First-trimester Placental Ultrasound Study

Pregnancy Complications Clinical Trial

— First PLUS  

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05326191
• Other study ID #: 22/WM/0039
• Status: Completed
• Start date: March 15, 2022
• Est. completion date: May 30, 2023

Study information

• Verified date: December 2023
• Source: Perspectum
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4000
• Est. completion date: May 30, 2023
• Est. primary completion date: November 14, 2022
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fetal Growth Complications
• Pregnancy Complications

Intervention

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.

Locations

Country	Name	City	State
United Kingdom	King's College Hospital NHS, Fetal Medicine Foundation	London

Sponsors (3)

Lead Sponsor	Collaborator
Perspectum	Fetal Medicine Foundation, University of Oxford

Country where clinical trial is conducted

United Kingdom, 

References & Publications (44)

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Cheong KB, Leung KY, Li TK, Chan HY, Lee YP, Tang MH. Comparison of inter- and intraobserver agreement and reliability between three different types of placental volume measurement technique (XI VOCAL, VOCAL and multiplanar) and validity in the in-vitro setting. Ultrasound Obstet Gynecol. 2010 Aug;36(2):210-7. doi: 10.1002/uog.7609. — View Citation

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Collins SL, Birks JS, Stevenson GN, Papageorghiou AT, Noble JA, Impey L. Measurement of spiral artery jets: general principles and differences observed in small-for-gestational-age pregnancies. Ultrasound Obstet Gynecol. 2012 Aug;40(2):171-8. doi: 10.1002/uog.10149. — View Citation

Collins SL, Stevenson GN, Noble JA, Impey L. Rapid calculation of standardized placental volume at 11 to 13 weeks and the prediction of small for gestational age babies. Ultrasound Med Biol. 2013 Feb;39(2):253-60. doi: 10.1016/j.ultrasmedbio.2012.09.003. Epub 2012 Dec 4. — View Citation

Collins SL, Welsh AW, Impey L, Noble JA, Stevenson GN. 3D fractional moving blood volume (3D-FMBV) demonstrates decreased first trimester placental vascularity in pre-eclampsia but not the term, small for gestation age baby. PLoS One. 2017 Jun 1;12(6):e0178675. doi: 10.1371/journal.pone.0178675. eCollection 2017. — View Citation

Cottrell E, Tropea T, Ormesher L, Greenwood S, Wareing M, Johnstone E, Myers J, Sibley C. Dietary interventions for fetal growth restriction - therapeutic potential of dietary nitrate supplementation in pregnancy. J Physiol. 2017 Aug 1;595(15):5095-5102. doi: 10.1113/JP273331. Epub 2017 Feb 27. — View Citation

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Dilworth MR, Andersson I, Renshall LJ, Cowley E, Baker P, Greenwood S, Sibley CP, Wareing M. Sildenafil citrate increases fetal weight in a mouse model of fetal growth restriction with a normal vascular phenotype. PLoS One. 2013 Oct 30;8(10):e77748. doi: 10.1371/journal.pone.0077748. eCollection 2013. — View Citation

Farina A. Systematic review on first trimester three-dimensional placental volumetry predicting small for gestational age infants. Prenat Diagn. 2016 Feb;36(2):135-41. doi: 10.1002/pd.4754. Epub 2016 Jan 19. — View Citation

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Gordijn SJ, Beune IM, Thilaganathan B, Papageorghiou A, Baschat AA, Baker PN, Silver RM, Wynia K, Ganzevoort W. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol. 2016 Sep;48(3):333-9. doi: 10.1002/uog.15884. — View Citation

Hafner E, Metzenbauer M, Hofinger D, Stonek F, Schuchter K, Waldhor T, Philipp K. Comparison between three-dimensional placental volume at 12 weeks and uterine artery impedance/notching at 22 weeks in screening for pregnancy-induced hypertension, pre-eclampsia and fetal growth restriction in a low-risk population. Ultrasound Obstet Gynecol. 2006 Jun;27(6):652-7. doi: 10.1002/uog.2641. — View Citation

Huang SF, Chang RF, Moon WK, Lee YH, Chen DR, Suri JS. Analysis of tumor vascularity using three-dimensional power Doppler ultrasound images. IEEE Trans Med Imaging. 2008 Mar;27(3):320-30. doi: 10.1109/TMI.2007.904665. — View Citation

Huang YH, Chen JH, Chang YC, Huang CS, Moon WK, Kuo WJ, Lai KJ, Chang RF. Diagnosis of solid breast tumors using vessel analysis in three-dimensional power Doppler ultrasound images. J Digit Imaging. 2013 Aug;26(4):731-9. doi: 10.1007/s10278-012-9556-5. — View Citation

Jones TB, Price RR, Gibbs SJ. Volumetric determination of placental and uterine growth relationships from B-mode ultrasound by serial area-volume determinations. Invest Radiol. 1981 Mar-Apr;16(2):101-6. doi: 10.1097/00004424-198103000-00005. — View Citation

Law LW, Leung TY, Sahota DS, Chan LW, Fung TY, Lau TK. Which ultrasound or biochemical markers are independent predictors of small-for-gestational age? Ultrasound Obstet Gynecol. 2009 Sep;34(3):283-7. doi: 10.1002/uog.6455. — View Citation

LEE TC, KASHYAP RL, CHU CN. Building Skeleton Models via 3-D Medial Surface Axis Thinning Algorithms. CVGIP: Graphical Models and Image Processing 1994;56:462-78

Looney P, Stevenson GN, Nicolaides KH, Plasencia W, Molloholli M, Natsis S, Collins SL. Fully automated, real-time 3D ultrasound segmentation to estimate first trimester placental volume using deep learning. JCI Insight. 2018 Jun 7;3(11):e120178. doi: 10.1172/jci.insight.120178. eCollection 2018 Jun 7. — View Citation

Looney P, Yin Y, Collins SL, Nicolaides KH, Plasencia W, Molloholli M, Natsis S, Stevenson GN. Fully Automated 3-D Ultrasound Segmentation of the Placenta, Amniotic Fluid, and Fetus for Early Pregnancy Assessment. IEEE Trans Ultrason Ferroelectr Freq Control. 2021 Jun;68(6):2038-2047. doi: 10.1109/TUFFC.2021.3052143. Epub 2021 May 25. — View Citation

Looney PT, Stevenson GN, Collins SL. 3D ultrasound file reading and coordinate transformations. J Open Source Softw. 2019;4(33):1063. doi: 10.21105/joss.01063. Epub 2019 Jan 11. — View Citation

Monier I, Blondel B, Ego A, Kaminiski M, Goffinet F, Zeitlin J. Poor effectiveness of antenatal detection of fetal growth restriction and consequences for obstetric management and neonatal outcomes: a French national study. BJOG. 2015 Mar;122(4):518-27. doi: 10.1111/1471-0528.13148. Epub 2014 Oct 27. — View Citation

Mosimann B, Pfiffner C, Amylidi-Mohr S, Risch L, Surbek D, Raio L. First trimester combined screening for preeclampsia and small for gestational age - a single centre experience and validation of the FMF screening algorithm. Swiss Med Wkly. 2017 Aug 25;147:w14498. doi: 10.4414/smw.2017.14498. eCollection 2017. — View Citation

Pijnenborg R, Vercruysse L, Hanssens M. The uterine spiral arteries in human pregnancy: facts and controversies. Placenta. 2006 Sep-Oct;27(9-10):939-58. doi: 10.1016/j.placenta.2005.12.006. Epub 2006 Feb 20. — View Citation

Pillay T, Modi N, Rivero-Arias O, Manktelow B, Seaton SE, Armstrong N, Draper ES, Dawson K, Paton A, Ismail AQT, Yang M, Boyle EM. Optimising neonatal service provision for preterm babies born between 27 and 31 weeks gestation in England (OPTI-PREM), using national data, qualitative research and economic analysis: a study protocol. BMJ Open. 2019 Aug 22;9(8):e029421. doi: 10.1136/bmjopen-2019-029421. — View Citation

Plasencia W, Akolekar R, Dagklis T, Veduta A, Nicolaides KH. Placental volume at 11-13 weeks' gestation in the prediction of birth weight percentile. Fetal Diagn Ther. 2011;30(1):23-8. doi: 10.1159/000324318. Epub 2011 Jun 23. — View Citation

Riley RD, Snell KI, Ensor J, Burke DL, Harrell FE Jr, Moons KG, Collins GS. Minimum sample size for developing a multivariable prediction model: PART II - binary and time-to-event outcomes. Stat Med. 2019 Mar 30;38(7):1276-1296. doi: 10.1002/sim.7992. Epub 2018 Oct 24. Erratum In: Stat Med. 2019 Dec 30;38(30):5672. — View Citation

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Salvesen K, Lees C, Abramowicz J, Brezinka C, Ter Haar G, Marsal K; Board of International Society of Ultrasound in Obstetrics and Gynecology (ISUOG). ISUOG statement on the safe use of Doppler in the 11 to 13 +6-week fetal ultrasound examination. Ultrasound Obstet Gynecol. 2011 Jun;37(6):628. doi: 10.1002/uog.9026. No abstract available. — View Citation

Shia WC, Chen DR, Huang YL, Wu HK, Kuo SJ. Effectiveness of evaluating tumor vascularization using 3D power Doppler ultrasound with high-definition flow technology in the prediction of the response to neoadjuvant chemotherapy for T2 breast cancer: a preliminary report. Phys Med Biol. 2015 Oct 7;60(19):7763-78. doi: 10.1088/0031-9155/60/19/7763. — View Citation

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Wareing M, Myers JE, O'Hara M, Baker PN. Sildenafil citrate (Viagra) enhances vasodilatation in fetal growth restriction. J Clin Endocrinol Metab. 2005 May;90(5):2550-5. doi: 10.1210/jc.2004-1831. Epub 2005 Feb 15. — View Citation

Welsh AW, Fowlkes JB, Pinter SZ, Ives KA, Owens GE, Rubin JM, Kripfgans OD, Looney P, Collins SL, Stevenson GN. Three-dimensional US Fractional Moving Blood Volume: Validation of Renal Perfusion Quantification. Radiology. 2019 Nov;293(2):460-468. doi: 10.1148/radiol.2019190248. Epub 2019 Oct 1. — View Citation

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Yin Y, Looney P, Collins SL. Standardization of blood flow measurements by automated vascular analysis from power Doppler ultrasound scan. Proc SPIE Int Soc Opt Eng. 2020 Feb;11314:113144C. doi: 10.1117/12.2549349. Epub 2020 Mar 16. No abstract available. — View Citation

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* Note: There are 44 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Preterm Birth	Birth =24+0 weeks <37+0 weeks	24 months
Secondary	Miscarriage	Live fetus at the first-trimester ultrasound scan but subsequent in utero fetal death or delivery <24+0 weeks	24 months
Secondary	Stillbirth	Baby born with no signs of life at =24+0 weeks' gestation	24 months
Secondary	Neonatal death	Baby born alive but dies within the first 28 days of life	24 months
Secondary	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