MCA Doppler and Fetal Anemia Guidance

Page Links:  Anatomy of Middle Cerebral Artery,  Ultrasound Anatomy,  History Doppler MCA-PSV and Fetal Anemia,  Fetal Doppler Studies and Anemia,  Evolution in 1990sCollaborative Group ReportSystematic ReviewStandard of CareFetal Growth Restriction (FGR) and MCA DopplerAlgorithm, MCA-PSV: Diagnosis and ManagementSampling Technique

 

Introduction

The application of middle cerebral artery Doppler to the diagnosis and management of fetal anemia is one of the singular achievements in perinatal medicine since the methodology accurately defines anemia, reduces the need for invasive procedures, and guides management. 1234–6

Recently, the Society for Maternal-Fetal Medicine (SMFM) recommended middle cerebral artery Doppler peak systolic velocity (MCA-PSV) as the primary method to detect and assess fetal anemia.7  This section will review the use of this non-invasive technique, define its rationale, briefly review pertinent literature, suggest an algorithm for management, and describe the methodology for obtaining accurate Doppler MCA waveforms. An accompanying section is devoted to the etiology of fetal anemia.

 

Anatomy of Middle Cerebral Artery

middle cerebral fetal arteries are paired vessels

Above. The middle cerebral fetal arteries are paired vessels which arise from the internal carotid arteries. The Circle of Willis is illustrated in blue, and while the MCAs do not connect to the Circle of Willis directly they have a connection to the anterior cerebral, posterior communicating and posterior cerebral arteries via the relationship of the internal carotid arteries to these vessels. (http://en.wikipedia.org/wiki/Circle_of_Willis)

 

MCA Doppler Ultrasound Anatomy

Ultrasound anatomy of the Circle of Willis and the MCA

Above. Ultrasound anatomy of the Circle of Willis and the MCA (middle cerebral artery). An axial view at the level of the thalami is obtained when the fetus is at rest. While the MCAs are paired vessels, the MCA nearest the transducer (proximal) is the vessel of interest for Doppler interrogation.

 

History Doppler MCA-PSV and Fetal Anemia

WEBdiagfeanemia-1

Above. In fetal anemia, the increased blood velocity is likely related to increased cardiac output and decreased blood viscosity,8 and the correlation of increased blood velocity in cases of fetal anemia is present in many arterial vessels while the MCA presents a confluence of vessel anatomy which facilitates the direct measurement of velocity.

 

Fetal Doppler Studies and Anemia

studies on Doppler and Fetal Anemia

Above. As noted by Mari9 investigations were carried out by groups on more than one continent beginning with his observation in 1987 of an inverse relationship between the PSV of the MCA waveform and fetal anemia before and after fetal blood transfusions. (PSV was lower after transfusions). Almost simultaneously, Rightmire and Nicolaides noted that anemic fetuses had higher mean Doppler velocities in the aorta and in the inferior vena cava than did normal fetuses.10

In 1990 Vyas and Nicolaides reported on Doppler examination of the MCA in 24 red cell isoimmunized pregnancies. The MCA mean blood velocity increased with anemia, suggesting that the hyperdynamic circulation was a consequence of decreased blood viscosity.11  At the same time, Mari et. al. noted that the PSV of the MCA was superior to the Doppler pulsitility index for the diagnosis of fetal anemia.9

 

Evolution of MCA-PSV in 1990s

Evolution of MCA-PSV in 1990s

Above. A number of related and confirmatory studies were published in the 1990s suggesting the value of MCA-PSV in the diagnosis and management of fetal anemia.12   Using Doppler assessment, renal blood flow increased in the anemic fetus following intravascular transfusion,13 and increases in fetal hematocrit significantly decreased the MCA-PSV in Rh alloimmunized fetuses following transfusion.14

 

Collaborative Group Report

MCA Doppler and Fetal Anemia Collaborative Group Report

Above. The definitive work on the noninvasive diagnosis of fetal anemia secondary to maternal red cell alloimmunization was published regarding 111 fetuses at risk in the New England Journal of Medicine in 2000.15  Increased PSV of the MCA detected moderate and severe anemia with a high sensitivity with or without the presence of hydrops and with a false positive rate of 12%.

 

MCA Doppler and Fetal Anemia Follow-up Studies

A number of follow-up studies addressed specific aspects of fetal anemia in relationship to MCA-PSV and include:

1.  change in the MCA-PSV after correction of fetal anemia by intrauterine fetal transfusion16

2.  prediction of fetal hemoglobin17

3.  longitudinal assessment of the healthy fetus and the fetus at risk for fetal anemia18

6.  timing for the second transfusion from red cell alloimmunized pregnancies19

7.  correlation between fetal anemia and MCA-PSV after 2 previous intrauterine transfusions20

8.  confirmation for its use in the diagnosis of parvovirus B-1921

9.  use in Kell-alloimmunized pregnancies.21

 

Systematic Review

systematic review and meta-analysis for detecting severe anemia

Above. A recent systematic review and meta-analysis suggests a positive likelihood ratio for detecting severe anemia with MCA-PSV of 4.3 (95% CI: 2.5 to 7.41) and negative likelihood ratio of 0.30 (95% CI: 0.13 to 0.69).2  While these authors acknowledge that higher positive likelihood ratios of > 10 and lower negative likelihood ratios of <.1 are criteria for an ideal test, they also acknowledge MCA-PSV’s “gold standard” in non-invasive testing.

 

MCA-PSV still gold standard for detection of fetal anemia

Above. Experience suggests that trending results over time rather than a single result may reduce false positives.3 In addition, a number of reviews define further principles and methodology and, emphasize the need for proper sonographer and physician training for MCA sampling.4–6

 

Standard of Care for Fetal Anemia

By 2005, the Doppler of the MCA-PSV was evolving as the standard of care for the diagnosis of fetal anemia.22 Again, caution was advised to establish the correct measurement technique and to consider referral of suspected fetal anemia to centers with adequately trained sonographers and physicians.

 

Fetal Growth Restriction (FGR) and MCA Doppler

fetuses at risk for anemia

Umbilical artery Doppler and MCA Doppler are used to assess the fetus for fetal growth restriction (FGR).5   In some growth restricted fetuses, waveforms of the MCA are characterized by increased diastolic velocities, suggesting a decrease in cerebral circulation resistance, which occurs under conditions of fetal hypoxic stress and is termed “blood flow redistribution” or “brain sparing” effect.
In comparing the anemic to the non-anemic fetus with FGR, the mechanism of high velocities in the MCA is different between the two groups.23

In fetuses at risk for anemia, the fetal hemoglobin is related to the MCA-PSV, while in fetuses with FGR the MCA-PSV is correlated with the state of fetal oxygenation and not the hemoglobin values. While MCA-PSV values are predictive of fetal anemia in the growth restricted fetus, the predictive accuracy is not sufficient to define fetal anemia in this setting.24

 

Diagnosis of Fetal Anemia

Diagnosis and screening for MCS-PSVprecise diagnosis of the fetal hemoglobin

Above. While the precise diagnosis of the fetal hemoglobin (Hgb) requires invasive fetal sampling, the MCA-PSV reliably detects fetal anemia beginning at 16 to 18 weeks through 35 weeks.25  An increase in the MCA-PSV correlates best when the fetal hemoglobin levels are low and correlates less precisely when the fetal hemoglobin levels are normal or when there is mild anemia.7,15

The screening test for fetal anemia is based upon a reference range for hemoglobin concentrations (grams per deciliter) as a function of gestational age and is expressed as a multiples of the median (MoM). Expected PSV of the MCA as a function of gestational age was established and >1.5 MoM identifies the severely anemic fetus.15

 

Algorithm, MCA-PSV:  Diagnosis and Management

suspect fetal anemia-1

Above. Each of the above causes of fetal anemia is covered in detail in the Fetal Anemia etiology chapter. In summary, the flow chart suggests potential management strategy for some causes of fetal anemia. Note in some cases individual judgement is required. Options are given for maternal Parvovirus B19 and management is individualized for monochorionic twins as well as for fetal and placenta tumors.

 

Sampling Technique

Proper sampling technique is critical to accurately detect fetal anemia and is summarized as follows [1]:

1.  Perform study during a period of fetal rest.

Obtain an axial section of the fetal brain

2.  Obtain an axial section of the fetal brain, which includes the thalamus and cavum septi pellucidi.

3.  Activate color Doppler and image the circle of Willis.

4.  Identify the middle cerebral artery which is nearest to the transducer (proximal).

Enlarge the proximal MCA

5.  Enlarge the proximal MCA so that it occupies more than 50% of the image.

WebMCA4

6.  Use a Doppler sample volume of 1 mm.

7.  Place the sample volume near the exit of the MCA from its origin from the internal carotid artery (about 2 mm.).

8.  The angle between the MCA blood flow and ultrasound beam should be as close to zero as possible without using angle correction.*

web.PSV

9.  Obtain between 15 and 30 waveforms with similar configuration.

10.  Measure the highest point of the waveform for the PSV.

11.  Repeat this sequence at least 3 times for each fetus.

*The Doppler shift is proportional to velocity flow and when the ultrasound incident beam or angle is zero, velocity flow of the circulation is measured directly.

 

Links

The original NEJM article is freely downloadable and all of the reference charts are available at:  http://www.nejm.org/doi/full/10.1056/NEJM200001063420102

In addition, the abstract for SMFM Clinical Guideline #8 is available. The full article covers the topic in detail and gives details as to methodology for fetal blood sampling and intrauterine fetal transfusions. http://www.ncbi.nlm.nih.gov/pubmed/

 

References

1.
van D., Klumper F., Sikkel E., et al. Non-invasive tests to predict fetal anemia in Kell-alloimmunized pregnancies. Ultrasound Obstet Gynecol 2005;25(4):341–5. [PubMed]
2.
Pretlove S., Fox C., Khan K., et al. Noninvasive methods of detecting fetal anaemia: a systematic review and meta-analysis. BJOG 2009;116(12):1558–67. [PubMed]
3.
Zimmerman R., Carpenter R., Durig P., et al. Longitudinal measurement of peak systolic velocity in the fetal middle cerebral artery for monitoring pregnancies complicated by red cell alloimmunisation: a prospective multicentre trial with intention-to-treat. BJOG 2002;109(7):746–52. [PubMed]
4.
Segata M., Mari G. Fetal anemia: new technologies. Curr Opin Obstet Gynecol 2004;16(2):153–8. [PubMed]
5.
Mari G. Doppler ultrasonography in obstetrics: from the diagnosis of fetal anemia to the treatment of intrauterine growth-restricted fetuses. Am J Obstet Gynecol 2009;200(6):613.e1-9. [PubMed]
6.
Samson J., Block D., Mari G. Middle cerebral artery Doppler for managing fetal anemia. Clin Obstet Gynecol 2010;53(4):851–7. [PubMed]
7.
Society for., Mari G., Norton M., et al. Society for Maternal-Fetal Medicine (SMFM) Clinical Guideline #8: the fetus at risk for anemia–diagnosis and management. Am J Obstet Gynecol 2015;212(6):697–710. [PubMed]
8.
Fan F., Chen R., Schuessler G., et al. Effects of hematocrit variations on regional hemodynamics and oxygen transport in the dog. Am J Physiol 1980;238(4):H545-22. [PubMed]
9.
Mari G. Middle cerebral artery peak systolic velocity for the diagnosis of fetal anemia: the untold story. Ultrasound Obstet Gynecol 2005;25(4):323–30. [PubMed]
10.
Rightmire D., Nicolaides K., Rodeck C., et al. Fetal blood velocities in Rh isoimmunization: relationship to gestational age and to fetal hematocrit. Obstet Gynecol 1986;68(2):233–6. [PubMed]
11.
Vyas S., Nicolaides K., Campbell S. Doppler examination of the middle cerebral artery in anemic fetuses. Am J Obstet Gynecol 1990;162(4):1066–8. [PubMed]
12.
Mari G., Adrignolo A., Abuhamad A., et al. Diagnosis of fetal anemia with Doppler ultrasound in the pregnancy complicated by maternal blood group immunization. Ultrasound Obstet Gynecol 1995;5(6):400–5. [PubMed]
13.
Mari G., Moise K., Deter R., et al. Doppler assessment of renal blood flow velocity waveforms in the anemic fetus before and after intravascular transfusion for severe red cell alloimmunization. J Clin Ultrasound 1991;19(1):15–9. [PubMed]
14.
Mari G., Rahman F., Olofsson P., et al. Increase of fetal hematocrit decreases the middle cerebral artery peak systolic velocity in pregnancies complicated by rhesus alloimmunization. J Matern Fetal Med 1997;6(4):206–8. [PubMed]
15.
Mari G., Deter R., Carpenter R., et al. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses. N Engl J Med 2000;342(1):9–14. [PubMed]
16.
Stefos T., Cosmi E., Detti L., et al. Correction of fetal anemia on the middle cerebral artery peak systolic velocity. Obstet Gynecol 2002;99(2):211–5. [PubMed]
17.
Mari G., Detti L., Oz U., et al. Accurate prediction of fetal hemoglobin by Doppler ultrasonography. Obstet Gynecol 2002;99(4):589–93. [PubMed]
18.
Detti L., Mari G., Akiyama M., et al. Longitudinal assessment of the middle cerebral artery peak systolic velocity in healthy fetuses and in fetuses at risk for anemia. Am J Obstet Gynecol 2002;187(4):937–9. [PubMed]
19.
Detti L., Oz U., Guney I., et al. Doppler ultrasound velocimetry for timing the second intrauterine transfusion in fetuses with anemia from red cell alloimmunization. Am J Obstet Gynecol 2001;185(5):1048–51. [PubMed]
20.
Mari G., Zimmermann R., Moise K., et al. Correlation between middle cerebral artery peak systolic velocity and fetal hemoglobin after 2 previous intrauterine transfusions. Am J Obstet Gynecol 2005;193(3 Pt 2):1117–20. [PubMed]
21.
Cosmi E., Mari G., Delle C., et al. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia resulting from parvovirus infection. Am J Obstet Gynecol 2002;187(5):1290–3. [PubMed]
22.
Mari G. Middle cerebral artery peak systolic velocity: is it the standard of care for the diagnosis of fetal anemia? J Ultrasound Med 2005;24(5):697–702. [PubMed]
23.
Hanif F., Drennan K., Mari G. Variables that affect the middle cerebral artery peak systolic velocity in fetuses with anemia and intrauterine growth restriction. Am J Perinatol 2007;24(8):501–5. [PubMed]
24.
Makh D., Harman C., Baschat A. Is Doppler prediction of anemia effective in the growth-restricted fetus? Ultrasound Obstet Gynecol 2003;22(5):489–92. [PubMed]
25.
Lindenburg I., van K., Oepkes D. Intrauterine blood transfusion: current indications and associated risks. Fetal Diagn Ther 2014;36(4):263–71. [PubMed]

 

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  1. Abstract: PMID: 15784760