Aim
The aim of this study is to determine reference values for the fetal myocardial deformation parameters strain and strain rate in healthy fetuses during gestation.
Study design
A prospective cohort study will be performed. This study is approved by the medical ethical committee of the Máxima Medical Centre, Veldhoven, The Netherlands (NL64999.015.18).
Setting
Fetal heart ultrasounds are performed at the Máxima Medical Centre, Veldhoven, The Netherlands. The Máxima Medical Centre is a tertiary care teaching hospital for obstetrics. The fetal heart ultrasounds are performed by certified and experienced sonographers.
Participants
Women with an uneventful singleton pregnancy will be included in the study after written consent. The second trimester anomaly scan should be without any congenital anomalies that could possibly interfere with cardiac function. Patients will be included from 19 to 21 + 6 weeks gestational age. Women must be at least 18 years old.
Exclusion criteria are multiple pregnancies, insufficient understanding of the Dutch language, fetal arrhythmia, any suspicion of fetal congenital anomalies that might influence fetal cardiac function, pre-existing maternal hypertensive disease and auto-immune disease including SLE or Diabetes Mellitus.
Women who develop fetal growth restriction, hypertensive disease or gestational diabetes after inclusion will be excluded from the cohort.
10 Weeks postpartum information about the delivery and neonatal parameters as birth weight and Apgar score will be collected from the primary caregiver. If the neonate turns out to have any unexpected congenital anomalies that might influence fetal cardiac function, the patient will be excluded from the cohort.
Sample size
To obtain normal values and 95% confidence intervals of healthy fetuses a study population of 100 uneventful pregnancies is needed [18]. 25 Participants are expected to be excluded due to pregnancy complications that appear after inclusion. Namely, 7–10% of uncomplicated pregnancies become complicated by FGR, 7–10% by maternal hypertensive disease and in 3–5% gestational diabetes will be diagnosed. This implicates that 10 participants are expected to be excluded due to fetal growth restriction, 10 due to hypertensive disease and 5 due to GDM. Anticipating on 25% insufficient data [19,20,21,22], another 25 participants will be excluded from the cohort. Therefore, to obtain 100 healthy participants in the cohort, 150 participants will be included initially.
Procedures
Conduction gel will be applied to the women’s abdomen to perform the fetal heart ultrasound scan. The ultrasound is performed with a Philips EPIQ 7 W ultrasound system (Philips, Eindhoven, The Netherlands) by an experienced sonographer. The ultrasound setting used is standardised for fetal heart echocardiography. The pregnant woman will be lying down in a semi-recumbent position to prevent aortocaval compression. The fetal heart ultrasounds will be performed every 4 weeks. The ultrasound examinations will start from the moment of inclusion. Women will be included from 19 to 21 + 6 weeks gestational age. The ultrasound follow up measurements will be performed until 41 weeks gestational age or delivery.
After the four chamber view is visualized, 3 to 6 DICOM clips of at least 3 heart cycles will be performed and stored offline. The DICOMs are acquired during fetal rest, with the pregnant woman holding her breath for a few seconds, to avoid as much artefacts as possible. The stored DICOM data will be examined offline using a fetal cardiac speckle tracking software program (2D Cardiac Performance 1.2) developed by TomTec Imaging Systems GmbH (Munich, Germany). To identify the beginning and end of a cardiac cycle, the anatomic M-Mode feature in the software will be used. A line will be drawn across the left ventricular wall through the ventricle and the septum. A corresponding M-Mode appears. The R waves in the M-Mode correspond to the opening and closure of the mitral valves and will be used to identify one heart cycle. After, the endocardial border for each ventricle will be traced from the junction of the lateral wall annulus to the apex and from the apex to the base of the junction of the septal wall annulus. After the tracing, an automated analysis detects the endocardial border during 1 heart cycle providing fetal cardiac deformation values. The same heart cycle in the same DICOM clip will be examined twice, preventing issues with the repeatability within consecutive cardiac cycles.
The obtained fetal cardiac deformation values will be used to determine reference values.
Study parameters
The fetal myocardial deformation parameters that will be obtained are:
Strain (%): strain represents myocardial deformation in response to an applied force.
Strain rate (1/strain): Strain rate describes the rate of deformation as a percentage of the original dimension.
Statistical analysis
The collected data will be analysed using SPSS_22. Several analysis will be performed.
Analysis of the images will be performed offline by 2 different researchers who are blinded for each other’s results. The images will be examined twice by the same examiner, leaving 4 weeks in between, so the examiner will be blinded for the first results. Inter-and intra-observer variability will be obtained by calculating intraclass correlation coefficients (ICC). Limits of agreement will be assessed using Bland-Altman analysis.
A linear mixed model analysis will be used to determine reference values of fetal cardiac deformation during gestation.