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A major route of tryptophan metabolism is via the hepatic and cerebral synthesis of kynurenine, a substance subsequently used by astrocytes in the brain for the production of the neuroactive substances kynurenic acid and quinolinic acid. Both kynurenic and quinolinic acids have been implicated in modulating the activity of excitatory amino acid pathways in the brain, the former as a neuroprotectant because of its antagonist properties, and the latter as an excitotoxin because of its agonist actions, at NMDA receptors. We therefore determined the concentrations of tryptophan and kynurenine in maternal venous and umbilical cord blood, and in amniotic fluid, of infants after labor and vaginal delivery, and after delivery by cesarean section. Concentrations of tryptophan and kynurenine were significantly higher in umbilical vein plasma compared with maternal venous plasma. Tryptophan and kynurenine concentrations in umbilical vein plasma and amniotic fluid were significantly higher after labor, compared with samples obtained from infants of the same gestational age delivered by cesarean section. There was no umbilical vein-to-artery concentration difference for kynurenine in samples obtained after either labor or cesarean section, but there was a significant gradient for tryptophan in samples obtained after vaginal delivery, indicating increased transfer of this amino acid during labor. There was a significant correlation between umbilical vein tryptophan and kynurenine concentrations for both the labor and cesarean section groups, and plasma kynurenine concentrations were also significantly correlated with both umbilical vein cortisol concentrations and the duration of the second stage of labor in the vaginally delivered infants. These results suggest that the placental transfer of tryptophan and the fetal synthesis of kynurenine are increased during labor. These findings have implications for understanding the vulnerability of the infant brain to ischemic/hypoxic damage in the perinatal period. By analogy with the adult brain, the molar ratio of these substances is likely to determine the susceptibility of the brain to seizure and excitotoxic damage.

Maternal, Umbilical, and Amniotic Fluid Concentrations of Tryptophan and Kynurenine after Labor or Cesarean Section