department of radio-diagnosis j.j.m.medical college
TRANSCRIPT
ROLE OF DOPPLER ULTRASONOGRAPHY IN
PREDICTION OF ADVERSE PERINATAL OUTCOME IN INTRAUTERINE GROWTH
RETARDATION
by
Dr. SHYLAJA.N. M.B.B.S.,
Dissertation submitted to the Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka
in partial fulfillment
of the requirements for the degree of
DOCTOR OF MEDICINE IN
RADIO-DIAGNOSIS
Under the guidance of Dr. KIRAN KUMAR HEGDE.S.
Associate Professor
DEPARTMENT OF RADIO-DIAGNOSIS J.J.M.MEDICAL COLLEGE.
DAVANGERE 2006-2009
I
Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka
DDEECCLLAARRAATTIIOONN BBYY TTHHEE CCAANNDDIIDDAATTEE
I here by declare that this dissertation titled “ROLE OF DOPPLER
ULTRASONOGRAPHY IN PREDICTION OF ADVERSE PERINATAL
OUTCOME IN INTRAUTERINE GROWTH RETARDATION”
is a bonafide and genuine research work carried out by me under the
guidance of Dr. KIRAN KUMAR HEGDE .S., Associate Professor,
Department of Radio-Diagnosis, J.J.M. Medical College. Davangere.
Dr. SHYLAJA. N. Post Graduate in Radio-Diagnosis
Place: Davangere J.J.M.MEDICAL COLLEGE Date: Davangere.
CCEERRTTIIFFIICCAATTEE BBYY TTHHEE GGUUIIDDEE
This is to certify that this dissertation titled “ROLE OF DOPPLER
ULTRASONOGRAPHY IN PREDICTION OF ADVERSE PERINATAL
OUTCOME IN INTRAUTERINE GROWTH RETARDATION” is a
bonafide work done by Dr. SHYLAJA.N., in partial fulfillment of the
requirement for the award of M.D. Degree in Radio-Diagnosis.
Date: Place: Davangere Dr. KIRAN KUMAR HEGDE . S. Associate Professor
Department of Radio-Diagnosis JJM Medical College, Davangere – 577 004
ENDORSEMENT BY THE HOD, PRINCIPAL/HEAD OF ENDORSEMENT BY THE HOD, PRINCIPAL/HEAD OF
THE INSTITUTIONTHE INSTITUTION
This is to certify that the dissertation entitled “ROLE OF DOPPLER
ULTRASONOGRAPHY IN PREDICTION OF ADVERSE PERINATAL
OUTCOME IN INTRAUTERINE GROWTH RETARDATION” is a
bonafide research work done by Dr. SHYLAJA .N, under the guidance of
Dr. KIRAN KUMAR HEGDE. S., Associate Professor, Department of
Radio-Diagnosis, J.J.M.Medical College, Davangere.
Date: / / 2008 Date: / / 2008
Place: Davangere Place: Davangere
Dr. RAMESH S. DESAI M.D., D.M.R.D., Professor and Head, Department of Radio-Diagnosis, J.J.M. Medical College, Davangere – 577 004.
Dr. H.R. CHANDRASEKHAR M.D., Principal, J.J.M. Medical College, Davangere – 577 004.
CCOOPPYYRRIIGGHHTT
DDeeccllaarraattiioonn bbyy tthhee CCaannddiiddaattee
I hereby declare that the Rajiv Gandhi University of Health Sciences,
Karnataka shall have the rights to preserve, use and disseminate this
dissertation/.thesis in print or electronic format for academic / research
purpose.
Date : / / 2008 Dr. SHYLAJA.N. Place: Davangere
© Rajiv Gandhi University of Health Sciences, Karnataka
AACCKKNNOOWWLLEEDDGGEEMMEENNTT
It gives me immense pleasure to express my deep sense of gratitude and
sincere thanks to my beloved teacher and guide Dr. KIRAN KUMAR
HEGDE S. M.D., Associate professor, Department of Radio Diagnosis, J.J. M. Medical
College, Davangere, who with his knowledge and professional expertise has provided
able guidance and constant encouragement throughout the course of study and in the
preparation of this dissertation.
I am extremely grateful and highly indebted to Dr. RAMESH S. DESAI M.D.,
D.M.R.D., Professor and Head, Department of Radio Diagnosis, J.J.M. Medical College,
Davangere, for his selfless devotion to his students, guidance, support and constant
encouragement during the period of my study.
I also express my sincere gratitude to Dr. V.N.NARVEKAR M.D, Former
Professor for inspiring me to take up this study and for his expert guidance, advice
and encouragement.
My sincere thanks to my Professors, Dr. J.PRAMOD SETTY M.D, Professor,
Dr. K.N.SHIVAMURTHY M.D, Professor, DR.R.SRINIVAS, M.D Professor, and
Dr. M. B. SIDDESH M.D. Assistant Professor, for their encouragement.
I express my sincere gratitude to DR. BHAGYAVATHI M, M.D, D.M.R.D.,
Associate Professor and Dr. JEEVIKAM.U.M.D, Reader, for their constatnt support
and encouraging words which has helped me to sail through hardships of life.
I am extremely thankful to Dr. H.R.CHANDRASEKHAR, M.D, Principal,
J.J.M. Medical College, Davangere, Dr. H.GURUPADAPPA, M.D , Director for
Postgraduate Students and Research, J.J.M. Medical College, Davangere, for their
valuable help and co-operation during this study.
VI
I also express my sincere thanks to the superintendents and technicians of
Chigateri General Hospital and Bapuji Hospital, Davangere, for allowing me to study
the patients of their hospital.
I wish to thank my parents Smt. NAGARATHNA. R. and
Sri, NAGARAJU .N for their unconditional support and blessings, they are a
constant guiding force in my life for which I will always feel blessed.
My heart felt thanks to my dear loving Husband Mr. PRASHANTH .G. for
his constant support and love which helps me to conquer any battle of life.
My heartful thanks to my inlaws Smt. ANASUYA and Sri. GOVINDRAJU
for their moral support and blessings throughout my study.
My special thanks to my friends Dr. RAVISHANKAR,
Dr. SUMATHI.M.E., Dr. MANJUNATH.B, Dr. RAMKUMAR, Dr. BHASKAR,
and Dr. RAJSHEKHAR for their moral support and help in preparation of this
dissertation.
I thank Mr. P.S. MAHESH , Chief Librarian and other staff of the Central
Library for their help during my research and cross reference work.
I would also like to thank all the staff members of THOMAS COMPUTERS
and BENAKA PRINTERS for their efficient work of this dissertation.
Lastly I thank everyone concerned, including the patients for their
cooperation, without whom this dissertation would have ever materialized.
I am ever greatful to the ALMIGHTY for his blessings on me.
PLACE: Davangere
DATE: / /2008 [Dr. SHYLAJA.N.]
LIST OF ABBREVIATIONS USED
AEDF - Absent End Diastolic Flow
AUAPI - Abnormal Umbilical artery PI
CS - Caesarian Section
EDF - End diastolic Flow
FVW - Flow Velocity wave forms
FN - False negative
FP - False Positive
IUGR - Intra Uterine Growth Retardation / Restriction
IUD - Intra uterine Death
IVH - Intra Ventricular Haemorrhage
LMP - Last Menstrual Period
MCA - Middle Cerebral Artery
MCAPI - Middle Cerebral Artery Pulsatility Index
NEC - Necrotising Enterocolitis
NICU - Neonatal Intensive Care Unit
NPV - Negative Predictive Value
NUAPI - Normal Umbilical Artery PI
PI - Pulsatility Index
PIH - Pregnancy Induced Hypertension
PO2 - Partial Pressure of Oxygen
PPV - Positive Predictive Value
RDS - Respiratory Distress Syndrome
RI - Resistive Index
S/D - Systolic: Diastolic Ratio
SD - Standard Deviation
SGA - Small for Gestational Age
TN - True negative
TP - True Positive
UA - Umbilical Artery
UAPI - Umbilical Artery Pulsatility Index
U/S - Ultra sound
VII
ABSTRACT
BACKGROUND AND OBJECTIVES:
The aims and objectives of our study was to evaluate the usefulness of middle
cerebral artery and umbilical artery Doppler indices as predictors of adverse perinatal
outcome in clinically suspected IUGR pregnancies and to establish the role of
Doppler ultrasound in the management of IUGR pregnancy.
MATERIALS AND METHODS:
The present study is a prospective study of Doppler Velocimetry of umbilical
artery and Middle cerebral artery in cases with clinical suspicion of IUGR between 31
to 40 weeks of gestation from September 2006 to September 2008. Pregnancies with
documented major congenital abnormality, multiple gestations and intrauterine death
at the time of first Doppler examination were excluded from the study. The outcome
for each pregnancy was obtained by examining the labor ward records and neonatal
intensive care unit records wherever appropriate. Findings of Doppler studies were
correlated with the following adverse Perinatal outcomes; Perinatal deaths,
Emergency CS for foetal distress, Low Apgar score (5 min Apgar <7), and admission
to NICU for complications of low birth weight. Pregnancy outcome was considered to
be Uneventful or Favourable when the above complications were absent.
The Umbilical artery Pulsatility index and the Middle cerebral artery
pulsatility index for the corresponding gestational age were compared with the
reference values. The Umbilical artery Pulsatility index was considered abnormal if
the value was above the 95th percentile of previously published values for gestational
age. The Middle cerebral artery pulsatility index was considered abnormal if the value
IX
was below the 5th percentile of previously published values for gestational age. A
single cut off value (1.08) was used for Cerebroplacental Ratio (MCA PI/UA PI),
above which the cerebroplacental ratio was considered normal and below which it
was considered abnormal.
RESULTS:
Acceptable wave forms were obtained from MCA and UA in all these cases.
All the cases were followed up for the perinatal outcome. Cerebroplacental ratio had
higher sensitivity (95.6%) and NPV (95.8%) than UAPI (Sensitivity 73.9%, PPV
94.4%) and MCA PI (Sensitivity 91.3% , PPV 70%) , UAPI had higher specificity
(96.2%) and PPV (94.4%) compared to cerebroplacental ration (Specificity 85.1%,
PPV 84.6% ) and MCAPI (Specificity 66.6%, PPV 70%).
Diagnostic accuracy of Cerebroplacental ratio (Accuracy=90%) was better
than UAPI (Accuracy=86%) and MCAPI (Accuracy=78%) in predicting adverse
outcomes.
CONCLUSION:
In suspected IUGR pregnancy, both Cerebroplacental ratio and Umbilical
artery PI are strong predictors of adverse perinatal outcome. Cerebroplacental ratio is
most sensitive and Umbilical artery PI is most specific index in predicting adverse
outcome. Absent or reversed end diastolic flow in an umbilical artery is an ominous
finding associated with major adverse perinatal outcome and mortality.
KEY WORDS: - Intrauterine growth retardation; Umbilical artery Doppler, Middle
cerebral artery Doppler; Fetal Doppler; Cerebro-placental Ratio;
X
TABLE OF CONTENTS
Page No.
1. Introduction 1 - 3
2. Objectives 4
3. Review of literature 5 - 38
4. Methodology 39 - 43
5. Results 44 - 56
6. Discussion 57 - 63
7. Conclusion 64
8. Summary 65 - 66
9. Bibliography 67 - 79
10. Annexure 80 - 85
* * * * *
XI
LIST OF TABLES
Sl.
No. Tables
Page
No.
1. Maternal complications of study group 44
2. Distribution Characteristics of Placental Maturity 45
3. Amniotic Fluid distribution in the study group 46
4. Gestational Age Distribution in study group 47
5. Pregnancy Outcome in the study group 48
6. Adverse Outcomes in the study group 49
7. Spectral Characteristics of Umbilical Artery 50
8. Performance Characteristics of Doppler Indices 51
XII
LIST OF FIGURES
Sl. No. Figures
Page
No.
1 Schematic Diagram showing Placental circulation 19
2 Schematic Diagram showing Fetal circulation 21
3 Normal Umbilical Artery Flow at 32 weeks Gestational Age 34
4 Normal Middle Cerebral Artery Flow at 32 weeks Gestational Age 34
5 Normal Umbilical Artery Flow at 34 weeks Gestation l Age 35
6 Normal Middle Cerebral Artery Flow at 34 weeks Gestational Age 35
7 Normal Umbilical Artery Flow at 36 weeks Gestational Age 36
8 Normal Middle Cerebral Artery Flow at 36 weeks Gestational Age 36
9 Normal Umbilical Artery Flow at 38 weeks Gestational Age 37
10 Normal Middle Cerebral Artery Flow at 38 weeks Gestational Age 37
11 Philips Enviser CHD 41
12 Decreased Diastolic Flow in Umbilical Artery 54
13 Increased Diastolic Flow in Middle Cerebral Artery - “Brain Sparing Effect” in the same patient 54
14 Absent Diastolic Flow in Umbilical Artery 55
15 Increased Diastolic Flow in Middle Cerebral Artery - “Brain Sparing Effect” in the same patient 55
16 Reversed Diastolic Flow in Umbilical Artery 56
17 Increased Diastolic Flow in Middle Cerebral Artery - “Brain Sparing Effect” in the same patient 56
XIII
LIST OF GRAPHS
Sl. No. Graphs
Page
No.
1. Distribution of Normal UAPI with Gestation age 38
2. Distribution of normal MCA PI with gestational age 38
3. Maternal complications of study group 44
4. Distribution Characteristics of Placental Maturity 45
5. Amniotic Fluid distribution in the study group 46
6. Gestational Age Distribution in study group 47
7. Pregnancy Outcome in the study group 48
8. Adverse Outcomes in the study group 49
9. Spectral Characteristics of Umbilical Artery 50
10. Performance Characteristics of Doppler Indices 52
11. Distribution of UA PI Values with gestation for pregnancies
with adverse outcome.
53
12. Distribution of MCA PI Values with gestation for pregnancies
with adverse outcome
53
XIV
INTRODUCTION
Intrauterine growth retardation (IUGR) is a common complication of
pregnancy which is most commonly associated with a failure of normal placental
invasion and development. IUGR is associated with an increased risk of perinatal
mortality, morbidity and impaired neurodevelopment1, 2, 3. The correct detection of the
compromised IUGR fetus to allow timely intervention is a main objective of antenatal
care.
Ultrasonographic (US) biometry helps to identify a heterogeneous group of
small–for–gestational age fetuses that include fetuses with IUGR, fetuses with small
constitution, and fetuses with appropriate growth (misdiagnosed as small). Not all
small for gestational age babies suffer from IUGR and its associated risks.
Doppler ultrasound allows a noninvasive assessment of fetal haemodynamics 4,5.
Doppler investigation of the umbilical arteries provides information concerning
perfusion of the fetoplacental circulation, while Doppler study of fetal vessels detects
the haemodynamic rearrangements that occur in response to fetal hypoxia.
Umbilical artery (UA) Doppler velocimetry is the most rigorously evaluated
test among the noninvasive tests of fetal well being 6. Several authors have
reported a low end diastolic velocity in the umbilical artery, a consequence of high
flow resistance in capillaries of the terminal villi. A metaanalysis of randomized
controlled trials of UA Doppler velocimetry in high risk pregnancies (mainly
pregnancies with associated pregnancy induced hypertension and suspected IUGR)
demonstrated that its use was associated with a trend towards reduction of perinatal
mortality 7.
1
In response to prolonged fetal hypoxic stress, circulatory adaptation occurs,
resulting in redistribution of the cardiac output to provide a constant oxygen supply to
the brain and other essential organs (i.e., heart and adrenal glands)8,9. This
compensatory adjustment, on which the brain sparing effect 10 is based, associated
with a rise in diastolic velocities in Doppler cerebral artery waveforms. This rise is
considered a manifestation of cerebral vasodilatation, causing a decrease in Doppler
indices such as the pulsatility index 11,12. At cordocentesis , a significant correlation
has been observed between hypoxemia in fetuses with IUGR and abnormal
middle cerebral artery(MCA) pulsatility index (PI.).
Recent studies indicate that the cerebroplacental ratio of pulsatility
index of MCA and UA is the most sensitive Doppler index for predicting
perinatal outcome in fetuses with IUGR 13,14
In the majority of the severely growth retarded fetuses, sequential
deterioration of arterial and venous Doppler precedes biophysical profile score
deterioration. At least one third of fetuses show early signs of circulatory deregulation
1 week before biophysical profile deterioration, and in most cases, Doppler
deterioration preceded biophysical profile deterioration by 1 day 15. This indicates the
significance of Doppler study in these patients for early detection of fetal
compromise.
Differences in study design, including the criteria for patient selection, the
definition of adverse outcomes, different cut off levels between normal and
abnormal test results makes direct comparison difficult.
Our study was an effort at establishing the role of UA and MCA Doppler
Ultrasound in predicting adverse perinatal out come in the clinically suspected
2
Pregnancies and to determine the role of Doppler velocimetry in clinical management
of such pregnancies.
3
AIMS AND OBJECTIVES
1) To evaluate the role of Doppler ultrasonography in predicting the adverse
perinatal outcome in IUGR pregnancies using umbilical and middle cerebral
artery Doppler indices.
2) To establish the role of Doppler Ultrasonography in the management of an
IUGR pregnancy
4
REVIEW OF LITERATURE
Doppler ultrasound provides a unique, non invasive and safe method of
studying blood flow characteristics in both the fetoplacental and uteroplacental
circulations that is being used in clinical evaluation of high risk pregnancies. The
growing availability of Doppler equipment in the mid to late 1980s led to an
outpouring of studies examining the use of this technique in pregnant women.
Many of these studies assessed the potential value of Doppler study of various
fetal vessels like, abdominal aorta, ductus venosus, middle cerebral artery and
umbilical arteries to assess the fetal haemodynamics in a clinically suspected IUGR.
In a study, perinatal indicators of fetal compromise were assessed according to
the results of continuous-wave Doppler umbilical velocimetry for 172 patients at risk
for intrauterine growth retardation (IUGR). They found that the last Doppler study
before delivery was abnormal in 48.8% of the growth-retarded infants but in only
13.2% of the infants without evidence of IUGR. Furthermore, in the growth-retarded
group, early delivery, reduced birth weight, decreased amniotic fluid at birth,
admission to the neonatal intensive care unit, neonatal complications associated with
IUGR, and a prolonged hospital stay were observed more frequently in those who
had an abnormal ratio than in those with a normal ratio. The sensitivity of the
systolic/diastolic ratio for an adverse perinatal outcome (operative delivery for fetal
distress, neonatal morbidity associated with IUGR, and/or perinatal death) was
significantly better for the infants with IUGR (66.7%) than for the infants without
IUGR (27.8%; P< .05). The predictive value of an abnormal ratio was also higher for
the pregnancies complicated with IUGR (57.1%) than for those without IUGR
(29.4%), but not to a statistically significant degree. These data suggest that
5
Doppler umbilical velocimetry studies are valuable in identifying those growth-
retarded fetuses at increased risk for an adverse perinatal outcome16.
In a study using Doppler U/S, flow velocity wave forms in the middle cerebral
artery were studied. In growth retarded fetuses pulsatility index in MCA was
significantly reduced compared with normal pregnancy suggesting participation of
MCA in a brain sparing effect in the presence of clinical fetal hypoxia17.
In a study of fetal middle cerebral artery in 81 small-for-gestational age
fetuses (SGA) using color flow imaging and pulsed Doppler studies, Impedance to
flow (pulsatility index; PI) was significantly lower, and mean blood velocity was
significantly higher, than the respective reference ranges with gestation. Fetal blood
sampling by cordocentesis was performed in all SGA fetuses and a significant
quadratic relation was found between fetal hypoxemia and the degree of reduction in
the PI of flow velocity waveforms (FVWs) from the fetal middle cerebral artery. They
concluded that maximum reduction in PI is reached when the fetal PO2 is 2-4 SD
below the normal mean for gestation and when the oxygen deficit is greater there is a
tendency for the PI to raise, presumably reflecting the development of brain edema18.
In a study the changes in fetal Doppler parameters with advancing gestation
was studied. Furthermore, they examined the alterations in fetal haemodynamics in
relation to fetal blood oxygen tension in samples obtained by cordocentesis from
small for gestational age (SGA) fetuses. They found that in SGA fetuses, increased
downstream impedance to flow in the umbilical artery, as demonstrated by the
absence of end-diastolic frequencies in the FVWs, is associated with fetal hypoxia
which presumably reflects the underlying derangement of placental structure and
function. The impedance to flow and mean blood velocity were also measured in
6
FVWs from the descending thoracic aorta and common carotid artery, obtained by
pulsed Doppler ultrasound, and from the middle cerebral and renal arteries obtained
by color flow imaging. There were significant correlations between the degree of fetal
hypoxia and alterations in Doppler parameters, which were compatible with the brain
sparing effect. Thus, in fetal hypoxia impedance to flow in the common carotid and
middle cerebral arteries was decreased, whereas impedance in the aorta and renal
artery was increased. They also found that there were simultaneous alterations in the
mean blood velocity in the opposite direction to those in impedance19.
In a study of 45 normal-growth and 45growth-retarded fetuses between 30-
41weeks gestation, velocity recordings were obtained from the middle cerebral artery
and umbilical artery to calculate the ratio between the two pulsatility indices. The
cerebral - umbilical Doppler ratio is usually constant during the last 10 weeks of
gestation. Therefore, a single cutoff value (1.08) was used, above which velocimetry
was considered normal and below which it was considered abnormal. The cerebral-
umbilical Doppler ratio provided a better predictor of small for gestational age
newborns and adverse perinatal outcome than either the middle cerebral artery or
umbilical artery alone. In fact, in predicting those newborns who were small for
gestational age, the cerebral-umbilical ratio had a 70% diagnostic accuracy [(true
positive + true negative)/total number of cases], compared with 54.4% for the middle
cerebral artery and 65.5% for the umbilical artery. The results were more encouraging
for prediction of adverse perinatal outcome; diagnostic accuracy for the cerebral-
umbilical Doppler ratio was 90%, compared with 78.8% for the middle cerebral artery
and 83.3% for the umbilical artery12.
In a study blood flow velocity waveforms were recorded from different
vascular districts including umbilical artery, descending aorta, renal artery, internal
7
carotid artery and middle cerebral artery in a population of 120 small for gestational
age fetuses free from structural and chromosomal abnormalities. The pulsatility index
from each vessel as well as the ratios between the pulsatility indices from peripheral
and cerebral vessels were calculated and related to perinatal outcome. They found that
the pulsatility index of middle cerebral artery resulted the most efficient measurement
to predict the development of perinatal adverse outcome when each vessel was
considered singularly, however, better results were achieved when the ratios between
pulsatility indices were related to perinatal outcome; This is most evident for the ratio
between the pulsatility indices of umbilical artery and middle cerebral artery
suggesting the usefulness of this ratio in differentiating small for gestational age
fetuses at risk of unfavorable outcome20.
In a study of out come of Doppler velocimetry of the umbilical artery in three
groups of pregnancies: Those with the positive end diastolic velocities (PEDV: n=
214), absent end diastolic velocities (AEDV: n = 178) and reversed end diastolic
velocity (REDV: n = 67), pregnancies complicated by IUGR had high risk of
developing absent or reversed end diastolic flow velocity waveforms (odd ratios 3.1).
Pregnancies complicated by both IUGR and hypertension had an even higher risk
(OR= 7.4). The over all perinatal mortality rate was 28%. Significantly more neonates
in the AEDV flow group needed admittance to the NICU, PEDV group 60%, AEDV
group 96%, REDV Group 98% 21.
In a study, fetal Doppler indices, in particular ratios that include measurements
obtained from the cerebral circulation help in the recognition of the small fetus that is
growth-retarded. At term, evidence of fetal hemodynamic redistribution may exist in
the presence of a normal umbilical artery PI. Fetal Doppler indices provide
information that is not readily obtained from more conventional tests of fetal well-
8
being. It therefore has an important role to play in the management of the growth-
retarded fetus22.
In a study, Arbielle and coworkers found that the cerebral-placental ratio
constant during the pregnancy during the last 10 weeks of gestation and suggested 1
as the cut off value; they considered all values below 1 as abnormal 23.
In a study 71 high-risk fetuses with weekly UA and MCA Doppler US
examinations until delivery were studied. They found that in 15.5% (11 of 71) of
fetuses, there was perinatal mortality or major morbidity, including major intracranial
hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, and major
neurological handicap (follow-up data in 24 cases and up to only 2 years of age). By
using the last Doppler US result for analysis, the UA/MCA resistance index ratio,
compared with the UA systolic-to-diastolic ratio, was more sensitive (75% vs. 64%)
but less specific (60% vs. 74%). They concluded that UA Doppler US was a better
predictor for each of the individual adverse outcomes when separate analyses were
performed24.
In a study vascular resistances of various fetal areas were assessed by Doppler
ultrasound. The PI, RI and S/D indices are measured on the cerebral, renal, aortic and
umbilical Doppler spectrum. Ratios of these indices based on the comparison of the
cerebral (Rc) and the umbilical (Rp) resistances, or carotid (Rcc) and umbilical
resistances, or cerebral (Rc) and aortic (Rao) resistances (Rc/Rp or Rp/Rcc, or
Rc/Rao), measure the flow redistribution between the placenta and brain. They found
that the umbilical resistance indices, when greater than the upper limit of the normal
range (>2 SD) are frequently associated with IUGR. (Sensitivity is about 65 to 70%).
Absent end diastolic flow is most of the time associated with severe IUGR and
9
hypoxia and poor fetal outcome. A fairly good correlation was found between the
existence of significantly decreased (<2 SD) cerebral resistance and the development
of post asphyxial encephalopathy in the neonate (Specificity 75% and Sensitivity
87%). The earliest detectors of IUGR and hypoxia are the cerebral-umbilical,
cerebral-carotid, or cerebral-aortic ratios (Sensitivity 85% and Specificity 90%).
When used as predictor of poor perinatal outcome in growth retarded fetuses, the
cerebral umbilical ratio shows a sensitivity of 90% compared with 78% of the middle
cerebral artery, and 83% for the umbilical artery indices. Changes of this ratio were
well correlated with the fetal PO2 changes25.
In a study two hundred ninety-three small–for–gestational age fetuses (24–39
weeks at recruitment and US-estimated weight or abdominal circumference below
10th percentile) were prospectively examined with Doppler US of the UA, MCA, and
RA. Clinicians were blinded to MCA and RA Doppler measurements. Seventy-six
fetuses (25.9%) had at least one major or minor adverse perinatal outcome. Major
outcomes included stillbirth, neonatal death, neurological complication, and
necrotizing enterocolitis. The MCA pulsatility index (PI), compared with the UA PI
and RA PI, was more sensitive (72.4% vs. 44.7% and 8.3%) but less specific (58.1%
vs. 86.6% and 92.6%) in predicting adverse outcome. The UA PI had the highest
positive likelihood ratio (ratio, 3.3); the MCA PI had the lowest negative likelihood
ratio (ratio, 0.48). When gestational age at the first Doppler US examination was less
than 32 weeks, the MCA PI had a sensitivity of 95.5% and negative predictive value
of 97.7% for major adverse outcome (negative likelihood ratio, 0.10). They concluded
that in suspected IUGR, an abnormal UA PI is a better predictor of adverse perinatal
outcome than an abnormal MCA or RA PI. While, a normal MCA PI may help to
10
identify fetuses without major adverse perinatal outcome, especially before 32 weeks
gestational age26.
In a study 120 random pregnancies were screened at 20, 28 and 34 weeks of
gestation. Pregnancies with a normal outcome were used for calculating the normal
range of various indices and for testing the specificity and negative predictive value
(NPV) of the study. Those pregnancies with an abnormal outcome (PIH and SGA
babies) were used for calculating the sensitivity and positive predictive value (PPV)
of the study. In normal pregnancies, the flow velocity waveforms (FVWs) showed a
good diastolic flow and fall in indices as pregnancy progressed. A low diastolic flow
and high indices characterized the pregnancies with abnormal outcomes. The uterine
artery had a better sensitivity and specificity as compared to the umbilical artery.
Among the various uterine waveform parameters, the diastolic notch had the highest
sensitivity and specificity. Among the umbilical indices, the PI had the highest
sensitivity and specificity27.
In a study umbilical artery and middle cerebral artery waveforms were studied
in structurally normal fetuses at 35 or more weeks of gestation. Fetuses with
aneuploidy and/or major structural abnormalities were excluded. Umbilical artery and
middle cerebral artery (MCA) Doppler waveforms were recorded and considered
abnormal if above 95th or below 5th percentiles, respectively. Amniotic fluid was
considered reduced if the maximum vertical cord-free pool was < 2 cm. The placenta
was considered mature if the Grannum grade was II or III. The head circumference
(HC)/abdominal circumference (AC) ratio was considered abnormal if > 95th
percentile for gestation. Fetal growth, amniotic fluid, biophysical profile score and
umbilical artery Doppler were used to advise the referring obstetrician about fetal
well-being and he/she independently decided both the timing and mode of delivery.
11
Forty-seven fetuses fulfilled the entry criteria. Thirty-four (72%) demonstrated normal
umbilical artery Doppler waveforms. Sixteen (34%) demonstrated middle cerebral
artery redistribution, of which nine (56%) had normal umbilical artery Doppler
waveforms. MCA blood flow redistribution was associated with an increased
incidence of cesarean delivery and need for neonatal admission. Of all gray-scale
parameters, an elevated HC/AC ratio has the strongest association with MCA blood
flow redistribution (15/16 vs. 1/31; P < 0.01). They concluded that MCA Doppler
may be a useful tool to assess the health of small fetuses in the late third trimester.
Redistribution may occur in the presence of normal umbilical artery Doppler and
should be suspected when the HC/AC ratio is elevated28.
In a study Doppler flow waveforms of umbilical artery, middle cerebral artery
and thoracic aorta were obtained from 100 pregnant women with intrauterine growth
restricted fetuses.The pregnancies were grouped according to the umbilical artery
Doppler results. There were 29, 30 and 41 fetuses with normal and high PI (pulsatility
index), and absent end-diastolic velocity (AEDV) in the umbilical artery respectively.
Birth weight and umbilical vein pH at birth significantly decreased and perinatal
mortality rates significantly increased with the worsening of the diastolic flow in the
umbilical artery (p<0.01). They found that increased umbilical artery PI was
significantly associated with increased thoracic aorta PI and decreased middle
cerebral artery PI (r=0.75 and −0.55, p<0.01 respectively). Perinatal mortality due to
fetal asphyxia in fetuses with AEDV in the umbilical artery and in both the umbilical
artery and thoracic aorta was 39.5% and 50% respectively29.
In prospective study performed to determine if the ratio of the middle cerebral
artery (MCA) S/D ratio (ratio of peak systolic blood flow velocity to diastolic
velocity) to the umbilical artery (UA) S/D ratio (MCA/UA S/D ratio) predicts the
12
degree of neonatal morbidity in fetuses suspected of having IUGR. They studied Sixty
one fetuses identified prospectively by sonography as having an estimated fetal
weight below the 10th percentile for gestational age. They found that adverse perinatal
outcome like respiratory distress syndrome and intracranial hemorrhage were not
associated with abnormal Doppler findings after correction for gestational age. The
interval between the abnormal Doppler examination and delivery (p < 0.001) and the
occurrence of fetal distress requiring cesarean section (p < 0.001) were significantly
related to the severity of Doppler findings. They concluded that in fetuses with
suspected IUGR, abnormal MCA/UA S/D ratios are strongly associated with low
gestational age at delivery, low birth weight, and low UA pH. Abnormal MCA/UA
S/D ratios are also significantly associated with shorter interval to delivery and the
need for emergent delivery30.
In a study, two hundred and thirty-one pregnancies of singleton pregnancy of
birth weight < 10th centile, without severe maternal complications and fetal anomalies
on the sonogram with normal umbilical artery Doppler and complete follow-up. At
the first antenatal sonogram classifying the fetus as SGA, Doppler analysis of the
uterine and middle cerebral arteries was performed and amniotic fluid volume was
assessed. Outcome variables included adverse perinatal outcome (perinatal death,
severe morbidity) and emergency cesarean section for fetal distress. Logistic
regression demonstrated that abnormal velocimetry of the uterine arteries and fetal
middle cerebral arteries were independently correlated with the occurrence of
Cesarean section. They concluded that SGA fetuses with normal umbilical artery
Doppler waveforms and abnormal uterine arteries and fetal middle cerebral artery
waveforms have an increased risk of developing distress and being delivered by
emergency Cesarean section. Particularly when both uterine and fetal cerebral
13
waveforms are altered at the same time, the risk is exceedingly high (86%) and
delivery as soon as fetal maturity is achieved seems advisable. On the other hand,
when both vessels have normal waveforms, the chances of fetal distress are small
(4%) and expectant management31
In a Retrospective study of Doppler velocimetry of 578 singleton pregnancies
with diagnosis of intrauterine growth restriction (IUGR, four subsets were formed:
normal umbilical artery pulsatility index (NUAPI; 334 fetuses); increased pulsatility
index but with preserved diastolic flow (abnormal umbilical artery pulsatility index
AUAPI; 137 fetuses); absent end-diastolic flow (AEDF; 70 fetuses); reversed end-
diastolic flow (RF; 37 fetuses). Fetal biometry, amniotic fluid and fetal-maternal
Doppler velocimetry were evaluated in all patients, with biophysical profile and
routine non-stress test, when indicated. The following outcomes were examined:
mean gestational age at delivery, number of preterm deliveries (< 34 weeks), mean
neonatal weight, Apgar score at 5 min < 7, prenatal and neonatal deaths (within the
first 28 days of life), admission to the NICU and number of days spent after birth in
hospital. Neonatal morbidity was analyzed, including respiratory distress syndrome
(RDS), intraventricular hemorrhage (IVH, grade 2-3), necrotizing enterocolitis (NEC)
and retinopathy of prematurity. They concluded that a strict correlation exists between
abnormal umbilical Doppler velocimetry and an increased incidence of perinatal
complications in IUGR fetuses32.
In a study absent or reverse end-diastolic flow (Doppler II/III) in umbilical
artery was correlated with poor perinatal outcome, particularly in intrauterine growth
restricted (IUGR) fetuses. They also studied the short- and long-term morbidity and
mortality among these children. Sixty-nine IUGR fetuses with umbilical Doppler
II/III were divided into three groups; Group 1, severe early IUGR, no therapeutic
14
intervention (n = 7); Group 2, fetuses with pathological biophysical profile,
immediate delivery (n = 35); Group 3, fetuses for which expectant management had
been decided (n = 27). There results were, in Group 1, stillbirth was observed after a
mean delay of 6.3 days. Group 2 delivered at an average of 31.6 weeks and two died
in the neonatal period (6%). In Group 3 after a mean delay of 8 days, average
gestational age at delivery was 31.7 weeks; two intrauterine and four perinatal deaths
were observed (22%). Long-term follow-up revealed no sequelae in 25/31 (81%) and
15/18 (83%), and major handicap occurred in 1 (3%) and 2 patients (11%),
respectively, for Groups 2 and 3. They concluded that fetal mortality was observed in
22% of this high risk group. After a mean period of follow-up of 5 years, 82% of
infants showed no sequelae. According to their management protocols IUGR
associated with umbilical Doppler II or III does not show any benefit from an
expectant management in term of long-term morbidity33.
In a study, 70 pregnant women with growth-restricted fetuses confirmed by
ultrasound were followed up with Doppler studies of the umbilical artery. The study
group consisted of 35 women, where the Doppler waveform in the umbilical
artery was compromised (either absent end diastolic flow [AEDF] or reversed end
diastolic flow [REDF]). These were compared with an equal number of controls,
where growth- restricted fetuses had normal Doppler waveforms. Outcome measures
were evaluated in both groups and analyzed. The periods Of gestation at delivery
were 27.2 +/- 3.5 weeks in group 1 and 37 +/- 3.3 Weeks in-group II, respectively.
Perinatal morbidity and mortality was significantly increased in the group with
compromised umbilical artery blood group. Birth weight in group I was 742 +/-
126 grams and in group II was 680 +/- 259 grams. This difference was
statistically significant (P=0.0001). In comparison to AEDF, REDF fetuses had more
15
morbidity. Perinatal mortality was also significantly increased in this group
(P=0.001). They concluded that Umbilical artery Doppler should be used in the
management of growth-restricted fetuses. In those fetuses in normal Doppler,
pregnancy can be prolonged. REDF is an indication for termination of pregnancy34.
In a retrospective cohort study of 121 singleton pregnancies with IUGR
(birth weight less the 5th percentile for gestation) excluding twins or fetuses with
aneuploidy and congenital malformations was conducted. Abnormal antenatal
testing such as NST which was non-reactive or with late decelerations: BPP <6
and abnormal Doppler as umbilical artery with absent and reversed diastolic
flow. The outcomes studied included: umbilical artery pH <7, respiratory distress
syndrome, periventricular leukomalacia, grades 3-4 intraventricular hemorrhage,
perinatal mortality, necrotizing enterocolitis and a composite of at least one
adverse outcome .statistical analysis included bivariate and multivariable
techniques. Of the testing modalities compared only abnormal Doppler
significantly predicted respiratory distress and composite of adverse outcome.
They concluded that in cases of IUGR the presence of abnormal Doppler is the
best predictor of adverse perinatal outcome35.
16
Anatomy of fetoplacental and uteroplacental circulation
Fetoplacental circulation 36 37
During fetal life oxygenation is carried out in the placenta. The fetal
surface of the placenta is covered by the transparent amnion, beneath which
the fetal chorionic vessels course.
Deoxygenated or venous like fetal blood flows to the placenta through the two
umbilical arteries. When the umbilical cord joins the placenta, the umbilical vessels
branch repeatedly beneath the amnion and again within the dividing villi, finally
forming capillary networks in the terminal divisions. Blood with significantly higher
oxygen content returns from the placenta to the fetus through a single umbilical vein.
The branches of the umbilical vessels that traverse along the foetal surface of the
placenta in the chorionic plate are referred to as the placental surface or chorionic
vessels. These vessels are responsive to vasoactive substances, but anatomically,
morphologically, histologically, and functionally, they are unique. The chorionic
arteries always cross over the chorionic veins. Identification of chorionic artery and
vein is most readily recognized by this interesting relationship, but they are difficult to
distinguish by histological criteria. In 65 percent of placentas, the chorionic arteries
form a fine network supplying the cotyledons .The remaining 35 percent of arteries
radiate to the edge of the placenta without narrowing. Both are end arteries, supplying
one cotyledon as each branch turns downward to pierce the chorionic plate.
The truncal arteries are the perforating branches of the surface arteries that
pass through the chorionic plate. Each truncal artery supplies one cotyledon. There is
a decrease in the smooth muscle of the vessel wall and an increase in the calibre of the
vessel as it penetrates through the chorionic plate. The loss in smooth muscle
17
continues as the truncal arteries branch into the rami, and the same is true of the vein
walls.
Materno placental circulation 36, 37
Maternal blood enters through the basal plate and is driven high up
towards the chorionic plate by maternal arterial pressure before lateral
dispersion occurs. After bathing the external micro villous surface of chorionic villi
the maternal blood drains back through venous orifices in the basal plate and enters
the uterine veins, maternal blood traverses the placenta randomly without preformed
channels, propelled by maternal arterial pressure. The Processes of trophoblast
invasion of the spiral arteries create low-resistance uteroplacental vessels, which can
accommodate the massive increase in uterine perfusion over the course of gestation.
Generally, the spiral arteries are perpendicular to, but the veins are parallel to,
the uterine wall, an arrangement that facilitates closure of the veins during a uterine
contraction and prevents squeezing of essential maternal blood from the
intervillous space. The number of arterial openings in to the intervillous space
becomes gradually reduced by cytotrophoblast invasion.
18
Fig 1: Schematic Diagram showing Placental circulation
Fetal circulation 36, 37
Oxygen and nutrition materials required for fetal growth and maturation
are delivered to the fetus from the placenta by the single umbilical vein. The
umbilical vein enters the fetus at umbilicus and runs along the free margin of the
falciform ligament of the liver. The vein then divides in to the ductus venosus
and the portal sinus. The ductus venosus is the major branch of the umbilical
vein and traverses the liver to enter the inferior venacava directly. Portal sinus
carries blood to the hepatic veins primarily on the left side of the liver, the
deoxygenated blood from the liver then flows back in to the inferior venacava,
which also receives deoxygenated blood from the lower body. The well
19
oxygenated blood tends to course along the medial aspect of the inferior
venacava and the less oxygenated blood stays along the lateral vessel wall,
facilitating their shunting in to opposite sides of the heart. In contrast to
postnatal life, the ventricles of the fetal heart work in parallel, not in series.
Well –oxygenated blood enters the left ventricle, which supplies the
heart and brain, and less oxygenated blood enters the right ventricle, which
supplies the rest of the body. Once the inferior venacava blood enters the right
atrium, the configuration of the upper interatrial septum, called the crista
dividens, is such that it preferentially shunts the well oxygenated blood from
the medial side of the inferior venacava and the ductus venosus through the
foramen ovale in to the left heart and then to the right heart and brain. The
less oxygenated blood coursing along the lateral wall of the inferior venacava,
less oxygenated blood from the brain and upper body through the superior
venacava, and deoxygenated blood from the heart through the coronary sinus
enters the right atrium and is deflected through the tricuspid valve to the right
ventricle. As a result of this blood in the right ventricle is 15-20% less
saturated than in left ventricle. Almost 90% of blood from the right ventricle
is shunted through the ductus arteriosus to the descending aorta The high
pulmonary vascular resistance and the comparatively lower resistance in the
ductus arteriosus and the umbilical-placental vasculature ensures that only 15%
of the right ventricular output goes to the lungs. Thus, one third of the blood
passing through the ductus arteriosus is delivered to the body. The remaining right
ventricular output returns to the placenta through the two hypogastric arteries,
which distally become the umbilical arteries. In the placenta, this blood picks
20
up oxygen and other nutrients and is then recirculated back through the
umbilical vein.
Fig 2: Schematic Diagram showing Fetal circulation
21
INTRAUTERINE GROWTH RESTRICTION
DEFINITION
Intrauterine growth retardation has been defined in a variety of ways
by different authors. Intrauterine growth retardation is a fetal growth disorder
most commonly defined on the basis of a weight below the 10th percentile for
the corresponding gestational age .Small for gestational age and IUGR has been used
interchangeably, but now IUGR is restricted for the clinical circumstance of a fetus
that is underachieving its growth potential38.
Intrauterine growth restriction is associated with increased risk of perinatal
morbidity and mortality. Growth restricted fetus have 4-8 times mortality when
compared to that of non IUGR fetuses. One half of surviving growth
restricted infants suffer serious short or long term morbidity including
meconium aspiration pneumonia and metabolic disorders39,40 .
CAUSES
IUGR has many causes including placental insufficiency which may be
primary or secondary to maternal disorder such as hypertension, collagen
vascular disease, poor nutrition, drug and alcohol abuse , fetal chromosomal
anomalies (trisomy 13 and 18) and fetal infections (cytomegalo virus and
toxoplasma)41,42, placental or cord abnormalities which include placental
infraction, chorioangioma, marginal or velamentous cord insertion, circumvallete
placenta, or placenta previa. primary placental insufficiency is the most common
cause of IUGR.
22
IUGR has been categorized as asymmetrical where growth restricted
fetal abdomen is disproportionately small in relation with head and limbs and
symmetrical where fetuses are proportionately small in size. The former is
more common variety, is the pattern expected in the most cases of primary
or secondary to placental insufficiency. The latter is seen in cases resulting
from an early insult. There is however, considerable overlap between these two
groups.
PATHOPHYSIOLOGY
IUGR is primarily the result of disturbances in placental vascular
development 43.In early pregnancy miscarriage may result from inhibited angiogenesis
and poor placental adherence. Later in gestation, inadequate trophoblastic invasion in
to maternal spiral and radial arteries leads to the failure of establishment of a low
resistance circuit that is a key to further fetal growth. The fetal response to
uteroplacental insufficiency (UPI) can be categorized in to early and late
cardiovascular adaptations that are relevant to sonographic assessment of fetal status.
Early adaptation is characterized by changes in blood flow to favor nutrient and
oxygen distribution to essential organs, especially the brain. Umbilical venous volume
is reduced in early stages of UPI, leading to oligohydramnios due to decreased renal
perfusion 44. This leads to greater diversion of the relatively nutrient oxygen rich
umbilical venous blood through the ductus venosus away from the liver and to the
fetal heart; through the foramen ovale, this blood then enters the left side of the heart,
and from there, moves on to the coronary and cerebral circulations 45. Facilitating this
shunting is an elevation in right ventricular after load owing to the high resistance of
the pulmonary vasculature as well as the rising placental resistance. A reduction in
left ventricular after load occurs as well owing to the drop in cerebral vascular
23
resistance.46, 47, 48,. Late changes occur with progressive UPI and increasing placental
resistance with development of oligohydramnios. Cardiac output declines owing to
the rising after load, resulting in reduced forward flow. As a result, the ability to
handle preload is also significantly diminished, leading to elevated central venous
pressure and inhibition in forward venous flow49,50 The final stage is global
myocardial dysfunction and dilatation51. Holosystolic tricuspid insufficiency and
spontaneous fetal heart rate deceleration herald impending death 52.
SHORT AND LONG TERM SEQUELAE
Significant immediate complications include increased mortality, transient
tachypnoea of newborn, hypothermia, hypoglycemia, polycythemia, hyperviscosity,
hyperbilirubinemia and impaired immune function53-57, Long term sequelae in
premature infants are increased risk for neurodevelopmental abnormalities and
cognitive impairment. Term IUGR babies are also at risk for learning difficulties,
behavioral problems and worse school performance58, 59
DIAGNOSIS
Sonographic diagnosis of IUGR
The definition of IUGR as a weight below the 10th percentile for
gestational age Suggests a straight forward method for diagnosis by obstetric
sonography: if the sonographically estimated fetal weight falls below the 10th
percentile for gestational age. Calculating the weight percentile requires three
steps60,61,62 First - a gestational age is assigned to the fetus., Second- fetal weight is
estimated, Third- the weight percentile is calculated from the estimated weight
and gestational age.
24
Once fetal age has been firmly established, the determination of fetal growth
becomes necessary in the high risk pregnancies. Inherent in determining interval
growth is necessary for at least two temporally spaced measurements of biometric
parameters. Given that growth is continuous rather than sporadic, and that the
identification of growth is limited by the technical capability of the ultrasound
equipment used, the recommended interval between ultrasound evaluations of fetal
growth is 3 weeks, because shorter intervals increase the likely hood of a false
positive diagnosis of abnormal growth.
Additional sonographic criteria for diagnosis of IUGR are elevated head
circumference/ abdominal circumference, elevated femur length/ abdominal
circumference, presence of advanced placental grade and oligohydramnios
without rupture of membranes. Others like trans cerebellar diameter/ abdominal
circumference, fractional thigh volume measurement (three dimensional ultrasound) ,
soft tissue and subcutaneous fat estimation63,64,65
Monitoring the growth retarded fetus
A growth retarded fetus should be delivered before term if the risks
associated with remaining in utero become greater than the risks of prematurity
outside the uterus. As these risks are not static, once IUGR has been
diagnosed and a lethal cause excluded, the fetus should be monitored closely
with sonography for the remainder of the pregnancy. The appropriate timing of
follow up sonograms depends on IUGR severity and gestational age; weekly or
semi weekly scans are typically called for in cases of third trimester IUGR.
Sonographic features to be followed include fetal growth, amniotic fluid
volume, biophysical profile, and spectral Doppler waveforms. A worsening trend
25
in one or more of these, especially if the change is abrupt, should prompt
consideration of early delivery.
Doppler velocimetry
Doppler ultrasound allows a noninvasive assessment of fetal haemodynamics.
Uteroplacental insufficiency is associated with progressive worsening of placental
Resistance. Increased resistance leads to decreased velocity in the feeding arteries,
especially during diastole, and to decreased volume of blood flow through the
placenta. Disproportionate slowing of diastolic relative to systolic flow leads to
elevation of a number of Doppler indices, including the systolic/diastolic ratio and the
pulsatility index. Therefore, proposed Doppler criteria for IUGR have included
elevated systolic/diastolic ratio or pulsatility index in the fetoplacental or
uteroplacental circulation (umbilical artery, other fetal arteries, or uterine arcuate
arteries) and decreased volume flow through the umbilical vein.66-72
Doppler interrogation of the fetal arterial system provides an indirect
assessment of placental resistance, where as the fetal venous system provides an
assessment of fetal cardiac function.
Doppler imaging in monitoring growth retarded fetus
Doppler imaging is of value for monitoring the pregnancy because it
can provide indirect evidence of fetal compromise. Numerous studies support
the value of Doppler waveform indexes of the umbilical artery and perhaps of
fetal cerebral Arteries for assessing the prognosis of fetuses with IUGR. In
particular, the frequencies of caesarean section for fetal distress, admission to
neonatal care unit, and perinatal mortality are all two fold to four fold higher
26
in growth retarded fetuses with abnormal umbilical artery waveforms and with
decreased systolic to diastolic ratio 73-78. In the fetal internal carotid and middle
cerebral arteries, a decreased systolic/diastolic ratio or pulsatility index suggests
fetal hypoxia, because the fetal response to hypoxia is to decrease resistance in
the cerebral circulation in order to increase blood flow to the brain 78-82 .The
Doppler finding with the greatest impact on pregnancy management is absent
or reversed end-diastolic flow in the umbilical artery81-86. Reversed flow is an
ominous finding associated with a high mortality rate within 1-7 days if the
fetus is left in utero 88. Absent flow suggests a poor prognosis as well,
although outcome in these fetuses is not as poor as in those with reversal
flow. With either of these findings prompt delivery must be seriously
considered.
PHYSICS OF DOPPLER ULTRASONOGRAPHY
Doppler ultrasound is based on the principle of the Doppler effect, so named
for Johann Christian Doppler, who identified this occurrence in 1842.The change in
the pitch of sound of a moving object caused by a relative caused by a
relative motion between the observer and the object is known as Doppler shift
and is a consequence of Doppler phenomenon.
When the frequency of the Doppler sound emitted from a stationary
source is fixed, and its insonation angle is known, the Doppler shift can be
calculated, as it is correlated to the velocity of the relative movement between
the target and the transducer. This relation is defined by the formula:
FD = 2 fo v Cos θ/c
27
Where FD the Doppler shift, fo is the frequency of the transmitted
ultrasound, v is the velocity of the relative movement, θ is the insonation
angle, and c is the velocity of sound within the tissue89
Continuous wave Doppler ultrasonography
In continuous wave Doppler, the system features separate emitting and
receiving Transducers that are arranged in a manner that their insonation axes
intersect at a certain range determined separately for each pair of transducers.
Continuous wave Doppler determines only the velocity of the blood but not
the position of the vessel.
Pulsed wave Doppler ultrasonography
In pulsed Doppler the ultrasonic waves is emitted in a pulsatile fashion.
Between the pulses of emission the same transducer operates as a receiver for
the backscattered echoes. Because the velocity of sound is presumed to be
constant, it is possible to analyze the back scattered echo alone from a
particular range. A circuit selectively permits only those signals from that arrive
to the receiver at a given time after the transmission. This allows a precise
determination of the size if the sample volume that can be located in a
particular area. the maximum Doppler shift frequency that could be measured is
related to half of the pulse repetition frequency (Nyquist limit). Beyond this
limit, Doppler signals will be distorted (aliasing).
Color flow imaging
In color Doppler imaging (CDI) color coded pulsed Doppler information
is superimposed on a B-Mode ultrasonic image. In this method color is assigned to
28
flow direction. Customarily flow towards the transducer is red and flow away
from the transducer is blue. The structures that do not move are represented in
basic gray-scale image. The color saturation is related to the magnitude of the
frequency shift. Color flow imaging facilitates the determination of small
vessels and slow blood-flow velocity.
Color Doppler energy
Color Doppler energy (CDE) detects the energy of Doppler signals
generated from the moving blood. The information obtained is different from that
of conventional CDI. the most distinctive feature of CDE is that it is
independent of the direction of blood flow.
Doppler velocimetry
Qualitative assessment:
Doppler spectrum is as series of spectra obtained by the Doppler signal
detected by the receiving transducer which contains mixture of Doppler shift
frequencies. Flow velocity waveforms are graphical drawings that show the
relative power of each frequency component that constitutes the entire Doppler
signal. The mean flow velocity waveforms(FVW) is therefore related to three
variables: time, frequency and power. The simplest qualitative method used in
Doppler data is to decide whether flow is present or not . This can be
achieved either visually or by listening to the Doppler signals. The color flow
data can also be regarded in this sense as a qualitative method and contribute
a great deal to the detection of blood flow.
29
Quantitative method:
The measurement of the velocity, acceleration, and volume of blood
flow can be achieved with Doppler data. When the angle between the
ultrasound beam and the longitudinal axis of the vessel is known, the Doppler
frequency shift can be achieved in to velocity by the equation:
FD = 2 fo v Cos θ/c
It can be seen from the equation that as the angle of insonation approaches 90
degrees the Doppler shift frequency decreases towards zero (cos 90º =0). There fore
the Doppler measurements are considered to be reliable as long as the insonation
angle is <60 deg90. The velocity measurements most commonly used in pulsed
Doppler studies are the maximum peak systolic velocity, the highest time averaged
maximum velocity and the minimum diastolic velocity.
Semi quantitative method:
Here the relationship between the systolic and diastolic components of the
waveform is evaluated and angle dependence, which is important in quantitative
method becomes less important. Different equations have been proposed to
define the properties of Doppler spectrum, the most common obstetric
applications being the pulsatility index(PI), and the resistive index(RI)(also
pourcelot index).
PI = S -- D/A
RI = S -- D/S
S/D ratio
30
Where S is the maximum peak systolic frequency, D is the end-diastolic, and
A is the mean Doppler shift frequency during a cardiac cycle. As can be seen from
the equations, when D=0 , the resistance index irrespective of the systolic
component will always be 1, where as pulsatility index will always be >1.
consequently under such circumstances, PI will be more informative than RI.
In addition PI takes the entire waveform in to account and not just the
maximum and minimum frequencies, as does RI91 .
Umbilical Artery and Middle Cerebral Artery Doppler in Normal and IUGR
Pregnancies
Umbilical artery
The umbilical artery was the first fetal vessel to be evaluated by Doppler
velocimetry has since become the most widely investigated part of fetal
circulation. This may be because of its easy accessibility and forms a vital
component acting as a lifeline between the fetus and the placenta.
The assessment of umbilical blood flow provides information on blood
perfusion of the fetoplacental unit. End-diastolic flow is not detected in the
umbilical artery before the end of 10 weeks gestation. End diastolic flow is
first detectable from the 11th to 14th weeks, although this initial flow is
inconstant. Constant end-diastolic flow, velocities are consistently detected after 14
weeks gestation although this initial flow is inconstant or complete. The increase in
the end diastolic flow with advancing gestation is due to increase in the number of
tertiary stem villi that takes place with maturation of placenta92.Thus the systolic/
diastolic ratio and pulsatility index decreases as the pregnancy advances.
31
Middle cerebral artery
Intracranial blood flow can be visualized as early as the 7th week of
gestation. An End-diastolic flow component is consistently observed in the
middle cerebral artery starting in the 12th week. The diastolic component is
less in the early second trimester, later diastolic component increases as the
gestation advances which is attributed to the decreased impedance with
development of the brain. The typical middle cerebral artery waveform at 28 to 32
weeks is characterized by high systolic velocities and minimal diastolic velocities,
resulting in high PI values, generally greater than 1.96. During pregnancy, there is a
continuous forward flow in all cerebral arteries through out the cardiac cycle.
The PI of the MCA decreases during the latter weeks of gestation and remains
unchanged in the early neonatal life.
Umbilical and middle cerebral artery Doppler changes in IUGR
In chronic placental insufficiency which is the most common cause for
IUGR, a substantial increase in the vascular resistance of the fetoplacental unit leads
to a decrease in end-diastolic flow velocity or its absence in the FVW. Initial studies
have demonstrated a relationship between abnormal flow velocity wave forms and
decrease in the number of small stem villi, irregular branching of distal villous tree, or
reduced vascularization or maldevelopment of intermediate and tertiary villi93-97.
These changes deteriorate the transplacental oxygen transport and lead to IUGR.
The association of abnormal UA FVW and fetal hypoxemia or acidemia in
IUGR fetuses has been documented in studies utilizing cordocentesis98. This is further
supported by the finding of a significant increase in the nucleated red blood cell
counts of neonates in whom abnormal UA FVW with or without signs of
32
redistribution and IUGR were diagnosed prenatally99,100. The appearance of a reversed
end-diastolic flow velocity is the final step in the cascade of events that may lead to
intrauterine fetal death. As a consequence of the placental insufficiency, in
response to prolonged fetal hypoxic stress, circulatory adaptation occurs, the
fetus shifts its blood flow to the vital organs such as brain, heart and adrenal
glands. The increased blood flow to the brain is called “Brain Sparing Effect”.
Brain sparing effect leads to cerebral vasodilatation leading to increased
diastolic flow which is seen as decreased pulsatility index in middle cerebral
artery Doppler velocimetry.
The redistribution in hypoxemic SGA fetuses may be transitory. With
worsening of oxygen deficit, the PIs tend to rise, which may be attributable to the
development of brain edema. A transition from previously detected low vascular
impedance to a high impedance flow with reversed diastolic component may precede
intrauterine death.
Various studies shows that the cerebroplacental ratio which is the ratio
of pulsatility index of cerebral artery to the umbilical artery is more sensitive in
predicting the perinatal outcome .
33
MATERIALS AND METHODS
Data for the study was collected from all patients of clinically suspected IUGR
pregnancies, referred to the department of Radio diagnosis, Bapuji hospital and
Chigateri hospital, attached to J.J.M. Medical College. Davangere. Study was done
for a period of two years from September 2006 to September 2008.
Women referred for antenatal Doppler were included in the study if the
following Inclusion criteria were met:
• Singleton pregnancy.
• Fetal gestational age of 30 to 40 weeks with clinically suspected intrauterine
growth retardation. (Estimated fetal weight <10th percentile for gestation)
• The gestational age was based on last menstrual period (LMP), ultrasound
biometry performed before the 20th gestational week, when the LMP is
uncertain or not known and early ultrasound before 13 weeks has not been
performed”.
• Exclusion criteria for the study included any pregnancy with
o Documented major congenital abnormality
o Multiple gestations
o Intrauterine death at the time of first Doppler examination.
Present study included a total number of 50 cases meeting the inclusion
criteria. Doppler US evaluation was performed following a detailed clinical history,
US biometry, and assessment of amniotic fluid and placental maturity. Follow up
Doppler studies were performed if clinically indicated to determine a favorable or a
worsening trend in the Doppler indices. However, only the results of the first Doppler
ultrasound were used for analysis of perinatal out come.
39
Doppler US Technique:
After ultrasound biometry assessment, all women were subjected to Doppler
studies of the umbilical artery (UA) and middle cerebral artery (MCA) serially
between 30-40 weeks. These assessments were performed by using an ultrasound
machine, the Philips Enviser CHD and a probe of 2-5MHz. the filter was set at 100
HZ. All measurements were plotted graphically in accordance with normograms
provided by the Harrington et al for Doppler indices.
The wave forms were obtained during fetal inactivity and apnea. Umbilical
artery Doppler flow velocity waveforms were obtained from a free loop of cord, and
measurements taken when a clear waveform was acquired in the absence of fetal
breathing or body movement.
For MCA Doppler US, a transverse image of the fetal head was obtained at the
level of the sphenoid bones. Color flow imaging was used to display the circle of
Willis. The MCA in the near field was insonated about 1 cm distal to its origin from
the internal carotid artery. The angle of insonation in both the cases are was less than
60deg.
The Pulsatility index (PI) was measured, and the presence or absence of end-
diastolic frequencies was noted. The PI was used as it continues to reflect changes in
resistance with progressive absence of end-diastolic frequencies or reverse flow.
40
Outcome Criteria
Doppler US results were analyzed for prediction of perinatal outcome. Outcome
variables included are:
Birth Weight (less than 10th percentile)
• Perinatal death
• Emergency CS for fetal distress
• Low APGAR score (5 min APGAR score less than 7)
• Admission to NICU for complications of Low Birth Weight.
• Pregnancy was considered to have “Adverse outcome” when any of the
following complications were present
o Perinatal death
o Emergency CS for fetal distress
o 5 minute Apgar score of less than 7
o Admission to NICU for complications of low birth weight.
Pregnancy outcome was considered to be Uneventful or Favorable when the
above complications were absent. The outcome for each pregnancy was obtained by
examining the labor ward records and neonatal intensive care unit records wherever
appropriate. The UA Pulsatility index ratios were considered abnormal if the value
was above the 95th percentile of previously published values for gestational age
22.The MCA pulsatility index was considered abnormal if the value was below the 5th
percentile of previously published values for gestational age 22.The MCA/UA PI ratio
(cerebro-placental ratio) is considered abnormal when it is less than 1.08 as given by
the Gramellini D et al 12.
42
Statistical analysis
Statistical analysis was done by using proportions. The sensitivity, specificity,
positive predictive value, negative predictive Value and diagnostic accuracy were
determined for all Doppler measurements using the following formulae.
A Sensitivity = ----- X 100 A + C D Specificity = ----- X 100 B + D A
Positive Predictive Value= -------- X 100
A + B
D Negative Predictive Value= ----------- X 100 C + D
A+D Diagnostic Accuracy = ------------- Total number of cases.
A = True positive B = False positive C = False negative D = True negative.
43
19.13
53.75
23.02
4.1
0
10
20
30
40
50
60
No.
of F
ibro
id (I
n Pe
rcen
tage
)
Normal 6-12 Weeks 12-20 weeks > 20 weeks
GRAPH IV : CLINICAL ASSESSMENT OF UTERINE SIZE
Results
RESULTS
The present study was performed during a period of 2 years from September
2006 to September 2008.
50 pregnancies with clinically suspected IUGR were evaluated with Doppler
ultrasonography. Acceptable waveforms were obtained in all the cases.
Table – 1 Maternal complications of study group
Maternal complications Percentage of cases
Pregnancy induced hypertension 42%
Anemia 20%
Gestational hypertension 6%
Out of 50 cases 42% (n=21) had pregnancy induced hypertension, 20 %
(n=10) had anemia and 3 had gestational hypertension at first Doppler examination.
Graph – 3: Maternal complications of study group
42%
20%
6%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
Perc
enta
ge
Pregnancy induced hypertension Anemia Gestational hypertension
Maternal Complications
Pregnancy induced hypertension
Anemia
Gestational hypertension
44
Table -2: Distribution Characteristics of Placental Maturity
Placental grading No of Cases (%)
2 29 (58)
3 21 (42)
Total 50 (100)
In our study 58 %( n=29) had grade 2 placenta, 21 %( n=42) had grade 2
placenta.
Graph -4: Distribution Characteristics of Placental Maturity
58%
42%
0%
10%
20%
30%
40%
50%
60%
Perc
enta
ge
2 3
Placental Grading
2
3
45
Table -3: Amniotic Fluid distribution in the study group
Amniotic fluid Present Normal
Oligo 14 7
Normal 12 17
Total 26 24
46% (n=23) had oligohydramnios and 54% (n=27) had normal amniotic fluid.
Graph -5: Amniotic Fluid distribution in the study group
1412
7
17
0
2
4
6
8
10
12
14
16
18
No o
f pat
ient
s
Present Normal
Amniotic Fluid
OligoNormal
46
Table -4: Gestational Age Distribution in study group
Gestational Age in weeks No of Cases (%)
30 10
31 2
32 26
34 34
36 26
38 2
Mean gestational age at the first Doppler US examination was 34weeks +/-
4weeks (2 SD).
Graph -6: Gestational Age Distribution in study group
10
2
26
34
26
2
0
5
10
15
20
25
30
35
Per
cenr
age
30 31 32 34 36 38Gestational Age in weeks
303132343638
47
Table -5: Pregnancy Outcome in the study group
Pregnancy
outcome No of cases Percentage
Outcome No of cases Percentage
Adverse 23 46%
Uneventful 27 54%
52% (n=26) fetuses had at least one abnormal outcome, of those; some (n=12) had
more than one abnormal outcome. Remaining 24 fetuses had normal outcome.
Graph -7: Pregnancy Outcome in the study group
Pregnancy Outcome
46%
54%
AdverseUneventful
48
Table -6: Adverse Outcomes in the study group
Adverse Outcomes No of cases
Intra uterine deaths 7 (30%)
Emergency CS 13(56%)
Low Apgar score 6(26%)
Admission to NICU 14(60%)
70% of neonates (n=35) had birth weight of less than 2.5 kg. There were 7
intra uterine deaths and 43 live births. Of the 43 live births,14 neonates were
admitted to NICU for low birth weight, 6 neonates had 5 min Apgar score of less than
7 and 13 babies were born by emergency ccesaerian section for fetal distress.
Graph -8: Adverse Outcomes in the study group
30
56
26
60
0
10
20
30
40
50
60
Perc
enta
ge
Intra uterine deaths Emergency CS Low Apgar score Admission to NICU
Intra uterine deathsEmergency CSLow Apgar scoreAdmission to NICU
49
Table 7: Spectral Characteristics of Umbilical Artery
Spectral Characteristics No Of Cases IUD Mortality
Absent EDF 06 3 50%
Reversed EDF 02 2 100%
Of the7 IUDs, 2 cases had reversal of diastolic flow and 4 had absent diastolic
flow. In all cases with reversal of diastolic flow, IUD of the fetus occurred with in one
week of diagnosis.
Graph 9: Spectral Characteristics of Umbilical Artery
50%
100%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Mor
talit
y
Absent EDF Reversed EDFSpectral Characteristics
Absent EDFReversed EDF
50
Table 8: Performance Characteristics of Doppler Indices
Parameters Sensitivity Specificity PPV NPV
Diagnostic
Accuracy
UAPI 73.9 96.2 94.4 81.2 86
MCAPI 91.3 66.6 70 90 78
MCAPI/
UAPI 95.6 85.1 84.6 95.8 90
Cerebroplacental ratio (MCA/UA PI Ratio was most sensitive (sensitivity
95.6%) than MCA PI sensitivity (sensitivity 91.3%) and UA PI sensitivity (sensitivity
73.9%)
Umbilical artery PI was the most specific (specificity96.2%), than
Cerebroplacental Ratio (specificity = 85.1%) and MCA PI (Specificity=66.6%)
Umbilical artery PI had highest Positive Predictive Value (PPV=94.4%) followed by
Cerebroplacental ratio (PPV=84.6%) and MCA PI (PPV=70%).
Negative Predictive Value of Cerebroplacental Ratio was 95.8% when
compared to 90% for MCA PI and 81.2% for UAPI.
Diagnostic accuracy of Cerebroplacental ratio (Accuracy=90%) was better
than MCA PI (Accuracy=78%) and UA PI (Accuracy=86%) in predicting adverse
outcomes.
51
Graph 10: Performance Characteristics of Doppler Indices
73.9
96.2 94.4
81.286
91.3
66.6 70
90
78
95.6
85.1 84.6
95.890
0
20
40
60
80
100
120
Sensitivity Specificity PPV NPV DiagnosticAccuracy
Parameters
Perc
enta
ge
UAPI
MCAPI
MCAPI/ UAPI
52
DISCUSSION
Intrauterine growth restriction is associated with increased risk of perinatal
morbidity, mortality and impaired neurological development1-3. It is a challenge to
differentiate the fetus with pathologic growth restriction and hence at risk for perinatal
complications from constitutionally small but healthy fetus.
Doppler velocimetry is a noninvasive technique that evaluates abnormal fetal
haemodynamics that takes place in response to changes in placental resistance. A
Doppler index that reflects both of these areas can be useful for identifying fetuses
with increased placental and decreased cerebral resistance.
Umbilical artery and middle cerebral artery Doppler ultrasound clearly depicts
the information about placental resistance and the changes in the fetal
haemodynamics in response to it. Umbilical arteries Doppler reflects the
maldevelopment of the placental tertiary stem villi which increases the placental
resistance leading to growth retarded fetus. Middle cerebral artery Doppler has
enabled the confirmation of brain sparing effect in IUGR. Hence we chose the UA PI,
MCA PI and MCA PI/UA PI i.e. cerebroplacental ratio as the tool for predicting the
perinatal out come in IUGR.
We studied the Doppler index of umbilical artery only after 30th week,
because in agreement with Schulman101, Gramellini 12, we believe that it is difficult to
define normal or abnormal umbilical flow velocity before 30th week, with the
exception of absent end diastolic flow velocity after 20th week.
We studied the Doppler index of middle cerebral artery because it is the most
accessible artery to see the cerebral redistribution as it is the main branch of the
circle of Willis and carries 80% of the blood flow to the ipsilateral cerebral
hemisphere, a constant 3%–7% of cardiac output throughout gestation.
57
The MCA PI and UA PI values for the corresponding gestational age
were compared with reference values given by Harrington et al 22 normograms.
MCA PI was considered abnormal when it is less than 5th percentile for that
gestational age and UA PI was considered abnormal when it is more than 95th
percentile for the corresponding gestational age.
It is possible to use a single cut off value for cerebroplacental ratio after 30th
week because cerebral-umbilical Doppler ratio does not vary significantly between
30th and 40th weeks as reported by Waldimiroff et al11 who observed a significant
differences in cerebroplacental ratio only between weeks 26-38. After 26th week, the
statistical comparison showed no significant differences between the intervals
considered. Arbeille23 et al also found the cerebral-placental ratio constant during the
pregnancy and suggested 1 as the cut off value and all values below 1 were
considered abnormal. We considered the study of Gramellini et al12 that
cerebroplacental ratio less than 1.08 as abnormal.
We have studied about 50 pregnancies with clinical suspicion of IUGR. 70%
of neonates (n=35) had birth weight of less than 2.5 kg. There were 7 intra uterine
deaths and 43 live births. Of the 43 live births, 14 neonates were admitted to NICU, 6
neonates had 5 min Apgar score of less than 7 and 13 babies was born by emergency
caesarian section for fetal distress. Of the7 IUDs, 2 cases had reversal of diastolic
flow and 4 had absent diastolic flow. In both cases with reversal of diastolic flow,
IUD of the fetus occurred with in one week of diagnosis.
.
Umbilical artery - It was found to have low sensitivity of 73.9% when
compared to MAC PI and cerebroplacental ratio. The sensitivity was comparable with
that of Fong KW et al26 and Gramellini et al12
58
Fong K W et al
Gramellini et al
Present study
44.7%
64% sensitivity 73.9%
86.6%
90.7% specificity 96.2%
54%
72.7% PPV 94.4%
81.7%
86.7% NPV 81.2%
The specificity of the UA PI 96.2% was found to be better than other
variables. The specificity was comparable with the above mentioned studies. The UA
PI is effective to rule in the possibility of adverse perinatal out come when it is
abnormal. The Positive Predictive Value of UA PI 94.4% was more than that of MCA
PI and Cerebroplacental ratio. It indicated the likelihood of adverse perinatal outcome
in growth retarded fetus with abnormal UA PI. The positive predictive value was
higher when compared to all other studies. The negative predictive value 81.2%
obtained in our study was comparable with the above mentioned studies. This was
less than that of MCA PI and cerebroplacental ratio.
Our findings confirms the results of Fong KW et al26, Chan et al24 and
Gramellini et al12 that abnormal UAPI is associated with adverse outcome like NICU
admission for low birth weight and low apgar scores than the one with normal UA PI.
It provides the most useful information for differentiating fetuses already
compromised or likely to become compromised from those that are
noncompromised.
59
Our findings agree with Harrington et al22 that umbilical artery can be normal
in term and near term with abnormal middle cerebral artery. In our study we had 7
false negative values out of which 4 patients were term gestation and 2 were near term
gestation.
Middle cerebral artery - was found to have a sensitivity of 91.3% less than
that of cerebroplacental ratio and more than that of UA PI. The values were not
comparable with the below mentioned studies.
Fong K W et al
Gramellini et al
Present study
Sensitivity 72.4% 24%
91.3%
Specificity 58.1% 100% 66.6%
PPV 37.7% 100%
70%
NPV 85.7% 77.3%
90%
It showed specificity 66.6% lesser than the other two parameters. It agrees
with Fong et al26 that MCA PI is less specific than cerebroplacental ratio and UA PI.
The study had more number of false positive values. There are several possible
explanations for the low Specificity of the MCA pulsatility index for adverse perinatal
outcome. Among several published normograms for MCA PI 8,96,97 the cutoff values
for an abnormal MCA pulsatility index are similar up to about 30 weeks gestational
age but differ after 32 weeks. The normograms we chose to use for analysis are from
the largest published cross-sectional study by Harrington K et al 22.
Positive predictive value of MCA PI 70% in predicting adverse perinatal
outcome is also less than that for other variables, which can be attributed to the more
false positive values.
60
The negative predictive value of 90% is comparable with that Fong et el study.
It is more than the UA PI, thus indicating the usefulness of MCA PI in ruling out the
possibility of adverse perinatal outcome.
Cerebroplacental ratio - It had the highest sensitivity value of 95.6% more
than any other variable. The values were not comparable with any other study because
of variation in the prevalence of IUGR.
The highest sensitivity of cerebroplacental ratio indicates its usefulness of
cerebroplacental ratio in ruling out the possibility of adverse perinatal outcome in
IUGR when the ratio is normal for the gestational age.
It showed the specificity of 85.1% which is less compared to UA PI and better
than the MCA PI. The values were comparable with Fong et al26 study.
Fong K W et al
Gramellini et al Present study
sensitivity 51.3% 68% 95.6%
specificity 80.6% 98.4% 85.1%
PPV 48.1% 94.4% 84.6%
NPV 82.5% 88.8% 95.8%
The positive predictive values 84.6% is less than UA PI and better than MCA
PI. The value was comparable with Gramellini et al12 study.
The negative predictive value 95.8% is better than that of UA PI and MCA
PI. The values were comparable with that of Fong et al K W et al26 and Gramellini et
61
al12 studies. It indicates that the likelihood of prediction of favorable outcome is better
when the cerebroplacental ratio is normal.
Our study agrees with that of Chan et al24 that the cerebroplacental ratio is
more sensitive than UA PI, but at the expense of decreased specificity.
Out of 33.3%(n=8) cases with absent or reversed end diastolic flow in
umbilical artery, 62.5% had perinatal death within one week .100% mortality was
seen in cases with reversed diastolic flow and 50% mortality in cases with absent
diastolic flow. This confirms the findings of Karsdrop etal21, which showed that
absent and reversed diastolic flow is better indicator of the adverse perinatal outcome.
The current study has shown that absent or reversed end – diastolic flow in the
umbilical artery is strongly associated with major perinatal morbidity with mortality.
This has been well recognized in the literature that there is strict correlation between
the abnormal UA PI and poor perinatal outcome in IUGR. Studies have shown that
absent and reversed diastolic flow in the umbilical artery is associated with increased
perinatal mortality and morbidity23, 35, 36, 37.
In our study when we compare the overall diagnostic accuracy in prediction of
adverse outcome in IUGR. Cerebroplacental ratio has the diagnostic accuracy of 90%
which is more than UA PI (86%), MCA PI (78%). The values obtained in our study
are comparable with that of Gramellini et al12.
62
Gramellini et al Present study
MCA/UA PI Ratio 90% 90%
UA PI 83.3% 86%
MCA PI 78.8% 78%
The primary aim of antepartum fetal surveillance is timely recognition of fetal
compromise to enable appropriate intervention and to prevent further serious
complications. If the fetus would otherwise die inutero, delivery might save its life,
but ill-adviced preterm delivery may be followed by postnatal death. Hence Doppler
of fetoplacental circulation plays a significant role in predicting the adverse perinatal
outcome in IUGR fetus which helps in the management of such fetuses.
Our results in evaluating the usefulness of umbilical artery and middle
cerebral artery Doppler in predicting the adverse perinatal outcome in IUGR indicate
that both abnormal umbilical Doppler indices and cerebral-umbilical ratio are strong
predictors of adverse outcome in IUGR. The MCA PI alone is not a reliable indicator
when used alone. The combination of umbilical and fetal cerebral Doppler indices
may increase the utility of Doppler ultrasound in clinically suspected IUGR.
63
CONCLUSION
• Doppler ultrasonography is the best noninvasive investigation to assess changes in
fetal haemodynamics in a clinically suspected IUGR.
• Fetal Doppler indices provide information that is not readily obtained from more
conventional tests of fetal well-being.
• Fetal vessels such as umbilical artery and middle cerebral artery Doppler helps to
differentiate the fetus with pathological growth restriction from that of other small
for gestational age fetuses.
• Both abnormal umbilical Doppler indices and cerebral-umbilical ratio are strong
predictors of adverse outcome in IUGR.
• Umbilical artery Doppler is more useful than middle cerebral artery in prediction
of outcome in IUGR when considered individually.
• Absent and reversed diastolic flow in umbilical artery in IUGR is an ominous
finding, associated with increased mortality and morbidity.
Fetal Doppler study plays a significant role in management of growth
restricted fetus by identifying compromised growth restricted fetus from that of
noncom promised growth restricted fetus.
Fetal Doppler study should be an integral part while evaluating in-utero health
of the growth restricted fetus.
64
SUMMARY
IUGR is associated with an increased risk of perinatal mortality,
morbidity and impaired neurodevelopment. The correct detection of the compromised
IUGR fetus to allow timely intervention is a main objective of antenatal care.
Doppler ultrasound allows a noninvasive assessment of fetal haemodynamics.
Doppler investigation of the umbilical arteries provides information concerning
perfusion of the fetoplacental circulation, while Doppler study of cerebral vessels
detects the haemodynamic rearrangements that occur in response to fetal hypoxia.
We have studied Umbilical and middle cerebral artery pulsatility index in
about 50 pregnancies with clinical suspicion of IUGR and correlated the findings with
the perinatal outcome. 70% of neonates (n=35) had birth weight of less than 2.5 kg.
There were 7 intra uterine deaths and 43 live births. Of the 42 live births 13 neonates
were admitted to NICU. 6 neonates had 5 min Apgar score of less than 7 and 16
babies was born by emergency caesarian section. Of the 7 IUDs 2 cases had reversal
of diastolic flow and 3 had absent diastolic flow. In all cases with reversal of diastolic
flow, IUD of the fetus occurred with in one week of diagnosis.
In our study MCA PI/UA PI ratio had a higher Sensitivity and negative
predictive value for predicting adverse perinatal outcome when compared to MCA PI
and the UA PI, UA PI had higher specificity and positive predictive value than MCA
PI and MCA PI/ UAPI, MCA PI had the least specificity. The overall diagnostic
accuracy was higher for MCA PI/UA PI than MCA PI and UA PI alone.
65
In our study Cerebroplacental ratio is most sensitive and Umbilical artery PI is
most specific index in predicting adverse outcome.MCA PI is least specific in
predicting adverse perinatal outcome. Absent or reversed end diastolic flow in an
umbilical artery is an ominous finding associated with major adverse perinatal
outcome and mortality.
Thus the umbilical and middle cerebral artery Doppler studies helps in the
prediction of adverse perinatal outcome and management of clinically suspected
suspected IUGR.
66
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79
PROFORMA
Patient Particulars
Name of the Patient: Ref Unit:
Age: Date of Admission:
Address: Date of Discharge:
IP/P Number:
Present Obstetric History
Gestational Age: (whether Dating Based on Early first trimester scan/second
trimester scan/ LMP)
Para: Fetal Movements
Gravida: Maternal Weight Gain:
Living: Any complaints.
Abortions: Warning Signs of Pre Eclampsia
First Trimester:
Second Trimester:
Past Obstetric History:
General Examination: Nutrition Status
Pallor, Icterus, Cyanosis, Edema, Lymphadenopathy.
80
Vitals:
Pulse B.P
Respiratory
Rate
Temperature
P/A Examination: Uterine Fundal Height, FHR,
CVS/RS :
P/V Examination:
Investigations:
Blood Sugar, Hb%, (Serum Uric Acid, HIV, HbsAg , VDRL if done )
Routine Urine analysis (for Albumin, sugar, Micro analysis).
Clinical Diagnosis:
Ultrasound Findings:
Fetal Lie, Position, Number,
Ultra Sound Biometry:
BPD
HC FHR:
AC
FL
Estimated Fetal Weight:
81
Mean Gestational Age:
Liquor:
Placental Maturity:
Any Anomalies:
Doppler Ultrasound Findings:
Value
UA PI .............
(Abnormal if >95th Percentile For Gestation)
MCA PI .............
Abnormal if <5th Percentile for Gestation )
Cerebroplacental Ratio (MCAPI / UA PI) = <1.08 or >1.08 (abnormal if <1.08)
82
KEY TO MASTER CHART
Sl No. - Serial Number
I.P. No. - In Patient Number
GEST - Gestational Age
G - Gravida
P - Para
L - Living
A - Abortions
BOH - Bad Obstetric History
OLIGO - Oligohydramnios
PE - Preeclampsia
IUGR - Intra Uterine Growth Retardation
RHD - Rheumatic Heart Disease
EFW - Estimated fetal weight
UA - Umbilical Artery
UA PI - Umbilical Artery Pulsatility Index
MCA PI - Middle Cerebral Artery Pulsatility Index
EM CS - Emergency Caesarian Section
IUD - Intra Uterine Death
NICU - Neonatal Intensive Care Unit
ADMN - Admission
85