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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Fetal Growth Restriction, Cardiac Remodeling, Ventricular, Placental Insufficiency, Air Pollution

Intervention / Treatment
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* Other: sample collection


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Fetal growth restricted<br>Observation of cardiac remodeling perinatal and postnatal | Other: sample collection<br>* 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<br>|
| Appropriately grown<br>Observation of cardiac remodeling perinatal and postnatal | Other: sample collection<br>* 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<br>|

What is the study measuring?
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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 |