Invasive procedures to evaluate the fetus.
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When any fetal blood group factor inherited from the father is not possessed by the mother, antepartum or intrapartum fetal-maternal bleeding may stimulate an immune reaction in the mother Maternal immune reactions also can occur from blood product transfusion. The formation of maternal antibodies, or"alloimmunization,' may lead to various degrees of transplacental passage of these antibodies into the fetal circulation. Depending on the degree of antigenicity and the amount and type of antibodies involved, this transplacental passage may lead to hemolytic disease in the fetus and neonate. Undiagnosed and untreated, alloimmunization can lead to significant perinatal morbidity and mortality. Advances in Doppler ultrasonography have led to the development of noninvasive methods of management of alloimmunization in pregnant women. Together with more established protocols, Doppler ultrasound evaluation may allow for a more thorough and less invasive workup with fewer risks to the mother and fetus. Prevention of alloimmunization is addressed in another Practice Bulletin (1).
Polyhydramnios is a relatively common obstetrical complication. Major causes include maternal diabetes, chromosomal disorders, isoimmunologic disease, congenital abnormalities, multiple gestations, and idiopathic reasons. Perinatal morbidity and mortality is high and maternal complications are frequent. Successful management depends upon appropriate diagnostic evaluation. Prolongation of the pregnancy for further fetal maturation may be achieved with timely therapeutic amniocenteses.
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Twenty-five babies with nonimmune hydrops fetalis were born during a 20-year period from 1967 to 1987 (1/1475). Sixteen were live-born, only three survived. Although hydrops can be caused by a myriad of diseases, a simple classification is proposed in order to allow efficient diagnostic workup. For the majority of cases of nonimmune hydrops no cause can be found. Vascular causes are most frequent, followed by chromosomal, placental, hematological, infectious, and a miscellaneous group of causes. Of the cases reviewed fetal causes dominate in 95 per cent of cases. Maternal causes are relatively rare and consist mainly of infections and diabetes. In order to reduce the high mortality rate of 98 per cent one should aim at early diagnosis of hydrops fetalis, extensive investigation of both the fetus and the mother, and referral to a center for intensive perinatal care.
Published reports, case studies, and articles from the English language regarding ultrasonographic detection of fetal anemia in red blood cell alloimmunization were obtained from a MEDLINE search from 1966 to November 1999 using the keywords Rh disease, hemolytic disease of the newborn, ultrasound, and Doppler flow studies and combinations thereof. All articles were cross-referenced. Ultrasound techniques including early findings associated with immune hydrops fetalis, multiple morphologic ultrasound markers, and Doppler flow studies that have been used to detect fetal anemia are reviewed and critically evaluated. Noninvasive sonographic techniques may reduce the number of invasive procedures that traditionally are used to follow fetuses at risk for anemia and decrease the associated risks from these procedures.
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PURPOSE OF REVIEW: Traditional methods of fetal evaluation require invasive procedures (e.g. amniocentesis) with an inherent, albeit low, risk of complications and pregnancy loss. As medical knowledge and ultrasound technology have advanced, noninvasive modes of fetal evaluation have become increasingly used. Two disorders in which this has been most applied are fetal aneuploidy and alloimmunization to red blood cell antigens. RECENT FINDINGS: First-trimester screening protocols for fetal aneuploidy combine ultrasound measurement of the fetal nuchal translucency with the measurement of two maternal serum hormones, free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A. This combination detects approximately 85% of women pregnant with fetuses with trisomy 21. An increase in the velocity of fetal middle cerebral artery blood flow occurs in the setting of moderate to severe fetal anemia and can be measured with Doppler ultrasound. Middle cerebral artery evaluation is equally sensitive in the prediction of anemia as amniocentesis for bilirubin breakdown products and has less associated risk. It has an additional benefit because it can also be applied to causes of anemia other than hemolysis. SUMMARY: Noninvasive methods of fetal assessment are becoming increasingly commonplace. There has been a dramatic decrease in the use of prenatal diagnostic services as screening strategies have become available. Doppler assessment of the velocity of blood flow through the fetal middle cerebral artery will allow for more judicious application of invasive procedures to pregnancies at significant risk for anemia.
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BACKGROUND: Although young women who are D- occasionally receive unintentional transfusions with D+ red blood cells (RBCs), there are little data to assist with management of such an event. Two cases of D- girls transfused with D+ RBCs are reported. In an effort to prevent formation of anti-D, RBC exchange followed by administration of intravenous (IV) Rh immune globulin (RhIg) was used. CASE REPORTS: Patient 1, a 56-kg, 16-year-old D- girl, was involved in a motor vehicle crash. She received 4 units of Group O uncrossmatched D+ RBCs. Thirty-six hours after admission, she underwent RBC exchange with 10 units of D- RBCs, followed by a total of 2718 microg of IV RhIg over 32 hours. Six months later, her antibody screen was negative. Patient 2, a 39-kg, 10-year-old D- girl with aplastic anemia, received 1 unit of D+ RBCs. She underwent RBC exchange on the same day with 5 units of D- RBCs, followed by a total of 900 microg of IV RhIg over 8 hours. Six months later her antibody screen was negative. CONCLUSION: RBC exchange followed by a calculated dose of IV RhIg was successful in preventing allo-immunization to D. Several small studies suggest that both trauma and hematology patients may be less capable of becoming immunized with the transfusion of D+ blood components. Until these findings are more clearly defined, there will be times when prevention of immunization of any D- girl is desired. RBC exchange followed by RhIg appears to be one way to achieve this goal.
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Anti-D haemolytic antibody concentration and chemiluminescence (CLT) opsonic index was measured in maternal blood obtained from 20 alloimmunized pregnancies at 17-28 weeks undergoing intrauterine fetal blood sampling for the estimation of fetal haemoglobin concentration. The fetal haemoglobin concentration was significantly associated with the maternal serum CLT opsonic index (r = -0.566, P < 0.01) but not with the maternal anti-D concentration (r = -0.329). The data of this study indicate that measurement of maternal serum CLT opsonic index may be more accurate than anti-D quantification in providing non-invasive prediction of the degree of fetal anaemia.
A sensitive PCR-based assay was developed to amplify fetal-derived rhesus D (RhD) sequence from peripheral blood of RhD-negative pregnant women with circulating anti-D. RhD-PCR positivity was detected in 7/22 samples from women bearing RhD-positive fetuses, despite the presence of varying levels of anti-D. Evidence is presented which suggests that rising maternal anti-D levels might reduce circulating fetal cell numbers. Further development of this assay may have implications in the clinical management of RhD-sensitized pregnancies and aid the understanding of the physiology of feto-maternal cell trafficking.
Nine years after allogenic bone marrow transplantation a strong anti-E was observed in a patient transplanted with bone marrow from his HLA-identical brother. This IgG anti-E, with a titre of 4000, was detected together with autoantibodies to red blood cells and platelets and was not induced by transfusion with E+ cells. The hypothesis is proposed that the anti-E represents either antigen-independent desuppression of the donor immune system sensitized at the time of bone marrow transplantation by E antigens in the recipient, or antigen-independent memory B-cell activation by Epstein-Barr virus infection.
The ability of the chemiluminescence test (CLT) to predict the severity of haemolytic disease of the newborn (HDN) was determined in 80 alloimmunized pregnant women who delivered antigen-positive babies. In 54 cases of alloimmunization to D, results from the CLT showed better correlation with fetal outcome than anti-D concentration measured by AutoAnalyzer (r = 0.70 and 0.36 respectively). Results from the CLT permitted a threshold level of antibody activity (30%) below which 15/20 babies were unaffected or had mild disease, and only one required transfusion therapy in utero. CLT results above 30% were associated with moderate or severe disease in all cases. Results from the AutoAnalyzer proved a less reliable predictor of disease severity; three women with anti-D levels > 20 iu/ml delivered unaffected babies, and two women with anti-D levels < 10 iu/ml delivered babies who had required transfusion in utero. The clinical usefulness of the CLT derives from the possibility of avoiding invasive monitoring procedures in women with high levels of anti-D which is relatively non-functional.