Tải bản đầy đủ

3 tom tat LA eng version nghiên cứu siêu âm doppler ống tĩnh mạch trong chẩn đoán suy thai ở thai chậm phát triển trong tử cung

MINISTRY OF EDUCATION AND TRAINING

MINISTRY OF

HEALTH

HANOI MEDICAL UNIVERSITY

DAO THI HOA

Study on Doppler ductus venosus in disgnosising fetal
distress in intrauterine growth restriction fetus

Specialization: Obstetrics and gynecology
No

: 62720131

SUMMARY OF MEDICAL DOCTORAL THESIS

HANOI - 2018



THIS DISSERTATION WAS COMPLETED AT
HANOI MEDICAL UNIVERSITY

SCIENTIFIC SUPERVISOR:
Prof. Dr. NGUYEN VIET TIEN
A/Prof. Dr. TRAN DANH CUONG

Defendant 1: A/Prof. Dr. BÙI VĂN LỆNH

Defendant 2: A/Prof. Dr. NGUYẾN DUY ÁNH

Defendant 3: A/Prof. Dr. LÊ HOÀNG

This dissertation was defensed against the Committee of
Evaluation at Hanoi Medical University

on Wednesday, 26 th Dec 2018

This dissertation is available at:
- National Library of Vietnam.
- Library, Hanoi Medical University.


LIST OF PUBLICIZED RESEARCHES BY
THE AUTHORS

1.

Dao Thi Hoa, Nguyen Viet Tien, Tran Danh Cuong,
(2017).The value of the Doppler umbilical artery and
Doppler Ductus venosus in the prediction of pregnancy
outcomes in fetal growth retardation. Journal of Practical
Medicine; 8 (1055): 210 – 213.

2.

Comparing study of abnormal a-wave in Doppler Ductus
venosus versus non-stress test evaluation for the prediction of


adverse fetal outcome in growth-restricted fetuses. Journal of
Practical Medicine; 8 (1055): 226 - 229.


1
INTRODUCTION
Intrauterine growth restriction fetus (IUGR) is a common pathology of
pregnancy, the second cause of perinatal mortality after preterm labor. IUGR, if
not detected and appropriately mornitored, will result many serious influences
as fetal distress, stillbirth, neonatal or perinatal mortality, perinatal morbility or
complications affecting on child’s movement, mental and physical
development.
Assessment of fetal well-being to detect early signs of fetal distress is very
important. Timing delivery in cases of IUGR fetus is problematic, as the
practicing obstetrician has to balance the dangers of prematurity with the risk of
intrauterine hypoxia and to limit the complications caused by IUGR fetus.
The ductus venosus (DV) connects the umbilical vein with the inferior vena
cava at its inlet to the right atrium. Due to the special anatomical architectural
arrangement, a pressure gradient is produced between the umbilical vein and
the atrium, resulting in the acceleration of the blood flow in the DV. Therefore,
DV plays an important role of distributing, adjusting the velocity and speed of
oxygen-riched blood flow from placenta to the fetus in cases of fetal hypoxia
and reduced circulation.
There are various methods of exploration which have been used to evaluate
fetal developmental and health status for identifying restricted fetuses at risk of
placental insufficiency and of fetal hemodynamic changes that occur during
oxygen deprivation, including Doppler ultrasonography, a method of noninvasive, very valuable and widely used method in obstetrics.
At present, in Vietnam, there are a number of studies on Doppler
ultrasonography but usually focus on the evaluation of arterial systems such as
the umbilical artery, middle cerebral artery, uterine artery. There is very few
researches on the Doppler of the venous system and especially the Ductus
venousus which is a vein, a physiological shunts that plays an important role in
circulatory regulation when fetal acute and chronic hypoxia. Therefore, we
conducted the thesis “Study on Doppler ductus venosus in disgnosising fetal
distress in intrauterine growth restriction fetus”.
Study objectives:
1. To study the value of Ductus venosus Doppler indices in predicting fetal
distress in fetal growth restriction in uterus.
2. To compare the effectiveness of different Doppler indices of Ductus venosus
ultrasound versus other Doppler artery assessment in predicting fetal distress
in intrauterine growth restriction fetuses. (umbilical artery, middle cerebral
artery, uterine artery)
New contributions of thesis
In Vietnam. this is the first study on the ductus venosus Doppler in


2
intrauterine growth restriction fetuses, determined the cut off points which were
applicable in clinical practice for monitoring and evaluating of fetal well-being
and prediction of fetal distress and intrauterine growth restriction.
Scientific contributions and pratical implications
Contribution to a new predictive and prognostic method that should be
practiced and applied clinically to predict fetal well being, fetal distress in
intrauterine growth restriction fetuses, to limit the bad outcome on the fetus,
neonates and children in the future.
Thesis layout
The thesis with 154 pages includes the following parts: Introduction (2
pages); Chapter 1. Literature review (39 pages); Chapter 2. Subjects and
methods (20 pages); Chapter 3. Results (42 pages); Chapter 4. Discussion:(48
pages); Conclusions (2 pages) and recommendation (1 page); List of related
researches and articles;. There were 37 tables, 21 figures, 12 pictures.
References; Appendix. there were 165 references including documents in
English, in French and in Vietnamese.
Chapter 1: LITERATURE REVIEW
1.1. Intrauterine growth restriction fetuses
1.1.1. Definition
FGR is an estimated fetal weight below the 10th percentile for gestational age
and states that it is frequently associated with placental insufficiency. This is the
most commonly used classification.
1.1.2. Diagnostic criteria of fetal growth restriction
Clinical: Fournié recommended according to the rules of assessment of fetal
development based on symphysis-fundal height. But according to many studies,
the sensitivity of this method varies from 41% to 86% depending on the author.
Based on ultrasonography: from the parameters as head circumference,
periapical diameter, diameter of abdomen, abdominal circumference, femur
length, formula for fetal weight and comparison with corresponding percentile
by gestational week.
Distinction between fetal growth restriction symmetric and asymmetric
Distinction between fetal growth restriction early and late
Diagnose the difference between fetal small-for-gestational and fetal growth
restriction
1.1.3. Etiologies
The etiology of fetal IUGR is multifactorial and may be subdivided into
maternal causes, fetal causes, and causes involving uteroplacental vascular
insufficiency.
Physiopathology of fetal IUGR


3
1.1.4. Consequences
In fetuses: fetal distress and stillbirth.
In neonates: neonatal deaths
In childhood and in adulthood: poorer neurodevelopmental outcomes,
cognitive development and cardiovascular or endocrine diseases.
1.2. Physiology of Fetal circulation
1.2.1. Characteristics
Physiology of Fetal circulation
The fetal circulation is the circulatory system of a fetus. The term usually
encompasses the entire fetoplacental circulation, which includes the umbilical
cord and the blood vessels within the placenta that carry fetal blood. Lowpressure placental circulation, with high circulating blood flow, accounts for
about 40% to 60% of the total circulation. In contrast, circulation in the lung is
high pressure, low circulation occurs 10% to 20% of the circulation.The role of
fetal circulation is to transport oxygenated blood from the placenta to the brain,
heart and other parts of the fetal body. Fetal circulation can be better through the
involvement of the shunt occurs during pregnancy
Oxygen-rich blood flows to the fetus via the umbilical vein. The first
partition at the level of the ductus venosus distributes the majority of umbilical
venous blood to the liver. Umbilical venous blood that continues towards the
heart is partitioned towards the left ventricle at the foramen ovale. This blood
supplies the brain and upper part of the body via the brachiocephalic circulation
and the myocardium via the coronary circulation. A minor proportion of blood
from the right ventricle supplies the lungs, while the remainder continues
through the ductus arteriosus towards the aorta. At the aortic isthmus, blood
streams directed towards the descending aorta are partitioned based on the
relationship of blood-flow resistance in the brachiocephalic and
subdiaphragmatic circulations.
Before birth, the blood circulating in the fetal circulation is mixed, between
oxygen-rich blood and low oxygenated blood, high levels of CO2 and other
metabolites. Circulating in the lungs is inactive, hemoglobin of the fetus has not
been associated with oxygen to provide for the development of the fetus so that
the placenta does the work of breathing instead of the lungs.
Uteroplacental circulation
The blood supply to the uterus comes mainly from the uterine arteries, with a
small contribution from the ovarian arteries. These vessels anastomose at the
cornu of the uterus and give rise to arcuate arteries that run circumferentially
round the uterus.
1.3. fetal compromise and IUGR.
IUGR is responsible associated decrease in uteroplacental blood flow,
characterized by severe hypoxia and metabolic acidosis and usually precedes


4
fetal death in a few days. In fetal hypoxemia, there is a redistribution in blood
flow, with increased blood supply to the brain, heart and adrenals and a
simultaneous reduction in the perfusion of the carcase, gut kidneys and lung.
When the redistribution capacity exceeds the fetal limit and threshold, fetal
distress occurs very rapidly. Therefore, clinically Doppler ultrasound should be
performed to assess blood circulation, detect early stages of decompensation of
the fetus (the ‘brain-sparing’), risk of fetal distress.
1.4. Ductus venosus and Fetal circulation
1.4.1. Anatomy, morphology and physiology of DV
The smaller diameter of the ductus venosus in relation to the umbilical vein
and its trumpet shape achieve significant blood-stream acceleration, so that
forward delivery of blood against the cardiac pressure gradient can be achieved.
It has a trumpet-like shape with the narrow portion (isthmus) measuring 0.5 mm
at mid-gestation to about 2 mm in late-gestation; the outlet width increases from
1.25 to 3 mm and the length of the DV attains 20 mm at term.

Figure 1.5: The architecture and dimensions of ductus venosus
1.4.2. The role of DV in fetal circulation
The DV connects intra-abdominal portion of the umbilical vein and the
inferior vena cava at the inlet of the right atrium and it is, therefore, important
when examining the fetus state of health.
The DV is originated from the umbilical vein. Under normal conditions, 75%
of the nutrient-rich umbilical venous blood goes to the liver and then to the heart
through the hepatic veins, while the remaining 25% reaches the heart directly
through the DV. As the DV structure is narrow, the blood entering the DV is at
high velocity and high pressure. The circulation rates are 29 cm / sec, 65 cm /
sec and 75 cm / sec in the first, second trimester of pregnancy in the and at term
respectively. Blood from the ductus venosus flows in the ventral and rightward
part of the inferior vena cava. The ventral and rightward stream, together with
blood from the superior vena cava is directed towards the right atrium and
through the tricuspid valve into the right ventricle. From there the blood is
ejected into the main pulmonary artery and most of it is shunted through the
ductus arteriosus into the descending aorta to the lower body . The shunt
dynamics in the ductus venosus – left portal vein system are responsive to
umbilical venous nutritional content, decreased umbilical venous volume flow
and marked elevations in placental blood-flow resistance. When there is


5
increased placental resistance resulting in decreased circulation to the umbilical
vein, the fetus will adjust by increasing the rate and amount of blood through the
DV then it reduces the umbilical vein circulation. On the other hand, a reduction
in umbilical venous volume flow results in ductal dilation and increased
umbilical venous diversion, maintaining overall ductus venosus contribution to
the heart. The volume of circulation DV can account for up to 60-70% of
umbilical venous blood flow.
1.5. Methods for assessment of fetal well-being
1.5.1. The dynamic evaluation of the fetal growth
The percentile: based on aged-specific physiological measurements, the
authors set up growth curves for gestational measurement and used that as the
reference standard for the study population.
1.5.2. Fetal biophysical profile of Manning
1.5.3. Cardiotocography (CTG)
CTG is a non-invasive important method, widely used in obstetrics to assess
fetal well-being. Based on observing the baseline fetal heart rate, fluctuations and
changes, abnormalities in the fetal heart rate when a uterine contraction occurs.
1.5.4. Amnioscopy
Nowadays, this method is not commonly used in clinical practice. It should
only be performed with fetuses greater than 37 weeks.
1.5.5. Ultrasonography assessment of fetal development
1.6. Doppler assessement of fetal well-being in IUGR fetus
1.6.1. Doppler assessement of fetal well-being
1.6.1.1. Principle of Doppler ultrasound: Doppler effect
1.6.1.2. Types of Doppler
1.6.2. Doppler signal analysis method
Audio Spectrum Analysis
Doppler spectrum analysis by observation of spectral morphology
Doppler spectrum analysis by measuring indices
Indices of measurement
+ Resistive Index (RI)
+ Systolic / diastolic ratio
+ Pulsatility Index (PI)
PI = (S - D) / A; (A= TAMX)
1.6.3. Ultrasonography assessment of fetal arteries
1.6.3.1. Umbilical artery Doppler (UMA)
The umbilical artery Doppler reflects placental vascular resistance, which is
strongly correlated with placental insufficiency. Increased resistance in the
umbilical arteries determines peripheral fetal vasoconstriction and augmented
umbilical artery pulsatility index.
The absent end-diastolic flow or reverse flow in umbilical artery are better
correlated with the fetal outcome than the Cerebroplacental ratio.
1.6.3.2. MCA Doppler (Middle cerebral artery)


6
The PI < 5 percentile is an efficient tool for the evaluation of the cerebral
vasodilatation. MCA can be evaluated using IR or IP, the results are similar.
1.6.3.3. Cerebroplacental ratio (CPR)
CPR is an evidence of redistribution of the fetal circulation. CPR
abnormalities (CPR<1) are very valuable in predicting fetal outcomes and very
valuable in tracking assessment of hypoxia, anemia, fetal distress.
Value: screening for all pregnancies IUGR at risk for fetal distress.
1.6.3.4. Uterine artery Doppler (UTA)
Value: screening for early detection of high-risk pregnancies and risk of abnormal
uteroplacental circulation.
1.6.3.4. Descending aorta Doppler
1.6.4. Ductus venosus Doppler
1.6.4.1. Ductus venosus Doppler Flow
An anterograde triphasic waveform is produced with a S-wave, the highest
pulse (ventricular systole), a D-wave (early diastole) and a a-wave (late diastole)
(Fig. 1.6). This latter wave presents the lowest velocity but always with forward
flow.
Physiology of the ductus venosus in the fetal circulation
- S-wave: is the peak corresponding to the strong current that is the systolic
phase, reflecting the pressure of the left ventricle .
- D-wave: corresponding to the diastolic phase, opening the AV valve, blood
flow passively to the right ventricle.
- a-wave: corresponding to the contraction phase of the atria, it ejects blood
into the right ventricle, reflecting the performance of fetal heart.

Figure 1.6: DV waveform.
1.6.4.2. Analysis of DV Doppler spectrum
* Qualitative analysis
Wave form: three peaks of the pulse wave S, D and a, normally positive
* Quantitative analysis of DV Doppler indices
- Time-averaged mean of the maximum velocity
- Time averaged maximum velocity (TAMX).
- Resistive Index (RI): RI= S-a/S


7
- Pulsatility index for veins (PIV): PIV = S-a/TAMX
- Ductus venosus index (DVI): DVI = S-a/D
- Perfusion index: PFI = TAMX/S
- Systolic / Diastolic ratio: S/D
- Systolic / atrial ratio: S/a
Abnormal DV Doppler spectrum
With advancing gestation, cardiac afterload decreases as placental flow
resistance declines, while cardiac compliance and contractility increase. The
increased efficiency of forward cardiac function leads to significant increase in
absolute S, D, and a-wave blood flow velocities. This produces a steady linear
decrease in venous pulsatility and a-wave related ratios
The D wave is much lower than the S wave.
The a- wave is low or lost, suggesting atrioventricular valve deficiencies.
The a - wave reversed
Increase venous pulsatility and a-wave related ratios
1.6.4.3.Factors involved and affect to results of DV Doppler
1.6.4.4. Studies on value of Doppler DV in the normal fetus
and IUGR fetus
Studies on the normal values of DV Doppler indices
Studies on value of DV Doppler in the pregnancy with abnormal chromosome
Studies on value of DV Doppler in the IUGR fetus
Hecher et al studied in the growth-restricted fetus findings that DV is very
valuable for prognosis neonatal outcome. Normal venous flow suggests
continuing fetal compensation, whereas abnormal flow indicates the breakdown
of hemodynamic compensatory mechanisms. Study also investigated when
atrial contraction were reduced to zero or even became negative always
combined with adverse perinatal poor outcome and abnormal Doppler
velocimetry of the ductus venosus was the only significant parameter associated
with perinatal death. In the other studies, Hecher and al, was found that DV
Doppler results are more valuable in the third trimester.
Baschat et al was performed Doppler velocimetry of the umbilical artery
(UMA), middle cerebral artery (MCA), inferior vena cava (IVC), ductus
venosus (DV) and free umbilical vein in 121 IUGR fetuses. Growth restricted
fetuses with abnormal venous flow have worse perinatal outcome compared to
those where flow abnormality is confined to the umbilical or middle cerebral
artery. In fetuses with low middle cerebral artery pulsatility, venous Doppler
allows detection of further deterioration. While abnormal venous flows can be
significantly associated with fetal demise, gestational age at delivery
significantly impacts on all short-term outcomes.
In order to identify specific estimates and predictors of neonatal morbidity


8
and mortality in early onset fetal growth restriction due to placental dysfunction,
Baschat has been operated a prospective multicenter study of prenatally
diagnosed growth-restricted liveborn neonates of less than 33 weeks of
gestational age Relationships between perinatal variables and major neonatal
complications, neonatal death, and intact survival. Research showed that ductus
venosus Doppler parameters emerge as the primary cardiovascular factor in
predicting neonatal outcome.
Schwarze were examined sventy-four fetuses with fetal IUGR and absent or
reversed end-diastolic (ARED) flow in the UMA at 24–34 weeks of gestation,
which were delivered before 34 weeks' gestation. Absent or reversed flow during
atrial contraction (a-wave) in the DV and pulsatile flow in the UMV were
examined to predict severe perinatal outcomes. Abnormal venous Doppler
waveforms in preterm IUGR fetuses with ARED flow are strongly related to
adverse fetal and perinatal outcomes before 32 weeks of gestation.
Chapter 2
SUBJECTS AND METHOD
2.1. Study subjects and study time
2.1.1. Study subjects and study time
The study was conducted at the National Obstetrics Hospital from
January 2011 to December 2015.
2.1.2. Sample selection criteria
Inclusion criteria
- One alive fetus with gestational age from 28 to 40 weeks.
-The gestational age was determined precisely based on morphological
ultrasonography results in the first trimester.
- There is no morphological abnormality.
- Patient information is complete
Exclusion criteria:
- Twins, multiple pregnancies.
- It is not possible to determine exactly the gestational age.
- Abnormal fetal morphology, chromosomes, stillbirths.
- Postpartum, newborns weight was significantly higher than the 10th
percentile curve for gestational age.
- Data collection is incomplete.
2.2. Research methods
2.2.1. Study design: A cross-sectional descriptive study used to to diagnose a
method of exploration
2.2.2. Sample size formula

N=
TP: true positive

TP + FN
Pdis


9
FN: false negative

TP + FN =

Zα2 x Pse (1 - Pse)
w2

Pdis: prevelance of Fetal distress in fetal IUGR in previous studies = 15%
Zα: the normal distribution coefficient, if the significant level. α =0.05.
Zα=1.96 , Psp: Power = 90%
w: The error of true positive and true negative
We intend to calculate the sample size based on the desired DV Doppler
sensitivity is 90%, the error of the probability measure is about 15%. The
required sample size was 230 patients.
Finally, our study was conducted on 252 pregnant women diagnosed with
fetal uterine retardation.
2.2.3. Study tools
- Ultrasound machine is Siemens Acuson X 150 with probe 3.5 MHz. The
Machine is equipped with Pulsatility Doppler ultrasound system, Color- Coded
Doppler, Doppler boost. Computing system is mounted in the machine.
- Obstetric and newborn records and preprinted questionnaires.
- Pregnancy tools and instruments: blood pressure monitor, neonatal weight.
- Syringes 1 ml, heparin coated, needle size 22 Gaucher.
- Roche Cobas 221b to analyze pH, blood gas and electrolyte blood of fetal
artery blood.
- Tables of percentile distributions of weight in different gestational ages in
healthy Vietnamese newborn weight of Phan Trường Duyệt (2007).
All tables of percentile distributions of physiological Doppler UTA, UMA,
MCA, CPR in different gestational ages in healthy maternal and fetal on normal
pregnancies of Tran Danh Cuong (2007). And tables of percentile distributions
of DV Doppler physiology is referenced of Nguyễn Thị Hồng, Turan, Bahlmann.
2.2.4. Research steps
2.2.4.1. Clinical examination
- Clinical examination procedures and tests specified basic clinical treatment
protocol of National Hospital of Obstetrics & Gynecology.
2.2.4.2. Survey ultrasound and Doppler assessment of fetuses:
- Ultrasound diagnosis of weight: fetus is diagnosed as retarded when birth
weight below the 10th percentiles of the fetal weight development chart of
Phan Truong Duyet (2007).
- Measuring biparietal diameter (BPD), head circumference, abdominal
circumference, anterior-posterior-abdominal diameter (APTD), transverse


10
abdominal diameter(TAD), measurement of femur length, measurement and
evaluation of amniotic fluid volume, evaluation of placental condition.
- Doppler assessment of fetuses: using Doppler ultrasound to evaluate UTA,
UMA and MCA to assess waveforms and measure indices including pulsatile
index (PI), resistance index (RI) and S/D ratio, cerebralplacenta ratio (the ratio
of RI of MCA and UMA).
* Doppler assessment Ductus venosus
- Identify position of the ductus venosus:
+ On the horizontal section along the fetal spine: need to find the umbilical
vein run in the liver and folded to the right angle.
+ On the longitudinal section: find the umbilical vein, the passage in the liver, the
end of a small blood vessels, almost poured directly into the heart that is ductus
venosus.

Figure 2.4. longitudinal and horizontal section for determine DV
- Position of Doppler DV measurements: narrow and at the beginning of DV,
near umbilical vein, that have the highest velocity of flow.
- According to studies in low-risk pregnancies, Doppler DV is considered
abnormal when a-wave is non-positive and PI elevates more than 95th percentile
in the comparison with physiological values at corresponding gestational age.
2.2.5. Research results and and monitor.
- Results of pregnancy in the study group: stillbirths during follow-up.
- Proceeding and recording results of Doppler ultrasound during 24 hours
prior the termination of pregnancy as Doppler arteries (UMA,MAC,CPR, UTA)
and Doppler DV.
- Umbilical artery blood sampling was used to analyze blood pH, pCO2 and
alkaline reserve BE.
- Neonatal status:
+ Birth weight
+ Apgar index.
+ Diagnosing fetal distress when blood umbilical artery with acidosis: pH ≤
7.15 or BE <- 8 mmol / liter (value below 5th percentile of pH and BE).


11
- Fetal complications were monitored and evaluated within 1 month postnatal
including neonatal mortality, perinatal death, neonatal morbidity.
Patients of the study were divided into two groups and based on neonatal
umbilical artery blood analysis and pregnancy results
+ First group: poor fetal outcome including at least one of the following
status: stillbirths; umbilical artery pH ≤ 7.15; BE <- 8 mmol /liter.
+ The second group: normal pregnancy outcome with normal birth results,
pH> 7.15 and BE> - 8 mmol / liter.
2.3. Data analysis
- Data were processed and analyzed using SPSS 21.0.
- The values of the Doppler DV, UMA,MAC, CPR, UTA were calculated
as the mean, standard deviation, percentage.
- Comparing the mean values by t-Student test, the percentages by test χ2.
- Determining the optimum cut-off value related to normal fetal outcome
of Doppler DV.
- Using the ROC curves method and calculating the area under the curve
(AUC). The area under the ROC-AUC curve represents the accuracy of the
evaluation method. The evaluation method was significant when AUC is greater
than 0.6
- Evaluate the diagnostic value by the parameters: sensitivity, specificity,
positive predictive value, negative predictive value.
- McNemar test is used to compare variables in predicting pregnancy
outcome, fetal distress.
- Comparisons were statistically significant when p is smaller than 0.05.
2.4. Research ethics:
The study was conducted after protocols approved by the Professional
Council of Obstetrics and Gynecology and our we followed strictly all steps of
the study.
Chapter 3: STUDY RESULT
3.1. Characteristics of sample
3.1.1. Maternal age
Mean maternal age was 29,0 ± 5,7, the youngest is 18, the oldest is 46, the
age group 25 to 29 is the most, accounts for 35,7%.
3.1.2. Gestational age at admission
The median age was 34.9 ± 2.6 weeks, the minimum age was 28 and one
case maximum was 40 weeks.
3.1.3. Method of delivery
The study group was divided into two groups: caesarean section of 225/252
(89.3%) and vaginal delivery group of 27/252 (10.7%).


12
Indications for caesarean section: IUGR fetus: 99/225 (44%); mother's disease
:44 /225 (19,5%); fetal distress 21/225 (9,3%); other 27,1%.
3.2. Newborn results.
3.2.1. Birth weight
Average birth weight: 1606 ± 486 grams. The fetal age range of 28 to 30
weeks had the lowest weight: 692 ± 215 grams, group gestational age ≥ 37
weeks with median weight: 2140 ± 333 grams.
3.2.2. pH of the umbilical artery blood
Blood gas results: mean umbilical artery blood pH of the study group: 7.30
± 0.09; High pCO2: 52.47 ± 19.1 mmHg; pO2 lower: 39.8 ± 16.75 mmHg and
average low alkaline reserve BE: 2.24 ± 3.49 mmol / l and HCO3: 24.66 ± 3.13
Results of umbilical artery blood pH
241/252 (95.6%) neonates were given umbilical artery blood for pH
and blood gas tests. 11/252 (4.4%) were not tested due to stillbirths during
fetal monitoring. Results: 186/252 (73.81%) of neonates had umbilical
arterial pH > 7.25; 39/252 (15.48%) pH: 7.15 newborn with low pH ≤ 7.15
3.2.3. Division of the studied patients
Based on the outcome of the fetus, with umbilical arterial blood test
results including pH, BE, the patient was divided into two groups:
Group 1: pregnant women with poor outcomes included cases of
stillbirths during follow-up and postpartum with fetal distress (poor fetal
outcome): 33 cases (13.09%) among them 22 cases of postpartum fetal distress
(blood pH ≤ 7.15 or BE <- 8 mmol). In the process of monitoring, 11 cases of
fetal distress evolved into stillbirths. All of these cases were adequately
monitored by tests and Doppler ultrasound in compliance with the research
standards. The 11 cases have shown flate decelerative flate and we at present,
diagnose a fetal distress on the basis of this sign.
Group 2: normal fetal outcome including normal neonates, normal pH
and BE results, no fetal distress: 219 cases (86.90%).
3.2.4. Neonatal outcomes
There were 17 deaths in which 17/18 were in the fetal distress group, only
one newborn died in the group of normal pregnancy.
19 cases with complications in which 18/19 in the group of fetal distress
and only 1 infant died in the group of normal pregnancy.
3.3.Characteristics of the studied group by gestational and
neonatal status


13

3.4.Results for study objective 1: determination cut-off

values of Doppler
DV in the prediction of fetal outcome in IUGR
Mean values of Doppler DV and pregnancy outcome groups.
Table 3.3. Value of DV Doppler spectrum
Fetal
Normal
Patients Studied
Distress
Outcomes
Result of DV
(N=225)
(N=219)
Doppler
S
D
a
TAMX

TB

SD

29.32

9.66

18.37

8.62

4.08

9.69

17.26

8.26

TB
36.3
7
28.0
6
16.6
5

SD

TB

SD

11.35

35.78

13.04

10.72

26.61

11.15

9.35

14.68

10.57

9.76

25.69

10.28

PI

1.76

0.83

27.0
3
0.81

0.42

0.97

0.65

RI
DVI

0.90
1.66

0.28
0.83

0.55
0.80

0.19
0.47

0.61
1.02

0.24
1.42

PFI
S/D

0.57
1.77

0.13
0.59

0.74
1.37

0.09
0.35

0.71
1.51

0.12
1.25

The average velocity of Doppler DV waves (S, D, a waves) is lower than
the physiological values of gestational age. The cases where the a-wave is less
than 0 (a negative) and 0 are only in the poor outcome fetus including fetal
distress and stillbirth. All stillbirths, fetal distress and poor outcome had PI
greater than 1.
3.4.1. Cut-off point values of a-wave of Doppler DV in predicting poor fetal
outcome
Table 3.5. Cut-off point values of a-wave in predicting poor fetal outcome
Value
a≤0
a ≤ 2.37
a ≤ 6.77
a ≤ 12.65

Se
(%)
69.7
69.7
84.8
87.9

Sp
(%)
95.4
95.0
84.9
66.2

VP +
(%)
69.7
67.6
45.9
28.2

VP –
(%)
95.4
95.4
97.4
97.3

Kappa
coefficient
0.65
0.64
0.51
0.28

CI 95%
0.51 – 0.79
0.5 – 0.78
0.38 – 0.64
0.19 – 0.38

At the cut-offs of a-wave with different values, we found that when the a-


14
waves is less than 2.37cm/sec and less than 0, both predicting values of pregnant
outcome have the same Se, Sp, VP (+), VP (-), and Kappa coefficients are
greater than 0.6, the area under the AUC curve is 0.883 with a ≤ 2.37.
ROC curve

Sensitivity

1 - Specificity
Chart 3.4. The relative ROC curve of value a wave to fetal outcome
3.4.2. Cut-off point values of S-wave of Doppler DV in predicting fetal
outcome in fetal IUGR
Table 3.7. Cut-off point values of S-wave in predicting fetal outcome
Value S

Se (%)

Sp (%)

S < 60
S ≤ 40.54
S ≤ 30.85
S ≤ 22.23

97.0
87.9
66.7
24.2

2.7
34.7
65.3
93.6

PV +
(%)
13.1
16.9
22.4
36.4

PV (%)
85.7
95.0
92.9
89.1

Kappa
coefficient
Very low
< 0.2

At Cut off Point S ≤ 40.54 cm /sec is most valuable in screening, predicting
fetal outcomes. The Kappa coefficient is very low <0.2. AUC: 0.678.
3.4.3. Cut-off point values of D-wave of Doppler DV in predicting fetal
outcome in IUGR fetus.
Table 3.9. Cut-off point values of D-wave in predicting fetal outcome
Kappa
Value
Se (%)
Sp (%)
PV + (%)
PV - (%)
coefficient
D < 55
100.0
1.4
13.3
100.0
very low
D ≤ 30
90.9
56.6
24.0
97.6
D ≤ 19.9
69.7
76.3
30.7
94.4
< 0.2
D ≤ 14.5
54.5
89.5
43.9
92.9
The cut-off point D ≤ 30 cm/sec has the best predictive value for fetal


15
distress. However, the Kappa coefficient is less than 0.2. Area under AUC curve
is 0.789.


16
3.4.4. Cut-off point values of PI index in predicting fetal outcome of Doppler
DV in IUGR fetus.
Table 3.11. Cut-off point values of PI index in predicting fetal outcome of
Doppler DV
Kappa
Index PI
Se (%)
Sp (%)
PV + (%) VP - (%)
coefficient
> 0.9
87.9
71.1
31.5
97.5
0.34
≥ 1.46
75.8
93.2
62.5
96.2
0.63
≥ 1.86
66.7
96.8
75.9
95.1
0.67
≥ 2.24
39.4
98.2
76.5
91.5
0.47
At cut off point PI ≥ 1.46 is the best predictive value for fetal distress.
The Kappa coefficient is 0.63. Area under the AUC curve is 0.886
ROC curve

Sensitivity

1 - Specificity
Chart 3.10. The relative ROC curve of value PI index to fetal outcome
3.4.5. Cut-off point values of RI index in predicting poor
fetal outcome of Doppler DV
Table 3.13. Cut-off values of RI index in predicting fetal outcome of
Doppler DV
Index RI

Kappa
coefficient

Se (%)

Sp (%)

PV + (%)

VP - (%)

RI > 0.6

87.9

69.4

30.2

97.4

RI ≥ 0.79

84.8

88.1

51.9

97.5

very low

RI ≥ 1.0

69.7

100.0

100.0

95.6

< 0.2

RI ≥ 1.27

6.3

100.0

100.0

88.0

At cut off point RI ≥ 0.79 have the best diagnostic value for gestational age.
But the Kappa coefficient is very low less than 0.2. AUC is 0.883


17
3.4.6. Cut-off point values of PFI index in predicting poor fetal outcome of
Doppler DV
Table 3.15. Cut-off point values of PFI index in predicting poor fetal outcome
Index PFI

Se (%)

Sp (%)

VP + (%)

VP - (%)

Kappa coefficient

< 0.7

90.91

67.12

29.41

98.00

0.31

≤ 0.62

84.85

86.76

49.12

97.44

0.55

≤ 0.5

45.45

97.26

71.43

92.21

0.51

At the PFI cut off point ≤ 0.62, the fetal outcome prognosis was not satisfactory.
Kappa coefficient is 0.55. AUC is 0.881.
3.4.8. Cut-off point values of a/S in predicting poor fetal outcome of Doppler DV
in IUGR fetus
Table 3.17. Cut-off point values of a/S in predicting poor fetal outcome
Kappa
Value
Se (%)
Sp (%)
PV + (%)
VP - (%)
coefficient
≤0
69.7
95.4
69.7
95.4
≤ 0.21
88.4
88.1
59.1
97.5
Very low
≤ 0.30
84.8
79.3
38.4
97.2
< 0.2
≤ 0.50
87.9
49.3
20.7
96.4
At the cut-off point a/S ≤ 0.21 had the highest value predicting poor
pregnancy outcome. The Kappa coefficient was very low (<0.2). Area under the
curve is 0.883
3.4.9. Cut-off point values of S/a in predicting poor fetal outcome of Doppler
DV in IUGR
Table 3.19. Cut-off point values of S/a in predicting fetal outcome of Doppler
DV in IUGR fetus
Index
S/a

Se (%)

Sp (%)

S/a ≤ -5

53.6

98.1

78.9

94.1

S/a ≤ 0

64.3

98.1

81.8

95.4

< 0.2

S/a ≤ 2

75.0

48.4

16.0

93.6

very low

S/a ≤ 3

78.6

20.2

11.5

87.8

PV + (%)

VP - (%)

Kappa
coefficient

When the ratio of S/a ≤ 0, meaning that in all cases of a-wave ≤ 0, neonates
are at risk for fetal distress with a sensitivity of 64.3% and a very high
specificity of 98.1%. The Kappa index is very low (<0.2). AUC: 0.75.
3.4.10. Cut-off point values of S/D in predicting poor fetal outcome of


18
Doppler DV in IUGR
Table 3.20. Cut-off point values of S/D in predicting poor fetal outcome of
Doppler DV in IUGR fetus
Ratio S/D

Se (%)

Sp (%)

PV + (%)

VP - (%)

Kappa coefficient

> 1,27

84.85

52.97

21.37

95.87

0.17

≥ 2,05

33.33

93.61

44.00

90.31

0.30

≥ 2,90

12.12

99.54

80.00

88.26

0.18

≥ 4,00

3.03

100.00

100.00

87.25

0.05

At the cut-off point, the S/D ratio>1.27 is the most significant predictor of
pregnancy outcomes. The Kappa coefficient is very low (0.17). AUC: 0.786 with
sensitivity of 84.85%, specificity of 52.9%.
3.4.11. Determine the probability of pregnancy outcome of the waves, the
incidence in the Doppler DV ultrasound results.
3.4.11.1. The diagnostic value of fetal outcomes of Doppler DV
ultrasonography in IUGR
Table 3.21. Comparison of fetal outcome predictors between wave and index
values in Doppler DV ultrasound
Se
Sp
PV +
VP –
Kappa
Value
(%)
(%)
(%)
(%)
coefficient
a ≤ 2,37
69.7
95.0
67.6
95.4
0.64
S ≤ 40,54
87.9
34.7
16.9
95.0
< 0.20
D ≤ 30.0
90.9
56.6
24.0
97.6
< 0.20
PI ≥ 1,46
75.8
93.2
62.5
96.2
0.63
RI ≥ 0,79
84.8
88.1
51.9
97.5
< 0.20
a/S ≤ 0,21
88.4
88.1
59.1
97.5
< 0.2
S/a ≤ 0,00
64.3
98.1
81.8
95.4
< 0.2
S/D ≥ 1,27
84.8
52.9
21.3
95.8
0.17
PFI≤ 0,62
84.8
86.7
49.1
97.4
0.55
The value of the a-wave ≤ 2.37cm/sec and the PI ≥ 1.46 of Doppler DV are
most valuable in evaluating and predicting the outcome of pregnancy with Sp
and PV (-) very high. Following is the value of the PFI irrigation index, which
has a Kappa coefficient of 0.55.


19
3.4.11.2. Comparison of the correlation coefficient between umbilical artery
blood pH with values of a, S, D waves and Doppler DV parameters
All pulse waves and Doppler DV indexes have a predictive value and a poor
prognosis. Among them, a-wave and PI are most closely related to fetal distress.
Table 3.23. Estimated fetal outcome of wave a and PI of Doppler DV
Abnormal Normal
Abnormal DV
Se
Sp
PV +
VP results
outcome
Doppler
(%)
(%)
(%)
(%)
(N=33)
(N=219)
a ≤ 2,37
23
10
69.7
95.0
67.6
95.4
PIV ≥ 1,46
25
8
75.8
93.2
62.5
96.2
If combination: a+PI
a ≤ 2,37 or PI ≥
25
15
75.8
93.2
62.5
96.2
1,46
Normal
8
204
Total
33
219
we chose: a ≤ 2.37 or PI ≥ 1.46
3.4.11.3. Relationship between DV Doppler abnormalities and pregnancy,
newborn outcomes.
A-wave strongly decreases, especially when it is smaller than 0, the fetal
outcome is worse. We also found that all pregnancies with poor fetal and
neonatal outcomes had PI of DV higher than 3 SD, but there was no significant
difference in PI between fetal outcome groups with P> 0.05.
3.5. Results for the second objective of our study
Comparison of fetal outcome predictive value, fetal distress predictive risk of
doppler DV with other arterial Doppler ultrasonography.
3.5.1. Results of arterial Doppler ultrasound
Table 3.26. Incidence of abnormal Doppler ultrasonography
in the study group
Normal results
Abnormal results
(N=252)
(N=252)
Ultrasound result
n
%
n
%
UTA
95
37.7
157
62.3
UMA
134
53.2
118
46.8
CPR
152
60.3
100
39.7
MAC
158
62.7
94
37.3
Amniotic fluid
194
77.0
58
23.0
DV
212
84.4
40
15.9
The most common abnormalities were uterine Doppler abnormalities.
The next is umbilical artery Doppler abnormalities, inverse CPR less than 1,
amniotic fluid changes and and the last is Doppler DV.


20
3.5.2. Estimated pregnancy outcome when combining DV doppler
ultrasound with another arterial Doppler ultrasound
Table 3.32. Predictive value of pregnancy outcome when combined doppler
DV with other arterial Doppler ultrasonography
Kappa
Chimethods
Se
Sp
VP+ VPP
coefficient square
UMA
90.9 59.8 25.4 97.8
0.24
29.64 <0.001
MAC
33.3 62.1 11.7 86.1
0.22
88.88 <0.001
CPR
93.9 68.5 31.0 98.7
0.34
88.88 <0.001
UTA
90.9 42.0 19.1 96.8
0.13
13.23 <0.001
DV
75.8 93.2 62.5 96.2
0.63
101.98 <0.001
DV - UMA
75.8 93.2 62.5 96.2
0.63
102.0 <0.001
DV - MAC
39.4 61.2 13.3 87.0
0.0032
0.004 <0.949
DV - CPR
93.9 68.5 31.0 98.7
0.34
46.7
<0.001
DV - UTA
90.9 42.0 19.1 96.8
0.13
13.23 <0.001
Table 3.34. Relationship between abnormal Doppler DV and Doppler artere
umbilical with fetal outcome (days)
Poor
Normal
Patients
Chioutcomes
outcomes
studied
square
Abnormal
p
TB
SD
TB
SD
TB
SD
DV
3.64
1,89
2.57
1.69
3.11 1.86
-2.238 0.029
UA
3.78
2.65
5.59
4.05
4.69 3.51
-1.948 0.058
There were statistically significant differences in the number of days of Doppler
DV abnormalities with poor pregnancy outcomes.
Chapter 4: DISCUSSION
4.1. Characteristics of the research group
4.1.1. General characteristics of the sample
4.1.2. Characteristics of pregnant women participating in the study
4.2. Newborn results
4.2.1. Birth weight
The average birth weight in the studied group was 1606 ± 486 gam with
ages from 28 to 40 weeks.
4.2.2. pH of the umbilical artery blood
All neonatal pH and neonatal outcomes demonstrated significant
biochemical changes related to circulatory changes, hypoxia and acidosis in fetal
IUGR. Our results are similar to that of Hecher et al in the study of DV Doppler
abnormalities and their relevance to fetal acidose, fetal distress, especially awave, PI, PFI.
4.3. Characteristics of the studied group by gestational and
neonatal status
4.4. Results and prognostic value of poor fetal outcome of Doppler DV.


21
4.4.1. Results of Doppler DV
Results of wave values and ratios of Doppler DV
In table 3.4, we found that the mean velocity of Doppler DV waves (S, D, a
waves) is lower than physiological value of gestational age. There are many
cases of a-wave negative and zero occurring in the poor fetal results including
fetal distress, stillbirth, complications with neonatal mortality. S-waves in all
groups were lower than the reference physiological values but were not
significantly different between the stillbirth group and the other groups.
According to Kessler and others, the normal physiology of S and D waves
increase with gestational age, therefore S/D ratios will also increase with
gestational age, D waves increase gradually until term. Therefore, the PI will
decrease gradually with gestational age. This is in line with our findings in
IUGR. Due to the redistribution of umbilical venous blood flow through the DV,
diastolic velocity decreases. The increase of PI depends on the degree of
disorders of the fetal circulation. There is a clear difference in the PI value
between the groups of pregnancy results. The higher the PI is, the worse the
outcome is. Especially, PI were highest (2.58 ± 0.67), respectively in descending
order of fetal abnormalities group, the next is the studied groups and the lowest
in the normal fetal results (0.81 ± 0.41). The mean RI of Doppler DV in our
study was highest in the stillbirth group (12 ± 0.10) and lowest in the normal
pregnancy group (0.55 ± 0.19).
The DV Doppler velocity index reflects fetal heart function, so in case of
suspected fetal heart dysfunction, if the Doppler DV pulse index is elevated, it is
necessary to analyze these parameters to evaluate the heart disorders.
Figure 3.9 has been shown to be significantly higher in postpartum PI than
in gestational age. The higher the PI on the 95th percentile is, the worse the
outcome for the fetus is. The results of our study are similar to some authors
that they have many studies on the value of Doppler DV in IUGR fetus such as
Baschat, Keserud. Similarly with Turan’study, in our research, there are many
cases where a wave decreases to 0 even in reverse less than 0 so all the index
related to a-wave as PI, S/a increase.
4.4.2. Estimation of pregnancy outcomes and cutoffs of Doppler DV
ultrasound-related pregnancy results in fetal IUGR
Table 3.22 shows the results of the values, cut-offs of waves, proportions,
and indexes of Doppler DV ultrasound (a, S, D, PI, RI, a/S, S/a, S/D, PFI) which
at these points are most valuable in poor fetal outcome in fetal development.
Based on the criteria for Se, Sp, VP (+), VP (-), the area under the ROC curve
and the Kappa coefficient of all the waves and Doppler DVs we found that all
the ratios changed. Particularly, abnormalities associated with a-wave are highly
predicted fetal distress, poor diagnosis of fetal outcomes with specificity and
especially high negative values. Almost all of the sites and indexes have a high
negative diagnostic value above 95%, meaning that if Doppler DV is normal,
over 95% of IUGR pregnancies will have good outcome predictors, risk of fetal
distress, pregnancy and neonatal complications are less than 5%. As a results, we
confirmed that Doppler DV is a very good for assessing fetal status.
Predictability of pregnancy results in the highest sensitivity of 90.9% with the


22
cutoff point D≤30 cm / s, followed by the cutoff point S ≤ 40.54 cm/sec and the
cut off point of a/S ≤ 0.21. The lowest sensitivity is 64.3% with the cut off point
S/a ≤ 0. In contrast, the highest specificity at the cutoff point S/a, to the wave a and
the pulse PI. The highest positive diagnostic value has been reported when
considering the ratio S / a to the value of wave a, pulse index. The diagnostic value
of most of the values and rates of Doppler DV is high, above 95%. Thus as, if the
Doppler DV spectrum is normal, there will be less than 5% of pregnancies with
poor prognosis. Therefore, Doppler DV will be a good probe for assessing fetal
status, accurately detecting fetal distress, risk of bad fetal outcome in IURG fetus.
Considering all of our results for the Doppler DV spectra with the Kappa
coefficient for evaluating the percent agree between the two methods, we found
that at the cutoff point of the wave a ≤ 2.37 cm / sec and at the cut-off point of
the PI pulse ≥ 1.46 was the most significant in the predicted outcome of fetal
outcomes. congestive heart failure, fetal heart failure. The next values are: PFI
irrigation index and a / S ratio. However, both of these averages have a Kappa
index of less than 6.
In combination with the analysis of table 3.23 on the correlation between
neonatal pH and Doppler DV spectral values, we also found that the a and PI
waves are the two values with the highest correlation coefficient. Table 3.24
shows that when combining values at the cutoff point a ≤ 2.37 cm / sec and PI ≥
1.46, the predicted negative result has a sensitivity of 84.8%, a specificity of
87.7% positive diagnostic value of 50.9% and very high diagnostic value of
97.5%. The results of our study are similar to that of the authors with many
studies on the value of Doppler DV on IUGR fetal as Baschat if wave a ≤ 0, Se
63.3% and Sp of 98.7% with predictive value perinatal death; 27% Se and 92%
Sp for neonatal mortality and of 37.1% of 95.3% specificity for blood acidosis.
4.5. Comparison of fetal outcome predictive value, fetal distress predictive
risk of doppler DV with other arterial Doppler ultrasonography
4.5.1. Diagnostic value of pregnancy when combining Doppler DV with each
Doppler ultrasound in IUGR fetus.
Table 3.27, Comparison between abnormal fetal doppler abnormalities of
fetal arteries with two groups of normal and unborn fetal outcomes, we found
that the order of the most common arterial Doppler abnormalities was Doppler
UTA, followed by Doppler UMA, MAC, CPR and finally DV.
In the studied group, 62.3% of UTA pathologists in one or both of the UTA
included an increase in the RI of ≥ 0.7 or a Notch sign. This is consistent with
the main features and causes of IUGR pregnancy due to blood vessels, our
findings are similar to that of Phan Truong Duyet, Pham Thi Huong Linh.
118/252 (46.8%) cases of UMA Doppler abnormalities have been reported to
diagnose IUGR causes due to chronic hypoxemia. 100/252 (37.3%) of women
with reversible CPR were less than 1, which is evidence of circulatory
regulation, favoring vital organs of the fetus, accompanied by decreased
amniotic fluid less and no amniotic fluid. In the past, if UMA Doppler
abnormalities were suspected, many studies have now indicated that
abnormalities of the UMA Doppler Doppler would not adequately assess the
pregnancy and decide to stop pregnancy in fetal IUGR.
Observed in Table 3.34, we found that the sensitivity in pregnancy outcomes


Tài liệu bạn tìm kiếm đã sẵn sàng tải về

Tải bản đầy đủ ngay

×