Non-invasive fetal electrocardiography, electrohysterography and speckle-tracking echocardiography in the second trimester: study protocol of a longitudinal prospective cohort study (BEATS-study)

Background Worldwide, hypertensive disorders of pregnancy (HDP), fetal growth restriction (FGR) and preterm birth remain the leading causes of maternal and fetal pregnancy-related mortality and (long-term) morbidity. Fetal cardiac deformation changes can be the first sign of placental dysfunction, which is associated with HDP, FGR and preterm birth. In addition, preterm birth is likely associated with changes in electrical activity across the uterine muscle. Therefore, fetal cardiac function and uterine activity can be used for the early detection of these complications in pregnancy. Fetal cardiac function and uterine activity can be assessed by two-dimensional speckle-tracking echocardiography (2D-STE), non-invasive fetal electrocardiography (NI-fECG), and electrohysterography (EHG). This study aims to generate reference values for 2D-STE, NI-fECG and EHG parameters during the second trimester of pregnancy and to investigate the diagnostic potential of these parameters in the early detection of HDP, FGR and preterm birth. Methods In this longitudinal prospective cohort study, eligible women will be recruited from a tertiary care hospital and a primary midwifery practice. In total, 594 initially healthy pregnant women with an uncomplicated singleton pregnancy will be included. Recordings of NI-fECG and EHG will be made weekly from 22 until 28 weeks of gestation and 2D-STE measurements will be performed 4-weekly at 16, 20, 24 and 28 weeks gestational age. Retrospectively, pregnancies complicated with pregnancy-related diseases will be excluded from the cohort. Reference values for 2D-STE, NI-fECG and EHG parameters will be assessed in uncomplicated pregnancies. After, 2D-STE, NI-fCG and EHG parameters measured during gestation in complicated pregnancies will be compared with these reference values. Discussion This will be the a large prospective study investigating new technologies that could potentially have a high impact on antepartum fetal monitoring. Trial registration Registered on 26 March 2020 in the Dutch Trial Register (NL8769) via https://www.trialregister.nl/trials and registered on 21 October 2020 to the Central Committee on Research Involving Human Subjects (NL73607.015.20) via https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm.

Evaluation of fetal cardiac function in maternal gestational diabetes mellitus by speckle tracking echocardiography

The aim of this study was to assess the cardiac function in fetuses of mothers with gestational diabetes mellitus (GDM) by using fetalHQ, a quantitative analysis software for the assessment of fetal cardiac function based on speckle tracking echocardiography. In this prospective cross-sectional study, 49 fetuses exposed to GDM and 50 normal fetuses were enrolled and fetal echocardiography were performed and analyzed. In the GDM group, left ventricular (24 ± 4 vs. 28 ± 4, p < 0.001) and right ventricular global longitudinal strain (23 ± 4 vs. 26 ± 4, p = 0.002) and right ventricular free wall strain (26 ± 6 vs. 29 ± 5, p = 0.006) were significantly lower compared with the control group, whereas there was no significant difference in global spherical index (1.2 ± 0.1 vs. 1.2 ± 0.1, p = 0.425). Additionally, 24-segment transverse fraction shortening of the right ventricle was more impaired than the left and the segments with reduced fraction shortening were mainly located in the mid and apical sections of the right ventricle, and mid section of the left ventricle. In conclusion, fetuses exposed to GDM may have cardiac dysfunction before the onset of cardiac morphologic abnormalities, and the right ventricle is more vulnerable than the left during fetal development.

Spectral Doppler, tissue Doppler, and speckle-tracking echocardiography for the evaluation of fetal cardiac function: an update

The functional assessment of the fetal heart has been incorporated into cardiac ultrasound screening as a routine procedure, encompassing fetuses with and without structural heart diseases. It has long been known that various cardiac and extracardiac conditions, such as fetal growth restriction, fetal tumors, twin-to-twin transfusion syndrome, fetal anemia, diaphragmatic hernia, arteriovenous fistula with high cardiac output, and congenital heart diseases (valvular regurgitation and primary myocardial disease), can alter hemodynamic status and fetal cardiac function. Several ultrasound and Doppler echocardiographic parameters of fetal cardiovascular disease have been shown to correlate with perinatal mortality. However, it is still difficult to identify the signs of fetal heart failure and to determine their relationship with prognosis. The aim of this study was to review the main two-dimensional Doppler ultrasound parameters that can be used in the evaluation of fetal cardiac function, with a focus on how to perform that evaluation and on its clinical applicability.

Echocardiographic assessment of fetal cardiac function in the uterine artery ligation rat model of IUGR

Background Intrauterine growth restriction (IUGR) leads to cardiac dysfunction and adverse remodeling of the fetal heart, as well as a higher risk of postnatal cardiovascular diseases. The rat model of IUGR, via uterine artery ligation, is a popular model but its cardiac sequelae is not well investigated. Here, we performed an echocardiographic evaluation of its cardiac function to determine how well it can represent the disease in humans. Methods Unilateral uterine artery ligation was performed at embryonic day 17 (E17) and echocardiography was performed at E19 and E20. Results Growth-restricted fetuses were significantly smaller and lighter, and had an higher placenta-to-fetus weight ratio. Growth-restricted fetal hearts had reduced wall thickness-to-diameter ratio, indicating left ventricular (LV) dilatation, and they had elevated trans-mitral and trans-tricuspid E/A ratios and reduced left and right ventricular fractional shortening (FS), suggesting systolic and diastolic dysfunction. These were similar to human IUGR fetuses. However, growth-restricted rat fetuses did not demonstrate head-sparing effect, displayed a lower LV myocardial performance index, and ventricular outflow velocities were not significantly reduced, which were dissimilar to human IUGR fetuses. Conclusions Despite the differences, our results suggest that this IUGR model has significant cardiac dysfunction, and could be a suitable model for studying IUGR cardiovascular physiology. Impact Animal models of IUGR are useful, but their fetal cardiac function is not well studied, and it is unclear if they can represent human IUGR fetuses. We performed an echocardiographic assessment of the heart function of a fetal rat model of IUGR, created via maternal uterine artery ligation. Similar to humans, the model displayed LV dilatation, elevated E/A ratios, and reduced FS. Different from humans, the model displayed reduced MPI, and no significant outflow velocity reduction. Despite differences with humans, this rat model still displayed cardiac dysfunction and is suitable for studying IUGR cardiovascular physiology.