6% Phe. diet before pregnancy received a normal diet after conception (6%: A).Offspring from each group were decapitated two days after birth. Their brains were removed and then divided into the cerebrum and the brain stem including the cerebellum. Total protein, RNA and DNA were measured biochemically. All kinds of markers of the newborn mice born to the 5% and 6% mothers, the weight and the contents of the protein, RNA and DNA, were reduced significantly in both the cerebrum and brain stem. In the 4% group, however, only the brain stem was affected. The 3% group showed reductions neither in the weight nor the protein and nucleic acids contents in both the cerebrum and brain stem. In the 6%:A group, in which the diet was returned to normal just after conception, total protein, RNA and DNA were reduced in the brain stem, but not in the cerebrum.These results suggest that the critical concentration of maternal blood phenylalanine during pregnancy in the mouse is 11mg/dl, which is that corresponding to the 3% group, and also suggest that it is too late to begin the low phenylalanine diet after conception.

The effects of maternal hyperphenylalaninemia on learning in mature rats

Pregnant rats were given a diet supplemented with 0.5% α-methylphenylalanine and 3% phenylalanine from the 12th day of gestation to term. Compared to unsupplemented controls, material serum phenylalanine was elevated 8–10-fold. Experimental litters did not differ from controls in number of offspring, birth weight, or subsequent growth on an unsupplemented diet. At 8 weeks of age, animals were tested for latent learning on a 4-arm maze, and at 10 weeks, they were tested for observational learning with littermates in a food preference paradigm. In both tests, experimental animals did learn, but significantly less than controls. The data suggest that material hyperphenylalaninemia, induced as a model for the inborn error, phenylketonuria, can lead to learning deficits later in the lives of offspring.

The Safety of Aspartame

To the Editor.— In Letter to the Editor, Dr Pardridge 1 interpreted our data 2 on effects of maternal hyperphenylalaninemia on offspring IQ as indicating a 10.5-point drop in the IQ of babies born of mothers with 250-μmol/L increments in the blood phenylalanine This is an inaccurate interpretation of the data, as we have previously pointed out. 3 By categorizing the information in Fig 1 of our report according to the maternal plasma phenylalanine levels represented in our sample, we obtained the following mean IQ scores for offspring: This does not represent 10.5-point drop in IQ of offspring for each 250-μmol/L increment in the maternal plasma phenylalanine level. In fact, the mean IQ of 119 for offspring at maternal plasma phenylalanine levels of 200 to 300 μmol/L—which are higher than the plasma phenylalanine levels that normal individuals or those who carry the gene for phenylketonuria have even