Abstract
Introduction
The mechanism for human labour remains poorly understood, limiting our ability to manage complications including spontaneous preterm birth and induction of labour (IOL). The study of fetal signals poses specific challenges. Metabolomic analysis of maternal blood, the cord artery (CA), and cord vein (CV), allows simultaneous interrogation of multiple metabolic pathways associated with different modes of labour onset and birth.
Methods
Global mass spectrometry metabolomics analysis was performed on serial samples collected from participants during pregnancy, in latent phase of labour, and following birth (CA, CV, and intervillous (IV) blood), from those who spontaneously laboured and birthed vaginally (SL group), had IOL and birthed vaginally (IOL group), or birthed via elective caesarean section (no labour; ECS group).
Results
There were clear differences in fetal and maternal steroid, arachidonate and sphingosine pathways between the SL and IOL groups, despite similar uterine contractions and vaginal birth. The CA/CV ratio for key steroids of the IOL group were more alike the ECS group than the SL group, including progesterone (CA/CV ratio: 3.5 SL group; 0.5 IOL group and 0.5 ECS group), and oestriol (CA/CV ratio: 4.3 SL group; 0.4 IOL group; and 0.2 ECS group). There were no such changes in the maternal samples.
Discussion
These findings indicate that spontaneous labour is triggered by signals from the fetus, with associated changes in placental metabolite production. The decreased placental progesterone production observed with spontaneous labour may represent a local intrauterine progesterone withdrawal, which would activate parturition pathways involving arachidonate and sphingosine metabolism.
The mechanism for human labour remains poorly understood, limiting our ability to manage complications including spontaneous preterm birth and induction of labour (IOL). The study of fetal signals poses specific challenges. Metabolomic analysis of maternal blood, the cord artery (CA), and cord vein (CV), allows simultaneous interrogation of multiple metabolic pathways associated with different modes of labour onset and birth.
Methods
Global mass spectrometry metabolomics analysis was performed on serial samples collected from participants during pregnancy, in latent phase of labour, and following birth (CA, CV, and intervillous (IV) blood), from those who spontaneously laboured and birthed vaginally (SL group), had IOL and birthed vaginally (IOL group), or birthed via elective caesarean section (no labour; ECS group).
Results
There were clear differences in fetal and maternal steroid, arachidonate and sphingosine pathways between the SL and IOL groups, despite similar uterine contractions and vaginal birth. The CA/CV ratio for key steroids of the IOL group were more alike the ECS group than the SL group, including progesterone (CA/CV ratio: 3.5 SL group; 0.5 IOL group and 0.5 ECS group), and oestriol (CA/CV ratio: 4.3 SL group; 0.4 IOL group; and 0.2 ECS group). There were no such changes in the maternal samples.
Discussion
These findings indicate that spontaneous labour is triggered by signals from the fetus, with associated changes in placental metabolite production. The decreased placental progesterone production observed with spontaneous labour may represent a local intrauterine progesterone withdrawal, which would activate parturition pathways involving arachidonate and sphingosine metabolism.
| Original language | English |
|---|---|
| Pages (from-to) | 111-118 |
| Number of pages | 8 |
| Journal | Placenta |
| Volume | 129 |
| Early online date | 19 Oct 2022 |
| DOIs | |
| Publication status | Published - 1 Nov 2022 |
Bibliographical note
Funding Information:We gratefully acknowledge the participants for taking part. We thank Metabolon, Inc. including Greg Michelotti, Brian Ingram, and Jose Martins.
Publisher Copyright:
© 2022 The Authors