Metabolomic profiles of mid-trimester amniotic fluid are not associated with subsequent spontaneous preterm delivery or gestational duration at delivery

Abstract

Introduction

Spontaneous preterm delivery (<37 gestational weeks) has a multifactorial etiology with still incompletely identified pathways. Amniotic fluid is a biofluid with great potential for insights into the feto-maternal milieu. It is rich in metabolites, and metabolic consequences of inflammation is yet researched only to a limited extent. Metabolomic profiling provides opportunities to identify potential biomarkers of inflammatory conditioned pregnancy complications such as spontaneous preterm delivery.

Objective

The aim of this study was to perform metabolomic profiling of amniotic fluid from uncomplicated singleton pregnancies in the mid-trimester to identify potential biomarkers associated with spontaneous preterm delivery and gestational duration at delivery. A secondary aim was to replicate previously reported mid-trimester amniotic fluid metabolic biomarkers of spontaneous preterm delivery in asymptomatic women.

Method

A nested case-control study was performed within a larger cohort study of asymptomatic pregnant women undergoing mid-trimester genetic amniocentesis at 14–19 gestational weeks in Gothenburg, Sweden. Medical records were used to obtain clinical data and delivery outcome variables. Amniotic fluid samples from women with a subsequent spontaneous preterm delivery (n = 37) were matched with amniotic fluid samples from women with a subsequent spontaneous delivery at term (n = 37). Amniotic fluid samples underwent untargeted metabolomic analyses using liquid chromatography-mass spectrometry. Multivariate random forest analyses were used for data processing. A secondary targeted analysis was performed, aiming to replicate previously reported mid-trimester amniotic fluid metabolic biomarkers in women with a subsequent spontaneous preterm delivery.

Results

Multivariate analysis did not distinguish the samples from women with a subsequent spontaneous preterm delivery from those with a subsequent term delivery. Neither was the metabolic profile associated with gestational duration at delivery. Potential metabolic biomarker candidates were identified from four publications by two different research groups relating mid-trimester amniotic fluid metabolomes to spontaneous PTD, of which fifteen markers were included in the secondary analysis. None of these were replicated.

Conclusions

Metabolomic profiles of early mid-trimester amniotic fluid were not associated with spontaneous preterm delivery or gestational duration at delivery in this cohort.

Keywords:

• Amniotic fluid
• gestational duration
• metabolomics
• mid-trimester
• spontaneous preterm delivery

Acknowledgements

We would like to express our gratitude to the staff at the Prenatal Clinic, for their help with recruitment and sampling, and the staff at the Perinatal Laboratory, Department of Obstetrics and Gynecology, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden for their help with recruitment and processing of samples.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

The work was supported by grants from Agreement concerning research and education of doctors, Sweden [under grant numbers ALFGBG-11522, ALFGBG-136431, ALFGBG-426411, ALFGBG-507701, ALFGBG-671611 and ALFGBG-717501], the Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, Sweden [under grant numbers VGFOUREG-231311, VGFOUREG-308151 and VGFOUREG-368351] and the foundation O. E. och Edla Johanssons vetenskapliga stiftelse, Sweden. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.