The feto-placental metabolome of spontaneous labour is not reproduced following induction of labour.

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 for: SL group=3.5; IOL group=0.5; and ECS group=0.5), and oestriol (CA/CV ratio for: SL group=4.3; IOL group=0.4; and for ECS group=0.2). There were no such changes in the maternal samples.

DISCUSSION: These findings indicate that IOL does not reproduce the pathways activated in spontaneous labour. The decreased placental progesterone production observed with spontaneous labour may represent a local intrauterine progesterone withdrawal, which, together with other signals, would activate parturition pathways involving arachidonate and sphingosine metabolism.