Administration Of Rh Immune Globulin Research Articles

RhD-Alloimmunization in Adult and Pediatric Trauma Patients

The actual risk of providing RhD-positive units to RhD-negative recipients remains debatable. There is no standard of care in the United States (US) to guide transfusion decisions regarding RhD type for patients with an unknown blood type, except for women of childbearing age and neonates. The risk of alloantibody formation by an RhD-negative patient exposed to RhD-positive blood is reported to be from 3% to 70%. Due to such wide variations, this review was undertaken to determine the prevalence of anti-D alloimmunization in trauma patients who are RhD-negative and were transfused RhD-positive blood products. This study used the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) approach to answer the question, “In trauma patients who were transfused blood, what is the prevalence of alloimmunization to the D-antigen?” The review included all published articles through April 3, 2022 in databases. Articles published after the search period found by the authors were added to the manuscript if they addressed the primary question and there was unanimous consensus. There were 1683 full-text articles that met the search criteria, with 19 studies meeting eligibility criteria. In addition, 57 references were added after the search period had closed. The incidence of anti-D alloimmunization in adult trauma patients receiving whole blood varied from 7.8% to 42.7%. In contrast, incidence varied in patients receiving red blood cells (RBCs), from 0 to 94%, depending on number of categories analyzed. Anti-D alloimmunization with platelet transfusions varied from 0% to 19%. The alloimmunization rate increased with age and was detected only in children older than 5 years. Recent guidelines recommend the administration of Rh immune globulin (RhIG) to all traumatically injured patients who are both RhD-negative and pregnant. However, there is no specific guidance focused on the RhD-negative patient, pregnant or nonpregnant, and who have received RhD-positive red blood cells (RBC) and platelets. While numerous studies have attempted to evaluate the frequency of RhD alloimmunization rate in trauma settings, emerging data suggests that many factors affect this phenomenon. Additionally, the role of RhIG administration in cases of RhD-incompatible transfusions within the trauma setting adds complexity. As our trajectory propels us towards precision medicine and tailored transfusion practices, gaining a big data approach becomes indispensable.

When and why is red blood cell genotyping applicable in transfusion medicine: a systematic review of the literature.

This review aims to provide a better understanding of when and why red blood cell (RBC) genotyping is applicable in transfusion medicine. Articles published within the last 8 years in peer-reviewed journals were reviewed in a systematic manner. RBC genotyping has many applications in transfusion medicine including predicting a patient's antigen profile when serologic methods cannot be used, such as in a recently transfused patient, in the presence of autoantibody, or when serologic reagents are not available. RBC genotyping is used in prenatal care to determine zygosity and guide the administration of Rh immune globulin in pregnant women to prevent hemolytic disease of the fetus and newborn. In donor testing, RBC genotyping is used for resolving ABO/D discrepancies for better donor retention or for identifying donors negative for high-prevalence antigens to increase blood availability and compatibility for patients requiring rare blood. RBC genotyping is helpful to immunohematology reference laboratory staff performing complex antibody workups and is recommended for determining the antigen profiles of patients and prospective donors for accurate matching for C, E, and K in multiply transfused patients. Such testing is also used to determine patients or donors with variant alleles in the Rh blood group system. Information from this testing aides in complex antibody identification as well as sourcing rare allele-matched RBC units. While RBC genotyping is useful in transfusion medicine, there are limitations to its implementation in transfusion services, including test availability, turn-around time, and cost.

Estimating the cost of Rh testing and prophylaxis in early pregnancy: A time-driven activity-based costing study

ObjectiveTo estimate the cost of Rhesus (Rh) testing and prophylaxis for first-trimester vaginal bleeding in the ambulatory setting. Study designWe used time-driven, activity-based costing to analyze tasks associated with Rh testing and prophylaxis of first-trimester vaginal bleeding at one hospital-based outpatient and two independent reproductive health clinics. At each site, we observed 10 patients undergoing Rh-typing and two patients undergoing Rh prophylaxis. We computed the costs of blood Rh-typing by both fingerstick and phlebotomy, cost of locating previous blood type in the electronic health record (available for 69.8% of hospital-based patients), and costs associated with Rh immune globulin prophylaxis. All costs are reported in 2021 US dollars. ResultsThe hospital-based clinic reviewed the electronic health record to confirm Rh-status (cost, $26.18 per patient) and performed a phlebotomy, at $47.11 per patient, if none was recorded. The independent clinics typed blood by fingerstick, at a per-patient cost of $4.07. Rh-immune globulin administration costs, including the medication, were similar across facilities, at a mean of $145.66 per patient. Projected yearly costs for testing and prophylaxis were $55,831 for the hospital-based clinic, which was the lowest-volume site, $47,941 for Clinic A, which saw 150 patients/month, and $185,654 for Clinic B, which saw 600 patients/month. ConclusionsRh testing and prophylaxis for first-trimester vaginal bleeding generates considerable costs for outpatient facilities, even for Rh-positive patients with a prior blood type on record. ImplicationsRh testing and prophylaxis for first-trimester bleeding generate considerable costs even for Rh-positive patients and those with a previously known blood type. These findings highlight the need to reconsider this practice, which is no longer supported by evidence and already safely waived in multiple medical settings in the United States and around the world.

Rh immune globulin immunoprophylaxis after RhD-positive red cell exposure in RhD-negative patients via transfusion: A survey of practices.

Current Association for the Advancement of Blood & Biotherapies (AABB) standards require transfusion services to have a policy on Rh immune globulin (RhIG) immunoprophylaxis for when RhD-negative patients are exposed to RhD-positive red cells. This is a survey of AABB-accredited transfusion services in the United States (US) regarding institutional policies and practices on RhIG immunoprophylaxis after RhD-negative patients receive RhD-positive (i.e., RhD-incompatible) packed red blood cell (pRBC) and platelet transfusions. Approximately half of the respondents (50.4%, 116/230) have policies on RhIG administration after RhD-incompatible pRBC and platelet transfusions, while others had policies for only pRBC (13.5%, 31/230) or only platelet (17.8%, 41/230) transfusions, but not both. In contrast, 18.3% (42/230) report that their institution has no written policies on RhIG immunoprophylaxis after RhD-incompatible transfusions. Most institutions (70.2%, 99/141) do not have policies addressing safety parameters to mitigate the risk of hemolysis associated with the high dose of RhIG required to prevent RhD alloimmunization after RhD-incompatible pRBC transfusions. With approximately half of US AABB-accredited institutions report having policies on RhIG immunoprophylaxis after both RhD-incompatible pRBC and platelet transfusions, some institutions may not be in compliance with AABB standards. Further, most with policies on RhIG immunoprophylaxis after RhD-incompatible pRBC transfusion do not have written safeguards to mitigate the risk of hemolysis associated with the high dose of RhIG required. This survey underscores the diverse and inadequate institutional policies on RhIG immunoprophylaxis after RhD exposure in Rh-negative patients via transfusion. This observation identifies an opportunity to improve transfusion safety.

Recent RhIG Administration Does Not Interfere with the Rosette Test

Abstract Introduction/Objective Administration of Rh immune globulin (RhIG) is indicated mid-gestation (28 weeks) and after delivery to prevent Rh D sensitization in Rh D negative women. Women with sporadic prenatal care may not receive the first dose at 28 weeks, and may end up receiving their first dose closer to delivery. The rosette test (RT) is a rapid screen for fetomaternal hemorrhage (FMH) that uses an IgM anti-D antibody to detect fetal Rh D positive red blood cells (RBC) in maternal circulation. It is not currently known if or how recent administration of RhIG prior to performance of a RT may interfere with RBC agglutination and test results. Methods/Case Report To approximate mixing of fetal Rh D positive RBC with maternal Rh D negative RBC during FMH, 2% volume of Rh D positive RBC from fetal cord and adult donor samples were spiked into Rh D negative RBC. These mixtures were then incubated with a physiologic concentration of RhIG to occupy all Rh D antigen sites on the Rh D positive cells prior to performing the RT. Results (if a Case Study enter NA) Addition of Rh D positive RBC and RhIG to Rh D negative RBC did not affect rosette formation. Rh D negative cells had 0 rosettes/LPF. Rh D negative cells spiked with 2% Rh D positive adult donor and fetal cord RBC by volume produced an average of 9.8 rosettes/LPF (SD: 2.8) and 11.2 (SD: 3.3), respectively. Addition of a physiologic concentration of RhIG to the spiked Rh D positive adult donor and fetal cord RBC produced an average of 13.0 rosettes/LPF (SD: 2.5) and 11.2 rosettes/LPF (SD: 2.6), respectively. Conclusion Incubation of Rh D positive RBCs with physiologic concentration of RhIG does not affect the rosette test. Clinicians and laboratorians should be reassured that the rosette test continues to be an accurate way to quantitate FMH after recent RhIG administration.

Adherence to Rh Immune Globulin Prophylaxis Guidelines: An Audit of a Modern Obstetric Cohort [34Q

INTRODUCTION: There is excellent evidence for postpartum Rh immune globulin (RhIG) prophylaxis efficacy and effectiveness. Continued adherence to RhIG prophylaxis guidelines is essential in preventing Rh alloimmunization and hemolytic disease of the newborn. This study aimed to perform an audit of RhIG prophylaxis practice in a modern obstetric cohort. METHODS: A retrospective chart review of 451 consecutive deliveries of Rh-negative women at a single-site tertiary medical center was performed. Fisher exact test was used for statistical analysis. RESULTS: The prevalence of Rh negativity was 8.9%. Of the Rh-negative women eligible to receive postpartum RhIG, 97.7% received RhIG and 98.9% were screened for fetomaternal hemorrhage (FMH). Of the Rh-negative women ineligible for RhIG administration, 4.6% inappropriately received RhIG and 91.9% were incorrectly screened for FMH. Evidence of FMH was demonstrated in 26.6% of Rh-negative women. Additionally, 1.7% of Rh-negative women had evidence of excessive FMH requiring additional administration of RhIG. Patients with FMH were more likely to have evidence of maternal acute blood loss anemia (47.8% versus 32.9%, P < .05). Mode of delivery was not associated with increased likelihood of FMH (P=.4). CONCLUSION: This audit revealed two key areas for improvement. First, the widespread practice of ordering an unnecessary laboratory test was identified. Second, the rates of failure to order RhIG and FMH screening were determined. Though multiple factors likely contribute to imperfect adherence to guidelines, RhIG prophylaxis has historically been physician-driven at our institution. Implementing a protocol-driven approach may improve adherence; however, further study will be necessary to determine a superior approach.

Two cases of the variant RHD*DAU5 allele associated with maternal alloanti-D

Rh is a complex blood group system with diverse genotypes that may encode weak and partial D variants. Standard serologic analysis may identify clinically significant D variants as D+; nevertheless, individuals with these D variants should be managed as D- patients to prevent antibody formation to absent D epitopes. Variant identification is necessary during pregnancy to allow for timely and appropriate Rh immune globulin (RhIG) prophylaxis for hemolytic disease of the fetus and newborn (HDFN) as D alloimmunization can occur with some D variants. Here, we describe two cases of the RHD*DAU5 allele associated with maternal alloanti-D in patients of African ancestry. Two obstetric patients were initially serologically classified as D+ with negative antibody detection tests on routine prenatal testing. Repeat testing at delivery identified anti-D in both patients with no history of RhIG administration or transfusion. DNA sequencing revealed that both patients possessed the RHD*DAU5 allele. Cord blood testing on both infants revealed positive direct antiglobulin test (DAT) results with anti-D eluted from the red blood cells (RBCs) of one of the infants. Despite the positive DAT, neither infant experienced anemia or hyperbilirubinemia. We document two cases of pregnant women whose RBCs expressed a partial D variant and were classified as D+ on the basis of standard serologic testing, resulting in subsequent failure to provide RhIG prophylaxis. Both cases were associated with alloanti-D formation but without significant HDFN. To our knowledge, these are the first reported cases of maternal alloanti-D associated with the RHD*DAU5 partial D variant.

Cost‐effectiveness of implementing molecular immunohematology

BackgroundMolecular immunohematology is practised in clinical laboratories and blood centres. It is based on red cell genotyping, which is a technology whereby DNA‐based techniques are used to evaluate genes for the particular single and multiple nucleotide substitutions, deletions, insertions and gene conversions that determine the expression of red cell antigens. Fetal red cell genotyping, and in particular RHD genotyping, using the discarded cell pellet of amniotic fluid was developed some 20 years ago. It replaced the need for fetal blood sampling and also can determine paternal zygosity with better certainty. Cell‐free fetal DNA in maternal plasma is now the non‐invasive (fetal) alternative to amniotic fluid as the biological material of choice. It is being used in Europe to reduce the exposure of Rh immune globulin for the routine Rh‐negative pregnancy. RHD genotyping is used to determine zygosity and resolve weak D antigen discrepancies as a cost equivalent alternative to the administration of Rh immune globulin. Since then, a plethora of data has accumulated on the value of screening donors for rare blood types. For common antigens, red cell genotyping as an historical test‐of‐record will create efficiencies in the labelling of antigen‐negative blood if care is taken in testing appropriate repeat donors. Certainly, it has been shown that exposing antigen‐negative types through the entire supply chain replaces shipping from a central facility.ConclusionMolecular immunohematology is not the implementation of cost reductions but the recognition of ‘effective’ processes and algorithms that incorporate molecular testing to provide tangible benefits to pregnant women and transfusion recipients.

Laboratory management of perinatal patients with apparently “new” anti-D

Despite the existence of long-standing, well-organized programs for Rh immune globulin (RhIG) prophylaxis, immune anti-D continues to be detected in the D– perinatal population. Between 2006 and 2008, 91 prenatal patients, found to have a previously unidentified anti-D, were followed up with a survey to their treating physician and with additional serologic testing where possible. The physician survey requested pregnancy and RhIG history information, including recent or distant potential alloimmunizing events, and the physicians were asked their opinion on the likely cause for the anti-D. Based on survey responses, updated RhIG information, and results of follow-up serology, anti-D was determined to be attributable to previously unreported RhIG in 44 of 91 (48.3%) cases and to active immunization (immune anti-D) in 36 of 91 cases (39.6%). A probable cause for alloimmunization was reported in 14 of 52 (26.9%) returned surveys. Anti-D alloimmunization continues to occur in our prenatal population despite a comprehensive approach to RhIG therapy. Observations from this prospective patient management strategy include the need for improved application of guidelines for RhIG administration and improved quality of information provided to laboratories assessing RhIG eligibility. A laboratory process for prospective follow-up when unexpected anti-D is detected in pregnancy is recommended.

RhOD immune globulin products for prevention of alloimmunization during pregnancy

The pharmacologic properties of Rhesus (Rh) immune globulin (RhIG) and clinical data on its effectiveness in preventing Rh-antigen alloimmunization in pregnant women are reviewed. RhIG is a human plasma derivative that targets red blood cells (RBCs) positive for Rh(O) antigen (also called D antigen). In the United States and other countries, the widespread use of RhIG has markedly reduced the occurrence of hemolytic disease of the fetus and newborn (HDFN), a devastating condition caused by D-antigen sensitization of a pregnant woman via exposure to fetal RBCs (usually during detachment of the placenta in labor) that results in a maternal immune response leading to severe hemolysis in the fetus. Routine administration of RhIG at 26-30 weeks' gestation and again within 72 hours of delivery has been shown to be highly effective in preventing maternal Rh alloimmunization, with very low rates of D-antigen sensitization (in the range of 0-2.2%) reported in multiple studies of at-risk women. The four RhIG products currently available in the United States have common clinical indications but differ in certain attributes. Pharmacists can play an important role in guiding other clinicians on the rationale for the use of RhIG, important differences between products, and appropriate timing of RhIG therapy. Routine administration of RhIG to women at risk for Rh alloimmunization is clinically effective and has made HDFN a rare clinical event. The available RhIG products are not the same and should be carefully reviewed to ensure that they are administered safely.

It's time to phase in RHD genotyping for patients with a serologic weak D phenotype. College of American Pathologists Transfusion Medicine Resource Committee Work Group.

It's time to phase in RHD genotyping for patients with a serologic weak D phenotype. College of American Pathologists Transfusion Medicine Resource Committee Work Group.

Unexpected suppression of anti‐Fya and prevention of hemolytic disease of the fetus and newborn after administration of Rh immune globulin

Rh immune globulin (RhIG) has been used successfully for many years for the antenatal suppression of anti-D in D- mothers carrying D+ babies to prevent hemolytic disease of the fetus and newborn. Although the mechanism of RhIG-induced immunosuppression remains unknown, a recent report (TRANSFUSION 2006;46:1316-22) has shown that women receiving RhIG produce elevated levels of transforming growth factor (TGF)β-1, a powerful immunosuppressant cytokine. It was suggested that induction of TGFβ-1 and immunosuppression may be independent of cognate antigen recognition by RhIG. Herein, we present a description of a mother and baby that supports this hypothesis. Red blood cells and serum were analyzed using saline-tube indirect antiglobulin test methods. RhIG (RhoGAM) was administered after each amniocentesis performed at 28, 31, and 36 weeks' gestation. A group A, D-(cde), K+, Fy(a-b+), MNs, Jk(a+b+) mother with no detectable anti-D had an anti-Fy(a) titer of 4096 before RhIG but only 256 after RhIG. Mother gave birth to a group O, D-(cde), Fy(a+b+) healthy baby boy having a weak-positive direct antiglobulin test with anti-Fy(a) eluted from his cells and the titer in the cord serum was 4. This case demonstrates the potential immunosuppressive properties of RhIG for down regulation of a possible clinically significant alloantibody, not anti-D, where no D+ antigen is in the circulation of the mother. The case illustrates the potential utility for using RhIG to modulate antibody levels in situations other than for classical suppression of anti-D production. Although the mechanism in this case is unknown, TGFβ-1-mediated or antibody-mediated immunosuppression to soluble nonparticulate antigens are possible mechanisms.

Antenatal administration of Rh‐immune globulin causes significant increases in the immunomodulatory cytokines transforming growth factor‐β and prostaglandin E2

Production of specific cytokines in response to administration of Rh-immune globulin (RhIG) was examined to assess the mechanism of inhibition of the anti-D production and prevention of hemolytic disease of the newborn (HDN). Plasma levels of 17 different cytokines before and 48 hours after antenatal administration of anti-D were measured in 10 women candidates for prophylaxis with RhIG. No striking changes were observed in levels of the cytokines interleukin (IL)-1 sRII, IL-12 p40, IL-16, or monocyte chemoattractant protein-1. Levels of IL-4, -5, -10, -13, and -17; macrophage inflammatory protein-1alpha; granulocyte-macrophage-colony-stimulating factor; tumor necrosis factor-beta; and interferon-gamma remained below detection levels both before and after testing. IL-1ra levels, however, showed a slight to moderate decrease in 7 of 10 women after RhIG administration. In contrast, levels of TGF-beta1 increased more than 1.3-fold in 7 of 10 women and more than 2-fold in 4 of 10 women; in 1 instance the increase was more than 5-fold and this woman also had a significant increase in TGF-beta2. In addition to TGF-beta, 5 of 10 women had a modest increase (>1.5-fold) in prostaglandin E2 (PGE2). Analyses of the combined results of the 10 women showed that increases in both TGF-beta1 and PGE2 after RhIG were significant. These results indicate that RhIG prophylaxis can induce higher than baseline levels of two strongly immunomodulatory cytokines, TGF-beta and PGE2. These findings represent one possible mechanism for the inhibition of the primary immune response to the D antigen in women receiving RhIG prophylaxis for prevention of HDN.

Red Blood Cell Alloimmunization: Principles and Management in Pregnancy

Despite significant advances in immunohematology, including the discovery of the Rhesus factor and the subsequent development of nationwide Rh immune globulin prophylaxis programs, the incidence of Rhesus alloimmunization is one to two per 1000 Rh-negative women. This is largely due to the lack of administration of Rh immune globulin in high risk situations. The identification of a sensitized pregnant patient requires an initial antibody screen with appropriate antibody titres and paternal red blood cell antigen pheno-typing. Fetuses, identified at high risk due to critical antibody titre levels, require invasive action with serial amniocenteses plus amniocyte antigen testing. Percutaneous umbilical blood sampling or intrauterine fetal transfusion may be dictated in severe situations.

Use of the gel agglutination technique for determination of fetomaternal hemorrhage.

Adequate administration of Rh immune globulin requires an accurate determination of the number of D-positive cells in the circulation of D-negative women. Although several tests have been described for the detection of fetomaternal hemorrhage, there is still a need for a rapid, simple, and clinically relevant screening test. Serial dilutions of a monoclonal anti-D were incubated with stock solutions (0.2 mL) of adult D-negative red cells in the absence or presence of various amounts of fetal D-positive cells (0.1, 0.2, 0.3, 0.4, and 0.5%). After incubation, the supernatants were tested against D-positive red cells by using the new, gel agglutination technique (GAT). After the GAT was adapted to detect D-positive cells at concentrations of > or = 0.2 percent, unselected postpartum samples from D-negative women (n = 420) who delivered D-positive infants were analyzed by both the new test and the Kleihauer-Betke test (KBT). Three of a total of 420 postpartum samples were positive (> or = 0.4% fetal cells), and 406 were negative in both tests. One had 0.5-percent fetal cells in the KBT and gave negative results in the GAT. The latter test was, however, performed after administration of Rh immune globulin. The KBT gave false-positive results in two cases, because of hereditary persistence of hemoglobin F, and the GAT gave a false-positive reaction in one case because of a maternal weak D variant. In the remaining seven cases, the KBT results were only weakly positive (0.2%) and could not be attributed solely to D positive red cells. The GAT is suited for routine screening. It provides rapid and specific detection of D-positive red cells at clinically relevant concentrations. The test may (rarely) yield false-negative results due to insufficient administration of Rh immune globulin before testing.

Detection of anti-D following antepartum injections of Rh immune globulin

Abstract Antepartum prophylaxis using Rh immune globulin (RhIG) at 28 weeks of gestation is routine in unsensitized Rh-negative women. As various sources state that anti-D may be detected up to 6 months after administration, we reviewed the medical and laboratory records of all Rh-negative women who delivered at our institution during 1995. For 385 evaluable women, only 137 (35.6%) had anti-D demonstrable in their sera at delivery; 97.8 percent of these delivered within 75 days after administration of RhIG. Of 248 women (64.4%) who delivered in < 76 days after administration of RhIG, 134 (54%) had demonstrable anti-D. For 123 women who delivered between 76 to 95 days after RhIG, only 3 (2.4%) had demonstrable anti-D. Of 14 women who delivered more than 96 days after RhIG, none had anti- D at delivery. These data show that the 300-μg dose used in the United States may not be adequate for antepartum protection and that the detection of anti-D more than 100 days after the administration of RhIG should be viewed with suspicion.

Detecting fetomaternal hemorrhage: a comparison of five methods

Appropriate postpartum administration of Rh immune globulin relies on sensitive detection and accurate quantitation of fetomaternal hemorrhage (FMH). Recently, the microscopic Du test (micro Du) enhanced with polyethylene glycol (PEG Du) and flow cytometry (FC) have been advocated for this purpose. Three qualitative methods (micro Du, rosette test, and PEG Du) and two quantitative methods (acid elution and FC) for assessing FMH were evaluated with particular attention given to PEG Du and FC. In vitro studies comprised 10 series of dilutions of D+ cord cells in D- adult cells to yield D+ cell concentrations of 0.06, 0.12, 0.25, 0.50, 0.75, 1.0, and 2.0 percent. Additionally, 26 postpartum samples were tested. Of the qualitative techniques, the micro Du test was the least sensitive with 20 percent false-negative results occurring at 0.5 percent fetal cells. The PEG Du test was only slightly more sensitive and offered no clinical advantage. The rosette test was the most sensitive, consistently detecting fetal cells at concentrations of 0.25 percent or greater. FC and acid elution showed similar results, with good correlation obtained between measured and expected quantities of fetal cells (r = 0.99 and 0.96, respectively). One of 26 postpartum samples was positive by all screening techniques; acid elution and FC detected 0.3-percent concentrations of fetal cells and 0.17-percent concentrations of D+ cells, respectively. Although acid elution is a more commonly used method for quantitating FMH, FC offers an acceptable alternative that is capable of analyzing large numbers of cells with objectivity and reproducibility.

Postinjection kinetics of antepartum Rh immune globulin

The disappearance kinetics of a standard dose of 300 (µd of Rh immune globulin given at 28 weeks' gestation was investigated. Ten Rh-negative unsensitized women were given 300 µg of Rh immune globulin at 28 weeks and blood samples were drawn at weekly intervals until delivery. Sera were titrated with Ror red blood cells in a saline solution-antiglobulin method. Titers ranged from 1 to 4 by the first week after injection. In nine of 10 patients the titers were zero at 49 to 70 days after injection. With R2R2 red blood cells and LISS, papain, polybrene, or a combination of methods, Rh immune globulin could still be detected until delivery in four of the nine patients. Because these serologic methods can detect 5 ng/ml anti-D, five of 10 subjects may not have been protected for 8 to 29 days before delivery. This study indicates that a titer of ≤ 4 is expected for passively acquired anti-D during pregnancy, and that antepartum administration of Rh immune globulin may not always produce detectable passive antibody for as long as theoretically predicted.

Prenatal screening

This report discusses the role of prenatal screening in preventing congenital abnormalities or, when prevention is not possible, in avoiding the conception or the birth of those who would have untreatable abnormalities. Women who are found by screening not to be immune to rubella can be safely vaccinated prior to pregnancy; those found to be at risk of having children with genetic disorders such as Tay-Sachs disease or thalassemia have the option of avoiding the conception of affected offspring. Screening during pregnancy permits the primary prevention of Rh disease and its sequelae when it results in the prophylactic administration of Rh-immune globulin to unsensitized Rh-negative women. Maternal serum alpha-fetoprotein screening identifies pregnant women who are at increased risk of carrying fetuses with neural tube defects or Down's syndrome, giving them the option of avoiding the birth of affected fetuses through abortion. Recombinant DNA technology will permit screening for many more genetic disorders as the disease-related genes and mutations are identified. For many of these disorders, the ability to predict the risk of disease will antedate preventive and therapeutic interventions by many years. During this lag phase, issues concerning the validity of the tests, the severity of the conditions for which screening is offered, the safety of the interventions, and the autonomy of the pregnant women in deciding to be screened are important.

The prevention of Rh immunization.

Administration of Rh immune globulin to the Rh-negative unimmunized woman at risk of Rh-immunization is highly effective if given in sufficient dose prior to active Rh-immunization. Remaining problems are: 1. treating all of those at risk, 2. protecting those who abort, 3. treating after amniocentesis, 4. instituting an antenatal prophylaxis program to protect the 1.8 percent immunized too early to be protected by post-delivery injection of Rh immune globulin, 5. protecting those who have had massive transplacental fetal hemorrhages. All physicians practicing obstetrics should ensure that all of their unimmunized Rh-negative women are protected against Rh-immunization.