Measuring sVAP-1 as a Predictor of Pregnancy Problems

Measuring Soluble Vascular Adhesion Protein-1 as a Potential Biomarker for Predicting Pregnancy Problems

Pre-eclampsia is a common pregnancy disorder defined as high blood pressure and protein in the urine after 20 weeks of pregnancy. It affects the function of the placenta and can cause severe complications, e.g, stroke, multiple organ damage and seizures for the mother, and fetal growth restriction or stillbirth for the baby. Pre-eclampsia can also cause long term health problems for mother and baby.

Currently, there is no test that can predict whether someone will develop pre-eclampsia, so nothing is done to intervene before the problems begin.

Results from their previous work suggest that the investigators may have found something that can be measured in a blood sample that can predict which women might develop pre-eclampsia. It is a protein known as Vascular Adhesion Protein-1 (VAP-1), and our evidence points at it being involved in the embryo attaching to the womb and also in helping the development of the placenta by helping to get the right cells to where they are needed.

The investigators will test blood samples from 451 pregnant women who come to the Leicester Royal Infirmary for routine bloods and their first pregnancy dating scan. The investigators will then follow the outcomes of the pregnancy to see if VAP-1 in the blood of women who develop pre-eclampsia (or other pregnancy complications) is different from the ones who do not develop pregnancy complications. The ability to predict women at higher risk of pregnancy complications would ensure the application of timely interventions and appropriate management of the conditions that may help to prevent complications both during pregnancy and later life.

The study is expected to last approximately 30 weeks and the participants will be asked to give one extra tube of blood whilst having their routine bloods taken and to also consent to follow up of medical records until the end of the pregnancy.

Study Overview

• Status: Terminated
• Conditions: Pregnancy Complications
• Intervention / Treatment: Diagnostic test: Blood test for soluble VAP-1 (sVAP-1).

• Study Type: Observational
• Enrollment (Actual): 102

Contacts and Locations

Study Locations

• United Kingdom
  • Leicester, United Kingdom
    • Leicester Royal Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

All patients being given an appointment for a routine dating scan and blood test at the Leicester Royal Infirmary will have a copy of the patient information sheet included within their appointment letter and will be invited to participate in the study.

Description

Inclusion Criteria:

• Female participants who are in early pregnancy (<20 weeks gestational age).
• 16 years and above
• Patient consents to take part in the study

Exclusion Criteria:

• Patient declines to be involved in the study
• Unsuccessful venepuncture

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pregnant women; Women aged 16+ in early pregnancy (before 20 weeks of gestation).	Diagnostic test: Blood test for soluble VAP-1 (sVAP-1).; ~5ml blood will be taken and sVAP-1 will be measure by Enzyme linked Immunosorbent Assay

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of sVAP-1 levels with pregnancy complications: Pre-eclampsia	Diagnosis of pre-eclampsia defined as: New-onset hypertension (>140 mm Hg systolic or >90 mm Hg diastolic) after 20 weeks of pregnancy and the coexistence of one or both of the following new-onset conditions: Proteinuria (urine protein:creatinine ratio ≥30 mg/mmol, or albumin:creatinine ratio ≥8 mg/mmol, or ≥1 g/L [2+] on dipstick testing) Other maternal organ dysfunction. sVAP-1 levels will be measured by ELISA	During pregnancy up to 42 weeks
Correlation of sVAP-1 levels with pregnancy complications: hypertension in pregnancy	Diagnosis of hypertension in pregnancy defined as: Systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mmHg. sVAP-1 levels will be measured by ELISA	During pregnancy up to 42 weeks
Correlation of sVAP-1 levels with pregnancy complications: Gestational diabetes.	Diagnosis of gestational diabetes defined as: A fasting plasma glucose level of 5.6 mmol/litre or above or A 2-hour plasma glucose level of 7.8 mmol/litre or above sVAP-1 levels will be measured by ELISA	During pregnancy up to 42 weeks
Correlation of sVAP-1 levels with Fetal outcomes: Stillbirth	Stillbirths will be defined as: The death of a baby before or during birth after 24 weeks of gestation. sVAP-1 levels will be measured by ELISA	During pregnancy from 24 to 42 weeks
Correlation of sVAP-1 levels with Fetal outcomes: Fetal growth restriction	Fetal growth restriction will be defined as: Estimated fetal weight >10th centile for gestational age. sVAP-1 levels will be measured by ELISA	During pregnancy up to 42 weeks
Correlation of sVAP-1 levels with Fetal outcomes: Fetal macrosomia	Fetal macrosomia,will be defined as: Estimated fetal weight >90th centile for gestational age. sVAP-1 levels will be measured by ELISA	During pregnancy up to 42 weeks
Correlation of sVAP-1 levels with Fetal outcomes: Preterm labour	Preterm labour be defined as: Birth <37 weeks. sVAP-1 levels will be measured by ELISA	During pregnancy up to 37 weeks
Correlation of sVAP-1 levels with Fetal outcomes: Miscarriage	Miscarriage will be defined as: Occurrence of spontaneous abortion <24 weeks' gestation. sVAP-1 levels will be measured by ELISA	During pregnancy up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of sVAP-1 levels with patient characteristics: Age	Age will be measured in years. sVAP-1 levels will be measured by ELISA	At time of recruitment
Correlation of sVAP-1 levels with patient characteristics: Weight	Weight will be measured in kilograms. sVAP-1 levels will be measured by ELISA.	During pregnancy up to 42 weeks
Correlation of sVAP-1 levels with patient characteristics: BMI	Weight and height will be combined to report BMI in kg/m^2. sVAP-1 levels will be measured by ELISA.	During pregnancy up to 42 weeks
Correlation of sVAP-1 levels with patient characteristics: Ethnicity	Ethnicity will be recorded as described on the medical records of the patient. sVAP-1 levels will be measured by ELISA.	At time of recruitment
Correlation of sVAP-1 levels with patient characteristics: Smoking status	Smoking status will be recorded as current/ex/never. sVAP-1 levels will be measured by ELISA.	During pregnancy up to 42 weeks
Correlation of sVAP-1 levels with patient characteristics: Gestation at time of recruitment	Gestation at time of recruitment will be measured in weeks. sVAP-1 levels will be measured by ELISA.	At time of recruitment
Correlation of sVAP-1 levels with patient characteristics: Parity	Parity will be recorded as the number of births with a gestational age of 24 weeks. sVAP-1 levels will be measured by ELISA.	At time of recruitment
Correlation of sVAP-1 levels with patient characteristics: Gravidity	Gravidity will be recorded as the total number of pregnancies. sVAP-1 levels will be measured by ELISA.	At time of recruitment
Correlation of sVAP-1 levels with patient characteristics: Pre-existing medical conditions	Pre-existing medical conditions will be recorded as reported on the patient's medical records. sVAP-1 levels will be measured by ELISA.	At time of recruitment
Correlation of sVAP-1 levels with patient characteristics: Medications at time of booking	Medications at time of booking will be recorded as reported on the patient's medical records. sVAP-1 levels will be measured by ELISA.	At time of recruitment

Collaborators and Investigators

• Sponsor: University of Leicester

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2021
• Primary Completion (Actual): October 7, 2021
• Study Completion (Actual): October 7, 2021

Study Registration Dates

• First Submitted: April 26, 2021
• First Submitted That Met QC Criteria: May 12, 2021
• First Posted (Actual): May 18, 2021

Study Record Updates

• Last Update Posted (Actual): August 11, 2022
• Last Update Submitted That Met QC Criteria: August 8, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Miscarriage; Pre-eclampsia; Gestational diabetes; Stillbirth; Fetal growth restriction; Hypertension in pregnancy; Large for gestational age
• Additional Relevant MeSH Terms: Pregnancy Complications
• Other Study ID Numbers: 0820; 289532 (Other Identifier: IRAS); 21/EM/0090 (Other Identifier: Leicester Central Research Ethics Committee)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We have no plans to share individual participant data.

Drug and device information, study documents

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