Placental Biology in Health and Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Pregnancy; Pre-eclampsia; Gestational Diabetes Mellitus (GDM); Fetal Growth Restriction (FGR); Placenta; Pregnancy Induced Hypertension (PIH)
• Intervention / Treatment: Other: There are no interventions for this study

Detailed Description

The study is a non-interventional, observational study focused on sample collection and laboratory-based analyses to investigate the role of placental EVs and soluble factors in maternal and fetal health. The study will focus on understanding the molecular mechanisms underlying pre-eclampsia, gestational diabetes mellitus and fetal growth restriction, with the ultimate aim of identifying biomarkers and therapeutic targets. To achieve this, the study will recruit participants with healthy, pathological and predisposed pregnancies alongside non-pregnant healthy controls.

• Study Type: Observational
• Enrollment (Estimated): 360

Contacts and Locations

• Study Contact: Name: Professor Manu Vatish; Phone Number: +441865 221009; Email: manu.vatish@wrh.ox.ac.uk

Study Locations

• United Kingdom
  • Oxford, United Kingdom
    • Recruiting
    • Oxford University Hospitals NHS Foundation Trust
    • Contact: Clinical Research Group; Phone Number: +441865 221107; Email: clinicalresearchgroup@wrh.ox.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

This study will recruit a diverse cohort of pregnant and non-pregnant participants to enable analysis of placental EVs and soluble factors across different physiological and pathological conditions.

Participants will include:

• Pregnant women with pre-eclampsia, gestational diabetes mellitus or fetal growth restriction to allow the study of disease-specific alterations in EVs and systemic responses.
• Pregnant women predisposed to pre-eclampsia to provide insights into risk factors and early-stage changes, aiding in biomarker discovery for prediction and prevention.
• Pregnant women with healthy pregnancies to understand normal EV release and immune regulation.
• Non-pregnant women to provide critical baseline data to differentiate the effects of pregnancy from underlying physiological processes.

Pregnant participants may be recruited at any gestational stage to ensure a comprehensive coverage of pregnancy progression.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pregnant women diagnosed with pre-eclampsia	Other: There are no interventions for this study; There are no interventions for this study
Pregnant women diagnosed with gestational diabetes mellitus	Other: There are no interventions for this study; There are no interventions for this study
Pregnant women diagnosed with fetal growth restriction	Other: There are no interventions for this study; There are no interventions for this study
Healthy pregnant women	Other: There are no interventions for this study; There are no interventions for this study
Healthy non-pregnant women	Other: There are no interventions for this study; There are no interventions for this study
Pregnant women predisposed to pre-eclampsia	Other: There are no interventions for this study; There are no interventions for this study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Enhanced understanding of the molecular and cellular mechanisms linking placental EVs to maternal systemic inflammation in PET and GDM.	Quantitative (number of particles/ml) and qualitative differences (protein cargo) in EV profiles	Baseline and at delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative and qualitative differences in inflammatory immune cells	Quantitative (cells/ml) and qualitative (protein and RNA composition/mg cell) will be measured	baseline and delivery
Sensitivity, specificity and predictive value of EVs for identifying PET, GDM and other pregnancy complications	Standard statistical analysis of EV parameters against clinical endpoints to derive sensitivity, specificity and PPV/NPV in these disease conditions	Baseline and delivery

Collaborators and Investigators

• Sponsor: University of Oxford

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2025
• Primary Completion (Estimated): May 31, 2030
• Study Completion (Estimated): May 31, 2030

Study Registration Dates

• First Submitted: December 10, 2025
• First Submitted That Met QC Criteria: March 9, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Pregnancy Complications; Glucose Metabolism Disorders; Diabetes Mellitus; Fetal Diseases; Growth Disorders; Hypertension; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Diabetes, Gestational; Pre-Eclampsia; Fetal Growth Retardation; Hypertension, Pregnancy-Induced
• Other Study ID Numbers: 18939

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No