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Correction of Fetal Anemia on the Middle Cerebral Artery Peak Systolic Velocity

From the Prenatal Diagnosis and Fetal Therapy Center, Department of Obstetrics and Gynecology, University of Virginia, Charlottesville, Virginia.

Address reprint requests to: Giancarlo Mari, MD, Department of Obstetrics and Gynecology, University of Virginia Health Science Center, P.O. Box 800712, Charlottesville, VA 22908. E-mail: gm6p{at}virginia.edu.

	ABSTRACT

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OBJECTIVE: To assess the effect of correction of fetal anemia on the middle cerebral artery peak systolic velocity values.

METHODS: With Doppler ultrasonography, middle cerebral artery peak systolic velocity was measured in 41 fetuses before and immediately after 54 intrauterine transfusions for severe red blood cell alloimmunization. The fetuses were divided into two groups: 17 fetuses studied at first transfusion (group A), and 24 fetuses enrolled to the study after the first transfusion (group B). Both fetal hemoglobin and middle cerebral artery peak systolic velocity were plotted over the respective reference ranges as a function of gestational age. Both values were expressed as multiples of the median and analyzed with paired t test.

RESULTS: The values of middle cerebral artery peak systolic velocity decreased in all but one fetus of group B (P < .05). The values of middle cerebral artery peak systolic velocity before transfusion were above the upper limit of the reference range in 60% of the fetuses of group A and in 38% of group B, respectively. After correction of anemia, only one value remained above the upper limit of the reference range.

CONCLUSION: The correction of fetal anemia with intrauterine blood transfusion decreases significantly and normalizes the value of the fetal middle cerebral artery peak systolic velocity.

Invasive procedures such as amniocentesis and funicentesis have been used to diagnose fetal anemia caused by red blood cell alloimmunization.^1,2 Recent studies have shown that when traditional criteria are used for timing a funicentesis, more than 70% of the fetuses are either nonanemic or mildly anemic.³ The fetal middle cerebral artery peak systolic velocity is increased in anemic fetuses and it may be used, noninvasively, for timing the need of a funicentesis.^3,4

In a preliminary study, it has been reported that the middle cerebral artery peak systolic velocity decreases after the first intrauterine transfusion.⁵ However, there are no data from animal or human studies reporting correlation between the middle cerebral artery peak systolic velocity values in anemic fetuses after correction of anemia, and the reference range as a function of gestational age. Additionally, there are no data distinguishing the changes of the middle cerebral artery peak systolic velocity based on the number of previous transfusions.

The aim of this study was twofold: to assess the values of the middle cerebral artery peak systolic velocity before and after intrauterine transfusion in fetuses never transfused and in fetuses previously transfused, and to determine if there is any difference between the middle cerebral artery peak systolic velocity values before and after transfusion when the values are plotted over the reference range for gestational age.

	MATERIALS AND METHODS

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This was a retrospective study. A search was done on the database of the collaborative group for the study of fetal anemia with Doppler ultrasonography. All cases with middle cerebral artery peak systolic velocity values obtained before and after intrauterine transfusion were selected. There were 41 fetuses fulfilling the criteria. The patients were enrolled over a 4-year period. All the fetuses were anemic and underwent one or more intrauterine blood transfusions. On 17 fetuses, the middle cerebral artery peak systolic velocity values were studied before and after the first transfusion (group A). Group B initially included 28 fetuses, however, four fetuses were included in group A and therefore were excluded from the analysis. In the 24 fetuses of group B, 37 transfusions were performed (Table 1).

Both fetal hemoglobin and middle cerebral artery peak systolic velocity were expressed as multiples of the median. These parameters follow a normal distribution.³ Paired t test was used to determine statistical comparison of the middle cerebral artery peak systolic velocity values before and after transfusion in the fetuses. The same test was used for the comparison of hemoglobin values before and after transfusion. A P value < .05 was considered statistically significant. In group B, we analyzed the first measurements obtained in the fetuses (n = 24) and the values reported in all the transfusions of the fetuses of this group (n = 37).

	RESULTS

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The data of the two groups are reported in Table 2. Middle cerebral artery peak systolic velocity values decreased and normalized after transfusion in all cases but one fetus of group B (P < .05). The difference was statistically significant. In the fetuses of group B, the difference was statistically significant either when we analyzed the first measurements in the 24 fetuses or the total number of transfusions.

View larger version (14K): [in this window] [in a new window]   Figure 1. The middle cerebral artery peak systolic velocity (MCA-PSV) values (cm/s) before and after the first intrauterine transfusion for correction of fetal anemia at different gestational ages (weeks) in fetuses of group A. The values are plotted on the reference range of MCA-PSV. The lines represent the mean and 95% prediction intervals ( = peak velocity before transfusion; = peak velocity after transfusion). Stefos. Fetal Anemia—Middle Cerebral Artery. Obstet Gynecol 2002.

View larger version (16K): [in this window] [in a new window]   Figure 2. The middle cerebral artery peak systolic velocity (MCA-PSV) values (cm/s) before and after transfusion for correction of fetal anemia at different gestational ages (weeks) in fetuses enrolled after the first transfusion (group B). The values are plotted on the reference range of MCA-PSV. The lines represent the mean and 95% prediction intervals ( = peak velocity before transfusion; = peak velocity after transfusion). Stefos. Fetal Anemia—Middle Cerebral Artery. Obstet Gynecol 2002.

	DISCUSSION

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In the current study, middle cerebral artery peak systolic velocity decreased after acute correction of anemia by intrauterine transfusion. Correction of fetal anemia decreases and normalizes the middle cerebral artery peak systolic velocity values both in fetuses never transfused and in fetuses previously transfused. It appears that our overall finding that intrauterine transfusion leads to a fall in fetal middle cerebral artery peak systolic velocity is valid despite the use of repeated measures on some of the fetuses.

To postulate an explanation for the decrease in blood velocity and normalization of it, one must examine the factors that may have contributed to these changes: heart rate, tissue oxygenation, and blood viscosity. Although fetal heart rate was not calculated in all the fetuses, several studies have not found a change in fetal heart rate after correction of anemia. Therefore, it would appear unlikely that the fetal heart rate could play a role in these changes. Another factor that could play an important role in the changes we observed is the tissue oxygenation. A low hemoglobin concentration is associated with tissue hypoxia and lactate production.⁹ The lower blood velocity observed after correction of anemia would suggest an increased cerebral impedance as a result of a higher oxygen concentration in the blood of these fetuses. Additionally, direct intravascular transfusion increases the blood viscosity. As a consequence of this phenomenon, the afterload increases and the stroke volume decreases.^10,11 This leads to a decrease in cardiac output. Therefore, the blood velocity would decrease after transfusion because of both an increased afterload caused by an increased blood viscosity, and an increased oxygen concentration in fetal blood.

The results of the current study strengthen previous findings of the correlation between the hemoglobin concentration and the middle cerebral artery peak systolic velocity. The measurement of middle cerebral artery peak systolic velocity value can contribute to decrease the number of unnecessary amniocenteses and funicenteses performed for diagnosing fetal anemia. Based on this assumption, the complications and the losses of the fetuses subjected to these invasive procedures could be decreased.

	COLLABORATIVE GROUP

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The data were obtained from the following centers of the collaborative group: Baylor College of Medicine, Houston, TX (Robert Carpenter, MD, Russell L. Deter, MD); King Faisal Hospital and Specialist Centre, Riyadh, Saudi Arabia (Feryal Rahman, MD); Klinik und Poliklinik fur Geburtshilfe, Universitatsspital, Zurich, Switzerland (Roland Zimmerman, MD); University Hospital for Women, Schanzeneckstrasse 1, Berne, Switzerland (Peter Duerig, MD); University of North Carolina, Chapel Hill, NC (Kenneth Moise, MD, Karen Dorman, RN); and University of Virginia Health System, Charlottesville, VA.

	Footnotes

 
The authors are indebted to Masashi Akiyama, MD, for his help with this manuscript.

PII S0029-7844(01)01724-0

Received June 25, 2001. Received in revised form October 9, 2001. Accepted October 18, 2001.

	REFERENCES

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1. Liley AW. Liquor amnii analysis in management of the pregnancy complicated by rhesus sensitization. Am J Obstet Gynecol 1961;82:1359–70.[Medline]

2. Daffos F, Cappella-Pavlovsky M, Forestier F. Fetal blood sampling during pregnancy with use of a needle guided by ultrasound: A study of 606 consecutive cases. Am J Obstet Gynecol 1985;153:655–60.[Medline]

3. Mari G, for the Collaborative Group for Doppler Assessment of Blood Velocity in Anemic Fetuses. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. N Engl J Med 2000; 342:9–14.[Abstract/Free Full Text]

4. Mari G, Adrignolo A, Abuhamad AZ, Pirhonen PY, Jones CD, Ludomirsky A, et al. Diagnosis of fetal anemia with Doppler ultrasound in the pregnancy complicated by maternal blood group immunization. Ultrasound Obstet Gynecol 1995;5:400–5.[Medline]

5. Mari G, Rahman F, Oloffson P, Ozcan T, Copel JA. Increase of fetal hematocrit decreases the middle cerebral artery peak systolic velocity in pregnancies complicated by rhesus alloimmunization. J Matern Fetal Med 1997;6: 206–8.[Medline]

6. Ludomirsky A, Weiner S, Ashamed GG, Librizzi RJ, Bolognese RJ. Percutaneous fetal umbilical blood sampling: Procedure safety and normal fetal hematologic indices. Am J Perinat 1988;5:264–6.[Medline]

7. Ghidini A, Sepulveda W, Lockwood CJ, Romero R. Complication of fetal blood sampling. Am J Obstet Gynecol 1993;168:1339–44.[Medline]

8. Detti L, Oz U, Guney I, Ferguson JE, Bahado-Singh R, Mari G. Doppler ultrasound velocimetry for timing the second transfusion in fetuses with anemia from red cell alloimmunization. Am J Obstet Gynecol 2001;185: 1048–51.[Medline]

9. Soothill PW, Nicolaides KH, Rodeck CH, Clewell WH, Lindrige J. Relationship of fetal hemoglobin and oxygen content to lactate concentration in Rh isoimmunized pregnancies. Obstet Gynecol 1987;69:268–71.[Abstract/Free Full Text]

10. Moise KJ Jr, Mari G, Fisher DJ, Huhta JC, Cano LE, Carpenter RJ Jr. Acute fetal hemodynamic alterations after intrauterine transfusion for treatment of severe red blood cell alloimmunization. Am J Obstet Gynecol 1990;163: 776–84.[Medline]

11. Fan FC, Chen RY, Schuessler GB, Chien S. Effects of hematocrit variations on regional hemodynamics and oxygen transport in the dog. Am J Physiol 1980;238:H545–52.

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