Speckle tracking echocardiography in growth restricted fetuses.

A promising tool in the evaluation of fetal wellbeing in fetal growth
restriction (FGR) is two-dimensional speckle tracking echocardiography (2D
STE). In 2D STE, movement of the entire myocardium is analyzed. The method does
not use Doppler information, making it less angle dependent, thus attractive to
use in the moving fetus.(1) Speckle tracking echocardiography is already
embedded in the field of adult cardiology (2) and has the potential for broad
application in fetal medicine. However, currently it is poorly integrated since
initially the software was only available on dedicated cardiovascular
ultrasound machines that were not generally available to the broader medical
community. With changes in imaging technology and the availability of
machine-independent software, it is now possible to obtain DICOM clips from
virtually any ultrasound machine used for fetal imaging and to analyze
deformation of the fetal heart with machine-independent software.(3)
One of the most commonly used parameters in 2D STE to assess cardiac function
is strain rate, defined as the velocity of the fractional change of the
myocardial wall. A recent review by van Oostrum et al. (1) shows that studies
on fetal myocardial deformation values (e.g. strain rate) in growth restricted
fetuses, give conflicting results. Patey et al. (4) demonstrate that growth
restricted fetuses have significantly higher left ventricle longitudinal strain
rate compared to pregnancies with normal outcome, suggesting that increased
longitudinal myocardial deformation is required under hypoxemic conditions to
maintain the same cardiac output as that of normal term fetuses. On the
contrary, Crispi et al. (5) and Krause et al. (6) showed no difference in
deformation values between growth restricted- and appropriate for gestational
age fetuses.
FGR increases the risk of (iatrogenic) preterm birth, hence growth restricted
fetuses are prone to receive antenatal steroids to promote fetal lung
maturation. Steroids are powerful regulators of vascular tone; if a
compensatory cardiac mechanism exists in a growth restricted fetus - as
suggested by Patey et al. (4) - administration of steroids might nullify this
mechanism. This, in turn, can lead to cardiac decompensation.
In conclusion, no unambiguous evidence exists concerning 2D STE values of
cardiac function in growth restricted fetuses compared with appropriate for
gestational age fetuses. Through this, it cannot be estimated if the effect of
antenatal steroids on cardiac function of growth restricted fetuses is
detrimental or beneficial.
The primary objective of this study is to investigate left ventricle
longitudinal strain rate in a population of growth restricted fetuses and in a
population of appropriate for gestational age fetuses at baseline (e.g., before
administration of antenatal steroids). We hypothesize - in line with Patey et
al.* (4) - that left ventricle longitudinal strain rate is increased at
baseline in growth restricted fetuses compared with appropriate for gestational
age fetuses.
The secondary objective of this study is to investigate the possible effect of
antenatal steroids on left ventricle longitudinal strain rate between growth
restricted fetuses and appropriate for gestational age fetuses (receiving
antenatal steroids because of an imminent preterm birth). This effect has - to
our knowledge - not yet been assessed using 2D STE. We hypothesize that
antenatal steroids cause a compensatory mechanism - that possibly exists in a
growth restricted fetus (identified by an increased strain rate) - to fade.
Given the fact that 2D STE parameters are not yet fully integrated in clinical
practice, we will also record conventional hemodynamical (Doppler)parameters
before and after administration of antenatal steroids.
The results of this study provide more insight into the baseline left ventricle
strain rate and possible changes in left ventricle strain rate after
administration of corticosteroids in the two study populations. The study is of
essential clinical importance, since the results possibly incite follow-up
comparative research in which is investigated which treatment strategy yields
an optimal balance between fetal lung development and cardiac performance.

*Our hypothesis is in line with Patey et al.(4) given the application of a
stricter FGR definition (estimated fetal weight below the 10th percentile AND
Doppler evidence for placental dysfunction) compared with Crispi et al.(5) and
Krause et al.(6) (both only estimated fetal weight below the 10th percentile,
irrespective of Doppler findings). Also, the study of Patey et al.(4) was
conducted more recently (2019) compared to the study of Crispi et al.(5) and
Krause et al.(6) (2014 and 2017 respectively).

References:
1. van Oostrum NHM, Derks K, van der Woude DAA, Clur SA, Oei SG, van Laar JOEH.
Two-dimensional Speckle tracking echocardiography in Fetal Growth Restriction:
a systematic review. Eur J Obstet Gynecol Reprod Biol. 2020;254:87-94.
2. Pastore MC, De Carli G, Mandoli GE, D*Ascenzi F, Focardi M, Contorni F, et
al. The prognostic role of speckle tracking echocardiography in clinical
practice: evidence and reference values from the literature. Heart Fail Rev.
2021;26(6):1371-81.
3. Devore GR, Polanco B, Satou G, Sklansky M. Two-Dimensional speckle tracking
of the fetal heart. J Ultrasound Med. 2016;35(8):1765-81.
4. Patey O, Carvalho JS, Thilaganathan B. Perinatal changes in fetal cardiac
geometry and function in diabetic pregnancy at term. Ultrasound Obstet Gynecol.
2019;54(5):634-42.
5. Crispi F, Bijnens B, Sepulveda-Swatson E, Cruz-Lemini M, Rojas-Benavente J,
Gonzalez-Tendero A, et al. Postsystolic shortening by myocardial deformation
imaging as a sign of cardiac adaptation to pressure overload in fetal growth
restriction. Circ Cardiovasc Imaging. 2014;7(5):781-7.
6. Krause K, Möllers M, Hammer K, Falkenberg MK, Möllmann U, Görlich D, et al.
Quantification of mechanical dyssynchrony in growth restricted fetuses and
normal controls using speckle tracking echocardiography (STE). J Perinat Med.
2017;45(7):821-7.

Primary objective:
To investigate baseline* left ventricle longitudinal strain rate values in a
population of growth restricted fetuses and to compare these with a population
of appropriate for gestational age fetuses.

Secondary objective:
To investigate the possible effect of antenatal steroids on left ventricle
longitudinal strain rate between growth restricted- and appropriate for
gestational age weight fetuses (receiving antenatal steroids because of an
imminent preterm birth).

*Before administration of antenatal steroids.

Prospective observational study.

The study population consists of singleton pregnant patients undergoing
antenatal steroids for medical indication: these patients will receive
antenatal steroids regardless of whether they participate in the study or not.
Not the research group, but the patients* attending physician decides whether
and when treatment with antenatal steroids is initiated. The administration of
antenatal steroids is part of standard care and is completely separate from
this (observational) study. The Dutch national guidelines are followed in this
regard; see guidelines from the Dutch Association for Obstetrics and Gynecology
(NL: Nederlandse vereniging voor Obstetrie en Gynaecologie, NVOG) on premature
birth (NL: NVOG richtlijn Dreigende vroeggeboorte) and fetal growth restriction
(NL: NVOG richtlijn Foetale Groei Restrictie (FGR)).
In the context of the study, ultrasound examination including measurements on
cardiac function and other hemodynamical parameters will be performed 3 times
in total:
- Before or within the first 8 hours after the first dose of antenatal steroids;
- 24 hours after the second dose* of antenatal steroids;
- 2-4 days after the second dose of antenatal steroids.

Each ultrasound examination takes up circa 20 minutes, but can be combined with
an ultrasound examination that is performed on clinical indication. Due to this
and the fact that patients receiving antenatal steroids are hospitalized,
participation in the study takes logistically seen little extra effort.

Participation in this study will not benefit the pregnant women nor the fetuses
personally. The present study investigates the effects of antenatal steroids on
cardiac function in growth restricted fetuses; knowledge about these effects
may change the view on current policy to administer antenatal steroids to
growth restricted fetuses.

The data of the ultrasound scans will be saved in Astraia (ultrasound
database). In case an ultrasound scan yields unexpected findings, which are of
importance for the pregnant participant and/or the fetus, the researcher will
discuss this with the attending physician. If needed, the attending physician
will discuss follow-up policy with the pregnant participant and her partner.

Ultrasound examination is not associated with risks for the pregnant patient
and the fetus and is therefore the imaging technique of choice for the pregnant
patient.

Consent to access the participants* medical file will be asked, only for
retrieval of demographic- and baseline characteristics of the participant, as
well as pregnancy- and neonatal outcomes. Participation in the study is
completed after the maternity period.

*The second dose of antenatal steroids is administered 24 hours after the first
dose of antenatal steroids.