Maternal Red Cell Alloimmunization Research Articles

Hemoglobin Electrophoresis versus Kleihauer Betke to Determine Bone Marrow Suppression in Fetuses Undergoing Intrauterine Transfusion.

Mainstay therapy for fetuses affected by maternal red cell alloimmunization is serial IUT (intrauterine transfusion). Testing to determine when fetal red cells have been replaced with donor cells historically involves the use of the KB (Kleihauer-Betke) test. Hgb (Hemoglobin) electrophoresis testing may be more rapid with a reduced cost of analysis. We aimed to determine the correlation between fetal Hgb electrophoresis versus the traditional KB test. This is a retrospective analysis on all alloimmunized singleton pregnancies undergoing IUT between 1/1/2021 and 7/1/2023. Maternal and fetal characteristics were collected along with indication for IUT. A final fetal blood sample was obtained at the conclusion of each transfusion and sent for KB testing and Hgb electrophoresis. The primary outcome was the assessment of these parameters in their ability to predict replacement of the fetal circulating red cell population with donor cells. Linear regression analysis and repeated measures analysis of variance were performed, P values less than 0.05 were considered significant. A total of 56 IUTs were performed in 16 patients. There were 39 (69.6%) final KB test values collected and compared to 30 (53.6%) final Hgb electrophoresis values. Hgb electrophoresis when compared to the KB test demonstrated a significant correlation (R2 = 0.93; 95% confidence interval, 0.61-0.76; P <0.001). This same finding held true when examining correlation at each individual IUT as well. The final KB test and Hgb electrophoresis value significantly decreased with each transfusion (P=0.003). A predominance of adult donor blood was noted by the third transfusion for both laboratory indices. Fetal Hgb electrophoresis obtained at the time of IUT demonstrates a significant correlation with the traditional KB test.

Magnitude of Red Blood Cell Alloimmunization Among Pregnant Women Attending Antenatal Care at Wolaita Sodo University Comprehensive Specialized Hospital, Southwest Ethiopia.

Maternal red cell alloimmunization occurs when a woman's immune system becomes sensitive to unfamiliar red blood cell antigens. This leads to the production of alloantibodies, which can have serious implications for the fetus and newborn. However, there is a lack of comprehensive information about the extent of red cell alloimmunization in underdeveloped countries like Ethiopia. Therefore, this study aimed to determine the magnitude of red cell alloimmunization among pregnant women attending antenatal care at Wolaita Sodo University Comprehensive Specialized Hospital from September 01 to November 30, 2022. In this institutional-based cross-sectional study, 422 pregnant women were participated and recruited using a systematic random sampling technique. Data on sociodemographic characteristics, obstetric history, and other clinical information were collected using structured questionnaires through face-to-face interview. Blood grouping and indirect antihuman globulin tests were performed. The relationship between red cell alloimmunization and the independent variables was determined using the chi-square test. P-value <0.05 was considered statistical significance. In this study, the blood group distributions among the participants were as follows: O, 177 (41.9%); A, 124 (29.4%); B, 76 (18%); and AB, 45 (3.86%). Among the pregnant women included in the study, a total of 51 (12.08%) were identified as RhD-negative. Out of these RhD-negative women, 5 (9.8%) were found to have developed alloimmunization with red blood cell antigens. Miscarriage and post-partum hemorrhage were found to be important factors associated with the occurrence of red cell alloimmunization in these women. This study showed that one out of ten pregnant women was alloimmunized. Therefore, antenatal blood grouping and indirect antihuman globulin screening should be performed routinely to manage and minimize the undesirable outcomes of alloimmunization during pregnancy.

Alloimmunization to Rh Antigen (D, C, E, C, E) Among Pregnant Women Attending Antenatal Care in South Western Uganda.

Maternal red cell alloimmunization to Rh antigen in pregnant women occurs when the immune system is sensitized by foreign red blood cell surface antigens, in this case fetal red blood cells, inducing an immune response. Various antigens of blood group systems may cause alloimmunization, especially the Rh, Kel, Fy, JK, and MNS systems. This study aimed to determine alloimmunization to the different frequencies of Rh antigen among pregnant women in South Western Uganda. A total of 1369 pregnant women consented and were recruited into a cross-sectional study during their regular antenatal visits during the period August 2020 to July 2021. Samples (4 mL) of anticoagulated and coagulated blood were obtained, and Rh blood grouping including Rh antigen and the indirect antiglobulin test (IAT) was carried out using the agglutination technology of the LISS ID-Card technique in the Ortho Biovue ID-Micro Typing System. Out of 1369 participants recruited to the study, 78 (5.7%) were D-, 1291 were D+, and 134 (9.8%) had alloantibodies. Among those with alloantibodies, 115 (85.8%) were D+ and 19 (14.2%) D-. The percentage alloimmunization according to the Rh antigens was highest in e (9.72%), c (2.48%), C (2.34%) and E (0.94%) antigens. With the ABO system, alloimmunization was highest in blood group B (10.7%), followed by A (10.6%), O (9.2%) and then AB (7.1%). Alloimmunization was more prevalent in D- (24%) than in D+ participants (8.9%). Rhesus antigen e was the most prevalent antigen (99.8%), followed by c. The alloimmunization rate of 9.8% among these participants is high, and appears in both D+ and D- women. The other Rhesus antigens are seen to cause alloimmunization, with antigen e causing the highest prevalence. In conclusion, there is a need to identify antibodies and study the outcome for clinical significance, especially in D+ women, to facilitate proper pregnancy management.

Immunomodulation for early-onset haemolytic disease of the fetus/newborn: Can we delay the need for intrauterine transfusions?

When cases of severe fetal anaemia due to maternal red-cell alloimmunization present in the early second trimester, standard treatment with intrauterine transfusion often results in fetal loss. The report by Vlachodimitropoulou et al. offers new insight into the use of maternal intravenous immune globulin to delay the need for intrauterine transfusion. Performing these procedures at a later gestational age increases the likelihood of technical success and subsequent perinatal survival. Commentary on: Vlachodimitropoulou et al. Intravenous immune globulin in the management of severe early onset of red cell alloimmunization. Br J Haematol 2023; 200:97-103.

Confirmatory Middle Cerebral Artery Doppler Testing in Alloimmunized Patients with Suspected Fetal Anemia.

This article aimed to evaluate pregnancy outcomes when a plan to perform fetal blood sampling (FBS) or delivery was based solely on the first abnormal middle cerebral artery peak velocity (MCA-PV) measurement compared with making a plan after a confirmatory test on a subsequent day. We performed a descriptive study of pregnancy outcomes including all patients in a single healthcare system with maternal red cell alloimmunization undergoing ultrasound between 2005 and 2017 who had at least one MCA-PV>1.5 multiples of the median (MoM). We excluded patients with any sign of hydrops prior to the index visit or abnormal MCA-PV at>35 weeks. The first exam with a MCA-PV>1.5 MoM was deemed the index visit. Fifty patients were identified. Twenty-one patients underwent intervention (FBS or delivery) based on the first abnormal MCA-PV. Of those, 9 had moderate or severe anemia (positive predictive value [PPV]: 43%), while 12 had mild or no anemia. The other 29 patients underwent a confirmatory MCA test between 2 and 8 days later. Of these, 13 patients had an abnormal confirmatory test and 11 of these underwent FBS and 7 had moderate or severe anemia (PPV: 54%). Sixteen patients undergoing confirmatory MCA Doppler had a normal test on repeat and did not undergo FBS. Of those, none developed moderate or severe anemia. A substantial number of patients (55%) had normal MCA-PV testing on repeat, allowing avoidance of invasive testing. Deferring FBS until the abnormal MCA-PV was confirmed was not associated with undetected moderate or severe anemia. · False-positive results from MCA-PV Doppler prediction of fetal anemia are common.. · Repeat noninvasive testing is normal in many patients with suspected fetal anemia.. · Invasive fetal testing can often be safely avoided by performing a confirmatory Doppler exam ination..

1110 Predictive value of elevated MCA doppler in patients with alloimmunization

To evaluate pregnancy outcomes after abnormal middle cerebral artery peak systolic value (MCA PSV) measurement managed with percutaneous umbilical blood sampling (PUBS) or delivery as compared to repeat MCA PSV within 7 days. We performed a descriptive study including all patients in a single tertiary care center between 2006 and 2016 with a MCA PSV > 1.5 multiples of the median (MoM) in the setting of maternal red cell alloimmunization. The index visit was the first exam with MCA PSV > 1.5 MoM. We excluded cases with fetal hydrops prior to the index visit or abnormal MCA PSV at > 35 weeks. Patients undergoing immediate intervention (PUBS or delivery) (group 1) were compared to patients with repeat MCA PSV performed within 7 days (group 2). All scans were interpreted by board-certified Maternal-Fetal Medicine physicians. Fifty patients were identified. 19 underwent intervention based on the first abnormal MCA PSV (group 1) and 31 underwent repeat MCA PSV (group 2). The gestational ages (GA) or MCA PSV at index exam did not vary between the groups (table 1). Fetal red blood cell genotypes were infrequently known in this population. MCA PSV values at index exam were not different regardless of anemia severity (none, mild, moderate /severe). In group 1, 14/19 (74%) had anemia, with 8/19 (42%) having moderate/severe anemia (Figure 1). In group 2, 11/31 patients underwent PUBS for a persistently abnormal MCA PSV, all of whom had anemia which was moderate/severe in 7/11 (64%). Of the remaining 20 patients (65%) in group 2, 19/20 (95%) never underwent PUBS or developed moderate/severe anemia. One fetus had an abnormal MCA PSV 13 days after the index and was transfused for severe anemia. Of patients who underwent repeat MCA PSV testing rather than immediate intervention, 65% had normal repeat MCA PSVs and safely avoided PUBS. Persistently elevated MCA PSVs were more predictive of anemia than single elevated values preceding intervention. Other factors contributing to the decision to immediately pursue intervention should be further evaluated.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Distribution of maternal red cell antibodies and the risk of severe alloimmune haemolytic disease of the foetus in a Chinese population: a cohort study on prenatal management

BackgroundHaemolytic disease of the foetus and newborn (HDFN) is the most common aetiology of haemolytic anaemia and hyperbilirubinaemia in foetuses and neonates. Studies on the distribution of antibodies that cause haemolytic disease of the foetus (HDF) in China are limited, and the effects of multiple antibodies on the severity of HDF need further evaluation.MethodsAn observational cohort study from January 2005 to December 2019 was conducted in two hospitals affiliated with Sun Yat-sen University. Maternal red cell alloimmunization was identified by the Guangzhou Blood Centre. In total, 268 pregnant woman-foetus pairs were divided into four groups according to the type of maternal alloantibodies: anti-D, anti-D combined with other antibodies, other single-antibody and other multiple antibodies. The obstetric history, antibody characteristics, incidence of severe HDF and foetal outcomes were collected and compared. Logistic regression analysis of the risk factors for HDF and survival analysis of the severe HDF-free interval were conducted.ResultsAnti-D was the most common cause of HDF, followed by anti-M. No anti-K- or isolated anti-c-associated HDF was found. The incidence of severe HDF was higher in the group with anti-D combined with other antibodies than in the group with anti-D alone (P = 0.025), but no significant difference was found in haemoglobin level and reticulocyte count in the anaemic foetuses between these two groups. Foetuses in the other single-antibody group had a lower reticulocyte count (P = 0.007), more IUTs (P = 0.007) and an earlier onset of severe HDF (P = 0.012). The maximum antibody titre was significantly lower in the other single-antibody group than in the anti-D group (P < 0.001). A high maternal antibody titre (P < 0.001), multiple affected pregnancies (P < 0.001) and other single-antibody (P = 0.042) were independent risk factors for HDF. A higher reticulocyte count (P = 0.041) was an independent risk factor for severe HDF in anaemia foetuses affected by Rh(D) alloimmunization.ConclusionsThe distribution of HDF-associated antibodies in China is different from that in Western countries. Other single non-Rh(D) antibodies could increase the risk of HDF, and anti-D combined with other antibodies would not influence the severity of foetal anaemia compared with anti-D alone.

Red cell alloimmunization: A 2020 update.

Management of maternal red cell alloimmunization has been revolutionized over the last 60 years. Advances in the prevention, screening, diagnosis, and treatment of alloimmune-induced fetal anemia make this condition an exemplar for contemporary practice in fetal therapy. Since survival is now an expectation, attention has turned to optimization of long-term outcomes following an alloimmunized pregnancy. In this review, the current management of red cell alloimmunization is described. Current research and future directions are discussed with particular emphasis on later life outcomes after alloimmune fetal anemia.

Management of severe fetal anemia by Doppler measurement of middle cerebral artery: are there other benefits than reducing invasive procedures?

ObjectiveDoppler measurement of peak velocity of systolic blood flow in the middle cerebral artery (PVS-MCA) can safely replace invasive testing in the diagnosis of fetal anemia in Rh-alloimmunized pregnancies and PSV-MCA is now the reference technique. However, no study has evaluated its impact in antenatal care and in survival rate. Our objective was to evaluate the impact of the measurement of PVS-MCA in antenatal management and neonatal outcome in maternal red cell alloimmunization requiring in utero transfusion (IUT). Study designRetrospective study between January 1999 and January 2013. We excluded all cases of hydrops without follow-up before first IUT. From 1999 to 2006, an IUT was indicated on the optical index at 450nm (Period 1) and was then replaced by the use of PVS-MCA (Period 2). Results77 patients were included, 39 in Period 1 (104 IUT) and 38 in Period 2 (89 IUT). 5 cases of hydrops fetalis (12.8%) were diagnosed during the follow up in Period 1 and none during Period 2. The average number of IUT, the delays between 2 IUT and between last IUET and birth were comparable. The total rate of complication per IUT during the first period was 9.6% vs 1.1% during the second one (p=0.01). The overall survival rate in our population was 34/39 (86.8%) during Period 1 vs 38/38 (100%) during Period 2. ConclusionPSV-ACM allowed an improved monitoring with fewer occurrences of hydrops. Conversely, it did not modify antenatal management and timing of delivery.

The risk assessment study for hemolytic disease of the fetus and newborn in a University Hospital in Turkey

Maternal red-cell alloimmunization occurs when a woman’s immune system is sensitized to foreign red-blood cell surface antigens, leading to the production of alloantibodies. The resulting antibodies often cross the placenta during pregnancies in sensitized women and, if the fetus is positive for red-blood-cell surface antigens, this will lead to hemolysis of fetal red-blood cells and anemia. The most severe cases of hemolytic disease in the fetus and newborn baby are caused by anti-D, anti-c, anti-E and anti-K antibodies. There are limited data available on immunization rates in pregnant women from Turkey. The aim of the present study was to provide data on the frequency and nature of maternal RBC alloimmunization in pregnant women in a tertiary care hospital. In this study, we retrospectively evaluated the indirect antiglobulin test results of Rh-negative pregnant women performed in our Blood Bank between 2006 and 2012. Indirect antiglobulin test positive women also underwent confirmatory antibody screening and identification. During the study period, 4840 women admitted to our antenatal clinics. With regards to the major blood group systems (ABO and Rh), the most common phenotype was O positive (38.67%). There were 4097 D-antigen-positive women (84.65%) and 743 women with D-antigen-negative phenotype (15.35%). The prevalence of alloimmunization was found to be 8.74% in D-antigen negative group. Despite prophylactic use of Rh immunglobulins, anti-D is still a common antibody identified as the major cause of alloimmunization in our study (anti-D antibody 68.57%, non-D antibody 31.42%). While alloimmunization rate to D antigen was 6.46%, non-D alloimmunization rate was 2.69% among Rh-negative pregnant women. Moreover, detailed identification facilities for antibodies other than anti-D are not available in most of centers across Turkey. However, large-scale studies on pregnant women need to be done in order to collect sufficient evidence to formulate guidelines and to define indications for alloantibody screening and identification.

ISUOG Practice Guidelines: use of Doppler ultrasonography in obstetrics

<scp>ISUOG</scp> Practice Guidelines: use of Doppler ultrasonography in obstetrics

Doppler assessment of middle cerebral artery peak systolic velocity in maternal red-cell alloimmunization

Doppler assessment of middle cerebral artery peak systolic velocity in maternal red-cell alloimmunization

441: Intravenous immunoglobulin for the treatment of severe maternal red cell alloimmunization

441: Intravenous immunoglobulin for the treatment of severe maternal red cell alloimmunization

Combined plasmapheresis and intravenous immune globulin for the treatment of severe maternal red cell alloimmunization

The objective of the study was to report the maternal and perinatal outcome in patients with severe red cell alloimmunization in pregnancy who were treated with immunomodulation therapy. This was a retrospective multicenter case series. Patients with a history of early second-trimester fetal loss secondary to severe maternal red cell alloimmunization or patients with markedly elevated maternal antired cell titers felt to be consistent with poor fetal outcome were offered treatment. Therapy consisted of serial plasmapheresis followed by weekly infusions of intravenous immune globulin (IVIG). Maternal titers were measured before and after plasmapheresis. Pregnant patients with either a history of a previous perinatal loss (n = 7) or markedly elevated maternal antibody titers (n = 2) were treated with combined plasmapheresis and IVIG. All 9 fetuses subsequently required intrauterine transfusions (median 4; range 3-8). All infants survived with a mean gestational age at delivery of 34 weeks (range 26-38 weeks). Maternal antired cell titers were significantly reduced after plasmapheresis (P < .01) and remained decreased during IVIG therapy. Serial peak middle cerebral artery velocities remained below the threshold for moderate to severe fetal anemia during therapy. Combined immunomodulation with plasmapheresis and IVIG represents a successful approach to the treatment of severe maternal red cell alloimmunization.

High additional maternal red cell alloimmunization after Rhesus- and K-matched intrauterine intravascular transfusions for hemolytic disease of the fetus

Intrauterine transfusion (IUT) is a life-saving therapy for the severely anemic fetus with hemolytic disease. However, maternal additional antibody formation is a complication of the procedure. In this study, we determined antibody formation after introduction of preventive Rh-D, -C, -c, -E, and -e and K matching of IUT donors. This was a retrospective follow-up study. During an 11-year period, 686 Rhesus- and K-matched IUTs were performed in 233 pregnancies and in 95% (652/686) posttransfusion antibody testing was performed after a median interval of 21 days. Twenty-five percent (53/212) of the women formed 64 new antibodies and, compared to our previous study, this incidence was not decreased by the use of Rhesus- and K-matched donors. After delivery, 72% (153/212) of the women had multiple RBC antibodies. Additional antibodies were in 48% (31/64) directed against Rhesus and K antigens, induced by the fetus, or as natural antibodies. In 52% (33/64) the antibodies were directed against non-Rhesus and -K antigens and in 65% (11/17) of eligible cases the IUT donor and not the fetus expressed the corresponding antigen(s). Despite Rhesus- and K-matching, women treated with IUTs still show strikingly broad red cell alloimmunization. More extensive IUT donor red cell matching, including FY, JK, and S antigens, to reduce the formation of new red cell antibodies should be explored.

An Audit of Outcome in Intravascular Transfusions Using the Intrahepatic Portion of the Fetal Umbilical Vein Compared to Cordocentesis

Introduction: Maternal red cell alloimmunization is a potential cause of perinatal morbidity and mortality. The outcome of severe disease has been transformed by the use of in-utero and particularly, fetal intravascular transfusion. In the majority of instances this is performed by cordocentesis. However, this cohort study represents the experience in a large tertiary referral centre in performing fetal intravascular transfusions via the intrahepatic vein (IHV). Methods: Over an 8-year period, 1997–2004, 221 in-utero transfusions (IUT) were performed for rhesus disease in 66 pregnancies. 86% had severe fetal anaemia caused by anti-D, 10.6% by anti-Kell and 3.4% by anti-c. The median maternal age of the cohort was 31 years (range 19–43). The median gestation at initial IUT was 25 weeks (interquartile range (IQR) 23–29 weeks). Results: A median number of three IUT were performed in each fetus (IQR 2–5) with a median haemoglobin at first fetal blood sampling of 7.3 g% (IQR 4.6–8.8 g%) (73% ≤5 SD and 27% ≤2 SD). Of the total intravascular transfusions, 170 were performed via the IHV (71.7%), 33 via cordocentesis (13.9%) and 1 by intracardiac puncture (0.5%). There were ‘transient’ bradycardias complicating 4.1% of all transfusions and amniorrhexis following 1.4%. 92% of babies were live born at a median gestation of 34 weeks (range 21–38) with a birth weight centile of 50 (range 3–90). There was no significant difference in intravascular transfusion complication rate when the procedure was performed via the IHV (7.6%) as compared to cord root puncture (3.0%) (Fisher’s exact test, p < 0.47). Conclusion: IUT performed by fetal IHV puncture is safe and carries no excess morbidity when performed for severe rhesus disease.

Correlation between middle cerebral artery peak systolic velocity and fetal hemoglobin after 2 previous intrauterine transfusions

The middle cerebral artery peak systolic velocity (MCA-PSV) has been successfully used for timing the first 2 transfusions in fetuses at risk for anemia because of maternal red cell alloimmunization. The objective of this study was to assess whether the correlation between the MCA-PSV and fetal hemoglobin is maintained in fetuses that had undergone 2 previous intrauterine transfusions. Doppler measurement of MCA-PSV was performed before cordocentesis in 39 fetuses. The timing of the third transfusion was based on traditional criteria. The values of MCA-PSV and hemoglobin were expressed as multiples of the median (MoM). Anemia was defined as mild (hemoglobin <0.84 MoM for a given gestational age, moderate (hemoglobin <0.65 MoM), and severe (hemoglobin <0.55 MoM). Regression analysis was used to assess the correlation between the MCA-PSV MoM and fetal hemoglobin MoM. Gestational age at Doppler study ranged from 22 to 35 weeks. Six fetuses (15%) had normal hemoglobin concentration; 21 (53%) had mild anemia; 7 (20%) had moderate anemia; and 5 (12%) had severe anemia. There was a linear correlation between fetal hemoglobin (y) and the MCA-PSV (x): y = 1.185 - 0.341x. Previously, concerns have been expressed about the accuracy of Doppler prediction of anemia after previous transfusions. Our data suggest that there is a good correlation between the MCA-PSV and fetal hemoglobin in fetuses that have undergone 2 previous transfusions. Our findings expand the clinical situation in which Doppler can be used to monitor red cell alloimmunized pregnancies.

Complications of intrauterine intravascular transfusion for fetal anemia due to maternal red-cell alloimmunization

The purpose of this study was to establish the true procedure-related complication rate of intrauterine transfusion therapy. A cohort study of 254 fetuses treated with 740 intrauterine blood transfusions for red-cell alloimmunization in a single center in the years 1988 to 2001. Our database was searched for perinatal deaths, emergency deliveries, infections, and preterm rupture of membranes associated with intrauterine blood transfusion. Complications were categorized by two independent obstetricians as procedure-related (PR) or not procedure-related (NPR). Logistic regression analysis was used to identify risk factors for complications. Overall survival was 225/254 (89%). Fetal death occurred in 19 cases (7 PR) and neonatal death in 10 cases (5 PR). There were two cases of intrauterine infection with Escherichia coli (both PR) and two other cases of preterm premature rupture of membranes (1 PR) within a week of a procedure. Emergency delivery after a transfusion was performed in 18 pregnancies (15 PR). The total PR complication rate was 3.1%, resulting in an overall PR loss rate of 1.6% per procedure. Arterial puncture, transamniotic cord puncture, refraining from fetal paralysis, and advancing gestational age were associated with the occurrence of PR complications. Our study shows that intrauterine transfusion is a safe procedure, with a relatively low PR perinatal loss rate. Arterial puncture and transamniotic cord needling carry a high risk for serious complications, whereas fetal paralysis improves the safety of the procedure. This information on risks of intrauterine transfusion therapy may help to further improve the safety of intrauterine transfusions. Data on complication rates of intrauterine transfusions are essential in counseling patients.

Doppler ultrasonography for timing the third transfusion in fetal anemia from red cell alloimmunization

ANEMIA FROM RED CELL ALLOIMMUNIZATION GIANCARLO MARI, ROLAND ZIMMERMANN, MARIA SEGATA, Wayne State University, Obstetrics & Gynecology, Detroit, Michigan, University Hospital of Zurich, Obstetrics and Gynecology, Zurich, Switzerland, UC, Ob/Gyn, Cincinnati, Ohio OBJECTIVE: The middle cerebral artery peak systolic velocity (MCA-PSV) has been successfully used for timing the first two transfusions in fetuses at risk for anemia because of maternal red cell alloimmunization. The objective of this study was to assess whether the correlation between the MCA-PSV and fetal hemoglobin is maintained in fetuses that had undergone two prior transfusions. STUDY DESIGN: Doppler measurement of MCA-PSV was performed before cordocentesis in 39 fetuses. The timing of the third transfusion was based on traditional criteria. The values of MCA-PSV and hemoglobin were expressed as multiples of the median (MoM). Anemia was defined as mild (hemoglobin !0.84 MoM for a given gestational age, moderate (hemoglobin !0.65 MoM), and severe (hemoglobin !0.55 MoM). Regression analysis was used to assess the correlation between the MCA-PSV and fetal hemoglobin. RESULTS: Gestational age at Doppler study ranged from 22 to 35 weeks. Six fetuses (15%) had normal hemoglobin concentration; 21 (53%) had mild anemia; 7 (20%) had moderate anemia; and 5 (12%) had severe anemia. There was a linear correlation between the MCA-PSV and fetal hemoglobin (R = .60) (P ! .05). CONCLUSION: Previously, concerns have been expressed about the accuracy of Doppler prediction of anemia after two prior transfusions. Our data suggests that there is a good correlation between the MCA-PSV and fetal hemoglobin in fetuses that have undergone two prior transfusions. Our findings expand the clinical situation in which Doppler can be used to monitor red cell alloimmunized pregnancies. 526 MIDDLE CEREBRAL ARTERY PEAK VELOCITY: ACCURACY AND RELIABILITY REBECCA PONDER, MICHAEL ESPLIN, ROBERT SILVER, YVETTE LACOURSIERE, JANICE BYRNE, University of Utah, Obstetrics and Gynecology, Salt Lake City, Utah, University of Utah, Department of OB/GYN, Salt Lake City, Utah OBJECTIVE: Peak systolic velocity of the fetal middle cerebral artery (MCA) has been used to identify fetal anemia in ‘‘at risk’’ pregnancies. Excellent accuracy has been reported in tertiary care centers with experienced sonographers and rigorous protocols. However, it is unclear if the test performs as well under less controlled circumstances. Our objectives were (1) to assess the accuracy of MCA peak velocity for the prediction of fetal anemia in patients at risk for red cell immunization, and (2) to assess the interand intra-observer variability of MCA peak velocity. STUDY DESIGN: (1) Retrospective cohort of women with red cell alloimmunization undergoing MCA doppler studies from 2000-2004. (2) Serial MCA Doppler studies were performed by 8 experienced sonographers without specific training in MCA doppler velocimetry in 4 uncomplicated pregnancies between 24-28 weeks gestation. Adequacy of studies was assessed by a blinded single investigator. RESULTS: 26 women at risk for red cell alloimmunization had 151doppler studies. 130/130 (100%) studies correctly predicted non-anemic fetuses. However, 10/21 (47%) studies indicating severe fetal anemia occurred in non-anemic fetuses (false positive rate: 47%). In the observer variability arm, 78 /108 (72%) studies were adequate. Interclass correlation coefficient (ICC) revealed no significant correlation between values obtained by practitioners on any individual subject, demonstrating poor reliability. CONCLUSION: Our false positive rate of 47% is substantially higher than previously reported and variability among practitioners was considerable. Published accuracy for MCA doppler may not be applicable to less experienced centers. While MCA doppler remains a good screening tool with a low false negative rate, the ‘‘positive’’ diagnosis of fetal anemia should be confirmed in non-hydropic cases. Specialized training, standardization, and quality assurance may improve accuracy of MCA Doppler for the detection of fetal anemia.

Doppler Ultrasonography in Assessment of Fetal Well-being

After completing this article, readers should be able to: 1. Describe the calculations used to measure fetal systemic and placental vascular impedance in the umbilical artery via Doppler ultrasonography. 2. Delineate the two primary uses of measurement of middle cerebral artery flow velocity. 3. List the fetal conditions in which Doppler flow velocity has been studied. The Doppler principle, discovered by Johann Christian Andreas Doppler in 1842, (1) was used initially in astronomy and later in the military, in various branches of industry, and more recently in medicine. Doppler shift is based on the perceived change in frequency of an energy waveform as the source and the receiver move toward or away from each other. The Doppler shift principle applies to light waves as well as sound waves. In biology, Doppler ultrasonography is used noninvasively, primarily to measure flow velocity in blood vessels. Flow velocity depends on the volume and speed of effluent relative to the diameter of the vessel. Estimating fetal vascular resistance through study of Doppler flow velocity provides a means to assess, albeit indirectly, fetal physiology and pathology. Johnson and colleagues (2) in 1965, made the earliest mention of the use of Doppler effect in obstetrics. The use of Doppler ultrasonography to investigate the pattern of waveforms in the umbilical artery during pregnancy initially was reported in 1977 by Fitzgerald and Drumm. (3) Subsequently, Wladimiroff and associates (4) reported on Doppler assessment of cerebral blood flow in the human fetus. The addition of color mapping has enhanced the utility of the Doppler effect in sonographic assessment of the fetus. The fetal umbilical artery (UA) and middle cerebral artery (MCA) have evolved as the primary targets of fetal Doppler studies (Figs. 1 and 2). Figure 1. Color Doppler view of circle of Willis. Arrows show anterior (ACA), middle (MCA), and posterior cerebral …