1. Doppler Ultrasound in Daily Practice
Wesam Kurdi, FRCOG
Head, Section of Maternal Fetal Medicine
Department of Obstetrics & Gynecology
King Faisal Specialist Hospital & Research Center
Riyadh,Saudi Arabia

2. Uses of Doppler Ultrasound in Obstetrics
Doppler in IUGR
Doppler in fetal anemia
Doppler in Multi-fetal pregnancy evaluation
Doppler in the assessment of the fetal heart
Doppler in fetal structural abnormalities
Doppler in placental and cord abnormalities
Doppler in early pregnancy evaluation
Doppler in screening for chromosomal abnormalities

3. Practical Points Factors affecting the waveform
Fetal breathing

4. Practical Points Factors affecting the waveform
The indices are higher at the fetal than at the placental end of the cord, usually free loop is used
Gestational age: end-diastolic velocity increases with advancing gestation
Fetal heart rate: can effect Doppler indices, but within the normal limits of the fetal heart rate (120 to 160 bpm), the changes in the Doppler indices are not significant.
Fetal behavioral states: no effect

5. Practical Points Factors affecting the waveform
Angle of insonation: the higher the angle, the smaller the waveform, preferable to keep the angle of insonation as close to zero as possible
Remember:
cos 0= 1
cos 30= 0.87
cos 60= 0.5
cos 90= 0
2f v cos c
fd =

6. Effects of the angle
Good angle
Bad angle

7. UTERINE ARTERY DOPPLER

8. UTERINE ARTERY DOPPLER

9. UTERINE ARTERY DOPPLER
Notching by Gestation
Highest risk Persistant bilateral notching after 24 weeks
Less risk Unilateral notches
Normalization by 24 weeks

10. UTERINE ARTERY DOPPLER
Persistent notching at 24 weeks

11. Uterine Artery Doppler
Screening studies for the prediction of pre-eclampsia
7-33%
low
Very good
24-77%
Very good
 CI, confidence interval; LR, likelihood ratio; NPV, negative predictive value; PPV, positive predictive value; Prev, prevalence; Sens, sensitivity; Spec, specificity; SPR, screen positive rate.

12. Uterine Artery Doppler
Screening studies for the prediction of fetal growth restriction below the 10th centile
higher
Lower
Borderline IUGR more heterogeneous
CI, confidence interval; LR, likelihood ratio; NPV, negative predictive value; PPV, positive predictive value; Prev, prevalence; Sens, sensitivity; Spec, specificity; SPR, screen positive rate.

13. Uterine Artery Doppler
Screening studies for the prediction of fetal growth restriction below the 5th and 3rd centile
12-19%
Very good
CI, confidence interval; FGR, fetal growth restriction; LR, likelihood ratio; NPV, negative predictive value; PPV, positive predictive value; Prev, prevalence;

14. Doppler Ultrasound in IUGR Why is it important to diagnose IUGR?
IUGR are at increased risk of complications:
Fetal hypoxia and acidemia
3-10 fold  risk of perinatal mortality and morbidity
Long-term intellectual and neurological impairment.
Perinatal/ Post-natal Problems
Asphyxia, Temperature instability, Hypoglycemia, Fetal Distress, Acidosis, Meconium aspiration, Polycythemia, Impaired growth and development, Adult disease: cardiac, diabetes

15. Umbilical Artery Doppler Screening in High Risk Pregnancy
Cochrane Database 2000
Reduces hospital admissions (OR 0.56, CI= )
Reduces IOL (OR 0.83, CI= )
Trend to lower Perinatal Mortality Rate (OR 0.71, CI= )
No difference for fetal distress (OR 0.81, CI= ), or CS rate ( OR 0.94, CI= )

16. Fetal and umbilical Doppler ultrasound in high-risk pregnancies
Eighteen completed studies involving just over 10,000 women were included.
RR 95%CI
Perinatal deaths to 0.98
IOL to 0.99
Caesarean sections to 0.97
Operative vaginal births to 1.14
Apgar  7 at 5min to 1.24
Numbers needed to treat 203
AUTHORS' CONCLUSIONS: Current evidence suggests that the use of Doppler ultrasound in high-risk pregnancies reduced the risk of perinatal deaths and resulted in less obstetric interventions. The quality of the current evidence was not of high quality, therefore, the results should be interpreted with some caution. Studies of high quality with follow-up studies on neurological development are needed.
Alfirevic Z, Cochrane Database Syst Rev. 2010

17. IUGR with normal UA Doppler
Neonatal and maternal outcomes
Twice-weekly Fortnightly monitoring (n=85) monitoring (n=82)
Neonatal outcome
Gestational age at delivery (d, mean  SD) 264   12*
Umbilical artery resistance index at delivery (mean  SD)   0.06
Abnormal umbilical artery resistance index at delivery (No.) 5 (6%) 1 (1%)
Female sex (No.) (51%) 46 (56%)
Birth weight (g, mean  SD)   412
Birth weight <10th percentile (No.) (55%) (69%)
Ponderal index (mean  SD)   0.28
Ponderal index <10th percentile (No.) (34%) 39 (48%)
Admission to neonatal nursery (No.) (31%) 28 (34%)
Neonatal hospital stay (d, median and range) (0-66) (1-27)
Acidosis at birth (No.) (5%) (4%)
Hypoglycemia (No.) (19%) 18 (22%)
Maternal outcome (No.)
Spontaneous onset of labor (9%) 21 (26%†)
Induction of labor (82%) 54 (66%†)
Cesarean delivery (15%) 11 (13%)
Cesarean delivery for fetal distress (8%) (9%)
Preeclampsia (5%) (1%)
Gestational hypertension (24%) 13 (16%)
*p<0.05
†p<0.02
McCowan et al IUGR fetuses

18. Clinical Management of IUGR How reassuring is a normal test result?
Stillbirth rate within one week of a normal test
NST / (5861 patients)
CST / (12656 patients)
BPP / (44828 patients)
Modified BPP (NST + AFI) 0.8/ (54617 patients)
UA Doppler 0/ (214 patients)

19. Umbilical Artery Doppler and Poor Fetal Outcome
Sensitivity Specificity PPV NPV
Abnormal outcome % % % %
SGA % % % %
FD, pH, Apgar, NICU % % % %
FD, pH, Apgar, NICU, Mec % % % %
Abnormal NST % 78% %
Fetal distress % 89% % %
CS for FD 9% 88.8% % %
1410 tests done
Increased RI occur prior to changes on NST
Simple, efficient
Mean time 6 min vs 27 min for NST

20. Umbilical Artery Doppler
+ve EDF ve EDF Reverse EDF P
IUFD % % % <0.001
Cesarean Section % % % <0.001
NICU % % % <0.001
Severe RDS % % % <0.001
Severe IVH % % % <0.01
NEC % % %
459 High Risk Pregnancies, Karsdorp et al, 1994
1126 cases of AEDV:
Stillbirth rate: 170/1000
ENMR 280/1000
cPMR 340/1000
Maulik, 2005

21. Can Umbilical Artery Doppler Predict the Sick IUGR?
Parameter AEDF REDF
Gest age 34 wks 29 wks
C/S % %
Fetal distress % %
Bt Wt < 3rd % %
Acidemia 4.5% %
115 fetuses with AC < 5th
Doppler performed 24 hours before delivery
Abnormal umbilical artery Doppler is more predictive of neonatal outcome than EFW.
If EDF present and PI > 2SD from mean, 90% will deliver vaginally.

22. A randomised trial of timed delivery for the compromised preterm fetus: short term outcomes GRIT Study Group, BJOG. 2003;110(1):27.
Randomized controlled trial, 69 hospitals in 13 European countries.
Pregnant women with fetal compromise between 24 and 36 weeks, an umbilical artery Doppler waveform recorded and clinical uncertainty whether immediate delivery was indicated.
METHODS: The interventions were 'immediate delivery' or 'delay until the obstetrician is no longer uncertain'. The data monitoring and analysis were Bayesian.
MAIN OUTCOME MEASURES: 'Survival to hospital discharge'
548 women (588 babies) recruited, outcomes were available on 547 mothers (587 babies).
Immediate gp Delayed gp
Median time-to-delivery intervals were 0.9 days 4.9 days
Death prior to discharge 10% 9% OR: 1.1, 95% CI cesarean section 91% 79% OR 2.7; 95% CI

23. MIDDLE CERABRAL ARTERY DOPPLER
Easy to study
Main branch of the circle of Willis
Carries 80% of blood flow to the ipsilateral cerebral hemisphere
Carries 3-7% of cardiac output throughout gestation

24. MIDDLE CERABRAL ARTERY DOPPLER
Relation to neurodevelopment
Decrease MCA PI is an adaptive process protecting the fetus against severe brain damage.
3 years follow-up failed to demonstrate neurodevelopmental abnormalities with decreased MCA PI.
Scherjon 1998
Drop in MCA PI may be protective against IVH but prematurity is the greatest predictor.
Mari 1996

25. Performance of single Doppler measurement for major adverse perinatal outcome at <32 weeks.
Sensitivity Specificity PPV NPV UA
MCA
UA - better for screening
MCA - reassurance if normal

26. Venous Doppler
The fetal venous system Doppler waveforms evaluates the fetal heart compensation to severe growth restriction.
The commonly studied vessels include:
Umbilical vein
Ductus venosus

27. Relation between UA and UV
AEDF in UA no pulsation: % mortality
pulsation: % mortality
Intra-abdominal part is more sensitive than the free loop, pulsation in the free loop is a very bad sign.

28. Progression of fetal growth restriction

29. Sequence of Doppler Changes in IUGR
Brain sparing
Asymmetrical IUGR
Oligohydramnios
2 weeks prior to CTG changes
Possibly with CTG changes

30. Arterial and Venous Doppler and Perinatal Death
Sensitivity Specificity PPV NPV UA
MCA UV DV
Ozcan et al

31. Duration of persistent abnormal ductus venosus flow and its impact on perinatal outcome in fetal growth restriction.
171 patients with 1069 examinations.
Duration of an absent/reversed a-wave in the DV (DV-RAV)
Stillbirth 6 days
Intact survivors 0 days P = 0.006
Major morbidity 0 days P = 0.001
Duration of brain sparing
Stillbirth 19 days
Intact survivors 9 days P = 0.02
Gestational age at delivery was a significant codeterminant of outcome for all arterial Doppler abnormalities when the DV a-wave was positive.
When DV-RAV is found, this was the only contributor to stillbirth
DV-RAV for>7 days predicted stillbirth 100% sensitivity, 80% specificity, LR = 5.0, P<0.0001
Neither neonatal death nor neonatal morbidity was predicted by the days of persistent DV-RAV.
CONCLUSIONS: The duration of absent or reversed flow during atrial systole in the DV is a strong predictor of stillbirth that is independent of gestational age. While prematurity remains the strongest predictor of neonatal risks it is unlikely that pregnancy can be prolonged by more than 1 week in this setting.
Turan OM, et al, Ultrasound Obstet Gynecol. 2011;38(3):295

32. Abnormal umbilical and MCA Doppler
Clinical Follow-up
Normal umbilical and MCA Doppler NST and venous Doppler not indicated
Abnormal umbilical and MCA Doppler
> 34 weeks
< 30 weeks
delivery
Venous Doppler + NST
30-34 weeks
Normal
Abnormal
Individualize according to findings, history and neonatal facilities
Steroids, close observation
Consider delivery

33. Timing of Delivery
The risk of death or cerebral palsy reduces as each week goes by, but if delivery is delayed until there is fetal circulatory collapse (very abnormal venous blood flows), the risk of death is also increased.
Harnington, Ultra OB Gyn 2000;16:

34. TAKE HOME MESSAGES
Umbilical artery Doppler can help to guide decision making and the need for further fetal monitoring.
Absent/ reversed EDF when linked with abnormal CTG increases the risk of poor cognitive outcome in childhood.
Arterial redistribution predicts hypoxemia.
Venous Doppler abnormalities predicts heart failure.
Venous system is the fine tuning area for planning the delivery.
Appearance of a reverse a wave in the DV or pulsation in the umbilical vein is a strong indication for delivery.
Gestational age has the greatest influence on fetal wellbeing

35. Practical Points
Overall survival of IUGR at < 26 weeks is <50%, intact survival is <50%.
Gestational age is more important than Doppler at < 26 weeks.
Intact survival are not much related to birth weight.
Outcome is better if less obvious CTG/ Doppler abnormalities are present.
Waiting reduces the risk of lung complications, but not NEC or IVH
Long term outcome: higher rates of disability in the earlier delivery group- mostly in < 30 weeks fetuses.
Once severe redistribution occurs, further follow-up with arterial Doppler is not very helpful for timing of delivery.
Between 26 and 29 weeks: each day in utero has been estimated to improve survival by 1-2%
Arterial changes have been reported to last for up to 6 weeks, depending on gestational age, presence of venous pulsation, and maternal disease.

37. Fetal Anemia Red cell immunization Parvovirus infection
Massive fetomaternal hemorrhage
Hematologic disorders: Alpha-thalassemia, G6PD
Large placental chorioangioma
Twin-twin transfusion syndromes
Intracranial hemorrhage

38. What are the Effects of Severe Fetal Anemia

39. Prediction of Fetal Anemia
A variety of ultrasonographic parameters have been used to detect fetuses at risk of anemia:
Placental thickness: not been considered to be very reliable and reproducible in clinical practice.
Hepatic length greater than or equal to the 95th percentile: the liver is difficult to visualize and measure adequately, particularly when the fetus is in an unfavorable position (back up or right side up).
Splenic enlargement: a splenic perimeter greater than 2 SD has predicted severe fetal anemia with a positive predictive value of 94%. It was found to be an excellent predictor of severe fetal anemia in cases before the first transfusion, with sensitivity and specificity of 100 and 94.7%, respectively, but the predictive value was not as good in patients with prior transfusion or with mild anemia.
Main splenic artery PSV: there was no risk of severe anemia with PSV below the median for gestational age, but the prediction is not good for mild anemia.

40. Prediction of Fetal Anemia
A prospective cohort study compared Doppler and ultrasound parameters to predict fetal anemia in alloimmunized pregnancies. Sensitivity MCA-PSV 100% Intrahepatic umbilical venous maximal velocity 83% Liver length 66% Spleen perimeter 33%
MCA-PSV is the best available noninvasive test in the prediction of fetuses at risk of anemia

41. Prediction of Fetal Anemia
Multicentric study the sensitivity of MCA-PSV for predictions of moderate and severe anemia prior to the first cordocentesis:
Sensitivity 100%
False positive rates 12% for 1.50 MoM
Multicenter trial for timing a cordocentesis:
MCA-PSV is an accurate method of monitoring pregnancies
Number of false positives increased following 35 weeks' gestation
Prospective study compared MCA-PSV with Delta OD 450:
Both procedures are useful in the prediction of fetal anemia
But Doppler ultrasound is less expensive and noninvasive than amniocentesis

42. MCA MoM > 1.5 MoM MCA peak velocity
Doppler and Fetal Anemia
Normal fetuses Anemic fetuses
MCA MoM > 1.5 MoM MCA peak velocity
Sensitivity 100%
False +ve 12%
Positive predictive rate 65%
Negative predictive rate 100%

43. Management of Rh(-) Immunized Patients
+ve antibody screen
Paternal genotype
Negative
Heterozygous
Homozygous
No further testing
(paternity!)
Consider fetal blood typing
Follow protocol
The RhD gene was cloned, PCR for fetal RhD status can be performed on amniocytes or CVS specimen, inaccuracy 0.3-2%
Fetal DNA in maternal circulation: 100% accuracy

44. Modern management of red-cell alloimmunization
MCA-PSV should be performed in fetuses at risk of fetal anemia on a weekly basis for three consecutive weeks.
Cordocentesis is indicated when the MCA-PSV value is over 1.5 MoM.
If the MCA-PSV remains below 1.5 MoM a regression line has to be obtained from the following three values.
Repeat weekly
Repeat Q1-2 wks
Repeat Q2-4 wks

45. Can the Peak Systolic MCA Doppler Assessment Be Used to Time Serial IUTs?
The decreasing sensitivity MCA-PSV after several IUTs has several explanations:
By the third IUT, most of the circulating red cells in the fetal circulation are donor cells that contain adult hemoglobin.
Correction of the fetal anemia through IUT raises the fetal hematocrit level, which also substantially increases whole blood viscosity.
Both of these will slow the speed at which blood moves through the fetal circulation.
The average drop in Hg following donor transfusion is 0.4gm/ day

46. Maisoon AlMugbel Fatima AlAbri Elham AlMardawi Maha Tulbah
Validity of MCA PSV in determining severe anemia in previously transfused fetuses
Wesam Kurdi
Maisoon AlMugbel Fatima AlAbri
Elham AlMardawi Maha Tulbah
Khalid Awartani
King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia

47. Objectives Patients and Methods
MCA PSV in previously transfused fetuses
To assess if the correlation between the MCA PSV and fetal hemoglobin is maintained in fetuses who received multiple IUT’s
Objectives
Patients and Methods
Retrospective analysis on all pregnant women who received IUT’s at King Faisal Specialist Hospital (January 2006 to December 2010).
Doppler measurement of MCA PSV performed before cordocentesis.
MCA PSV and fetal Hb expressed as multiples of the median (MoM).
MCA PSV ≥ 1.5 MOM used as a predicator for severe anemia (Hb ≤ 0.55 MoM)

48. Results MCA PSV in previously transfused fetuses
28 pregnancies, non-hydropic fetuses; GA at 1st visit wks
Parity: 5.2 (range 1-11); Living children: 4.1 (range 1-8)
64% had IUTs in previous pregnancy
n GA Hb g/L Hb ≤ FPR DR
Before 1st (14-95) 57% 43% 100%
Before 2nd (10-114) 48% 54% 92%
Before 3rd (50-127) 33% 61% 78%
Before 4th-6th (45-110) 33% 76% 81%
Any anemia, PSV cut-off 1.5 MoM % 81%
Any anemia, PSV cut-off 1.4 MoM % 91%
GA at delivery: 36.3 wks; Delivery at >35 wks: 66%
Survival rate: 83%; Postnatal mean Hb: 124g/L

49. MCA PSV in previously transfused fetuses
Conclusions
In the prediction of severe fetal anemia by MCA PSV: The FPR increases and DR decreases with increasing number of IUT’s
Severity of anemia is reduced with repeated IUT’s
Reducing the MCA PSV to 1.4 MoM after the 3rd IUT improves the DR to 91%
What should our end point be for mature fetuses: any anemia or severe anemia?

50. Kell alloimmunization
The mechanism of anemia in Kell alloimmunization is in direct suppression of erythropoiesis in conjunction with sequestration of sensitized red cells.
Evaluation of at-risk fetuses with MCA PSV has a sensitivity and specificity of 89% for the detection of fetal anemia, similar to the detection of fetal anemia in RhD alloimmunization.

51. How to Suspect/ Diagnose Other Causes of Fetal Anemia?
Severe anemia causes Hydrops
All cases of fetal Hydrops: must check MCA PSV

52. Parvovirus B19 infection
The measurement of MCA PSV predict fetal anemia with a sensitivity of 94.1%.
All cases with moderate and severe anemia were detected either by MCA PSV alone or in combination with real-time ultrasonography.
A threshold of 1.29 MoM has been proposed; this will lead to the detection of cases of mild anemia.
Because frank hydrops has been reported to resolve spontaneously in as many as 30% of cases, a threshold value of the MCA velocity of 1.5 MoM is better for timing of IUT.

53. Fetomaternal Hemorrhage
An increased MCA-PSV has been reported in cases of acute severe fetomaternal hemorrhage.
In most of these cases, other clinical signs such as decreased fetal movement or a sinusoidal heart rate pattern have also been present.
The suspicion of severe fetal anemia can assist in the decision for early delivery, with blood immediately available for neonatal transfusion in the delivery room.
IUT in these cases has been successful only rarely because of the continued passage of fetal blood into the maternal circulation.

54. KFSH&RC Experience in Isoimmunization
Challenging Case:
Rh Isoimmunization with Glanzmann Thrombasthenia
1st pregnancy IUFD hydrops
2nd pregnancy: 6 intrauterine transfusions with pre-procedure platelets transfusion and Trenaxemic acid, IOL and SVD at 37 weeks
3rd pregnancy: severe intraabdominal bleed following intrauterine transfusion, found to have antiplatelet antibodies.
With modern management: only 3 transfusions were needed.

55. Conclusions Fetal anemia is commonly seen in our practice
Anemia is seen both in immune or non-immune hydrops
MCA-PSV is the new gold standard for the detection of fetal anemia
In Immune hydrops, we do not start intervention till MCA PSV is  1.5 MoM
After the third in-utero transfusion, we do not depend on MCA PSV for predicting anemia or timing of transfusions
Please remember to include MCA PSV in your scanning reports in all cases of non-immune hydrops