Introduction

Small for gestational age (SGA) may be associated with neonatal morbidity and mortality. Our understanding of the molecular pathways implicated is poor.

Objectives

Our aim was to determine the metabolic pathways involved in the pathophysiology of SGA and examine their variation between maternal biofluid samples.

Methods

Plasma (Cork) and urine (Cork, Auckland) samples were collected at 20 weeks’ gestation from nulliparous low-risk pregnant women participating in the SCOPE study. Women who delivered an SGA infant (birthweight < 10th percentile) were matched to controls (uncomplicated pregnancies). Metabolomics (urine) and lipidomics (plasma) analyses were performed using ultra performance liquid chromatography-mass spectrometry. Features were ranked based on FDR adjusted p-values from empirical Bayes analysis, and significant features putatively identified.

Results

Lipidomics plasma analysis revealed that 22 out of the 33 significantly altered lipids annotated were glycerophospholipids; all were detected in higher levels in SGA. Metabolomic analysis identified reduced expression of metabolites associated with detoxification (D-Glucuronic acid, Estriol-16-glucuronide), nutrient absorption and transport (Sulfolithocholic acid) pathways.

Conclusions

This study suggests higher levels of glycerophospholipids, and lower levels of specific urine metabolites are implicated in the pathophysiology of SGA. Further research is needed to confirm these findings in independent samples.

中文翻译：

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与小于胎龄儿病理生理学相关的甘油磷脂和解毒途径：SCOPE 队列中的发现代谢组学分析

介绍

小于胎龄 (SGA) 可能与新生儿发病率和死亡率有关。我们对所涉及的分子途径的理解很差。

目标

我们的目的是确定 SGA 病理生理学中涉及的代谢途径，并检查它们在母体生物体液样本之间的差异。

方法

血浆（科克）和尿液（科克，奥克兰）样本是在怀孕 20 周时从参与 SCOPE 研究的未产低风险孕妇身上收集的。分娩 SGA 婴儿的妇女（出生体重 < 10%）与对照组（无并发症妊娠）相匹配。使用超高效液相色谱-质谱法进行代谢组学（尿液）和脂质组学（血浆）分析。根据经验贝叶斯分析的 FDR 调整 p 值对特征进行排序，并推定识别出重要特征。

结果

脂质组学血浆分析显示，在标注的 33 种显着改变的脂质中，有 22 种是甘油磷脂；所有这些都在 SGA 中以更高的水平被检测到。代谢组学分析发现与解毒（D-葡萄糖醛酸、雌三醇-16-葡萄糖醛酸）、营养吸收和运输（硫叶胆酸）途径相关的代谢物表达减少。

结论

该研究表明较高水平的甘油磷脂和较低水平的特定尿液代谢物与 SGA 的病理生理学有关。需要进一步研究以在独立样本中证实这些发现。