PlaCEUS: Feasibility Study of Contrast-enhanced Ultrasound to Visualize Maternal Uterine Spiral Arteries Postpartum.

Обзор

During pregnancy, unique blood vessels form within the uterine wall, known as spiral arteries. These vessels originate from the uterine artery, which is the main artery supplying blood to the uterus. Throughout pregnancy, spiral arteries undergo significant changes to increase blood and oxygen flow to the placenta, ensuring the developing baby receives adequate nutrients. When these arteries fail to remodel properly, complications such as pre-eclampsia or fetal growth restriction can occur. Until now, direct observation and evaluation of spiral arteries during pregnancy has not been feasible. Contrast-enhanced ultrasound may provide a breakthrough in this area. In this study, the investigators aim to use this imaging technique to visualize spiral arteries after the placenta has been delivered. If successful, this could allow to assess their structural quality. Additionally, the investigators will employ ultrasound to monitor physiological changes in the uterine artery during late pregnancy (after 37 weeks), during labour, and postpartum. By conducting these measurements, the investigators hope to develop methods for detecting spiral artery abnormalities earlier in pregnancy. Early identification could enable timely interventions and help prevent severe complications.

Подробное описание

Adequate blood flow to the placenta is critical for normal fetal development and positive pregnancy outcomes. A key component of this process is the maternal uterine spiral arteries, which undergo significant physiological remodeling during pregnancy to meet the growing demands of the fetus. When this remodeling is impaired, it has been linked to complications such as preeclampsia, fetal growth restriction, and placental abruption.

Despite its importance, directly and non-invasively assessing the maternal uterine microvasculature-particularly spiral arteries-remains difficult. Conventional Doppler ultrasound only provides indirect insights by estimating vascular resistance at a macroscopic level and cannot visualize spiral arteries or directly evaluate placental perfusion. Contrast-enhanced ultrasound (CEUS) represents a promising alternative, as it improves visualization of small vessels through the use of ultrasound contrast agents (UCAs). Since UCAs are currently not approved for use during pregnancy, this study focuses on assessing the feasibility of CEUS for visualizing persistent spiral arteries in the immediate postpartum period, as an initial step toward investigating the maternal side of the placenta. In addition, Doppler waveform analysis of the uterine arteries will be performed at three time points: before delivery, during labor, and after birth. Combining CEUS with Doppler imaging may provide a more comprehensive understanding of dynamic uteroplacental vascular changes around delivery.

The primary objectives are to determine whether maternal uterine spiral arteries remain present after delivery and to evaluate the feasibility of CEUS with UCAs in visualizing and characterizing these arteries within four hours postpartum.

Secondary objectives include assessing uterine artery Doppler parameters before, during, and after delivery to describe peripartum hemodynamic changes, and correlating CEUS findings at four hours postpartum with Doppler measurements.

Вмешательства

• Диагностический тест SonoVue (sulphur hexafluoride microbubbles)
  SonoVue will be used in this study as ultrasound contrast agents for contrast enhanced ultrasound to assess the feasibility in visualizing and charactering the persistence of maternal uterine spiral arteries within 4 hours postpartum.

Первичные конечные точки

• Number of participants with persisting spiral arteries detected by contrast enhanced ultrasound within 4 hours postpartum. [Срок оценки: Within 4 hours postpartum]
• Feasibility of Contrast Enhanced Ultrasound (CEUS) with Sonovue for visualizing spiral arteries within 4 hours postpartum. Dichotomous outcome; visible or invisible spiral arteries. [Срок оценки: Within 4 hours postpartum]

Вторичные конечные точки (4)

• Change in uterine artery Resistance Index (RI) across peripartum period [Срок оценки: Before delivery (after 37 weeks of gestation), during delivery (when in active labour or at the same day prior to a Caesarean delivery), and within 4 hours postpartum.]
• Change in uterine artery Pulsatility Index (PI) across peripartum period [Срок оценки: Before delivery (after 37 weeks of gestation), during delivery (when in active labour or at the same day prior to a Caesarean delivery), and within 4 hours postpartum.]
• Change in uterine artery Systolic/Diastolic Ratio across peripartum period [Срок оценки: Before delivery (after 37 weeks of gestation), during delivery (when in active labour or at the same day prior to a Caesarean delivery), and within 4 hours postpartum.]
• Correlating CEUS findings with uterine artery Doppler parameters within 4 hours postpartum [Срок оценки: Within 4 hours postpartum]

Критерии участия

Критерии включения

• Pregnant patient at a minimum age of 18 years
• Singleton pregnancy at term (≥37 weeks gestation)
• Planning to deliver at the Máxima Medical Centre
• Able to provide informed consent
• Intravenous access present at the time of delivery

Критерии исключения

• Multiple gestation pregnancy
• Contra-indications to CEUS, e.g. known allergy for constituents of SonoVue™
• Planning on breastfeeding
• Medical emergency during or after delivery, which makes CEUS impossible or undesirable
• No intravenous access present at the time of delivery
• Body Mass Index >40 kg/m2.
• Pre-eclampsia requiring medication
• Foetal growth restriction < p3

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Нидерланды · 1 центр

• Máxima Medical center — Veldhoven

Публикации

• 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. PMID 22102536
• Roberts VHJ, Morgan TK, Bednarek P, Morita M, Burton GJ, Lo JO, Frias AE. Early first trimester uteroplacental flow and the progressive disintegration of spiral artery plugs: new insights from contrast-enhanced ultrasound and tissue histopathology. Hum Reprod. 2017 Dec 1;32(12):2382-2393. doi: 10.1093/humrep/dex301. PMID 29136193
• Li Q, Yang K, Ji Y, Liu H, Fei X, Zhang Y, Li J, Luo Y. Safety Analysis of Adverse Events of Ultrasound Contrast Agent Lumason/SonoVue in 49,100 Patients. Ultrasound Med Biol. 2023 Feb;49(2):454-459. doi: 10.1016/j.ultrasmedbio.2022.09.014. Epub 2022 Nov 7. PMID 36357252
• Claudon M, Cosgrove D, Albrecht T, Bolondi L, Bosio M, Calliada F, Correas JM, Darge K, Dietrich C, D'Onofrio M, Evans DH, Filice C, Greiner L, Jager K, Jong Nd, Leen E, Lencioni R, Lindsell D, Martegani A, Meairs S, Nolsoe C, Piscaglia F, Ricci P, Seidel G, Skjoldbye B, Solbiati L, Thorelius L, Tranquart F, Weskott HP, Whittingham T. Guidelines and good clinical practice recommendations for contr PMID 18270887
• Dassen S, Monen L, Oei G, Mischi M, van Laar J. Safety of contrast-enhanced ultrasound using microbubbles in human pregnancy: A scoping review. Ultraschall Med. 2025 Jun;46(3):259-269. doi: 10.1055/a-2351-0747. Epub 2024 Jun 24. PMID 38914129
• European Medicines Agency (EMA). SonoVue, INN-sulphur hexafluoride: EPAR - Product Information. EMA. Last updated: 05 June 2023. Available from: https://www.ema.europa.eu/en/documents/product-information/sonovue-epar-product-information_en.pdf

Идентификаторы

NCT: NCT07422181 · NL010727

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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