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: email@example.com.
The authors are indebted to Masashi Akiyama, MD, for his help with this manuscript.
Received June 25, 2001. Received in revised form October 9, 2001. Accepted October 18, 2001.
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
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).
The middle cerebral artery peak systolic velocity was evaluated before and immediately after correction of anemia. The values were plotted over the reference range for gestational age previously reported.4 The middle cerebral artery peak systolic velocity was studied by Doppler ultrasonography as previously described.4 The angle between the ultrasound beam and the blood flow was close to 0 degrees, and the highest point of the waveform (peak systolic velocity) was measured. The hemoglobin levels were recorded before and after transfusion. Anemia was defined as mild, moderate, and severe according to criteria previously published.3
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).
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.
Figure 1 demonstrates the middle cerebral artery peak systolic velocity values of group A plotted over the reference range for gestational age. Sixty percent (ten of 17) of the values before transfusion were above the upper limits of the reference range. The values normalized after transfusion. In this group, ten fetuses had mild anemia, six severe, and in one case the anemia was moderate.
Figure 2 demonstrates the middle cerebral artery peak systolic velocity values of group B plotted over the reference range for gestational age. Thirty‐eight percent (14 of 37) of the values before transfusion were above the upper limit of the reference range. After correction of anemia, only one value remained above the upper limit of the reference range. In this group, 15 fetuses were mildly anemic, six severely anemic, and three moderately anemic.
Amniocentesis and funicentesis are invasive procedures associated with several potential complications.6,7 The fetal middle cerebral artery peak systolic velocity is a noninvasive tool that may be an alternative to these invasive procedures for diagnosing fetal anemia. It diagnoses moderate and severe anemia in fetuses never transfused with a sensitivity of 100% at a false positive rate of 12%.3 It can also be used for timing the need of the second transfusion.8 One of the limitations of the middle cerebral artery peak systolic velocity is that it diagnoses mild anemia with a sensitivity of 83%.3 This is the reason why several values in anemic fetuses were within the reference range in the two groups of fetuses.
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.
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.
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