Untargeted Metabolomic Analysis of Amniotic Fluid in the Prediction of Preterm Delivery and Bronchopulmonary Dysplasia

PLoS One. 2016 Oct 18;11(10):e0164211. doi: 10.1371/journal.pone.0164211. eCollection 2016.

Abstract

Objective: Bronchopulmonary dysplasia (BPD) is a serious complication associated with preterm birth. A growing body of evidence suggests a role for prenatal factors in its pathogenesis. Metabolomics allows simultaneous characterization of low molecular weight compounds and may provide a picture of such a complex condition. The aim of this study was to evaluate whether an unbiased metabolomic analysis of amniotic fluid (AF) can be used to investigate the risk of spontaneous preterm delivery (PTD) and BPD development in the offspring.

Study design: We conducted an exploratory study on 32 infants born from mothers who had undergone an amniocentesis between 21 and 28 gestational weeks because of spontaneous preterm labor with intact membranes. The AF samples underwent untargeted metabolomic analysis using mass spectrometry combined with ultra-performance liquid chromatography. The data obtained were analyzed using multivariate and univariate statistical data analysis tools.

Results: Orthogonally Constrained Projection to Latent Structures-Discriminant Analysis (oCPLS2-DA) excluded effects on data modelling of crucial clinical variables. oCPLS2-DA was able to find unique differences in select metabolites between term (n = 11) and preterm (n = 13) deliveries (negative ionization data set: R2 = 0.47, mean AUC ROC in prediction = 0.65; positive ionization data set: R2 = 0.47, mean AUC ROC in prediction = 0.70), and between PTD followed by the development of BPD (n = 10), and PTD without BPD (n = 11) (negative data set: R2 = 0.48, mean AUC ROC in prediction = 0.73; positive data set: R2 = 0.55, mean AUC ROC in prediction = 0.71).

Conclusions: This study suggests that amniotic fluid metabolic profiling may be promising for identifying spontaneous preterm birth and fetuses at risk for developing BPD. These findings support the hypothesis that some prenatal metabolic dysregulations may play a key role in the pathogenesis of PTD and the development of BPD.

MeSH terms

  • Amniotic Fluid / metabolism*
  • Area Under Curve
  • Bronchopulmonary Dysplasia / diagnosis*
  • Bronchopulmonary Dysplasia / metabolism
  • Chromatography, High Pressure Liquid
  • Discriminant Analysis
  • Female
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Least-Squares Analysis
  • Male
  • Mass Spectrometry
  • Metabolome
  • Metabolomics*
  • Pregnancy
  • Premature Birth
  • ROC Curve

Grants and funding

This study was supported by “Bando Ricerca Pediatrica 2012–2014” Fondazione Cassa di Risparmio di Padova e Rovigo and, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH). The funding sources had no involvement in the study design, the collection, analysis, and interpretation of data, the writing of the report, and the decision to submit the manuscript for publication. The funding sources and the company S-IN Soluzioni Informatiche (MS) did not provide support in the form of salaries for any of the authors. S-IN Soluzioni Informatiche did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of the authors are articulated in the ‘author contributions’ section.