Cardiac Output Monitoring to Predict Pre-Eclampsia and Restricted Growth (COMPaRE)

Study Overview
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Brief Summary
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Pre-eclampsia (PET) and fetal growth restriction (FGR) are common complications of pregnancy that affect up to 15% of pregnancies in the UK. These conditions can have potentially devastating consequences to mothers and babies in pregnancy. Pre-term birth, that is often medically indicated to treat severe PET and FGR can cause cerebral palsy, breathing difficulty, developmental delay and even death in affected babies. Mothers who suffer from PET are at risk of seizures, strokes, multi-organ failure and future chronic hypertension. It is now thought that PET and FGR may result from poor adaptation of the maternal cardiovascular system to normal pregnancy. This project aims to study the patterns within the maternal cardiovascular system and haemodynamic profile in women who are at high risk of PET and FGR by using non-invasive methods to gather information about the functions of their hearts and major blood vessels. The investigators hope to elucidate the patterns that may offer an early warning to mothers who may develop PET and whose fetuses may be growth restricted. This would be an opportunity to more closely monitor, modify risk factors and treat earlier women who develop these conditions. Women who are at a high risk of PET and FGR as stipulated in the relevant Royal College of Obstetrics & Gynaecology and National Institute of Clinical Excellence guidelines and who give their consent will be eligible for the study.

Official Title
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Serial Maternal Haemodynamic Monitoring in Pregnancy for the Prediction of Pre-eclampsia and Fetal Growth Restriction in a High-risk Population

Conditions
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Fetal Growth Retardation, Pre-Eclampsia

Intervention / Treatment
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* Diagnostic Test: Non-invasive haemodynamic assessment
* Diagnostic Test: Maternal ophthalmic artery doppler


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women aged ≥18 at time of conception Case subjects are at high risk of PET by NICE guidelines ( ≥1 high risk factor or >1 moderate risk factor) or high risk of SGA by RCOG Guidelines (≥1 major risk factor or ≥3 minor risk factors). Control subjects do not meet this criteria Exclusion Criteria: Maternal age <18 years of age at time of booking Fetal structural or genetic abnormality Multiple pregnancy Known underlying maternal cardiac condition

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Low Risk<br>These patients are screened to be low-risk for pre-eclampsia and fetal growth restriction by the guidelines set out by the National Institute for Health and Care Excellence; and the Royal College of Obstetricians & Gynaecologists, respectively. | Diagnostic Test: Non-invasive haemodynamic assessment<br>* Maternal non-invasive haemodynamic assessment: a pressure cuff (similar to the one used to measure blood pressure) is applied to the arm and thigh, and a further neck sensor applied. Information about the function of heart and major blood vessels are recorded<br>Diagnostic Test: Maternal ophthalmic artery doppler<br>* Maternal ophthalmic artery doppler: an ultrasound probe is applied gently over the eyelid for a few seconds to study the blood flow of the main artery to the eye<br>|
| High Risk<br>These patients are screened to be high-risk for pre-eclampsia and fetal growth restriction by the guidelines set out by the National Institute for Health and Care Excellence; and the Royal College of Obstetricians & Gynaecologists, respectively. | Diagnostic Test: Non-invasive haemodynamic assessment<br>* Maternal non-invasive haemodynamic assessment: a pressure cuff (similar to the one used to measure blood pressure) is applied to the arm and thigh, and a further neck sensor applied. Information about the function of heart and major blood vessels are recorded<br>Diagnostic Test: Maternal ophthalmic artery doppler<br>* Maternal ophthalmic artery doppler: an ultrasound probe is applied gently over the eyelid for a few seconds to study the blood flow of the main artery to the eye<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnosis of pre-eclampsia | This is defined as hypertension of >140/90 mmHg and significant proteinuria. This is defined as urinalysis showing proteinuria of >1+ or laboratory-quantified urine protein:creatinine ratio of >30mg/mmol. These are assessed at every study visit. | From 20 weeks gestation to 12 weeks post-partum. | 
| Diagnosis of fetal growth restriction | This is diagnosed on ultrasound or at birth. During ultrasound scans at visits 2 and 3, fetal weight is estimated using the Hadlock formula from measurements of the fetal abdominal circumference, femur length and head circumference. This is then plotted onto customised growth chart. Fetal growth restriction is diagnosed antenatally when the estimated fetal weight is under the 3rd centile or under the 10th centile in the presence of abnormal ultrasound dopplers. Abnormal ultrasound dopplers are defined as raised pulsatility index in the fetal umbilical artery, middle cerebral artery or ductus venosus. At birth, fetal growth restriction is diagnosed when the measured birthweight plots under the 10th centile on the customised growth chart. | From 20 weeks gestation to birth. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy outcome | This is concerned with the 3 possible outcomes of the pregnancy: livebirth, stillbirth or neonatal death. | From birth to 12 weeks of age | 
| Gestational age at delivery | This is the recorded age of gestation at the time of delivery, in weeks and days | At delivery | 
| Birthweight centile | This is a measure of the baby's weight at birth, in grams. This is then plotted onto a customised growth chart, accounting for maternal ethnicity and body mass index. | At birth | 
| Duration of neonatal unit admission | This is concerned with whether the baby is admitted to the neonatal admission unit following delivery. If admitted, duration would be quantified in days and hours. | At delivery | 
| Intrapartum or immediate postpartum complications. | This is concerned with the development of complications in the mother, in relation to haemorrhage and hypertensive disorders. | From the onset of active labour (4cm cervical dilatation and regular contractions of 3-4:10 minutes) till 48 hours post-delivery | 
| Persistence of maternal haemodynamic changes | Maternal haemodynamic changes assessed postpartum showing the persistence of haemodynamic changes noted antenatally | 6-12 weeks postpartum (during study visit 4) |