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 ¼ 37) were matched with amniotic fluid samples from women with a subsequent spontaneous delivery at term (n ¼ 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 midtrimester 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.

Metabolomic Profiling of Second-Trimester Amniotic Fluid for Predicting Preterm Delivery: Insights from NMR Analysis

“…Interestingly, as previously discussed, a recent study [16] found no significant differences in metabolite profiles associated with spontaneous PTD. This outcome may be attributed to variations in stratification and research protocols.…”

“…Research studies [11][12][13][14][15] suggest that conducting a metabolomic analysis on AF obtained during the prenatal period holds the potential to identify metabolic deviations before PTD occurs. However, a recent study using untargeted LC-MS mid-trimester amniotic fluid metabolic profiling on two groups of 37 pregnant women (full term/preterm) that underwent amniocentesis showed no evidence of metabolite differentiation for spontaneous PTD [16].…”

Utilizing Amniotic Fluid Metabolomics to Monitor Fetal Well-Being: A Narrative Review of the Literature

“…The method used in this study [ 30 ] was first developed on a HILIC system comprised of UHPLC with detection on a triple quadrupole mass spectrometer operating in both positive and negative electrospray ionization modes and validated with amniotic fluid samples from 250 second-trimester pregnant women [ 31 ]. On the contrary, based on mid-trimester metabolic profiling, there was no evidence of grouping about spontaneous preterm delivery according to a very recent study using untargeted LC-MS amniotic fluid metabolomic profiling [ 32 ]. Perhaps, extended targeted analysis on multiple pregnancy time points could offer clarification, but it is rather challenging due to the invasive sample collection method of amniocentesis.…”