Placental Biology in Health and Disease

Summary

Pre-eclampsia (PET) is a condition characterised by high blood pressure and damage to other organs, and is a leading cause of maternal and fetal complications such as fetal growth restriction (FGR). Gestational diabetes mellitus (GDM) involves abnormal blood sugar levels during pregnancy and can have both short and long-term impacts on the health of the mother and child. Both conditions are linked to placental dysfunction but the precise mechanisms behind these links remain unclear. A major focus of this study is on extracellular vesicles (EVs) which are tiny, bubble-like particles released by the placenta into the mother's and baby's bloodstreams. These EVs act as messengers, carrying proteins, lipids and genetic material that can influence how cells function, even in parts of the body far from the placenta. Notably, the number and content of these EVs change in conditions like PET and GDM, suggesting they may play a role in the development of these complications. This single-site, observational, laboratory study aims to investigate how these EVs contribute to maternal health and disease. To enable analysis across different physiological and pathological conditions pregnant participants with healthy pregnancies, pregnancies predisposed to PET and pregnancies complicated by GDM, FGR and PET will be recruited alongside healthy non-pregnant controls. Recruitment will be from the Oxford University Hospitals NHS Foundation Trust and the Nuffield Department of Women's and Reproductive Health, University of Oxford (who fund the research). Demographic and clinical data will be collected as well as blood, urine, breath, placenta, umbilical cord, umbilical cord blood, amniotic fluid and/or uterine vein blood samples. Through examining EV content and function, it is hoped a better understanding of their role in pregnancy complications will be gained, including their potential as non-invasive biomarkers for early detection and targeted treatments, improving outcomes for mothers and babies worldwide.

Eligibility

Inclusion Criteria:

* Female, aged 18 years or above
* Willing and able to give informed consent for participation in the study
* Able to read and understand written and spoken English to comprehend study materials and give informed consent
* Non-pregnant women in good general health OR pregnant women who fall into one of the following:

  * Healthy pregnancy
  * Pre-eclampsia (PET) - defined by clinical diagnostic criteria, including hypertension and proteinuria
  * Gestational diabetes mellitus (GDM) - diagnosed by standard glucose tolerance tests during pregnancy
  * Fetal growth restriction (FGR) - diagnosed based on fetal weight or Doppler abnormalities
  * Predisposed to PET - high-risk factors for PET such as maternal type 1 or type 2 diabetes, autoimmune diseases or multiple pregnancies

Exclusion Criteria:

* Non-pregnant participants with active health conditions that could confound study outcomes
* Pregnant participants with conditions unrelated to PET, GDM or FGR that could influence EV profiles e.g. active infections or malignancies

Conditions7

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