Metabolite Changes in Maternal and Fetal Plasma Following Spontaneous Labour at Term in Humans Using Untargeted Metabolomics Analysis: A Pilot Study

Abstract

The mechanism of human labour remains poorly understood, limiting our ability to manage complications of parturition such as preterm labour and induction of labour. In this study we have investigated the effect of labour on plasma metabolites immediately following delivery, comparing cord and maternal plasma taken from women who laboured spontaneously and delivered vaginally with women who were delivered via elective caesarean section and did not labour. Samples were analysed using ultra high-performance liquid chromatography-tandem mass spectrometry. Welch’s two-sample t-test was used to identify any significant differences. Of 826 metabolites measured, 26.9% (222/826) were significantly altered in maternal plasma and 21.1% (174/826) in cord plasma. Labour involves changes in many maternal organs and poses acute metabolic demands in the uterus and in the fetus and these are reflected in our results. While a proportion of these differences are likely to be secondary to the physiological demands of labour itself, these results present a comprehensive picture of the metabolome in the maternal and fetal circulations at the time of delivery and can be used to guide future studies. We discuss potential causal pathways for labour including endocannabinoids, ceramides, sphingolipids and steroids. Further work is necessary to confirm the specific pathways involved in the spontaneous onset of labour.

Ceramides during Pregnancy and Obstetrical Adverse Outcomes

“…In this context, Signorelli et al [30] proposed ceramide as a ther-apeutic target in inflammatory labor complications based on differences in total ceramide and serine-palmitoyl transferase between vaginal and cesarean deliveries. Similar patterns of ceramide accumulation in the maternal and cord plasma were observed in a pilot comparison between laboring and non-laboring women [31]. Based on comprehensive profiling of numerous metabolites, the endocannabinoid/ceramide/sphingolipid pathway has the potential to stimulate labor [31].…”

“…Similar patterns of ceramide accumulation in the maternal and cord plasma were observed in a pilot comparison between laboring and non-laboring women [31]. Based on comprehensive profiling of numerous metabolites, the endocannabinoid/ceramide/sphingolipid pathway has the potential to stimulate labor [31]. In addition, ceramides play signaling roles in various reproductive tissues [32] and mediate vascular function during healthy pregnancy [33].…”

Neurodevelopment and Metabolism in the Maternal-Placental-Fetal Unit

“…We speculate that these unexpected findings are related to a metabolic switch that occurs during the perinatal transition . Labor is a highly coordinated process, associated with changes in maternal and fetal metabolism . Birth itself is associated with profound metabolic and transcriptomic changes in the newborn to maintain energy supply after losing the steady supply of maternal nutrients .…”

“… 30 Labor is a highly coordinated process, associated with changes in maternal and fetal metabolism. 31 , 32 Birth itself is associated with profound metabolic and transcriptomic changes in the newborn to maintain energy supply after losing the steady supply of maternal nutrients. 33 , 34 The placental and cord serum metabolomes were collected at the same postdelivery time point and likely reflect profound metabolic changes in this critical window, whereas maternal serum collected during the third trimester reflects a different developmental window.…”