Cardiac Functions as a New Method for Evaluation of Fetal Anemia Pre and Post Intrauterine Fetal Blood Transfusion
Cardiac Functions as a New Method for Evaluation of Fetal Anemia Pre and Post Intrauterine Fetal Blood Transfusion
INTRODUCTION

 Circulatory changes associated with fetal anemia have an important role in maintaining
 sufficient tissue oxygenation. With fetal anemia, hyperdynamic circulation and increased
 cardiac output occurred. In current practice, using Doppler in assessment of the peak
 systolic velocity (PSV) of the middle cerebral artery (MCA) is the main parameter in
 screening of fetal anemia. Myocardial performance index (MPI) is a noninvasive technique that
 evaluates systolic and diastolic cardiac function by pulsed Doppler.

 Patients and Methods:

 This prospective study will be carried out on Women with singleton pregnancies with Rh
 isoimmunization who are scheduled to have intrauterine blood transfusion. Selected patients
 will be monitored weekly from 18 weeks gestational age till 28 weeks of gestational age.

 Venous and arterial Doppler indices:

 1. Middle cerebral artery (MCA) peak systolic velocity (PSV)

 2. Umbilical Artery Pulsitility Index (PI) and Resistant Index (RI)

 3. Ductus venosus (DV) Doppler

 Cardiac functions:

 1. Global cardiac function evaluated by Modified Myocardial Performance Index (Mod-MPI)

 2. Diastolic cardiac function evaluated by relationship between the maximal velocities of
 the E and A waveforms of ventricular filling (E/A ratio)
INTRODUCTION

 Circulatory changes associated with fetal anemia have an important role in maintaining
 sufficient tissue oxygenation. With fetal anemia, hyperdynamic circulation and increased
 cardiac output occurred. This is due to reduced the viscosity of blood, increased the
 contractility of heart, and peripheal vasodilatation due to hypoxia. In current practice,
 using Doppler in assessment of the peak systolic velocity (PSV) of the middle cerebral artery
 (MCA) is the main parameter in screening of fetal anemia. Severe fetal anemia causes
 continuous loss of adaptive mechanisms due to lack of oxygen delivered to the tissues.
 Finally, fetal acidosis results as a sequence of metabolic changes so increasing perinatal
 morbidity and mortality. Cardiac decompensation is not the principal mechanism involved in
 the development of overt fetal hydrops, however, severe anemia may cause cardiac ischemia,
 reduced contractility, and dysfunction. Myocardial performance index (MPI) is a noninvasive
 technique that evaluates systolic and diastolic cardiac function by pulsed Doppler. Tsutsumi
 et al. was the first described Fetal MPI evaluation then several studies have shown that it
 is a simple and replicable technique. Many have demonstrated significant changes in fetal MPI
 in intrauterine growth restriction, recipient fetuses of twin-twin transfusion syndrome,
 diabetes, and fetal inflammatory response syndrome. Similarly, fetal anemia causes changes in
 cardiac contractility and MPI as one of cardiac functions may have a role in the evaluation
 of disease severity and prognosis.

 Patients and Methods:

 This prospective study will be carried out at a tertiary referral center for fetal medicine
 (Fetal Medicine Unit, Cairo University, Egypt) from April 2017 till April 2018. Women with
 singleton pregnancies with Rh isoimmunization will be asked to participate in the study.
 Informed consent will be obtained from all participants. The ethical committee approval for
 the study will be from Bioethical Committee of the National Research Centre (number: 17 008,
 admission date: January 2017).

 This will be a prospective study. Patients will be selected from Rh isoimmunized patients
 (positive titer of indirect coomb's test) who are scheduled to have intrauterine blood
 transfusion. This intrauterine blood transfusion is due to fetal anemia, and it is detected
 when the measurement of PSV (peak systolic velocity) of middle cerebral artery is more than
 1.5 MoM (multiple of the median) according to Fetal Medicine unit of Cairo University
 protocol. All fetuses are free of structural and functional Fetal and echocardiographic
 anomaly scan.

 Gestational age will be obtained from the first date of the last menstrual period (LMP). If
 the patient is unsure of her dates, gestational age will be based on the first ultrasound
 scan. Selected patients will be monitored weekly from 18 weeks gestational age till 28 weeks
 of gestational age.

 All examinations will be carried out abdominally with a curved 3.5-5.0-MHz probe and Voluson
 E10 equipment (General Electric Medical Systems, Austria). Data will be entered into an
 electronic spreadsheet (Excel,Microsoft Corporation, USA).

 Fetal Hemoglobin (Hb) levels will be measured in blood samples collected prior to transfusion
 and after blood transfusion before withdrawing of the needle from umbilical vein.

 Venous and arterial Doppler indices:

 1. Middle cerebral artery (MCA) peak systolic velocity (PSV):

 The greatest measurement of three consequent PSV will be recorded. the course of the
 fetal MCA will be identified by using color Doppler. An axial brain section of the
 fetus, including the thalami and the cavitas septi pellucid (CSP), will be obtained. And
 the MCA will be captured along the great wing of the sphenoid bone. The artery will be
 examined close to its origin with angle of insonation < 20 degrees.

 2. Umbilical Artery Pulsitility Index (PI) and Resistant Index (RI):

 Both umbilical arteries will be sampled close to the placental insertion and ultrasound
 3.5-5-MHz convex probes will be used, the insonation angle will be <30° and the sample
 volume will be adjusted to cover the entire vessel.

 3. Ductus venosus (DV) Doppler:

 The flow velocities from the DV will be identified using color Doppler imaging in a right
 ventral midsagittal plane. The pulsed Doppler gate will be placed in the distal portion of
 the umbilical sinus. When the typical DV waveform is obtained, at least three consecutive
 waveforms will be recorded with insonation angle < 30. The following variables will be
 measured: S-wave, D-wave, pulsatility index for veins (PIV) and resistance index (RI).

 Cardiac functions:

 1. Global cardiac function evaluated by Modified Myocardial Performance Index (Mod-MPI):

 All estimations will be done in the absence of fetal corporal and respiratory movements
 and with the mother in voluntary suspended respiration. Special attention will be given
 to the velocity of the Doppler sweep representation on the ultrasound screen using the
 highest velocity available (15 cm/s) for clear identification of the components of the
 Doppler tracing. Additionally, the E/A waveform will always be displayed as positive
 flow. The angle of insonation will always be kept below 30◦ and the mechanical and
 thermal indices will never exceeded 1. A cross-sectional image of the fetal thorax in
 the four-chamber view and an apical projection of the heart will be obtained. The
 Doppler sample volume will be placed on the lateral wall of the ascending aorta, below
 the AV (aortic valve) and just above the MV (mitral valve). The Doppler trace will show
 a clear echo corresponding to the opening and closure of the two valves at the beginning
 and at the end of the E/A (mitral valve) and AF (aortic flow) waveforms. The time
 periods will then be estimated as follows: the isovolumetric contraction time (ICT) will
 be estimated from the closure of the MV, to the opening of the AV, the ET (ejection
 time) from the opening to the closure of the AV, and the IRT (the isovolumetric
 relaxation time ) from the closure of the AV to the opening of the MV. The final value
 for the Mod-MPI will be calculated as: (ICT+IRT)/ET.

 2. Systolic cardiac function using the four-dimensional (4D) spatiotemporal imaging
 correlation (STIC) ultrasound technique:

 Fetal heart ventricular volumes will be measured using the four-dimensional (4D)
 spatiotemporal imaging correlation (STIC) ultrasound technique. TheVirtual Organ
 Computer-aided AnaLysis (VOCAL) technique will be used to obtain a sequence of six
 sections of each ventricular volume in systole and diastole. Each volume will be
 obtained after a 60 degree rotation from the previous one around a fixed axis extending
 from the apex of the heart to the point that divides symmetrically each atrioventricular
 valve. The contour of each ventricle will be drawn manually and the 4D volumes of the
 left and right ventricle in systole and diastole will be estimated. The stroke volume
 for each ventricle will then be calculated by subtracting the one in systole from the
 one in diastole and the cardiac output will be calculated by multiplying the stroke
 volume by the fetal heart rate.

 3. Diastolic cardiac function evaluated by relationship between the maximal velocities of
 the E and A waveforms of ventricular filling (E/A ratio):

 Assessment of the fetal diastolic component of the cardiac cycle is performed with spectral
 Doppler through the atrioventricular (AV) valves. The Doppler sample gate is located just
 below the AV valves where a biphasic waveform is usually displayed in normal fetus and is
 kept gate between 2 and 3 mm. The first component is known as the E (early or passive) wave
 and is related to the process of myocardial relaxation and negative pressure applied by the
 ventricles. The second component is the A (atrial, active, or late) wave and it represents
 the atrial contraction during ventricular filling. The ratio is obtained by the division of
 the peak velocities of the E over the A waveforms. Recordings are obtained at the level of
 the 4-chamber view of the fetal heart in either a posterior or an anterior apical projection.
 The interventricular septum must be visualized and aligned at 0 degree with the Doppler beam
 and angle of insonation < 20 degrees.
Inclusion Criteria:

 -  Rh isoimmunized patients (positive titre of indirect coomb's test) who are scheduled
 to have intrauterine blood transfusion.

 Exclusion Criteria:

 -  Less than 15 weeks gestational age and more than 28 weeks gestational age

 -  fetuses with structural or functional Fetal or echocardiographic anomalies.