, Volume 8, Issue 5, pp 919–929 | Cite as

Pathogenesis of neural tube defects: the story beyond methylation or one-carbon unit metabolism

Original Article


A metabolomic study was performed to investigate the biochemical perturbation of the serum samples from neural tube defects affected pregnant women (cases, n = 80) and normal pregnant subjects (controls, n = 95). The serum metabolome was detected using ultra performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC/TOF–MS). The acquired UPLC-MS data were normalized and processed by principal components analysis and orthogonal partial least squares discriminant analysis. The distinctive biochemical differences between the healthy subjects and NTDs-affected pregnant women were displayed by the pattern recognition methods. According to the data, several potential biomarkers were identified: sphingosine-1-phosphate, galactosylsphingosine, 3-oxohexadecanoic acid, fructose-6-phosphate, docosahexaenoic acid, dehydroepiandrosterone sulfate, and linoleic acid were found with decreased concentrations in the cases, and lysophosphatidylcholine and leukotrienes were found with increased concentrations in the cases. On the basis of the relevant literature and pathway databases, the biological significance of the present study is discussed. And the conclusion was obtained that there must be some other metabolic cycles that could contribute to the occurrence of neural tube defects besides the one-carbon unit metabolism.


Metabolomics Neural tube defects UPLC/TOF–MS Biomarker 



Neural tube defect


Ultra-performance liquid chromatography tandem time of flight mass spectrometry


Principal components analysis


Orthogonal partial least squares-discriminant analysis




Dehydroepiandrosterone sulfate






Docosahexaenoic acid


Relative standard deviations


Exact mass/retention time pair


US public health service


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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education)Tsinghua UniversityBeijingChina
  2. 2.School of PharmacyEast China University of Science and TechnologyShanghaiChina

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