First-trimester Placental Ultrasound Study

Study Overview
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Brief Summary
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An observational cohort study to assess the clinical utility of the OxNNet Toolkit for the prediction of adverse pregnancy outcomes.

Detailed Description
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The First PLUS study is a single centre, prospective, observational study recruiting 4000 women from The Harris Birthright Centre, which provides ultrasound scanning for all women who would attend King's College Hospital NHS Foundation Trust for their pregnancy care. This study aims to develop a tool to provide reliable measurements of placental size and estimate the blood flow within the placenta during the first trimester of pregnancy. These metrics hope to develop a screening tool for fetal growth restriction (FGR), which is a condition in which a baby fails to grow to its full potential and can cause adverse pregnancy outcomes and is the single most common cause of stillbirth. This devastating outcome could potentially be reduced by stratifying pregnancies into high risk, allowing women to undergo additional monitoring and limiting clinician resource to those in need of it most. Stillbirth is also a serious adverse pregnancy outcome that NHS England is looking to reduce the rate of as part of their long-term plan. Women 18 years of age or older, attending their first trimester scan during 11-14 weeks of pregnancy, who has a viable pregnancy with no more than one baby with no major defects identified during the scan will be eligible to take part. The study will take place over 24 months and participants will undergo a single study visit in which their demographics and routine medical history will be recorded, an additional research ultrasound scan will be conducted alongside their routine scan, and blood from a sample taken as part of routine care will be used to assess the level of Placental Growth Factor (PlGF). Participants will then be followed up until the completion of their pregnancy via their pregnancy records (remote follow up) and the outcome of their pregnancy will be recorded.

Official Title
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First-trimester Placental Ultrasound Study (First PLUS): an Observational Cohort Study to Assess the Clinical Utility of the OxNNet Toolkit for the Prediction of Adverse Pregnancy Outcomes.

Conditions
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Fetal Growth Complications, Pregnancy Complications

Intervention / Treatment
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* Diagnostic Test: Ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant 18 years of age, or older Presenting for first-trimester combined test screening between 11+0 and 13+6 weeks of pregnancy Participant is willing and able to give informed consent for participation in the investigation. Able to understand written or verbal English and able to access methods of translation. In the opinion of the investigator, the participant is not at risk or under stress or limited in their ability to participate in the study activities. Exclusion Criteria: Participant with a multiple pregnancy (more than one viable fetus) discovered at the scan Participant with a non-viable pregnancy discovered at the scan (no detectable heartbeat) Pregnancies with major defects identified during 11+0 to13+6 week scan Any pregnancy subsequently found to be chromosomally abnormal as a result of either prenatal or postnatal testing

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Ultrasound|All study interventions/procedures will happen during the participants routine clinic visit in which they will receive their routine Ultrasound scan, followed by an additional research scan, which will take approximately 2-3 minutes. A blood sample will also be taken from participants as part of their routine pregnancy care. Residual blood from the same sample will be used to conduct an additional test to quantify Placental Growth Factor (PlGF). Participants will also be asked questions about their relevant medical history and demographic data which is also routinely collected as part of their pregnancy record.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fetal Growth restriction (FGR) | Fetal Growth restriction (FGR) defined according to the ISUOG Delphi consensus guidelines for diagnosis of FGR, at the time of delivery. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Small for Gestational Age (GSA) | Defined if <10 centile on population-based centiles or <10th centile on customised centiles, at the time of delivery. | 24 months | 
| Pre-eclampsia (with, and without, severe features) | Defined by the ACOG guidelines for hypertensive disorders of pregnancy: Pre-term pre-eclampsia (delivery <37 weeks) Late onset pre-eclampsia (delivery ≥37 weeks) | 24 months | 
| Gestational hypertension (PIH) | Defined by the ACOG guidelines for hypertensive disorders of pregnancy: Pre-term gestational hypertension (delivery <37 weeks) Late onset gestational hypertension (delivery ≥37 weeks) | 24 months | 
| Haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome | Defined by the ACOG guidelines for hypertensive disorders of pregnancy: Pre-term HELLP (delivery <37 weeks) Late onset HELLP (delivery ≥37 weeks) Pre-term pre-eclampsia (delivery <37 weeks) | 24 months | 
| Eclampsia | Defined by the ACOG guidelines for hypertensive disorders of pregnancy(22) Pre-term eclampsia (delivery <37 weeks) Late onset eclampsia (delivery ≥37 weeks) | 24 months | 
| Gestational diabetes | Defined as fasting plasma glucose level ≥5.6 mmol/L and/or 2-h plasma glucose level ≥7.8 mmol/L after ingestion of 75g oral glucose. | 24 months | 
| Preterm Birth | Birth ≥24+0 weeks <37+0 weeks | 24 months | 
| Miscarriage | Live fetus at the first-trimester ultrasound scan but subsequent in utero fetal death or delivery <24+0 weeks | 24 months | 
| Stillbirth | Baby born with no signs of life at ≥24+0 weeks' gestation | 24 months | 
| Neonatal death | Baby born alive but dies within the first 28 days of life | 24 months | 
| Neonatal morbidity | Neonatal intensive care unit admission and length of stay Neonatal ventilation - defined as need of positive pressure (CPAP, NCPAP or intubation) Respiratory distress syndrome - defined as need of ventilation with or without surfactant Intraventricular haemorrhage (IVH) grade II or above - defined as bleeding into the ventricles Neonatal sepsis confirmed bacteraemia in cultures Anaemia - defined as low haemoglobin and / or haematocrit requiring blood transfusion Necrotizing enterocolitis requiring surgical intervention | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ultrasound, Fetal Growth, Pregnancy