Cause Of Fetal Anemia Research Articles

A case of fetal parvovirus b19 myocarditis that caused terminal heart failure.

Parvovirus B19 is a well-established cause of fetal anemia and nonimmune fetal hydrops in pregnancy. Fetal parvovirus infection can cause severe destruction of erythroid progenitor cells, resulting in fetal anemia, hydrops, and intrauterine death. However, viral myocarditis with subsequent heart failure is another possible mechanism for hydrops formation as viral infection of fetal myocardial cells has been reported in postmortem examinations. We herein report a case of fetal cardiomegaly and massive pericardial effusion secondary to myocarditis as a result of parvovirus B19 infection. The case developed hydrops as consequence of severe anemia and experienced terminal heart failure, which led to the fetus dying an intrauterine death at 22 weeks of gestation. This case demonstrates that there may be an association between myocarditis caused by intrauterine parvovirus B19 infection and a poor outcome. The presence of viral myocarditis may be the determining prognostic factor in that situation.

Severe hemolytic disease of the fetus due to anti-Kpa antibody

Introduction: Anti-Kpa antibodies are an uncommon cause of hemolytic disease of the fetus and newborn (HDFN). Screening for antibodies to low frequency antigens such as Kpa is not routine, so detecting them can present a challenge. Case Report: We report a case of hydropic HDFN due to anti-Kpa antibodies discovered incidentally with direct antiglobulin testing of a fetal blood sample in the course of work-up and treatment for presumed acute parvovirus B19 induced hydrops fetalis. Six intrauterine red blood cell transfusions and one simple neonatal red blood cell transfusion were required. Conclusion: The cause of fetal anemia needs to be properly diagnosed in order to provide appropriate clinical care in affected pregnancies. Sensitization from uncommon antigens is more difficult to diagnose due to the lack of routine screening. This case illustrates the importance of performing direct antiglobulin testing on fetal blood before intrauterine transfusion in any case of fetal anemia despite presumed alternative etiologies.

A Study of Fetal Middle Cerebral Artery Peak Systolic Velocity to Diagnose Fetal Anemia in Rural Obstetric Population

ABSTRACTGlobally, fetal middle cerebral artery peak systolic velocity (MCA-PSV) is used for noninvasive diagnosis of fetal anemia. Although, incidence of anemia is common in rural setup, scientific studies describing utilization of this modality are lacking. This study throws light on how the use of fetal MCAPSV to diagnose fetal anemia can help in the decision-making process even in a rural setup.ContextFetal anemia can be adequately tackled only if it is diagnosed on time. Fetal MCA-PSV has the potential to reliably predict fetal anemia. Scientific studies across the globe are testimony to this fact. As such studies from rural setups are lacking, this study was initiated.AimsA study of fetal middle cerebral artery peak systolic velocity to diagnose fetal anemia in rural obstetric population.Settings and designThe study was conducted in the ultrasound section of a rural medical college. Clearance from institutional ethical and research committee was obtained. Written informed consent was obtained from the pregnant mother. A prospective observational study was conducted over the last 12 months.Materials and methodsFetal MCA-PSV was measured in 26 pregnant women referred for ultrasound due to clinical suspicion of fetomaternal abnormality. Middle cerebral artery peak systolic velocity was measured by a single experienced radiologist on color Doppler ultrasound machine.Statistical analysis usedThe observations were entered in Microsoft Excel sheet, and statistical analysis was done by comparing with internationally accepted values at that gestational age. Karl Pearson's correlation coefficient was used to study the relation between fetal MCA-PSV and gestational age. Standard t-test was used to study the significance of difference.ResultsThere was a steady increase in MCA-PSV with rising gestational age suggestive of positive correlation between them. When compared with internationally accepted values, significantly raised fetal MCA-PSV values were seen in six patients. These patients were followed up and the cause of fetal anemia in each was identified.ConclusionFetal MCA-PSV can be successfully used to evaluate for anemia in fetuses in a rural setup provided correct methods are followed. An attempt to measure fetal MCA-PSV in face of every fetomaternal adversity is recommended so that none of the cases of fetal anemia go undiagnosed.Key messagesProper knowledge and routine measurement of fetal MCA-PSV value can be a life saving noninvasive practice to diagnose fetal anemia in a rural setup.How to cite this articleKachewar S, Gandage SG, Pawar HJ. A Study of Fetal Middle Cerebral Artery Peak Systolic Velocity to Diagnose Fetal Anemia in Rural Obstetric Population. Int J Infertility Fetal Med 2013;4(3):83-87.

Fetal Anemia of Unknown Cause – A Diagnostic Challenge

To assess the spectrum of underlying diseases in cases of fetal anemia in which the cause was unknown at the time of first and second transfusion or thereafter. All patients who underwent intrauterine transfusion were identified in the perinatal databases of two tertiary referral centers for prenatal medicine and treatment between 2002 and June 2010. 82 fetuses received intrauterine transfusion in the study period. A total of 356 transfusions were performed in these patients. The causes of fetal anemia in our cohort were alloimmunization (32), parvovirus infection (23), feto-fetal transfusion syndrome (9), sacrococcygeal teratoma (2) and cytomegalovirus infection (1). In the remaining 15 cases, the cause of fetal anemia was unknown at the time of first and second transfusion, and could only be ascertained in the further course of pregnancy, in the postnatal period or was ultimately left in doubt. In all cases markedly elevated peak systolic velocities in the middle cerebral artery accurately predicted fetal anemia. The final diagnosis in these cases was fetomaternal hemorrhage (4), Blackfan-Diamond anemia (1), diffuse neonatal hemangiomatosis with chorangioma (1), kaposi-like hemangioendothelioma (1), elliptocytosis (1), neonatal hemochromatosis (1), mucopolysaccharidosis type VII (1) and in 5 cases the cause of fetal anemia remained unexplained. The latter 5 cases had an uneventful postnatal course and did not require further transfusions in infancy. In cases of fetal anemia with negative indirect Coombs test and TORCH serology, rare causes of anemia have to be considered. Fetal studies should therefore include reticulocyte count, parameters of hemolysis, peripheral blood smear and fetal liver function tests. Maternal studies should involve a search for fetal red cells using flow cytometry rather than Kleihauer-Betke test.

Predictive factors of perinatal mortality in transfused fetuses due to maternal alloimmunization: what really matters?

Introduction: Alloimmunization is the main cause of fetal anemia. There are not many consistent analyses associating antenatal parameters to perinatal mortality in transfused fetuses due to maternal alloimmunization. The study aimed to determine the prognostic variables related to perinatal death. Material and Methods: A cohort study analyzed 128 fetuses treated with intrauterine transfusion (IUT), until the early neonatal period. Perinatal mortality was associated with prognostic conditions related to prematurity, severity of fetal anemia and IUT procedure by univariated logistic regression. Multiple logistic regression was used to compute the odds ratio (OR) for adjusting the hemoglobin deficit at the last IUT, gestational age at birth, complications of IUT, antenatal corticosteroid and hydrops. Results: Perinatal mortality rate found in this study was 18.1%. The hemoglobin deficit at the last IUT (OR: 1.26, 95% CI: 1.04–1.53), gestational age at birth (OR: 0.53, 95% CI: 0.38–0.74) and the presence of transfusional complications (OR: 5.43, 95% CI: 142–20.76) were significant in predicting fetal death. Conclusion: Perinatal mortality prediction in transfused fetuses is not associated only to severity of anemia, but also to the risks of IUT and prematurity.

Managing the difficult case of fetal anemia

Objectives. To describe a series of complex fetal anemia cases,detail the appropriate investigations and management, and review the literature.Methods. Four cases of non-red cell alloimmunization orinfective cases of fetal anemia are presented.Results. Of the four cases presented, one was a neonatal death,one pregnancy was terminated, one case was diagnosed with Diamond Blackfan anemia, and onecase was due to recurrent feto-maternal hemorrhages despite negative Kleihauer tests.Conclusions. Non-alloimmune causes of fetal anemia can bedifficult to manage. Some cases require repeated and frequent intrauterine transfusions. Theperinatal mortality and preterm delivery rates are increased, and some cases requireconsiderable long-term treatment including regular transfusions. We present our experienceof a series of non-immune fetal anemia managed in a tertiary unit, review the literature,and suggest appropriate management.

Fetal and neonatal anemia associated with anti‐Jra: A case report showing a poorly hemolytic mechanism

Although recently published case reports suggest the significance of Jr(a) alloimmunization in the obstetric setting, the involved mechanism still remains unclear. Here we report a case of severe fetal and neonatal anemia associated with anti-Jr(a) alloimmunization, which was successfully managed using Doppler assessment of peak systolic velocity of the fetal middle cerebral artery (MCA-PSV). A Japanese woman with anti-Jr(a) (titer 1024) was referred to our department at 20 weeks' gestation. As fetal MCA-PSV exceeded 1.5 multiple of median, labor was induced and a female neonate of 1998 g was delivered vaginally at 33 weeks and 5 days of gestation. The infant's hematocrit and hemoglobin levels were 25.4% and 82 g/L, respectively, but her total bilirubin level (15 µmol/L; 0.9 mg/dL) and reticulocyte counts (4.5%) were low. During the course, the infant showed no apparent signs of hemolysis. Jr(a) alloimmunization should be recognized as a possible cause of fetal anemia with no direct hemolytic process.

Strip of the Month: July 2010

Strip of the Month: July 2010

Using Middle Cerebral Artery Peak Systolic Velocity to Time In Utero Transfusions in Fetomaternal Hemorrhage

Fetomaternal hemorrhage is a rare cause of fetal anemia and hydrops fetalis. Early and severe fetomaternal hemorrhage may benefit from in utero transfusion(s); however, hemorrhage rate is unpredictable, and reliable criteria are needed to identify recurrent anemia. Fetal hydrops due to massive fetomaternal hemorrhage was diagnosed at 29 weeks. After the first in utero transfusion, daily monitoring of middle cerebral artery peak systolic velocity suggested recurrent fetal anemia, requiring two additional in utero transfusions at 1-week intervals. One day after the third in utero transfusion, a sudden increase in fetomaternal hemorrhage rate was suspected on a rapid elevation of middle cerebral artery peak systolic velocity, leading to immediate delivery at 32 weeks. Middle cerebral artery peak systolic velocity is a relevant, noninvasive tool for the timing of repeated in utero transfusions and of fetal delivery in case of chronic fetomaternal hemorrhage.

Le point sur le suivi des allo-immunisations érythrocytaires

Anti-RhD allo-immunisation has become rare since anti-D prophylaxis was introduced in the seventies; however, it remains the first cause of fetal anemia. It may cause severe fetal complications such as fetal hydrops, cerebral anoxic lesions and fetal death. In the neonatal period, severe jaundices and anemias requiring transfusion or exsanguino-transfusion are still common in case of severe allo-immunisation. Neonatal death and sequellae due to bilirubin encephalopathy have not fully disappeared. Follow-up of pregnancies with maternal allo-immunisation requires identification of the antibody (anti-RhD, anti-Kell and anti-c are the most frequently responsible for fetal complications), dosage and titration. In RhD allo-immunization, feto-maternal incompatibility may be confirmed by non-invasive RHD genotyping of the fetus in maternal blood. In cases at risk for fetal anemia, weekly Doppler assessment of middle cerebral artery peak systolic velocity (MCA-PSV) allows identification of fetal anemia before the occurrence of fetal hydrops. The reference treatment of fetal anemia is in utero fetal transfusion. The risk of fetal loss due to in utero transfusion (IUT) is 3% per procedure. The cumulated risk of fetal loss can thus exceed 10% in case of early occurrence of fetal anemia requiring up to five or six IUTs in a single pregnancy.

Fetal hemolytic anemia and intrauterine death caused by anti‐M immunization

Antibodies with anti-M specificity are detected in 10 percent of pregnant women with a positive antibody screen, but anti-M is only rarely associated with hemolytic anemia in the fetus. This study reports on three pregnancies in one family that all resulted in severe fetal anemia. The first fetus died in utero with hydrops fetalis during the 20th gestational week and the second child was delivered after 28 weeks of gestation with hydrops fetalis and a hemoglobin level of 16 g per L whereas the third affected child was treated with intrauterine red cell (RBC) transfusions before delivery at 28 weeks of gestation. The direct antiglobulin test was negative but anti-M in a low titer was detected through the three pregnancies, and its clinical relevance, which initially was uncertain, was confirmed by pronounced in vivo hemolysis in maternal blood of chromate ((51)Cr)-labeled M+ RBCs and normal survival of (51)Cr labeled M- RBCs. It is concluded that anti-M immunization in a few cases may cause severe fetal hemolytic anemia and intrauterine death. It remains to be elucidated why a normally clinically insignificant antibody is this aggressive in a small proportion of cases. Because the condition is treatable, anti-M must be considered as a possible cause of fetal anemia and intrauterine death.

EL DOPPLER DE LA ARTERIA CEREBRAL MEDIA REEMPLAZA A LA ESPECTROFOTOMETRÍA DEL LÍQUIDO AMNIÓTICO COMO EL ESTÁNDAR EN EL MANEJO DE LA ISOINMUNIZACIÓN FETAL

SUMMARY Fetal anemia could be a devastating condition to the fetus. The main cause of fetal anemia is red-cell alloimmunization. The standard of care for this condition has been the serial amniocentesis to measure bilirubin levels by spectrophotometry of the amniotic fluid. Amniotic fluid bilirubin measurements are of limited value in the second trimester and in other causes of fetal anemia, besides amniocentesis is an invasive method with fetal risk. During the last 10 to 12 years a non invasive method to predict fetal anemia become available: measurement of the peak systolic velocity of the middle cerebral artery. Increased velocity may reflect fetal anemia. Here we present the evidence to support the use of this non invasive method to replace amniocentesis as the standard care in the management of red-cell alloimmunization and other causes of fetal anemia.

Middle Cerebral Artery Peak Systolic and Ductus Venosus Velocity Waveforms in the Hydropic Fetus

The purpose of this study was to assess whether Doppler assessment of the middle cerebral artery (MCA) peak systolic velocity (PSV) and ductus venosus (DV) velocity waveforms during sonography of hydropic fetuses may specify the cause of fetal hydrops. A level II sonographic examination was performed in 16 hydropic fetuses, and the MCA PSV and DV velocity waveforms were assessed. The MCA PSV values divided hydropic fetuses into anemic (group 1) and nonanemic (group 2) fetuses. In group 2 fetuses, the DV was defined as normal or abnormal. Sonographic examination and Doppler assessment of these vessels specified the cause of hydrops and indicated the use of specific investigations for diagnosing the etiology of fetal hydrops. Seven of 16 fetuses had MCA PSV values greater than 1.50 multiples of the median (group 1). Nine of 16 fetuses had normal MCA PSV values (group 2); among them, 7 of 9 had either absent or reversed flow in the DV, and 2 had a normal DV. In group 1, the cause of fetal anemia was investigated by maternal serum tests, and 5 cordocentesis procedures were performed. In group 2, 7 of 9 fetuses had reversed flow in the DV, which suggested a cardiac abnormality confirmed by echocardiography. Five cordocentesis procedures were performed for fetal karyotype, and in 2 fetuses, the cause of hydrops was idiopathic. Our data suggest that assessment of the MCA PSV and DV velocity waveforms in the hydropic fetus may further our knowledge of the etiology of hydrops and may indicate which investigations among the many available should be used for diagnosing the cause of fetal hydrops.

Fetal anemia: new technologies.

The purpose of this review is to summarize recently published studies on noninvasive diagnosis of fetal anemia in order to give recommendations for the use of these new tools. Red cell alloimmunization remains one of the most common causes of fetal anemia. Amniocentesis and cordocentesis have been used for many years to diagnose fetal anemia due to red cell aloimmunization. These techniques, however, are invasive and many complications are associated with their use. Noninvasive diagnosis of fetal anemia has been performed with Doppler ultrasonography. Based on robust data, several authors recommend the use of middle cerebral artery peak systolic velocity in the management of fetuses at risk for anemia because of red cell alloimmunization. This Doppler parameter can also diagnose fetal anemia due to other conditions. Middle cerebral artery peak systolic velocity appears to be the best test for the noninvasive diagnosis of fetal anemia. It is important to emphasize that training of sonographers and sonologists is the 'conditio sine qua non' for the correct sampling of the middle cerebral artery.

Infection by Parvovirus B 19 During Pregnancy: A Review

Fetal infection by Parvovirus B 19 is a common cause of fetal anemia and nonimmune hydrops fetalis and may result in fetal death. Recent improvements in diagnosing parvovirus infections by sensitive molecular biology techniques now allow for a new insight into its pathogenic rule, immunology, and the varied clinical manifestations. The estimated overall risk of fetal loss after maternal exposure is about 6.5 percent, which is much less than previously thought. Inasmuch as complete spontaneous reversal of fetal hydrops has been commonly described, controversy exists regarding the management of the fetus with clinical signs of infection by Parvovirus B 19. According to the experience that has accumulated, it seems that only cases with severe fetal anemia or signs of fetal compromise should be managed by intrauterine transfusion. This procedure, however, is not without risk. Although an association between fetal viral infection and structural abnormalities has been described, it has not been proved yet. However, infection by Parvovirus B 19 has been recently proposed as a causative factor for congenital red blood cell aplasia.

Production of pigs expressing multiple transgenes for use in xenotransplantation studies

Flow cytometry (FC) has been primarily applied to the diagnosis of hematological malignancies, and thereafter, to detection and quantification of CD34+ cells in bone marrow transplants, and granulocytes in neutropenias and paroxysmal nocturnal hemoglobinuria (PNH). In PNH and hereditary spherocytosis, changes in some of the erythrocyte membrane proteins are tested (CD59, CD55, and band 3). The purpose of this paper is to focus on the use of FC in RBC testing. With anti-D, -HbF, and -CA (carbonic anhydrase), we can detect RhD+, HbF+, and CA- fetal RBCs in the maternal RhD-, HbF-, and CA+ blood sample. Obtained results allow to select the appropriate dose of anti-D Ig in the RhD prophylaxis of feto-maternal incompatibility, or to detect the cause of fetal anemia. Expression of antigens and their weak variants, and concentration of specific antibodies, can also be assessed. It is possible to observe changes in selected CD molecules during storage of RBC units. If RBCs for transfusion are unavailable, due to patient's unusual antibody specificity, some of the available RBCs are opsonised, and then phagocytosis with the recipient monocytes is assessed. The microscopic time-consuming and subjective assay is usually used. Stained CD14+ monocytes and CD235a+ erythrocytes are visible on cytograms as well as their interaction. It makes evaluation of phagocytosis easier and objective. Microparticles of RBCs released during storage are also detected. They are 235a+. In differentiation of hemolysis causes, it is important to measure osmotic fragility, and that can be also achieved using FC. Flow cytometry should be applied to immunohematological testing of red blood cells more often than now.

Infection by parvovirus B 19 during pregnancy: a review.

Fetal infection by Parvovirus B 19 is a common cause of fetal anemia and nonimmune hydrops fetalis and may result in fetal death. Recent improvements in diagnosing parvovirus infections by sensitive molecular biology techniques now allow for a new insight into its pathogenic rule, immunology, and the varied clinical manifestations. The estimated overall risk of fetal loss after maternal exposure is about 6.5 percent, which is much less than previously thought. Inasmuch as complete spontaneous reversal of fetal hydrops has been commonly described, controversy exists regarding the management of the fetus with clinical signs of infection by Parvovirus B 19. According to the experience that has accumulated, it seems that only cases with severe fetal anemia or signs of fetal compromise should be managed by intrauterine transfusion. This procedure, however, is not without risk. Although an association between fetal viral infection and structural abnormalities has been described, it has not been proved yet. However, infection by Parvovirus B 19 has been recently proposed as a causative factor for congenital red blood cell aplasia.