{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:03:31Z","timestamp":1784178211421,"version":"3.55.0"},"reference-count":28,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: The tryptophan catabolic pathway may play an important role in maternal\u2013fetal 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. Methods: In this cross-sectional study, 73 women delivering by cesarean section at a mean gestational age of 38.9 \u00b1 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\u2013Whitney U tests, associations were assessed with Spearman\u2019s rank correlations, and selected outcomes were analyzed in multivariable linear regression models. Results: 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. Conclusions: Maternal and fetal tryptophan\u2013kynurenine 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.<\/jats:p>","DOI":"10.3390\/life16071166","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T01:05:58Z","timestamp":1784077558000},"page":"1166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tryptophan\u2013Kynurenine Pathway Metabolites in Women Undergoing Caesarean Delivery"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7729-0670","authenticated-orcid":false,"given":"Maciej","family":"Zi\u0119tek","sequence":"first","affiliation":[{"name":"Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University, 71-460 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arkadiusz","family":"Bieleninik","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Nowy Szpital in \u015awiebodzin, 66-200 \u015awiebodzin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9808-0624","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Szczuko","sequence":"additional","affiliation":[{"name":"Department of Bromatology and Nutritional Diagnostics, Pomeranian Medical University, 71-460 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6401-627X","authenticated-orcid":false,"given":"Edyta","family":"Zagrodnik","sequence":"additional","affiliation":[{"name":"Clinical Department of Anesthesiology and Intensive Care of Adults and Children, Pomeranian Medical University, 71-460 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9415-2758","authenticated-orcid":false,"given":"Krzysztof","family":"Safranow","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 71-460 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"U\u0142an","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Pomeranian Medical University, 70-204 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogus\u0142aw","family":"Czerny","sequence":"additional","affiliation":[{"name":"Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University, 71-460 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela","family":"Uzar","sequence":"additional","affiliation":[{"name":"Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University, 71-460 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Poeggeler, B., Singh, S.K., and Pappolla, M.A. (2022). Tryptophan in Nutrition and Health. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105455"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/j.1469-7793.2001.0405i.x","article-title":"Characterisation of L-tryptophan transporters in human placenta: A comparison of brush border and basal membrane vesicles","volume":"531","author":"Kudo","year":"2001","journal-title":"J. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.cmet.2023.06.004","article-title":"Tryptophan Metabolism in Health and Disease","volume":"35","author":"Xue","year":"2023","journal-title":"Cell Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1038\/s12276-023-01028-7","article-title":"Immune Regulation through Tryptophan Metabolism","volume":"55","author":"Seo","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1093\/humupd\/dmag001","article-title":"The Placental Tryptophan Pathway across Gestation: Implications for Pregnancy Outcomes","volume":"32","author":"Karahoda","year":"2026","journal-title":"Hum. Reprod. Update"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"103361","DOI":"10.1016\/j.jri.2021.103361","article-title":"Tryptophan Metabolism and Immune Regulation in the Human Placenta","volume":"147","author":"Silvano","year":"2021","journal-title":"J. Reprod. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s12958-025-01436-6","article-title":"Pregnancy Complications Affect Kynurenine Pathway Metabolite Concentrations in Umbilical Cord Blood","volume":"23","author":"Broekhuizen","year":"2025","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1093\/hmg\/ddab169","article-title":"Prenatal Inflammation as a Link between Placental Expression Signature of Tryptophan Metabolism and Preterm Birth","volume":"30","author":"Karahoda","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1093\/nutrit\/nuaf127","article-title":"Tryptophan Metabolism in Developmental Origins of Health and Disease","volume":"84","author":"Barros","year":"2026","journal-title":"Nutr. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11786469221135545","DOI":"10.1177\/11786469221135545","article-title":"The Role of the Kynurenine Pathway in the (Patho)physiology of Maternal Pregnancy and Fetal Outcomes: A Systematic Review","volume":"15","author":"Broekhuizen","year":"2022","journal-title":"Int. J. Tryptophan Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Li, Y., Pan, K., McRitchie, S.L., Harville, E.W., and Sumner, S.C.J. (2023). Untargeted Metabolomics on First Trimester Serum Implicates Metabolic Perturbations Associated with BMI in Development of Hypertensive Disorders: A Discovery Study. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1144131"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"150922","DOI":"10.1016\/j.bbrc.2024.150922","article-title":"Maternal Immune Activation Induces Neurodevelopmental Impairments of Adult Offspring through Alterations in Tryptophan\u2013Kynurenine Pathway in the Placenta","volume":"737","author":"Hasegawa","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e2464","DOI":"10.1210\/clinem\/dgac078","article-title":"The Kynurenine Pathway Metabolites in Cord Blood Positively Correlate with Early Childhood Adiposity","volume":"107","author":"Tan","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Prescott, S., Billeci, N., Gotcher, M., Patel, S., Almon, A., Morgan, H., Abukhalaf, D., and Groer, M. (2025). Tryptophan as a Biomarker of Pregnancy-Related Immune Expression and Modulation: An Integrative Review. Front. Reprod. Health, 6.","DOI":"10.3389\/frph.2024.1453714"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1203\/00006450-199809000-00017","article-title":"Maternal, Umbilical, and Amniotic Fluid Concentrations of Tryptophan and Kynurenine after Labor or Cesarean Section","volume":"44","author":"Kazda","year":"1998","journal-title":"Pediatr. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2044723","DOI":"10.1080\/19490976.2022.2044723","article-title":"Bifidobacterium longum Mediated Tryptophan Metabolism to Improve Atopic Dermatitis via the Gut\u2013Skin Axis","volume":"14","author":"Fang","year":"2022","journal-title":"Gut Microbes"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2541031","DOI":"10.1080\/19490976.2025.2541031","article-title":"Longitudinal Analysis of Fecal Tryptophan Metabolites and Microbiome Composition in Very Preterm Infants: Impact of Birth Mode and Feeding Type","volume":"17","author":"Wieser","year":"2025","journal-title":"Gut Microbes"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Karahoda, R., Abad, C., Horackova, H., Kastner, P., Zaugg, J., Cerveny, L., Kucera, R., Albrecht, C., and Staud, F. (2020). Dynamics of Tryptophan Metabolic Pathways in Human Placenta and Placental-Derived Cells: Effect of Gestation Age and Trophoblast Differentiation. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.574034"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e00261","DOI":"10.1042\/BSR20150197","article-title":"Tryptophan Metabolism, Disposition and Utilization in Pregnancy","volume":"35","author":"Badawy","year":"2015","journal-title":"Biosci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Broekhuizen, M., Danser, A.H.J., Reiss, I.K.M., and Merkus, D. (2021). The Function of the Kynurenine Pathway in the Placenta: A Novel Pharmacotherapeutic Target?. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph182111545"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e01566","DOI":"10.1002\/brb3.1566","article-title":"The Role of Kynurenine Pathway and Kynurenic Aminotransferase Alleles in Postpartum Depression following Cesarean Section in Chinese Women","volume":"10","author":"Quan","year":"2020","journal-title":"Brain Behav."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41366-024-01647-8","article-title":"Epigenetic Programming of Obesity in Early Life through Modulation of the Kynurenine Pathway","volume":"49","author":"Gharipour","year":"2025","journal-title":"Int. J. Obes."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1007\/978-3-031-63657-8_21","article-title":"Tryptophan Metabolism in Obesity: The Indoleamine 2,3-Dioxygenase-1 Activity and Therapeutic Options","volume":"1460","author":"Engin","year":"2024","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1093\/humrep\/deae046","article-title":"First Trimester Maternal Tryptophan Metabolism and Embryonic and Fetal Growth: The Rotterdam Periconceptional Cohort (Predict Study)","volume":"39","author":"Willemsen","year":"2024","journal-title":"Hum. Reprod."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Jasim, Z.A., Al-Hakeim, H.K., Zolghadri, S., and Stanek, A. (2023). Maternal Tryptophan Catabolites and Insulin Resistance Parameters in Preeclampsia. Biomolecules, 13.","DOI":"10.3390\/biom13101447"},{"key":"ref_26","first-page":"101","article-title":"Tryptophan and its metabolite concentrations in human plasma and breast milk during the perinatal period","volume":"45","author":"Kamimura","year":"1991","journal-title":"Acta Med. Okayama"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/0378-4347(92)80208-8","article-title":"Difference in the concentration of tryptophan metabolites between maternal and umbilical foetal blood","volume":"576","author":"Morita","year":"1992","journal-title":"J. Chromatogr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.placenta.2017.02.013","article-title":"Altered placental tryptophan metabolic pathway in human fetal growth restriction","volume":"52","author":"Murthi","year":"2017","journal-title":"Placenta"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/7\/1166\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:17:49Z","timestamp":1784175469000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/7\/1166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,14]]},"references-count":28,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["life16071166"],"URL":"https:\/\/doi.org\/10.3390\/life16071166","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,14]]}}}