Oxford Maternal & Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, UK.
Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, UK.
Nat Commun. 2024 Nov 11;15(1):9752. doi: 10.1038/s41467-024-53597-4.
The pathways involved in the pathophysiology of fetal growth restriction (FGR) and small for gestational age (SGA) are incompletely understood. We conduct a systematic review to identify metabolomic signatures in maternal and newborn tissues and body fluids samples associated with FGR/SGA. Here, we report that 825 non-duplicated metabolites were significantly altered across the 48 included studies using 10 different human biological samples, of which only 56 (17 amino acids, 12 acylcarnitines, 11 glycerophosphocholines, six fatty acids, two hydroxy acids, and eight other metabolites) were significantly and consistently up- or down-regulated in more than one study. Three amino acid metabolism-related pathways and one related with lipid metabolism are significantly associated with FGR and/or SGA: biosynthesis of unsaturated fatty acids in umbilical cord blood, and phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, and phenylalanine metabolism in newborn dried blood spot. Significantly enriched metabolic pathways were not identified in the remaining biological samples. Whether these metabolites are in the causal pathways or are biomarkers of fetal nutritional deficiency needs to be explored in large, well-phenotyped cohorts.
胎儿生长受限（FGR）和小于胎龄儿（SGA）的病理生理学涉及的途径尚未完全阐明。我们进行了系统评价，以确定与 FGR/SGA 相关的母体和新生儿组织及体液样本中的代谢组学特征。在这里，我们报告使用 10 种不同的人类生物样本，在 48 项纳入研究中，有 825 种非重复代谢物发生了显著变化，其中只有 56 种（17 种氨基酸、12 种酰基辅酶 A、11 种甘油磷酸胆碱、6 种脂肪酸、2 种羟基酸和 8 种其他代谢物）在超过一项研究中显著且一致地上调或下调。与 FGR 和/或 SGA 显著相关的有 3 条氨基酸代谢相关途径和 1 条与脂质代谢相关的途径：脐带血中不饱和脂肪酸的生物合成，以及新生儿干血斑中苯丙氨酸、酪氨酸和色氨酸的生物合成、缬氨酸、亮氨酸和异亮氨酸的生物合成和苯丙氨酸代谢。在其余生物样本中未发现显著富集的代谢途径。这些代谢物是否在因果途径中，或者是否是胎儿营养缺乏的生物标志物，需要在大型、表型良好的队列中进行探索。
