Tryptophan-Kynurenine Pathway Metabolites in Women Undergoing Caesarean Delivery

The tryptophan catabolic pathway may play an important role in maternal-fetal immune tolerance, placental function, and metabolic programming, yet its clinical correlates in uncomplicated term pregnancies are not well defined. This study examined how maternal and umbilical artery blood tryptophan metabolites relate to maternal characteristics in women undergoing cesarean section.

In this cross-sectional study, 73 women delivering by cesarean section at a mean gestational age of 38.9 ± 0.96 weeks were enrolled. Maternal venous and umbilical cord arterial blood were collected at delivery, and serum tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN) were measured using ELISA. Maternal anthropometry, pregnancy complications, antibiotic treatment, and indications for cesarean section were obtained from medical records. Group comparisons used Mann-Whitney U tests, associations were assessed with Spearman's rank correlations, and selected outcomes were analyzed in multivariable linear regression models.

Umbilical concentrations of TRP, KYN, KYNA, and QUIN were higher than the corresponding maternal levels. Maternal TRP was inversely associated with gestational age at delivery and was independently higher in women treated with antibiotics during pregnancy. Cord KYNA correlated positively with pre-pregnancy and pre-delivery BMI, with a stronger association for postpartum BMI, and remained independently associated with pre-delivery BMI in multivariable analysis. Maternal QUIN was higher in women undergoing intrapartum or emergency cesarean section and in those delivered by cesarean section for breech presentation, and both indications were independently associated with higher QUIN in the regression model. No robust associations were observed between TRP, KYN, KYNA, or QUIN and most pregnancy complications, neonatal birth weight, or Apgar scores.

Maternal and fetal tryptophan-kynurenine metabolites show distinct, domain-specific relationships with gestational timing, maternal antibiotic exposure during pregnancy, adiposity, and indications or mode of cesarean delivery in term pregnancies. Maternal TRP levels may primarily reflect gestational age and concurrent inflammatory status. Cord blood KYNA may mirror maternal metabolic condition, whereas maternal QUIN appears to be more closely associated with complex obstetric phenotypes than with neonatal status. These exploratory, uncorrected findings suggest that kynurenine pathway metabolites may be associated with selected maternal anthropometric and obstetric factors; none of these associations survived correction for multiple comparisons, and they are strictly hypothesis-generating, requiring confirmation in larger, prospectively designed studies before any biomarker application can be considered. The parallel elevation of the cord KYN/TRP and KYNA/KYN ratios, together with a relative reduction in the QUIN/KYN ratio in the fetal compartment, suggests a metabolic profile characterized by preferential conversion of kynurenine toward the KYNA branch rather than the QUIN branch. This pattern may be consistent with a more neuroprotective metabolic environment in the fetal circulation; however, mechanistic studies are required to confirm this interpretation. The maternal QUIN should be regarded as a marker of obstetric complexity rather than a direct consequence of delivery mode. The study included only women undergoing cesarean delivery; therefore, the findings cannot be generalized to vaginal deliveries.