Department of Chemical and Geological Sciences, University of Cagliari, Cagliari, Italy.
NICU, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
PLoS One. 2017 Dec 6;12(12):e0189120. doi: 10.1371/journal.pone.0189120. eCollection 2017.
Chorioamnionitis is a leading cause of preterm birth worldwide, with higher incidence at lower gestational ages. An early and reliable diagnosis of histological chorioamnionitis (HCA) in preterm infants may be helpful in guiding postnatal management, especially the administration of prophylactic antibiotics to prevent early-onset sepsis. The main aim of this study was to investigate metabolomic analysis of urines collected in the first 24 hours of life as diagnostic tool of HCA.
Gestational age-, birth weight-, delivery mode- and sex- matched (1:2) preterm neonates (< 35 weeks' gestation) born to mothers with or without HCA were enrolled from an observational study. Gas chromatography-mass spectrometry (GC-MS)-based metabolomic analysis was performed on urine samples non-invasively collected in the first 24 hours of life. Univariate analysis, partial least square discriminant analysis (PLS-DA) and its associated variable importance in projection (VIP) score were performed. The most affected metabolic pathways were examined by Metabolite Sets Enrichment Analysis (MSEA).
Fifteen cases (mean GA 30.2 ± 3.8 weeks, mean BW 1415 ± 471.9 grams) and 30 controls (mean GA 30.2 ± 2.9 weeks, mean BW 1426 ± 569.8 grams) were enrolled. Following univariate analysis, 29 metabolites had a significantly different concentration between cases and controls. The supervised PLS-DA model confirmed a separation between the two groups. Only gluconic acid, an oxidation product of glucose, was higher in cases than in controls. All other VIP metabolites were more abundant in the control group. Glutamate metabolism, mitochondrial electron transport chain, citric acid cycle, galactose metabolism, and fructose and mannose degradation metabolism were the most significantly altered pathways (P < 0.01).
For the first time, urinary metabolomics was able to discriminate neonates born to mothers with and without HCA. The identification of specifically altered metabolic pathways may be helpful in understanding metabolic derangement following chorioamnionitis.
绒毛膜羊膜炎是全球导致早产的主要原因，在较低的孕龄发病率更高。对早产儿进行组织学绒毛膜羊膜炎（HCA）的早期和可靠诊断，可能有助于指导产后管理，特别是预防性使用抗生素以预防早发性败血症。本研究的主要目的是探讨在生命的头 24 小时内收集的尿液的代谢组学分析，作为 HCA 的诊断工具。
从一项观察性研究中，纳入胎龄、出生体重、分娩方式和性别匹配（1:2）的、母亲有或没有 HCA 的早产儿（<35 周妊娠）。对生命的头 24 小时内非侵入性采集的尿液样本进行气相色谱-质谱（GC-MS）-基于代谢组学分析。进行单变量分析、偏最小二乘判别分析（PLS-DA）及其相关变量重要性投影（VIP）得分。通过代谢物集富集分析（MSEA）检查受影响最大的代谢途径。
纳入 15 例（平均胎龄 30.2±3.8 周，平均体重 1415±471.9 克）和 30 例对照（平均胎龄 30.2±2.9 周，平均体重 1426±569.8 克）。经单变量分析，29 种代谢物在病例组和对照组之间的浓度有显著差异。经监督的 PLS-DA 模型证实了两组之间的分离。仅葡萄糖酸，葡萄糖的氧化产物，在病例组中高于对照组。所有其他 VIP 代谢物在对照组中更为丰富。谷氨酸代谢、线粒体电子传递链、柠檬酸循环、半乳糖代谢以及果糖和甘露糖降解代谢是受影响最显著的途径（P<0.01）。
这是首次通过尿代谢组学能够区分母亲有和没有 HCA 的新生儿。识别特定改变的代谢途径可能有助于了解绒毛膜羊膜炎后的代谢紊乱。
