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American Journal of Hematology Apr 2012The prevention of Rhesus D alloimmunization through Rh immune globulin (RhIg) administration is the major indication for the accurate detection and quantification of... (Review)
Review
The prevention of Rhesus D alloimmunization through Rh immune globulin (RhIg) administration is the major indication for the accurate detection and quantification of fetomaternal hemorrhage (FMH). In the setting of D incompatibility, D-positive fetal cells can sensitize the D-negative mother, resulting in maternal anti-D alloantibody production. These anti-D alloantibodies may lead to undesirable sequelae such as hemolytic disease of the newborn (HDN). Since the widespread adoption of FMH screening and RhIg immunoprophylaxis, the overall risk of Rh alloimmunization and infant mortality from HDN has substantially decreased. The rosette screen, the initial test of choice, is highly sensitive in qualitatively detecting 10 mL of fetal whole blood in the maternal circulation. As the screen is reliant on the presence of the D antigen to distinguish fetal from maternal cells, it cannot be used to detect FMH in D-positive mothers or in D-negative mothers carrying a D-negative fetus. The Kleihauer-Betke acid-elution test, the most widely used confirmatory test for quantifying FMH, relies on the principle that fetal RBCs contain mostly fetal hemoglobin (HbF), which is resistant to acid-elution whereas adult hemoglobin is acid-sensitive. Although the Kleihauer-Betke test is inexpensive and requires no special equipment, it lacks standardization and precision, and may not be accurate in conditions with elevated F-cells. Anti-HbF flow cytometry is a promising alternative, although its use is limited by equipment and staffing costs. Hematology analyzers with flow cytometry capabilities may be adapted for fetal cell detection, thus giving clinical laboratories a potentially attractive automated alternative for quantifying FMH.
Topics: Acids; Female; Fetal Blood; Fetal Hemoglobin; Fetomaternal Transfusion; Flow Cytometry; Humans; Isoantibodies; Pregnancy; Rh Isoimmunization; Rh-Hr Blood-Group System; Rho(D) Immune Globulin; Rosette Formation; Sensitivity and Specificity; Solubility; Staining and Labeling
PubMed: 22231030
DOI: 10.1002/ajh.22255 -
BMJ Sexual & Reproductive Health Jul 2022The aim of this review was to systematically review the outcome of routine anti-D administration among unsensitised rhesus (RhD)-negative individuals who have an... (Meta-Analysis)
Meta-Analysis Review
AIM
The aim of this review was to systematically review the outcome of routine anti-D administration among unsensitised rhesus (RhD)-negative individuals who have an abortion. This review is registered with Prospero.
METHODS
A search for all published and ongoing studies, without restrictions on language or publication status, was performed using the following databases from their inception: EBM Reviews Ovid - Cochrane Central Register of Controlled Trials, MEDLINE Ovid (Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily), Embase.com, Popline and Google Scholar. Study types included: randomised controlled trials, controlled trials, cohort and case-control studies from 1971 onwards. The population included women who undergo an abortion (induced, incomplete, spontaneous or septic abortion), medical or surgical <12 weeks, and isoimmunisation in a subsequent pregnancy. The primary outcomes were: (1) development of a positive Kleihauer-Betke test and (2) development of Rh alloimmunisation in a subsequent pregnancy.
RESULTS
A total of 2652 studies were screened with 105 accessed for full-text review. Two studies have been included with high bias appreciated. Both studies found few women to be sensitised in forming antibodies after an abortion. The limited studies available and heterogeneity prevent the conduction of a meta-analysis.
CONCLUSIONS
Rh immunoglobulin has well-documented safety. However, it is not without risks and costs, is a possible barrier to delivering efficient services, and may have limited availability in some countries. The evidence base and quality of studies are currently limited. There is unclear benefit from the recommendation for Rh testing and immunoglobulin administration in early pregnancy. More research is needed as clinical practice guidelines are varied, based on expert opinions and moving away from testing and administration at time of abortion.
IMPLICATIONS
There is limited evidence surrounding medical benefit of Rh testing and immunoglobulin administration in early pregnancy. Further research is needed to define alloimmunisation and immunoglobulin benefit to update standards of care. Additionally, other factors should be considered in forming clinical policies and guidelines such as costs, feasibility and impact on access to care for patients.
Topics: Abortion, Induced; Abortion, Spontaneous; Cohort Studies; Female; Humans; Pregnancy; Rh Isoimmunization
PubMed: 34819315
DOI: 10.1136/bmjsrh-2021-201225 -
Revista Brasileira de Ginecologia E... 2024RhD alloimmunization in pregnancy is still the main cause of hemolytic disease of the fetus and neonate (HDFN). Nevertheless, there are other antigens that may be... (Review)
Review
RhD alloimmunization in pregnancy is still the main cause of hemolytic disease of the fetus and neonate (HDFN). Nevertheless, there are other antigens that may be associated with the occurrence of this phenomenon and that have been growing in proportion, given that current prevention strategies focus only on anti-RhD antibodies. Although not widespread, the screening and diagnostic management of the disease caused by these antibodies has recommendations in the literature. For this reason, the following review was carried out with the objective of listing the main red blood cell antigen groups described - such as Rh, ABO, Kell, MNS, Duffy, Kidd, among others - addressing the clinical importance of each one, prevalence in different countries, and recommended management when detecting such antibodies during pregnancy.
PubMed: 38765509
DOI: 10.61622/rbgo/2024AO22 -
Journal of Clinical Neonatology Apr 2013Hemolytic conditions in preterm neonates, including Rhesus (Rh) disease, can lead to mortality and long-term impairments due to bilirubin neurotoxicity. Universal access... (Review)
Review
Hemolytic conditions in preterm neonates, including Rhesus (Rh) disease, can lead to mortality and long-term impairments due to bilirubin neurotoxicity. Universal access to Rh immunoprophylaxis, coordinated perinatal-neonatal care, and effective phototherapy has virtually eliminated the risk of kernicterus in many countries. In the absence of jaundice due to isoimmunization and without access to phototherapy or exchange transfusion (in 1955), kernicterus was reported at 10.1%, 5.5%, and 1.2% in babies <30, 31-32, and 33-34 wks gestational age, respectively. Phototherapy initiated at 24±12 hr effectively prevented hyperbilirubinemia in infants <2,000 g even in the presence of hemolysis. This approach (in 1985) reduced exchange transfusions from 23.9% to 4.8%. Now with 3 decades of experience in implementing effective phototherapy, the need for exchange transfusions has virtually been eliminated. However, bilirubin neurotoxicity continues to be associated with prematurity alone. The ability to better predict this risk, other than birthweight and gestation, has been elusive. Objective tests such as total bilirubin, unbound or free bilirubin, albumin levels, and albumin-bilirubin binding, together with observations of concurrent hemolysis, sepsis, and rapid rate of bilirubin rise have been considered, but their individual or combined predictive utility has yet to be refined. The disruptive effects of immaturity, concurrent neonatal disease, cholestasis, use of total parenteral nutrition or drugs that alter bilirubin-binding abilities augment the clinical risk of neurotoxicity. Current management options rely on the "fine-tuning" of each infant's exposure to beneficial antioxidants and avoidance of silent neurotoxic properties of bilirubin navigated within the safe spectrum of operational thresholds demarcated by experts.
PubMed: 24049745
DOI: 10.4103/2249-4847.116402 -
Clinics in Perinatology Sep 1995Dramatic improvements have been made in the management of Rh disease. Anti-D immune globulin has reduced the incidence of Rh sensitization. Intrauterine transfusions... (Review)
Review
Dramatic improvements have been made in the management of Rh disease. Anti-D immune globulin has reduced the incidence of Rh sensitization. Intrauterine transfusions have become routine to treat fetal anemia. Once an affected infant is born, several recent improvements in neonatal care have aided in the treatment of hyperbilirubinemia. These include improved phototherapy, such as fiberoptic delivery systems, and intravenous immunoglobulin. Experience with heme oxygenase inhibitors is accumulating, and they may prove efficacious in Rh disease. Double-volume (and perhaps single-volume) exchange transfusion remains an effective method to control hyperbilirubinemia when other therapies fail. Erythropoietin may have a role in treating late, hyporegenerative anemia. Finally, better ways to assess the risk of brain injury in patients with hyperbilirubinemia may become available. Cooperation between the obstetric and neonatal teams to treat Rh-sensitized mothers and their babies is essential.
Topics: Anemia, Neonatal; Erythroblastosis, Fetal; Exchange Transfusion, Whole Blood; Female; Humans; Immunoglobulins, Intravenous; Infant, Newborn; Pregnancy; Pregnancy Complications, Hematologic; Rh Isoimmunization
PubMed: 8521682
DOI: No ID Found -
British Medical Journal Jun 1977
Topics: Age Factors; Coronary Disease; Heart; Humans; Myocardial Contraction
PubMed: 861675
DOI: No ID Found -
PloS One 2020Existing systematic reviews of Rh immunoprophylaxis include only data from randomized controlled trials, have dated searches, and some do not report on all domains of...
BACKGROUND
Existing systematic reviews of Rh immunoprophylaxis include only data from randomized controlled trials, have dated searches, and some do not report on all domains of risk of bias or evaluate the certainty of the evidence. Our objective was to perform an updated review, by including new trials, any comparative observational studies, and assessing the certainty of the evidence using the GRADE framework.
METHODS
We searched MEDLINE, Embase and the Cochrane Library from 2000 to November 26, 2019. Relevant websites and bibliographies of systematic reviews and guidelines were searched for studies published before 2000. Outcomes of interest were sensitization and adverse events. Risk of bias was evaluated with the Cochrane tool and ROBINS-I. The certainty of the evidence was performed using the GRADE framework.
RESULTS
Thirteen randomized trials and eight comparative cohort studies were identified, evaluating 12 comparisons. Although there is some evidence of beneficial treatment effects (e.g., at 6-months postpartum, fewer women who received RhIg at delivery compared to no RhIg became sensitized [70 fewer sensitized women per 1,000 (95%CI: 67 to 71 fewer); I2 = 73%]), due to very low certainty of the evidence, the magnitude of the treatment effect may be overestimated. The certainty of the evidence was very low for most outcomes often due to high risk of bias (e.g., randomization method, allocation concealment, selective reporting) and imprecision (i.e., few events and small sample sizes). There is limited evidence on prophylaxis for invasive fetal procedures (e.g. amniocentesis) in the comparative literature, and few studies reported adverse events.
CONCLUSION
Serious risk of bias and low to very low certainty of the evidence is found in existing RCTs and comparative observational studies addressing optimal effectiveness of Rh immunoprophylaxis. Guideline development committees should exercise caution when assessing the strength of the recommendations that inform and influence clinical practice in this area.
Topics: Female; GRADE Approach; Humans; Immunologic Factors; Postnatal Care; Pregnancy; Prenatal Care; Randomized Controlled Trials as Topic; Rh Isoimmunization; Rh-Hr Blood-Group System
PubMed: 32913362
DOI: 10.1371/journal.pone.0238844 -
Blood Transfusion = Trasfusione Del... Jan 2013
Topics: Erythroblastosis, Fetal; Female; Fetomaternal Transfusion; Humans; Immunoglobulin G; Isoantibodies; Pregnancy; Rh Isoimmunization; Rh-Hr Blood-Group System
PubMed: 22790264
DOI: 10.2450/2012.0059-12 -
Canadian Medical Association Journal Feb 1977The number of Rh-isoimmunized pregnancies in Manitoba has been reduced from 223 and 228 in the years ending Oct. 31, 1963 and 1964 to 60 and 62 in the years ending Oct....
The number of Rh-isoimmunized pregnancies in Manitoba has been reduced from 223 and 228 in the years ending Oct. 31, 1963 and 1964 to 60 and 62 in the years ending Oct. 31, 1974 and 1975. The number per 1000 total births in the same years has decreased from 10.0 and 10.6 to 3.4 and 3.5 Perinatal mortality rates in those years decreased from 13.8 amd 15.7% to 0 and 2.2%, respectively. The number of perinatal deaths has been reduced from 55 in the first 2 years reported to 1 in the last 2 years. Among the 121 isoimmunized women pregnant in the 2-year period ending Oct. 31, 1975, isoimmunization was due to failure to give Rh immune globulin after delivery in 33 and failure to give it during pregnancy in 48. Of the remaining 40, 37 were immunized before Rh immune globulin became available. Complete prevention of Rh isoimmunization and therefore of all perinatal deaths from Rh erythroblastosis can only be achieved through universal Rh testing prenatally and immediately after delivery, and institution of an antenatal Rh prophylaxis program.
Topics: Antibody Formation; Erythroblastosis, Fetal; Female; Humans; Immunoglobulin G; Infant, Newborn; Manitoba; Pregnancy; Rh-Hr Blood-Group System
PubMed: 402178
DOI: No ID Found -
Indian Pediatrics Jan 2023
Topics: Humans; Infant; Rh Isoimmunization; Iron Overload
PubMed: 36639977
DOI: No ID Found