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<p>Metabolites influencing miscarriage outcomes remain understudied. We hypothesized that aberrant metabolism impacts threatened miscarriage outcomes and that understanding these pathways could offer new management strategies. This case-control study analyzed serum metabolomics from 80 women between 5 and 12 weeks’ gestation at KK Women’s and Children’s Hospital, Singapore, comparing three groups: women with threatened miscarriage who miscarried (TM<sub>MC</sub>), those with ongoing pregnancies (TM<sub>O</sub>), and women with normal pregnancies (NP). Using untargeted liquid chromatography-mass spectrometry and pathway analysis through MetaboAnalyst 5.0 and the Kyoto Encyclopedia of Genes and Genomes, 267 metabolites across 12 enriched pathways were identified. Dysregulations in steroid (AUC 0.82), folate (AUC 0.59), fatty acid (AUC 0.70), and glucosaminoglycan (AUC 0.64) pathways distinguished women who miscarried from those with ongoing pregnancies (TM<sub>MC</sub> vs TM<sub>O</sub>). We provide initial insights into the metabolic profile associated with miscarriage, highlighting disruptions in steroid hormone, fatty acid, folate, and glucosaminoglycan biosynthesis. Further validation may support biomarker development for prognostication.</p>

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Untargeted metabolomics reveals key pathways in miscarriage: steroid, folate, fatty acid & glycosaminoglycan metabolism

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月13日

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  • Chee Wai Ku,
  • Yu Bin Tan,
  • Kuan Yang Chew,
  • Chee Onn Ku,
  • Shi Tong Carissa Ng,
  • Thiam Chye Tan,
  • Yie Hou Lee

摘要

Metabolites influencing miscarriage outcomes remain understudied. We hypothesized that aberrant metabolism impacts threatened miscarriage outcomes and that understanding these pathways could offer new management strategies. This case-control study analyzed serum metabolomics from 80 women between 5 and 12 weeks’ gestation at KK Women’s and Children’s Hospital, Singapore, comparing three groups: women with threatened miscarriage who miscarried (TMMC), those with ongoing pregnancies (TMO), and women with normal pregnancies (NP). Using untargeted liquid chromatography-mass spectrometry and pathway analysis through MetaboAnalyst 5.0 and the Kyoto Encyclopedia of Genes and Genomes, 267 metabolites across 12 enriched pathways were identified. Dysregulations in steroid (AUC 0.82), folate (AUC 0.59), fatty acid (AUC 0.70), and glucosaminoglycan (AUC 0.64) pathways distinguished women who miscarried from those with ongoing pregnancies (TMMC vs TMO). We provide initial insights into the metabolic profile associated with miscarriage, highlighting disruptions in steroid hormone, fatty acid, folate, and glucosaminoglycan biosynthesis. Further validation may support biomarker development for prognostication.