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

IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY
Sofie K.M. van Zundert , Michelle Broekhuizen , Mina Mirzaian , Lenie van Rossem , A.H. Jan Danser , Sten P. Willemsen , Pieter H. Griffioen , Anton H.J. Koning , Annemarie G.M.G.J. Mulders , Ron H.N. van Schaik , Régine P.M. Steegers-Theunissen
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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.
第一胎母体色氨酸代谢物、子宫胎盘(血管)发育和妊娠高血压疾病:鹿特丹围孕期队列。
背景:妊娠期高血压疾病(HDP)是导致孕产妇和围产期死亡和发病的一个重要原因。人们对与胎盘相关的妊娠高血压病理生理学的了解正在不断增加。由于母体色氨酸代谢物参与了胎盘的形成,我们研究了第一胎色氨酸代谢物与子宫胎盘(血管)发育和 HDP 发生之间的关系。在妊娠 8.1 ± 1.4 周时测定血清色氨酸代谢物。胎盘容积(PV)和子宫-胎盘血管容积(uPVV)分别在妊娠 7、9 和 11 周时测定。HDP包括早孕高血压、妊娠高血压和子痫前期,均来自医疗记录。使用混合模型评估了PV和uPVV轨迹的相关性,并通过逻辑回归模型估计了HDP风险,同时对混杂因素进行了调整。还进行了中介分析,以评估血压是否是子宫胎盘(血管)发育相关性的中介因素:结果:发现犬尿氨酸与 PV 轨迹之间存在负相关(β = -0.129,95%CI = -0.220 至 -0.039),且不受血压影响。其他色氨酸代谢物与 PV 和 uPVV 轨迹之间没有发现明显的关联。较高的 5- 羟色氨酸与孕早期高血压有关(OR = 1.405,95%CI = 1.210-1.681),并与这些妇女发生子痫前期的风险增加有关。没有发现色氨酸代谢物与其他高密度脂蛋白血症之间存在关联:第一胎犬尿氨酸浓度较高与子宫胎盘(血管)发育受损有关。妊娠初期5-羟色氨酸浓度较高与妊娠早期高血压和子痫前期风险增加有关,这表明其作为生物标志物在未来预测、预防和治疗HDP方面具有临床潜力。
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来源期刊
Placenta
Placenta 医学-发育生物学
CiteScore
6.30
自引率
10.50%
发文量
391
审稿时长
78 days
期刊介绍: Placenta publishes high-quality original articles and invited topical reviews on all aspects of human and animal placentation, and the interactions between the mother, the placenta and fetal development. Topics covered include evolution, development, genetics and epigenetics, stem cells, metabolism, transport, immunology, pathology, pharmacology, cell and molecular biology, and developmental programming. The Editors welcome studies on implantation and the endometrium, comparative placentation, the uterine and umbilical circulations, the relationship between fetal and placental development, clinical aspects of altered placental development or function, the placental membranes, the influence of paternal factors on placental development or function, and the assessment of biomarkers of placental disorders.
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