Cardiac Functions as a New Method for Evaluation of Fetal Anemia Pre and Post Intrauterine Fetal Blood Transfusion
Condition: Fetal Anemia as Antepartum Condition (Diagnosis); Rh Incompatible Blood Transfusion Nos
MeSH terms: Anemia
Study type: Interventional

Summary: 
      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)
    

Detailed description: 
      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.
    

Intervention name(s): Mid trimesteric fetal ultrasonography
Intervention type(s): Radiation
Intervention description(s): Venous and arterial Doppler indices:
Middle cerebral artery (MCA) peak systolic velocity (PSV):
Umbilical Artery Pulsitility Index (PI) and Resistant Index (RI):
Ductus venosus (DV) Doppler:
Cardiac functions:
Global cardiac function evaluated by Modified Myocardial Performance Index (Mod-MPI):
Systolic cardiac function using the four-dimensional (4D) spatiotemporal imaging correlation (STIC) ultrasound technique:
Diastolic cardiac function evaluated by relationship between the maximal velocities of the E and A waveforms of ventricular filling (E/A ratio)
Other intervention name(s): Voluson E10 equipment (GE Medical Systems, Austria)
Intervention model: Single Group Assignment
Intervention model description: This will be a prospective study. Patients will be selected from Rh isoimmunized patients (positive titre of indirect coomb's test) who are scheduled to have intrauterine blood transfusion.Selected patients will be monitored weekly from 15 weeks gestational age till 28 weeks of gestational age.
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Cardiac functions; Intrauterine fetal anemia; Intrauterine Fetal blood transfusion; Myocardial performance index; spatiotemporal imaging correlation