Conventional management of maternal red cell alloimmunization compared with management by Doppler assessment of middle cerebral artery peak systolic velocity

OBJECTIVE: This study was undertaken to compare management of red blood cell alloimmunization by Doppler measurement of middle cerebral artery peak systolic velocity (MCA-PSV) to conventional management with amniocentesis. STUDY DESIGN: A historical cohort of 28 fetuses at risk for anemia caused by red blood cell alloimmunization was followed between 1999 and 2002 at a single institution. The decision to perform percutaneous umbilical cord blood sampling (PUBS) was based on conventional management. MCA-PSV Doppler was measured before amniocentesis or PUBS but not used clinically. RESULTS: Twenty-eight fetuses were followed up: 4 had severe anemia, 1 had moderate anemia, 3 had mild anemia, and 20 were nonanemic. Conventional management had a sensitivity and positive predictive value for moderate-to-severe anemia of 80% and 44%, with a false-positive rate of 56%. In the same patients, MCA-PSV Doppler had a sensitivity and positive predictive value for moderate-to-severe anemia of 100% and 71%, with a false-positive rate of 28%. CONCLUSION: Compared with conventional management, MCA-PSV Doppler may have a better predictive accuracy for moderate-to-severe fetal anemia in red blood cell alloimmunization. Management by MCA-PSV Doppler may eliminate the need for amniocentesis and reduce the number of PUBS performed in red blood cell-alloimmunized pregnancies.     

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Objective.?To assess fetal middle cerebral artery (MCA) peak systolic velocity (PSV) in cases of rhesus alloimmunization and to establish whether MCA-PSV is valid for the prediction of fetal anemia.

Methods.?The study population included 157 pregnant women diagnosed with rhesus alloimmunization. MCA-PSV measurements were obtained within 3 days of blood sampling for estimation of hemoglobin concentration either at delivery or cordocentesis by the same operator and by means of the same ultrasound machine using techniques described previously. To evaluate the measurements of the MCA-PSV as the multiples of median (MoM) for gestation we used original nomograms for various gestational ages derived from a group of 273 normal fetuses between 22 and 40 weeks of gestation, not at risk for anemia. Receiver–operator characteristic (ROC) curves were employed to evaluate the relation of the sensitivity (the true positive rate) and the false positive rate (100% specificity) of different threshold values of the MCA-PSV.

Results.?The sensitivity of the MCA-PSV was 94.4% in the case of the subgroup of fetuses with severe anemia. The sensitivity of the MCA-PSV test decreased in less anemic fetuses and was 77.3% in the subgroup with moderate anemia and 32% in the subgroup with mild anemia. According to ROC curves, we selected the optimal MCA-PSV threshold values of 1.15, 1.44, and 1.53 MoM for the prediction of mild, moderate, and severe anemia, respectively.

Conclusions.?MCA-PSV is a significant Doppler index valid for the prediction of moderate and severe fetal anemia.     

Ultrasound assessment of the fetal middle cerebral artery peak systolic velocity: A comparison of the near-field versus far-field vessel

OBJECTIVE: Doppler assessment of the fetal middle cerebral artery peak systolic velocity may obviate the need for more invasive procedures in the alloimmunized patient. The purpose of this study was to compare middle cerebral artery peak systolic velocity measurements in the near field and far field. STUDY DESIGN: Patients between 16 and 42 weeks of gestation with normal fetuses were eligible (n=151). Peak systolic velocity measurements were obtained at the proximal portion of each middle cerebral artery at its origin in the internal carotid artery, as well as the most distal portion before its division, for a total of 4 measurements per fetus. Comparisons were made among the 4 locations and the data were analyzed using a mixed-model analysis of variance adjusted for gestational age. Results were presented using both P values and 95% CIs. P values <.05 were considered statistically significant. Where appropriate, P values and 95% CIs were adjusted using the Tukey multiple comparison procedure. A subanalysis was performed using 11 patients to assess interobserver reliability, which was calculated using the intraclass correlation coefficient (ICC). RESULTS: All four measurements were obtained for 120 fetuses (79%). The mean gestational age was 27.0 weeks. Statistically significant differences were noted between distal sites (95% CI, -0.05 to 0.01; P<.01) as well as the two sites on each vessel (95% CI, 0.03-0.07 and 0.07-0.12; P<.001 for both vessels). There was no significant difference between the two proximal locations (95% CI, -0.01 to 0.03; P=0.77). CONCLUSION: By which of the 2 vessels the fetal middle cerebral artery peak systolic velocity is affected is selected, as well as the location on the vessel. If the near-field proximal site cannot be interrogated, the far-field proximal site may be the best alternative.     

The usefulness of middle cerebral artery Doppler assessment in the treatment of the fetus at risk for anemia

The use of Doppler ultrasound evaluation to measure the peak systolic velocity of the fetal middle cerebral artery (MCA) has been a major breakthrough in the noninvasive detection of fetal anemia. An elevated peak MCA velocity of >1.5 multiples of the median is useful in the timing of the initial intrauterine transfusion (IUT) in the red cell-alloimmunized pregnancies. Data reported to date suggest that a threshold of 1.32 multiples of the median can be used to time the second IUT; the MCA Doppler evaluation does not appear sensitive for the timing of subsequent IUTs in these pregnancies. The peak MCA velocity has also proved useful in the detection of other anemic states that include Kell alloimmunization, fetal parvovirus infection, fetomaternal hemorrhage, alphathalassemia, and after-laser therapy for twin-twin transfusion.     

Prediction of fetal anemia by middle cerebral artery Doppler

ObjectivesTo assess the value of peak systolic velocity in the middle cerebral artery (MCA) in prediction of fetal anemia as a non invasive method in non hydropic fetuses.MethodsThe study included 30 pregnant women with non hydropic fetuses and with known red cell antibodies. Full ultrasound examination was done and peak velocity of systolic cerebral blood flow in MCA was measured. If severe anemia was suspected, fetal blood sampling by cordocentesis was performed.ResultsThirty fetuses were examined, 22 were anemic and eight had a hemoglobin value within a normal range. The mean MCA peak systolic velocity for fetus with the normal hemoglobin (Hb) was 48.98 ± 13.94 while that for the anemic fetus was 64.79 ± 11.97 and P = 0.004.Sensitivity of increased peak velocity of systolic blood flow in MCA for prediction of fetal anemia was 90.5% and specificity was 78.6%.ConclusionDoppler of peak velocity of systolic blood flow in MCA can be reliable in predicting anemia so delaying invasive methods until treatment (blood transfusion) is expected to be necessary.     

Prediction of fetal anemia by Doppler of the middle cerebral artery and descending thoracic aorta

BACKGROUND: Despite significant advances, perinatal hemolytic disease has not been eradicated and is still associated with significant morbidity and mortality, especially in developing countries. An accurate method for antenatal diagnosis and quantification of fetal anemia is a crucial step prior to the performance of invasive procedures, which are not risk-free. The middle cerebral artery peak systolic velocity (MCA-PSV) is currently the most popular non-invasive diagnostic method used to quantify fetal anemia and determine the exact timing for transfusion The combined use of MCA-PSV and descending thoracic aorta mean velocity (DTA-MV) has not been previously evaluated. Since this strategy has the potential to decrease false positive results it could reduce unnecessary cordocenteses, therefore minimizing fetal risks. This study aimed to evaluate the accuracy of MCA-PSV associated with DTA-MV in the prediction of fetal anemia. METHOD: Retrospective analysis of 90 cordocenteses performed on alloimmunized pregnancies in a single hospital MCA-PSV and DTA-MV were performed immediately before cordocentesis. The Dopplervelocimetry findings were compared with fetal hemoglobin concentration. Sensitivity, specificity, positive and negative predictive values and accuracy of MCA-PSV and DTA-MV in the prediction of moderate/severe fetal anemia were calculated. RESULTS: The individual sensitivity of MCA-PSV and DTA-MV was 100 and 95.7%, specificity was 65 and 100% and accuracy was 92.2 and 96.7%, respectively. The combination of both vessels produced a higher overall accuracy (98.6%). CONCLUSION: MCA-PSV is more sensitive and DTA-MV is more specific in the detection of fetal anemia. The highest diagnostic accuracy was obtained by the association of both Doppler evaluations.     

Middle cerebral artery Doppler and hemoglobin changes immediately following fetal transfusion

Objective: To determine the relationship between the change in middle cerebral artery peak systolic velocity (MCA-PSV) and the change in fetal Hemoglobin (Hb) immediately following intrauterine transfusion (IUT). Materials and methods: Study data included all IUTs performed for suspected fetal anemia from 2007–2011. Results: Sixty-eight IUTs were performed for 23 pregnancies, demonstrating a statistically significant MCA-PSV decrease for up to four IUTs. Significant correlations between changes in Hb levels and MCA-PSV were not detected. Conclusion: MCA-PSV values were highly variable in the immediate post-operative period and did not correlate with the Hb change.     

Fetal middle cerebral artery peak systolic velocity as a predictor of fetal anemia in unselected women giving birth at or near term

Objective

This study was performed to evaluate the application of fetal middle cerebral artery peak systolic velocity (MCA-PSV) for prediction of newborn anemia with umbilical cord blood hemoglobin concentration at birth (UCB-Hb) < 10.0 g/dL among infants born at gestational week (GW) ≥ 36 to unselected women.

Combined use of the cardiofemoral index and middle cerebral artery Doppler velocimetry for the prediction of fetal anemia

Objective

To assess the accuracy of the combined use of the cardiofemoral index (CFI) and the middle cerebral artery peak systolic velocity (MCA-PSV), converted to multiples of the median (MoM), as noninvasive means to detect severe fetal anemia.

Method

We measured CFI and MCA-PSV MoM in 37 fetuses just before their first (n = 37), second (n = 22), and third (n = 14) cordocenteses and transfusions. Then, using 2 different criteria for severe fetal anemia detection (Hb deficit ≥ 7 g/dL and hemoglobin level ≤ 0.55 of MoM), we assessed their hemoglobin status during cordocentesis and the accuracy of CFI and MCA-PVS was determined.

Results

At the first cordocentesis the mean hemoglobin level was 8.5 ± 3.6 g/dL and 15 fetuses (40.5%) had hydrops. In a total of 81 fetal evaluations, 58 (71.6%) of the CFIs and 34 (42.0%) of the MCA-PSV MoM measurements were abnormal. The result of one of these tests was abnormal in 65 evaluations (80.3%) and the results of both tests were abnormal in 27 evaluations (33.3%). All fetuses diagnosed as being severely anemic by at least one of the hemoglobin criteria during cordocentesis had an abnormal result by at least one of the noninvasive tests. Before the second and third transfusions, the combined use of the CFI and MCA-PSV MoM predicted severe fetal anemia with 100% sensitivity. When the CFI and MCA-PSV MoM measurements were normal, the negative likelihood ratio was zero.

Conclusion

When associated, CFI and MCA-PSV MoM were accurate predictors of severe fetal anemia.     

Polyhydramnios as a sole ultrasonographic finding for detecting fetal hemolytic anemia caused by anti-c alloimmunization

ObjectiveThe prenatal course of a rare case with fetal anemia caused by maternal anti-c alloimmunization was reported.Case reportA 39-year-old female with anti-c and anti-E antibodies against red cells had previously experienced a stillbirth. At her present pregnancy, titers of maternal antibodies and fetal middle cerebral artery peak systolic velocity (MCA-PSV) were frequently monitored to investigate the severity of fetal hemolytic anemia. Rather than manifesting as an increase in MCA-PSV, the anemic fetus was delivered at 32 weeks and one day of gestation with a sole presentation: polyhydramnios. Neonatal hospitalization course were compatible with hemolytic anemia. The baby was discharged at 48 days of age.ConclusionThis case illustrated the complexities of dealing with maternal red cell alloimmunization during pregnancy and the limitations of noninvasive diagnostic modalities for detecting fetal anemia, and highlighted that obstetricians should refer all available clinical parameters in order to offer appropriate perinatal care.     

Relationship between Cardiofemoral Index and the plasma concentration of brain natriuretic peptide in anemic fetuses associated with Rh alloimmunization

Background  Fetal anemia is a common result of alloimunization and is an important cause of fetal congestive heart failure resulting in heart dilation. Fetuses suspected of having heart failure present a higher Cardiofemoral Index and an increase in plasma BNP levels, because the cardiac hormonal system is activated by increased heart wall stretch due to increased left ventricular volume and pressure overload. Methods  Our group studied 33 pregnant women (22–31 weeks’ gestation at the first cordocentesis) referred for intrauterine fetal transfusion due to severe red blood cells isoimmunization. Up to 6 h prior to each cordocentesis, all fetuses were submitted to ultrasonography measurements where the Cardiofemoral Index was calculated. Samples of blood from the umbilical vein were collected for hemoglobin concentration and blood gas measurements. Plasma levels of BNP were determined with the use of plasma that had previously been frozen and thawed once. Plasma BNP was measured by radioimmunoassay. Pearson’s correlation test and regression analysis were used to determine the association between the plasma concentration of BNP and the Cardiofemoral Index of the anemic fetuses with RH alloimmunization. Results  Anemia was severe in 17 (50%) fetuses, mild in 9 (26.47%) and in 8 patients (23.53%) the fetuses were not anemic; hemoglobin ranged from 3.10 to 15.70 g/dl. The Cardiofemoral Index ranged from 0.43 to 0.87 and it was altered (≥0.59) in 23 fetuses. A significant positive correlation was observed between BNP plasma fetal concentration and Cardiofemoral Index (Pearson r = 0.61, P < 0.0001). Conclusions  These results suggest that fetal plasma concentration of BNP may increase in fetuses with heart dilation leading to a positive association between Cardiofemoral Index and plasma concentration of BNP. An erratum to this article can be found at     

A retrospective review of isoimmunized pregnancies managed by middle cerebral artery peak systolic velocity

OBJECTIVE: The purpose of this study was to determine the clinical outcome of isoimmunized pregnancies managed primarily by middle cerebral artery peak systolic velocity. STUDY DESIGN: A retrospective chart review was conducted of isoimmunized pregnancies that underwent ultrasound examinations from January 1, 2001, through May 1, 2003. Ultrasound reports, laboratory tests, and maternal and neonatal charts were reviewed. RESULTS: Women with a clinically significant red blood cell antibody and titer value were included. The study population consisted of 39 women (40 pregnancies, 42 fetuses). Patients with a middle cerebral artery peak systolic velocity of > or =1.5 MoM were offered amniocentesis. Seven pregnancies had an abnormal middle cerebral artery peak systolic velocity. Three of these infants had significant anemia. Six of the 7 pregnancies required an exchange transfusion. None of the 33 pregnancies (35 neonates) with normal middle cerebral artery peak systolic velocity measurements resulted in a neonate with significant anemia or severe hyperbilirubinemia. CONCLUSION: The clinical outcome of these pregnancies supports the use of middle cerebral artery peak systolic velocity measurements in the management of isoimmunized pregnancies.     

Cardiofemoral index as an ultrasound marker of fetal anemia in isoimmunized pregnancy.

OBJECTIVE: To test a new noninvasive ultrasound method for diagnosing fetal anemia in red blood cell isoimmunized pregnancies. METHODS: A diagnostic accuracy study was carried out to determine the cutoff point of an ultrasound measurement, the cardiofemoral index (CFI), calculated using the biventricular outer dimension (BVOD) and femur length to diagnosis severe anemia. The CFI measurement was performed before each of the 336 cordocenteses on 131 fetuses. Diagnosis test analysis and receiver-operating characteristics (ROC) curves were used and the area under the curve (AUC) was calculated to compare the overall accuracy of the CFI for anemia diagnosis, between fetuses with or without previous intrauterine transfusions (IUT). RESULTS: At first cordocentesis (n=131) the AUC was 0.75 (95% CI, 0.66-0.84). For cases where fetuses had undergone 1 previous transfusion (n=88) the AUC was 0.76 (95% CI, 0.64-0.88) and at the time of the third cordocentesis for IUT (n=53) it was 0.73 (95% CI, 0.59-0.86). For a 0.59 CFI threshold to diagnosis fetuses with hemoglobin deficit above 5 g/dL, sensitivity values were 87.2%, 88.0%, and 94.1% respectively for fetuses without IUT, with 1 IUT, and with 2 IUTs. Likelihood ratios for positive (LR+) and negative (LR-) test results were 1.98, 2.05, 1.69 and 0.23, 0.21, 0.13 respectively. CONCLUSION: The cardiofemoral index may be an effective noninvasive marker of severe fetal anemia in high-risk fetuses, with accuracy similar for fetuses either with or without previous transfusions.     

The value of middle cerebral artery peak systolic velocity in the diagnosis of fetal anemia after intrauterine death of one monochorionic twin

OBJECTIVE: The purpose of this study was to assess the value of the fetal middle cerebral artery peak systolic velocity in the prediction of anemia within 24 hours of the death of one monochorionic twin in twin-to-twin-transfusion syndrome and to establish the correlation between middle cerebral artery peak systolic velocity and hemoglobin concentration in fetuses who are at risk for acute anemia. STUDY DESIGN: Doppler examination of the middle cerebral artery peak systolic velocity was performed in 20 monochorionic survivors of pregnancies that were complicated by twin-to-twin-transfusion syndrome that occurred between 20 and 34 weeks of gestation. Doppler examination was performed before cordocentesis and after intrauterine transfusion when appropriate. Both hemoglobin concentration and middle cerebral artery peak systolic velocity were expressed in multiples of the median. Severe anemia was defined as hemoglobin concentration of <0.55 multiples of the median, and we used the cutoff point of 1.50 times the median values at any gestational age to calculate the sensitivity and specificity of middle cerebral artery peak systolic velocity in detecting moderate or severe anemia. RESULTS: Fetal anemia was confirmed in 10 of 20 fetuses. We performed seven intrauterine transfusions. The sensitivity and specificity of middle cerebral artery peak systolic velocity in the prediction of severe fetal anemia were of 90%, with a false-negative rate of 10%. The correlation between peak systolic velocity and hemoglobin concentration both before and after transfusion was evaluated by regression analysis and was strongly significant. CONCLUSION: In fetuses who are at risk of acute anemia, the measurement of middle cerebral artery peak systolic velocity was found to be a reliable noninvasive diagnostic tool and may be helpful in counseling and planning invasive assessment.     

Transcranial Doppler Findings of Cerebral Vasospasm in Preeclampsia

The objective of this study was to evaluate the effect of preeclampsia and its severity on maternal mean middle cerebral artery blood flow velocity (mean MCA-CBFV) using transcranial doppler sonography (TCD), as well as the effect of magnesium on mean MCA-CBFV in preeclampsia.

This study used a prospective, comparative design. TCD was used to examine maternal mean MCA-CBFV in both healthy subjects (controls) and preeclamptic subjects (cases). The two groups were similar in age, gestational age, and parity. Healthy subjects were categorized into three groups: Group I, 6–14 weeks, n = 10; Group 11, 24–40 weeks, n = 27; Group HI, postpartum n = 15, 12–36 h. Serial TCD examinations of the middle cerebral artery were completed in 21 preeclamptic subjects at four different points in time: Time I is an initial measurement before delivery; Time 2 is also before delivery but after magnesium had been administered; Time 3 is postpartum while on magnesium (12–24 h), Time 4 is postpartum off magnesium, (24–48 h).

Preeclamptic subjects had significantly increased mean MCA-CBFV when compared to healthy subjects: antepartum (mean 78.2 vs. 55.1 cm/sec, P < 0.0005); postpartum (mean 101.3 vs. 69.8 cm/sec, P < 0.0001). Severe preeclamptics had significantly higher mean MCA-CBFV than mild preeclamptics at each point in time: Time 1: P < 0.016; Time 2: P < 0.040; Time 3: P < 0.002; and Time 4: P < 0.028. These data support the theory that cerebral vasospasm of the smaller diameter vessels is a major component of preeclampsia.