Serum levels of kynurenine in pregnancies with fetal growth restriction and oligohydramnios

Abstract

Objectives Kynurinine (KYN) and its metabolites, which are released during the metabolism of tryptophan, an essential amino acid, have many important functions, such as cellular energy production, regulation of vascular tone, and regulation of the immune system. In this study, we aimed to detect serum KYN levels, which may be an indicator of KYN pathway activity, in idiopathic fetal growth restriction (FGR) and oligohydramnios cases whose pathophysiology is known to be affected by multiple factors, such as placental hypoperfusion, immune dysregulation, and maternal nutrition disorder, and to investigate their relationship with these common obstetric complications. Methods This cross-sectional case-control study was carried out in the antenatal outpatient clinics of Ankara City Hospital between July and December 2021. While the study group consisted of pregnant women with idiopathic isolated FGR and oligohydramnios, the control group consisted of low-risk patients who did not have any problems. The clinical features of the patients, such as age, body mass indexes, and gestational week, were recorded by measuring basic laboratory parameters and serum KYN levels. Results A total of 110 patients were included in this study. The patients were divided into three groups: FGR, oligohydramnios, and the control group. There was no significant difference between the patients’ ages, weeks of gestation, or body mass indexes. Serum KYN level was calculated as 57.8 ± 13.4 pg/mL in IUGR, 75.3 ± 10.8 pg/mL in oligohydramnios and 95.1 ± 13.3 pg/mL in the control group (p<0.001). Conclusions Serum KYN levels were lower in pregnant women complicated with FGR and oligohydramnios more prominently in pregnant women diagnosed with FGR than in normal pregnancies. The results suggest that KYN plays an important role in either the etiopathogenesis or the response to these two obstetric pathologies.

First trimester maternal tryptophan metabolism and embryonic and fetal growth: the Rotterdam Periconceptional Cohort (Predict Study)

“…In line with our findings, a recent study reported lower maternal KYN concentrations in the third trimester in pregnancies complicated by FGR ( Yaman et al , 2023 ). Explanations for the positive association between first trimester maternal KYN concentrations and SGA involve the several essential functions of the KYN pathway during pregnancy, including its role in neovascularization, vasodilatation of placental arteries, and immune regulation ( Wang et al , 2010 ; Mondal et al , 2016 ; Badawy, 2017a ; Broekhuizen, et al , 2021 ; Worton et al , 2021 ).…”

“…Throughout pregnancy, the TRP metabolite concentrations are closely regulated, and alterations of KYN pathway or serotonin pathway metabolites have been associated with pregnancy complications, such as pre-eclampsia and fetal growth restriction (FGR) ( Gumusoglu et al , 2021 ; van Zundert et al , 2022a ). In late pregnancy, maternal TRP and KYN concentrations were inversely associated with FGR ( van Zundert, et al , 2022a ; Yaman et al , 2023 ). Studies investigating TRP metabolism in the placenta showed that in placentas of FGR pregnancies the KYN pathway was downregulated, while the serotonin pathway was upregulated ( Ranzil et al , 2019 ).…”