Speckle Tracking Echocardiography as a Tool for Early Diagnosis of Impaired Fetal Growth Twin Pregnancies (HEART)

Speckle Tracking Echocardiography as a Tool for Early Diagnosis of Impaired Fetal Growth in Twin Pregnancies

In this project there are 2 time points during the pregnancy included, namely at 21 weeks and 30 weeks of gestation, to measure the predictive values of FGR, strain and strain rate. The fetal growth parameters will be collected at the same time points, to define the growth (differences) throughout gestation of both fetuses. A maternal blood sample will be taken at 21 weeks of gestation to identify the level of exposure to air pollution (black carbon) and the level of biochemical markers of placental dysfunction. Doppler ultrasounds will be used for antenatal identification of placenta insufficiency. At birth, umbilical cord blood and the placenta will be collected. The placenta will be examined, to identify morphological findings which are associated with FGR. The umbilical cord blood and placental biopsy will be used for the level of exposure to air pollution and the level of oxidative stress. One to three days after birth, neonatal strain and strain rate will be measured to define postnatal cardiac remodeling as well as the neonatal blood pressure as cardiovascular risk factor.

Study Overview

• Status: Recruiting
• Conditions: Air Pollution; Placental Insufficiency; Fetal Growth Restriction; Cardiac Remodeling, Ventricular
• Intervention / Treatment: Other: sample collection

Detailed Description

Fetal growth restriction (FGR) is diagnosed in 5-10% of the pregnancies. After preterm birth, it is the second leading cause of perinatal morbidity and mortality. Twin pregnancies have a higher occurrence of FGR than singletons, in monochorionic (MC) twin pregnancies it's diagnosed in 19.7% of the cases and in dichorionic (DC) twin pregnancies in 10.5% of the cases. Fetuses with FGR are at greater risk of perinatal morbidity and mortality and even long-term health defects. From a public health perspective, it's important to correctly diagnose FGR to adjust the antenatal and postnatal care and to have more insight into the factors influencing early onset cardiovascular disease. STE has a strong predictive value for cardiovascular function, therefore it would be a promising tool to add in the routine pregnancy clinical care. Speckle tracking echocardiography (STE) is a relative new technique especially in the pregnancy follow up, which permits offline calculation of myocardial velocities and deformation parameters. These parameters, including strain and strain rate, provide information about the fetal myocardial function. Apart from investigating if STE can be used for the prediction of FGR, we will also investigate the association between fetal exposure to air pollution and in utero cardiac remodeling. Indeed, it is known that inhalation of particulate matter (e.g. black carbon) during the pregnancy can reach the placenta and lead to alterations in the placenta's function including increases in oxidative stress markers. Early life exposure to black carbon has been associated with adverse cardiovascular health outcomes and reduction of fetal growth, especially in multiple gestation pregnancies.

In this project we will include 2 time points during the pregnancy, namely at 21 weeks and 30 weeks of gestation, to measure the predictive values of FGR, strain and strain rate. The fetal growth parameters will be collected at the same time points, to define the growth (differences) throughout gestation of both fetuses. A maternal blood sample will be taken at 20 weeks of gestation to identify the level of exposure to air pollution (black carbon) and the level of biochemical markers of placental dysfunction. Doppler ultrasounds will be used for antenatal identification of placenta insufficiency. At birth, umbilical cord blood and the placenta will be collected. The placenta will be examined, to identify morphological findings which are associated with FGR. The umbilical cord blood and placental biopsy will be used for the level of exposure to air pollution and the level of oxidative stress. One to three days after birth, neonatal strain and strain rate will be measured to define postnatal cardiac remodeling as well as the neonatal blood pressure as cardiovascular risk factor.

• Study Type: Observational
• Enrollment (Estimated): 360

Contacts and Locations

• Study Contact: Name: Eline Meireson; Phone Number: 0032 9 332 78 17; Email: eline.meireson@uzgent.be

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Recruiting
    • Ghent University Hospital
    • Contact: Kristien Roelens, prof. dr.
  • Leuven, Belgium, 3000
    • Not yet recruiting
    • Universitair Ziekenhuis Leuven
    • Contact: Liebeth Lewie, prof. dr.
• Netherlands
  • Eindhoven, Netherlands, 5631
    • Not yet recruiting
    • Maxima Medical Center
    • Contact: Judith van Laar, dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

The number of subjects that will be included in this study is: 600 neonates (200 twin pairs and 200 singletons) and 400 pregnant mothers.

The fetuses are divided into following sub-groups:

• Appropriately grown
• Fetal growth restricted
• Selective fetal growth restricted (specific for twins)

Description

Inclusion Criteria:

• Singleton or dichorionic twin pregnancy
• Pregnant women 21 weeks ( ± 2 weeks) of gestation at the first visit
• Women ≥ 18 years

Exclusion Criteria:

• Women pregnant of multiples of higher order (≥3 siblings) Monochorionic twin pregnancy
• Fetal arrhythmia
• Known fetal congenital or genetic abnormalities
• Any suspicion of congenital fetal anomalies that might influence fetal cardiac function
• Pre-existing maternal hypertensive disease
• Autoimmune disease including systemic lupus erythematosus
• History of stillbirth
• Diabetes mellitus (mother)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Fetal growth restricted; Observation of cardiac remodeling perinatal and postnatal	Other: sample collection; blood sample at 21 weeks of gestation clips of the fetal heart at 21 weeks of gestation, 30 weeks of gestation and 1-3 days after birth collection of umbilical cord blood at birth collection of the placenta at birth
Appropriately grown; Observation of cardiac remodeling perinatal and postnatal	Other: sample collection; blood sample at 21 weeks of gestation clips of the fetal heart at 21 weeks of gestation, 30 weeks of gestation and 1-3 days after birth collection of umbilical cord blood at birth collection of the placenta at birth

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the change in strain measured by speckle tracking echocardiography as a tool for early diagnosis of impaired fetal growth in multiple gestations	to determine the change in fetal strain and strain rate in twin pregnancies in comparison with fetal growth	Prenatal to 1-3 days after birth
To determine the intra-pair differences in fetal growth and strain (cardiac remodeling) in multiple gestations.	to compare changes in strain and strain rate with fetal growth within 1 twin pair	Prenatal to 1-3 days after birth
To compare the strain values (cardiac remodeling) between singletons and twin pregnancies	to compare the changes in strain and strain rate between singletons and twin pregnancies	Prenatal to 1-3 days after birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To investigate the association between placenta functioning and in utero cardiac remodeling	to evaluate placenta insufficiency (Doppler ultrasound, biochemical marker) with strain and strain rate	Prenatal to 1-3 days after birth
To explore in utero cardiac remodeling in association with neonatal cardiovascular health	to evaluate strain and strain rate with the neonatale blood pressure and heart rate	Prenatal to 1-3 days after birth
To study the association between prenatal air pollution exposure and in utero cardiac remodeling	to evaluate prenatal air pollution (black carbon particles in blood sample mother and placenta) with strain and strain rate	Prenatal to 1-3 days after birth
To investigate placenta functioning as a mediator between air pollution and cardiac remodeling	To evaluate prenatal air pollution (black carbon particles in blood sample mother and placenta) with placenta insufficiency (biochemical marker, Doppler ultrasound)	Prenatal to 1-3 days after birth

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: KU Leuven; Hasselt University; Maxima Medical Center
• Investigators: Principal Investigator: Kristien Roelens, University Hospital, Ghent

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2023
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: May 31, 2022
• First Submitted That Met QC Criteria: June 14, 2022
• First Posted (Actual): June 21, 2022

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Anatomical; Fetal Diseases; Pregnancy Complications; Placenta Diseases; Growth Disorders; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Fetal Growth Retardation; Ventricular Remodeling; Placental Insufficiency
• Other Study ID Numbers: ONZ-2022-0193

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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