First-trimester maternal tryptophan metabolites, utero-placental (vascular)development and hypertensive disorders of pregnancy: The Rotterdam periconceptional cohort

• Published in: Placenta (Eastbourne) 2024-12, Vol.158, p.105-112
• Main Authors: van Zundert, Sofie K.M., Broekhuizen, Michelle, Mirzaian, Mina, van Rossem, Lenie, Danser, A.H. Jan, Willemsen, Sten P., Griffioen, Pieter H., Koning, Anton H.J., Mulders, Annemarie G.M.G.J., van Schaik, Ron H.N., Steegers-Theunissen, Régine P.M.
• Format: Article
• Language: English
• Subjects: 5-Hydroxytryptophan; Adult; Cohort Studies; Female; Humans; Hypertension; Hypertension, Pregnancy-Induced - blood; Hypertension, Pregnancy-Induced - epidemiology; Kynurenine; Placenta; Placenta - blood supply; Placenta - metabolism; Placentation; Pre-Eclampsia - blood; Pre-Eclampsia - epidemiology; Preeclampsia; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Tryptophan - blood; Tryptophan - metabolism
• ISSN: 0143-4004; 1532-3102; 1532-3102
• DOI: 10.1016/j.placenta.2024.10.006

Hypertensive disorders of pregnancy (HDP) are a significant cause of maternal and perinatal mortality and morbidity. Knowledge on the placenta-related pathophysiology of HDP is increasing. Since maternal tryptophan metabolites are involved in placentation, we investigated associations between first-trimester tryptophan metabolites and utero-placental (vascular) development, and the occurrence of HDP. 911 women were included from a prospective tertiary hospital cohort. Serum tryptophan metabolites were determined at 8.1 ± 1.4 weeks gestation. Placental volume (PV) and utero-placental vascular volume (uPVV) were determined at 7, 9 and 11 weeks gestation. HDP, including hypertension in early pregnancy, gestational hypertension, and preeclampsia, were retrieved from medical records. Associations with PV- and uPVV-trajectories were assessed using mixed models, and HDP risks were estimated by logistic regression models, adjusted for confounders. A mediation analysis was performed to evaluate whether blood pressure was a mediator in the associations with utero-placental (vascular) development. A negative association between kynurenine and PV-trajectories was found (β = −0.129, 95%CI = −0.220 to –0.039), which was not mediated by blood pressure. No significant associations between other tryptophan metabolites and PV- and uPVV-trajectories were observed. Higher 5-hydroxytryptophan was associated with hypertension in early pregnancy (OR = 1.405, 95%CI = 1.210–1.681), and with an increased risk of preeclampsia in these women. No associations between tryptophan metabolites and other HDP were found. Higher first-trimester kynurenine concentrations were associated with impaired utero-placental (vascular) development. Higher first-trimester 5-hydroxytryptophan concentrations were associated with early pregnancy hypertension, and an increased risk of preeclampsia, indicating its clinical potential as biomarker for future prediction, prevention and treatment of HDP. •Higher first-trimester kynurenine levels may reduce placental volume.•Higher first-trimester 5-hydroxytryptophan levels may increase the risk of HDP.•Placental development can be assessed using 3D ultrasound and virtual reality.