Clinical trial NCT05423665: Speckle Tracking Echocardiography as a Tool for Early Diagnosis of Impaired Fetal Growth Twin Pregnancies
Official title: Speckle Tracking Echocardiography as a Tool for Early Diagnosis of Impaired Fetal Growth in Twin Pregnancies
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Fetal Growth Restriction
Cardiac Remodeling, Ventricular
Placental Insufficiency
Air Pollution
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: KU Leuven
name: Maxima Medical Center
name: Hasselt University
First posted: 2022-06-21
Enrollment: 360
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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)

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: To assess the change in strain measured by speckle tracking echocardiography as a tool for early diagnosis of impaired fetal growth in multiple gestations
timeFrame: Prenatal to 1-3 days after birth
measure: To determine the intra-pair differences in fetal growth and strain (cardiac remodeling) in multiple gestations.
timeFrame: Prenatal to 1-3 days after birth
measure: To compare the strain values (cardiac remodeling) between singletons and twin pregnancies
timeFrame: Prenatal to 1-3 days after birth
Secondary outcomes:
measure: To investigate the association between placenta functioning and in utero cardiac remodeling
timeFrame: Prenatal to 1-3 days after birth
measure: To explore in utero cardiac remodeling in association with neonatal cardiovascular health
timeFrame: Prenatal to 1-3 days after birth
measure: To study the association between prenatal air pollution exposure and in utero cardiac remodeling
timeFrame: Prenatal to 1-3 days after birth
measure: To investigate placenta functioning as a mediator between air pollution and cardiac remodeling
timeFrame: Prenatal to 1-3 days after birth
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Ghent University Hospital
city: Leuven
country: Belgium
facility: Universitair ziekenhuis Leuven
city: Eindhoven
country: Netherlands
facility: Maxima medical center
Study officials:
affiliation: University Hospital, Ghent
name: Kristien Roelens
role: PRINCIPAL_INVESTIGATOR
References: