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A maternal serum metabolite ratio predicts fetal growth restriction at term

Ulla Sovio1,2, Neil Goulding3,4,5, Nancy McBride3,4,5

  • 1Department of Obstetrics and Gynaecology, University of Cambridge; NIHR Cambridge Biomedical Research Centre, Cambridge, UK. us253@medschl.cam.ac.uk.

Nature Medicine
|March 13, 2020
PubMed

Insights

A new metabolite ratio in maternal serum can predict fetal growth restriction (FGR), a major cause of stillbirth. This biomarker shows improved prediction compared to existing methods, offering hope for better screening and intervention.

Area of Science:

  • Biochemistry
  • Perinatal Medicine
  • Metabolomics

Background:

  • Fetal growth restriction (FGR) is a leading cause of stillbirth and is linked to adverse neonatal outcomes and long-term health issues.
  • Effective screening and intervention for FGR remain critical unmet clinical needs in obstetrics.
  • Current predictive biomarkers for FGR have limitations in their diagnostic accuracy.

Purpose of the Study:

  • To identify novel predictive metabolites for term fetal growth restriction (FGR) in maternal serum.
  • To develop and validate a predictive biomarker for FGR using metabolomic profiling.
  • To compare the predictive performance of the novel biomarker against existing angiogenic markers.

Main Methods:

  • Ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) metabolomics was performed on maternal serum samples.
  • Serum samples were collected at 12, 20, and 28 weeks of gestational age from a cohort of FGR cases and controls.
  • A novel metabolite ratio was identified and validated in independent cohorts, including the Pregnancy Outcome Prediction (POP) and Born in Bradford (BiB) studies.

Main Results:

  • A specific ratio of four metabolites (P-18:0/18:1, 1,5-anhydroglucitol, 5α-androstan-3α,17α-diol disulfate, and N1,N12-diacetylspermine) significantly predicted term FGR.
  • The metabolite ratio demonstrated superior predictive performance (AUC 0.78) compared to the soluble fms-like tyrosine kinase 1:placental growth factor (sFLT1:PlGF) ratio (AUC 0.64).
  • The predictive accuracy of the metabolite ratio was validated in demographically diverse cohorts, confirming its robustness.

Conclusions:

  • A novel maternal serum metabolite ratio effectively predicts fetal growth restriction at term.
  • This biomarker offers a promising tool for enhanced fetal monitoring and timely intervention, potentially reducing stillbirth and neonatal complications.
  • Integration of this metabolite ratio with ultrasound imaging could improve screening strategies for FGR around 36 weeks of gestation.

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