THE VALUE OF MIDDLE CEREBRAL TO UMBILICAL ARTERY PULSATILITY INDEX RATIO IN THE PREDICTION OF ADVERSE NEONATAL OUTCOME IN PREECLAMPSIA

A protocol of thesis submitted for partial fulfillment of Master Degree in Obstetrics and Gynecology

Presented by

Shimaa Abdou Soubh (M.B.B.Ch.)2004,Cairo university

Resident Obstetrics& Gynecology doctor at Damietta specialized hospital

Supervised by

Prof. Dr. Mohamed Mahmoud Waly

Prof. of Obstetrics & Gynecology Faculty of Medicine

Cairo University

Prof. Dr. Abdalla Yahya El Kateb Assist. Prof. of Obstetrics & Gynecology

Faculty of Medicine Cairo University

Faculty of Medicine Cairo University

2012  

Acknowledgement 

        First of all I thank God for all his giving throughout my life, I thank my family for their continuous support through all the hard and difficult times.

I would like to express my deepest gratitude and thanks to Prof. Dr. Mohammed Mahmoud Waley Professor of Obstetrics & Gynecology Faculty of Medicine- Cairo University, who gave me the honor of working under her supervision and follow up of the progress of this work..

I wish to express my deepest thanks and gratitude to Dr. Abdalla yahya Elkateb, assistant professor of Obstetrics & Gynecology, Faculty of Medicine- Cairo University, for guiding me all through this thesis and revising all my work so I give her all my sincere thanks for her effort and time .

Dedication        

To my Father and my Mother who taught me the principles and patience

To my husband who support me

To son abd elrahman

To all my professors and colleagues  

 

 

 

 

 

 

 

 

Contents

Page

Introduction and Aim of the work 1 Review of literature

• Doppler velocimetry

• Preeclampsia

• Methodology of Doppler assessment of placenta & fetal circulation

• Doppler study in fetal hypoxic hypoxia

6

36

85

112

Patients and methods Results Discussion Summary Conclusion References Arabic summary

165 171 189 196 198 199

 

 

 

ABSTRACT OBJECTIVE. Our aim was to assess the accuracy of the Middle cerebral to Umbilical Artery (PI) ratio in predicting fetal out come in pregnancies complicated by preeclampsia. METHODS. We evaluate 75 pregnant women representing clinical forms of preeclampsia. Seventy-five cases with no signs of preeclampsia were accepted as controls. Pulse wave color Doppler with 3.5MHz probe was used in the assessments of fetal and maternal circulation. Cerebral to umbilical ratio was obtained by the division of MCA PI to UA PI. Apgar score will be assessed at 5 minutes after birth. Apgar score < 7 at 5 minutes and or neonatal admission to neonatal intensive care unit (NICU) will indicate neonatal morbidity.

Perinatal outcome was evaluated in relation to the indices.  RESULTS. Umbilical artery showed elevated indices in preeclamptic patient than control group, Absent end diastolic velocity (AEDV) and reversed end diastolic velocity (REDV) were seen in 9 cases respectively and were associated with poor perinatal outcome. MCA values were decreased in preeclamptic patient and had poor perinatal outcome in terms of need for lower segment cesarean section (LSCS) for fetal distress, apgar <7 at 5minute, and admission to nursery. Cerebroumbilical (C/U) ratio of <1.1 was similarly associated with poor perinatal outcome. Conclusions: In normal pregnancy there is gestational age related fall in impedance in umbilical and middle cerebral arteries. cerebral–umbilical ratio is strong predictors of IUGR and of adverse perinatal outcome in preeclampsia. The MCA PI alone is not a reliable indicator. The combination of umbilical and fetal cerebral Doppler indices may increase the utility of Doppler ultrasound in preeclamptic subjects. Key Words: Doppler velocimetry, Preeclampsia, Methodology of Doppler assessment of placenta & fetal circulation, Doppler study in fetal hypoxic hypoxia.

List of Tables

Page Title Table no

76 Laboratory finding in preeclampsia 1 77

Criteria for the diagnosis of severe preeclampsia

2

100 umbilical artery Doppler indices in normal pregnancy

3

104 Factors affecting umbilical artery Doppler flow velocity waveforms

4

109 middle cerebral artery Doppler indices in normal pregnancy

5

125

Umbilical artery indices in preeclampsia and normal pregnancy

6

127 the mean values of Umbilical Artery Doppler Velocimetric indices in hypertensive and normotensive groups

7

131 Fetal systemic vascular responses during hypoxemia induced by uteroplacental insufficiency

8

132

Hemodynamic changes occurring in fetal arterial vessels during hypoxemia and acidemia induced uteroplacental insufficiency. by

9

140 cerebroplacental ratio (C/U) ratio in normal pregnancies

10

142 Doppler indices of normal pregnancies and preeclamptic patients with or without IUGR

11

156 Follow up studies of children exposed to absent or reverse end diastolic flow in utero.

12

176 Comparison between both studied groups as regard general data

13

176 Comparison between both studied groups as regard parity

14

177 Comparison between both studied groups as regard hemodynamic parameters

15

180 Comparison between both studied groups as regard Apgar 5 score and fetal weight

16

180 Comparison between both studied groups as regard blood pressure

17

181 Distribution of the studied cases as regard diagnosis

18

181 Distribution of the studied cases as regard NICU 19 182 Correlation between CPR versus general data

among the cases 20

182 Correlation between CPR versus general data among controls

21

184 Correlation between CPR versus blood pressure among the cases

22

186 Correlation between CPR versus blood pressure among controls

23

186 Correlation between CPR versus Apgar and fetal weight among cases

24

187 Correlation between CPR versus Apgar and fetal weight among controls

25

187 Comparison between mild versus severe preeclampsia as regard CPR

26

189 Relation between NICU admission versus CPR 27 190 Validity of CPR in prognosis of preeclampsia 28 191 Validity of CPR in prognosis of fetal outcome

(NICU) 29

List of figures Page 1 (A) Continuous wave Doppler transducer ,

(B) pulsed wave Doppler transducer 13

2 Doppler indices 16 3 An illustration of the aliasing effect of an

arterial spectrum where the peak velocities have been too fast to measure with the particular pulse repetition frequency of a pulsed Doppler system

24

4 Flow velocity waveforms of the umbilical artery with advancing gestation.

29

5 Typical umbilical artery and vein waveform. 32 6 The normal values for the umbilical artery. 33 7 Normal placental implantation shows

proliferation of extravillous trophoblasts, forming a cell column beneath the anchoring villus.

44

8 Pathophysiological considerations in the development of hypertensive disorders due to pregnancy

46

9 Normal pregnancy development of the uterine artery

92

10 Diagrammatic representation of the effects of spiral artery conversion on the inflow of maternal blood into the intervillous space

92

11 Umbilical arterial flow 95 12 umbilical arterial flow: The volume flow in

the umbilical artery increases with advancing gestation.

98

13 Systole (Sys) and diastole (D) are identified in green Note that diastole is less at 20 weeks (yellow ellipse) than at 36 weeks (red

98

ellipse). 14 Normal pregnancy development of the

umbilical artery 99

15 Scattered diagram of umbilical artery pulsatility index from free loop of the cord against period of gestation with 5th,50th and 95th percentile line.

102

16 scattered diagram of umbilical artery systolic/diastolic ratio from the free loop of the cord against period of gestation with 5th,50th and 95th percentile line.

102

17 Transverse view of the fetal head with color Doppler showing the circle of Willis (left). Flow velocity waveforms from the middle cerebral artery at 32 weeks of gestation (right).

107

18 Normal Pregnancy - Development of the Middle Cerebral Artery

108

19 Pulsatility index (left) and mean blood velocity (right) in the fetal middle cerebral artery with gestation

110

20 individual measurements and calculated reference ranges for the pulsatility index (PI) in the MCA.

111

21 Absent blood flow during diastole in the umbilical artery

121

22 Reversed blood flow during diastole in the umbilical artery

121

23 Abnormal development of the umbilical artery.

122

24 Color Doppler examination of the circle of Willis (left). Flow velocity waveforms from the middle cerebral artery in a normal fetus with low diastolic velocities (right, top) and in a growth-restricted fetus with high diastolic velocities (right, bottom)

130

25 brain sparing phenomenon; (A) Middle cerebral artery waveform in a fetus 31 weeks with normal flow, pulsatility index for this fetus 2.02. ( B) a fetus at 32 weeks with brain sparing, as evidenced by an increased MCA diastolic flow velocity waveform that corresponds to a decreased pulsatility index, the pulsatility index for this fetus 0.90

136

26 CPR from 21 weeks to 42 weeks in normal pregnancies

141

List of Abbreviations

Abbreviation Meaning (CW)Doppler continuous wave Doppler (PW)Doppler pulsed wave Doppler (FD) Doppler shift (SPTA) Doppler spatial peak-temporal average-intensity (CPD) Color power Doppler PI Pulsatility index RI Resistance index FIP Frequency index profile S/D Ratio systolic/diastolic ratio (EVT) extravillous trophoblast HLA Human leucocytic antigen (NK) cells Natural killer cells (TNF) Tumor necrosis factor (NO) Nitric oxide VEGF Vascular endothelial growth factor (PIGF) Placental Growth Factor FDP Fibrin degradation products BP BLOOD PRESSURE PIH pregnancy induced hypertension IUGR intrauterine growth retardation MCA Middle cerebral artery UA Umbilical artery FVW flow velocity waveform ( AEDV) Absent end diastolic velocity (REDV) Reversed end diastolic velocity FBP Fetal biophysical profile C/U ratio cerebroumbilical ratio GA Gestational age DV Ductus venosus IUFD Intrauterine fetal death SGA Small for gestational age

Introduction and Aim of the Work

1 

 

INTRODUCTION

Techniques of Doppler Ultrasonography (US) have been

available to clinicians for nearly 40 years. The Doppler effects as

developed by sound propagation in human tissues and with the

velocities observed for the human vasculature produces shifts in the

frequencies of returning echo signals. These signals can be

processed in a manner that allows the observer to determine the

condition of the blood flow (Boote, 2003).

Preeclampsia, a hypertensive disorder of pregnancy which

usually develops after 20 weeks of gestation characterized by

elevated blood pressure, proteinuria and /or edema. (Maynard et al.,

2008).

Preeclampsia remains a major cause of maternal and neonatal

morbidity and death (Norwitz et al.,2008).

In normal pregnancy impedance to flow in the uterine arteries

decrease with gestation and histopathological studies suggest that

this is due to trophoplastic invasion of the spiral arteries and their

conversion into low resistance vessels, failure of trophoplastic

invasion is associated with complications of uteroplacental

insufficiency (Papageorghiou et al., 2004).

Preeclampsia is a pregnancy specific syndrome characterized

by reduced organ perfusion secondary to vasospasm and endothelial

pathophysiology. This condition is the leading cause of maternal

Introduction and Aim of the Work

2 

 

mortality and is responsible for considerable perinatal morbidity and

mortality (Lewis et al; 2001).

Doppler velocimetry studies of placenta and fetal circulation

can provide important information regarding fetal well being

providing an opportunity to improve foetal outcome (Serap et al.,

2003).

Pulsatility index:

A measure of the variability of blood velocity in a vessel,

equal to the difference between the peak systolic and minimum

diastolic velocities divided by the mean velocity during the cardiac

cycle abnormal MCA PI/ UA PI (CU ratio) were defined as the

ratio < 1.08 (Mosbyet al; 2009).

 

Doppler indices

Max = Maximum peak velocity in systole (S)

Min = Minimum peak velocity in diastole (D)

V = Venous velocity ("constant"). S/D = Svstolic: diastolic ratio

Introduction and Aim of the Work

3 

 

Resistance index Pulsatility index

In normal pregnancy, pulsatility index decrease with

advancing gestation in Umbilical Artery. But in preeclampsia first

there is decrease diastolic flow in the Umbilical Artery due to

increase in the resistance that occurs in small arteries and arterioles

of terminal villi. As the placental insufficiency worsen, the diastolic

flow decreases, then become absent and later reverses ( Eixarch et

al; 2008).

Fetal Middle cerebral Artery (MCA) is a low resistance

circulation throughout pregnancy and accounts for 7% of cardiac

output. Increase in diastolic flow with decreased pulsatility index

shows the brain sparing taking place in fetuses of preeclamptic

patients. The ratio of PI of MCA/UA is more sensitive than MCA PI

alone in predicting adverse neonatal outcome (Gerber et al; 2006).

Doppler screening of the fetal Middle cerebral Artery wave

forms during labour can be useful in the evaluation of intrapartum

hypoxia in complicated pregnancies (Kassanos et al., 2003).

MCA/UA ratio reflects not only the circulatory insufficiency

of the Umbilical velocimetry of the placenta, manifested by

alterations in the Umbilical S/D ratio,(ratio of peak systolic blood

flow velocity) but also the adaptative changes resulting in

modification of the Middle cerebral S/D ratio (Sterne et al., 2001).

Introduction and Aim of the Work

4 

 

(MCA/UA) ratio is a good predictor of neonatal out come and

could be used to identify fetuses at risk of morbidity and mortality in

this study they evaluated the predictive value of Umbilical Artery,

the MCA/UA ratio and the cerebral index for foetal prognosis in the

third trimester in preeclamptic women (Sterne et al., 2001).

Several studies have reported higher sensitivities and

specificities for Middle cerebral Artery, Umbilical Artery

(MCA/UA) Doppler ratio compared with Umbilical velocimetry

alone for prediction of fetal prognosis (Makhseed et al., 2000).

As a result of impaired uteroplacental blood flow,

manifestations of preeclampsia may be seen in the fetal placental

unit. These include intrauterine growth restriction (IUGR),

oligohydraminos, placental abruption, and nonreassuring fetal status

found on antepartum surveillance by Doppler ultrasound (ACOG ;

2002).

High flow resistance in the capillaries of the terminal villi

leads to low end diastolic velocity in the Umbilical Artery and

consequent hypoxia (Huppertz B. 2008)

As a result of the prolonged fetal hypoxia, circulatory

adaptation occurs in the form of cerebral vasodilatation, resulting in

the redistribution of the cardiac output to provide an adequate

oxygen supply to the brain. These changes, which help fetus to adapt

to a hostile environment, may correlate with fetal neonatal health

(Mosby et al; 2009).

Introduction and Aim of the Work

5 

 

AIM OF THE WORK

To assess the accuracy of the Middle cerebral to Umbilical

Artery (PI) ratio in predicting fetal out come in pregnancies

complicated by preeclampsia.

 

Review Of Literature

6

DOPPLER ULTRASONOGRAPHY

In 1959, Satomura first described the clinical application of

Doppler ultrasound technology. In 1977 Fitzgerald and Drumm was

the first application of Doppler ultrasound in obstetrics. The simplest

type of Doppler is continuous wave (CW). Early CW transducers

were not very specific because they unable to distinguish whether

flow moved toward or away from the transducer. This deficit was

overcome with the addition of spectrum analyzers and audible

signals, which allowed estimation of frequency of the Doppler shift

and the direction of flow. In the late 1960s Pulsed wave (PW)

Doppler was introduced, which adds information on the location of a

moving target. (Gill RW et al., 1985).

Duplex Doppler imaging-PW Doppler was used in conjunction

with two-dimensional ultrasound imaging-helps guide the Doppler

sampling from ultrasound vessel visualized. Color flow mapping and

color power Doppler provide color- coded flow direction and aid in

vessel identification. Contrast agents, the most recent development,

are .increasing the signal strength to make imaging small vessels

much easier (Schleif, 1993).

Review Of Literature

7

1- Basic Principles of Doppler

Doppler Theory

The Theory and understanding of Doppler ultrasound require

an analysis of two basic physical systems. The Doppler shift

phenomena states that sound waves striking object will be returned

at a different frequency. The returning signal or sound wave

frequency should be affected by the speed and direction of the

moving object, and the distance between the origination and

reception. Doppler transducers transmit a signal of known

frequency,- capture the returning echoes, and analyze them. The

unknown are the angle of incidence and the velocity of the source,

the blood cells in the vessels, the second principle needed is that of

vector analysis (Kremkau, 1992).

The ultrasound signal strikes the red call mass and the

magnitude of the reflection is dependent on the cosine of the angle of

incidence. The velocity of ultrasound in tissue is 1540 m/second;

therefore, a correction from the frequency measurements can be

made, to summarize:

Doppler shift (FD) = Frequency reflected (FR) - Frequency at

origination (Fo)

The frequency can be equated to sound velocity in tissue and

correction made for the angle of incidence.

Review Of Literature

8

The following equation emerges:

Fr =

The optimum angle range for most studies is approximately 30ato

60° (Schulman, 1994).

Doppler Effect:

Doppler effect describes a phenomenon of perceived changes

in frequency of propagating energy waves consequent to any motion

between the source of energy emission and an observer, when the

source and observer move a part, the perceived frequency decreases,

conversely, the frequency increases when the source and observer

move closer. These changes will occur irrespective of whether the

observer or the source moves, moreover, the magnitude of the

changes in the frequency is proportional to the velocity of the

movement at the source or the receiver. This phenomenon is

applicable to all forms of energy waves, and is known as the

"Doppler frequency shift". This effect was first reported on light

waves by an Austrian mathematician, Johanna Christian Doppler in

1843 and on sound waves by (Maulik, 1997).

To date, Doppler and real-time ultrasound have not been

associated with any ill effects to fetus or mother. The U.S. food and

drug administration (PDA) guidelines state that there are no known

risks associated with use of Doppler ultrasound at the recommended

power levels. There are specific PDA guidelines for fetal ultrasound,

including that the Doppler spatial peak-temporal average-intensity

Review Of Literature

9

(SPTA) be less than 49 mw/cm2 in situ. SPTA is a unit used to

measure ultrasound energy intensity (Evans DH et al., 1989).

Doppler Equation:

In medical application, the Doppler effect is usually used by

insonating the Doppler effect moving blood and assessment of

Doppler shift of ultrasound scattered on erythrocytes. The general

methods of measurements consist of transmission of bundled

ultrasound into the body at a general angle theta (a) to the flow. The

following equation of Doppler shift is valid to sufficient

approximation (Taylor and Holland, 1990).

∆F= cos α

Where:

∆F = is the Doppler shift

Fo = is the transmitted wave frequency (usually 2-10 MH3)

V = is the velocity of the moving target

α = is the angle among the ultrasound beam and flow direction.

C = is the ultrasound propagation speed in tissues assumed to be 1

540 m/sec.

In actual clinical practice, the equation leads to the following

relationships: 1) the change in frequency is proportional to the

velocity of the movin Type equation here. g reflector, 2) The higher

the-original frequency, the greater the shift for a given velocity, 3)

The frequency increases as the reflector moves toward the transducer