Metabolomic analysis for first-trimester Down syndrome prediction

Am J Obstet Gynecol. 2013 May;208(5):371.e1-8. doi: 10.1016/j.ajog.2012.12.035. Epub 2013 Jan 8.


Objective: The objective of the study was to perform first-trimester maternal serum metabolomic analysis and compare the results in aneuploid vs Down syndrome (DS) pregnancies.

Study design: This was a case-control study of pregnancies between 11+0 and 13+6 weeks. There were 30 DS cases and 60 controls in which first-trimester maternal serum was analyzed. Nuclear magnetic resonance-based metabolomic analysis was performed for DS prediction.

Results: Concentrations of 11 metabolites were significantly different in the serum of DS pregnancies. The combination of 3-hydroxyisovalerate, 3-hydroxybuterate, and maternal age had a 51.9% sensitivity at 1.9% false-positive rate for DS detection. One multimarker algorithm had 70% sensitivity at 1.7% false-positive rate. Novel markers such as 3-hydroxybutyrate, involved in brain growth and myelination, and 2-hydroxybutyrate, involved in the defense against oxidative stress, were found to be abnormal.

Conclusion: The study reports novel metabolomic markers for the first-trimester prediction of fetal DS. Metabolomics provided insights into the cellular dysfunction in DS.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Algorithms
  • Biomarkers / blood
  • Case-Control Studies
  • Decision Support Techniques
  • Down Syndrome / diagnosis*
  • False Positive Reactions
  • Female
  • Humans
  • Logistic Models
  • Magnetic Resonance Spectroscopy
  • Maternal Serum Screening Tests / methods*
  • Metabolomics*
  • Pregnancy
  • Pregnancy Trimester, First / blood*
  • Principal Component Analysis
  • Prospective Studies
  • ROC Curve
  • Sensitivity and Specificity


  • Biomarkers