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This Clinical Practice Update provides revised guidance on Rh testing and Rh D immune globulin administration for individuals undergoing abortion or experiencing pregnancy loss at less than 12 0/7 weeks of gestation. This document updates Practice Bulletin No. 225, Medication Abortion Up to 70 Days of Gestation (Obstet Gynecol 2020;136:e31-47); Practice Bulletin No. 200, Early Pregnancy Loss (Obstet Gynecol 2018;132:e197-207); and Practice Bulletin No. 181, Prevention of Rh D Alloimmunization (Obstet Gynecol 2017;130:e57-70)., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: 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., Results: 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., Discussion: 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., Conclusion: 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., (© 2024 AABB.)

Objective: This guideline provides recommendations for the prevention of Rh D alloimmunization (isoimmunization) in pregnancy, including parental testing, routine postpartum and antepartum prophylaxis, and other clinical indications for prophylaxis. Prevention of red cell alloimmunization in pregnancy with atypical antigens (other than the D antigen), for which immunoprophylaxis is not currently available, is not addressed in this guideline., Target Population: All Rh D-negative pregnant individuals at risk for Rh D alloimmunization due to potential exposure to a paternally derived fetal Rh D antigen., Outcomes: Routine postpartum and antepartum Rh D immunoprophylaxis reduces the risk of Rh D alloimmunization at 6 months postpartum and in a subsequent pregnancy., Benefits, Harms, and Costs: This guideline details the population of pregnant individuals who may benefit from Rho(D) immune globulin (RhIG) immunoprophylaxis. Thus, those for whom the intervention is not required may avoid adverse effects, while those who are at risk of alloimmunization may mitigate this risk for themselves and/or their fetus., Evidence: For recommendations regarding use of RhIG, Medline and Medline in Process via Ovid and Embase Classic + Embase via Ovid were searched using both the trials and observational studies search strategies with study design filters. For trials, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects via Ovid were also searched. All databases were searched from January 2000 to November 26, 2019. Studies published before 2000 were captured from the grey literature of national obstetrics and gynaecology specialty societies, luminary specialty journals, and bibliographic searching. A formal process for the systematic review was undertaken for this update, as described in the systematic review manuscript published separately., Validation Methods: The authors rated the quality of evidence and strength of recommendations using the SOGC's modified GRADE approach. See Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations)., Intended Audience: The intended users of this guideline include prenatal care providers such as obstetricians, midwives, family physicians, emergency room physicians, and residents, as well as registered nurses and nurse practitioners., Tweetable Abstract: An updated Canadian guideline for prevention of Rh D alloimmunization addresses D variants, cffDNA for fetal Rh type, and updates recommendations on timing of RhIG administration., Summary Statements: RECOMMENDATIONS., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Targeted routine antenatal anti-D prophylaxis was introduced to the national prophylaxis program in Finland in late 2013. The aim of this study was to assess the incidence, time-points, and risk factors for Rhesus D immunization after the implementation of routine antenatal anti-D prophylaxis, in all women in Finland with antenatal anti-D antibodies detected in 2014-2017., Material and Methods: In a nationwide population-based retrospective cohort study, the incidence, time-points, and risk factors of anti-D immunizations were analyzed. Information on antenatal screening was obtained from the Finnish Red Cross Blood Service database, and obstetric data from hospital records and the Finnish Medical Birth Register., Results: The study included a total of 228 women (197 with complete data for all pregnancies). After the implementation of routine antenatal anti-D prophylaxis, the prevalence of pregnancies with anti-D antibodies decreased from 1.52% in 2014 to 0.88% in 2017, and the corresponding incidence of new immunizations decreased from 0.33% to 0.10%. Time-points for detection of new anti-D antibodies before and after 2014 were the first screening sample at 8-12 weeks of gestation in 52% vs 19%, the second sample at 24-26 weeks in 20% vs 50%, and the third screening at 36 weeks in 28% vs 32%., Conclusions: The incidence of new anti-D immunizations decreased as expected after the implementation of routine antenatal anti-D prophylaxis. True failures are rare and they mainly occur when the prophylaxis is not given appropriately, suggesting a need for constant education of healthcare professionals on the subject., (© 2021 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: The development of rh immune globulin (RhIG) for the prevention of Rhesus D (RhD) alloimmunization has significantly decreased the incidence of RhD alloimmunization. Despite long-standing prevention, the experiences of RhD negative women with pregnancy is absent in the literature., Aim: The purpose of this study was to explore the experiences of RhD negative women with pregnancy., Methods: Utilizing an Interpretive Description approach, semi-structured interviews were conducted with RhD negative women about their pregnancies. This study took place within the geographic context of northern British Columbia (BC). The analysis involved a two-cycle approach to identify themes within the data., Findings: Sixteen RhD negative women that live in northern BC participated in this study. The analysis identified that RhD negative women are uninformed and want to be involved in the decision-making process regarding the prevention of RhD alloimmunization. The themes that emerged from the interview data were communication, information-seeking behaviour, out of sight out of mind, choice and trust, and patient advocacy., Discussion: The participants in this study described lacking information regarding the prevention of RhD alloimmunization. They sought information to overcome the gaps in knowledge and a desire to be involved in the decision-making process., Conclusion: RhD negative women want information and to be involved in the decision-making process in the prevention of RhD alloimmunization. Working with RhD negative women to develop decision-aids and/or other educational tools to aid in the decision-making process are warranted., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Rhesus D (RhD) negative pregnant women carrying an RhD positive fetus are at risk of developing anti-D during or after pregnancy. Anti-d-immunoglobulin (RhIg), which is mainly produced from special plasma donated in a few countries for the whole world, is able to prevent an anti-D alloimmunization. Through the introduction of ante- and postnatal anti-d-prophylaxis into clinical routine, the frequency of hemolytic disease of fetus and newborn decreased considerably. Postnatal prophylaxis from the beginning in the 1960s has been applied only to women who delivered an RhD positive newborn. Because the fetal RhD status can be determined with high sensitivity and accuracy from the mother's peripheral blood, targeted antenatal anti-d-prophylaxis is becoming a new standard procedure in more and more countries. Phototherapy and exchange transfusion are still the main pillars for the treatment of RhD hemolytic disease of the newborn. The efficacy of IVIg in the management of these neonates is not conclusive and cannot be recommended until a larger randomized, double-blind, placebo-controlled study is performed., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Objectives: D-negative patients are at risk of developing an alloantibody to D (anti-D) if exposed to D during transfusion. The presence of anti-D can lead to haemolytic transfusion reactions and haemolytic disease of the newborn. Anti-D alloimmunization can also complicate allogeneic haematopoietic stem cell transplantation (HSCT) with haemolysis and increased transfusion requirements. The goal of this study was to determine whether cancer centres have transfusion practices intended to prevent anti-D alloimmunization with special attention in patients considered for HSCT., Methods and Materials: To understand transfusion practices regarding D-positive platelets in D-negative patients with large transfusion needs, we surveyed the 28 cancer centres that are members of the National Comprehensive Cancer Network ® (NCCN ® )., Results: Nineteen centres responded (68%). Most centres (79%) avoid transfusing D-positive platelets to RhD-negative patients when possible. Four centres (21%) avoid D-positive platelets only in D-negative women of childbearing age. If a D-negative patient receives a D-positive platelet transfusion, 53% of centres would consider treating with Rh immune globulin (RhIg) to prevent alloimmunization in women of childbearing age. Only one centre also gives RhIg to all D-negative patients who are HSCT candidates including adult men and women of no childbearing age., Conclusion: There is wide variation in platelet transfusion practices for supporting D-negative patients. The majority of centres do not have D-positive platelet transfusion policies focused on preventing anti-D alloimmunization specifically in patients undergoing HSCT. Multicentre, longitudinal studies are needed to understand the clinical implications of anti-D alloimmunization in HSCT patients., (© 2020 International Society of Blood Transfusion.)

Background: All non-sensitized Rhesus D (RhD)-negative pregnant women in Germany receive antenatal anti-D prophylaxis without knowledge of fetal RhD status. Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal plasma could avoid unnecessary anti-D administration. In this paper, we systematically reviewed the evidence on the benefit of NIPT for fetal RhD status in RhD-negative pregnant women., Methods: We systematically searched several bibliographic databases, trial registries, and other sources (up to October 2019) for controlled intervention studies investigating NIPT for fetal RhD versus conventional anti-D prophylaxis. The focus was on the impact on fetal and maternal morbidity. We primarily considered direct evidence (from randomized controlled trials) or if unavailable, linked evidence (from diagnostic accuracy studies and from controlled intervention studies investigating the administration or withholding of anti-D prophylaxis). The results of diagnostic accuracy studies were pooled in bivariate meta-analyses., Results: Neither direct evidence nor sufficient data for linked evidence were identified. Meta-analysis of data from about 60,000 participants showed high sensitivity (99.9%; 95% CI [99.5%; 100%] and specificity (99.2%; 95% CI [98.5%; 99.5%])., Conclusions: NIPT for fetal RhD status is equivalent to conventional serologic testing using the newborn's blood. Studies investigating patient-relevant outcomes are still lacking.

Background: Rhesus D (RhD) incompatibility is still the most important cause of hemolytic disease of the fetus and newborn (HDFN) worldwide. The aim of this study was to investigate the incidence, causes, and consequences of anti-D alloimmunizations in pregnancy in Iceland, prior to implementation of targeted routine antenatal anti-D prophylaxis (RAADP) in 2018., Study Design and Methods: This was a nation-wide cohort study of 130 pregnancies affected by RhD alloimmunization in Iceland in the period from 1996 through 2015. Data were collected from transfusion medicine databases, medical records, and the Icelandic Medical Birth Register., Results: Of 130 RhD alloimmunizations, 80 cases (61.5%) represented new RhD immunization in the current pregnancy. Sensitization was discovered in the third trimester in 41 (51.3%) and occurred in the first pregnancy in 14 cases (17.5%). The most likely causative immunization event was the index pregnancy for 45 (56.25%), a previous pregnancy/birth for 26 (32.5%), abortion for 3 (3.75%), and unknown for 6 women (7.5%). Higher anti-D titers were associated with shorter gestational length, cesarean sections, positive direct antiglobulin test (DAT), and severe HDFN. Intrauterine transfusion (IUT) was performed in five pregnancies (3.8%), and 35 of 132 (26.5%) live-born neonates received treatment for HDFN; 32 received phototherapy (24.2%), 13 exchange transfusion (9.8%), and seven simple blood transfusion (5.3%)., Conclusion: In about half of cases, RhD alloimmunization was caused by the index pregnancy and discovered in the third trimester. Thus, the newly implemented RAADP protocol should be effective in reducing the incidence of RhD immunization in Iceland in the future., (© 2019 AABB.)

Severe morbidity and death because of Rh disease have only been reduced by approximately 50% globally during the last 50 years, despite the advent of anti-Rh(D) immunoglobin prophylaxis, which has resulted in >160,000 perinatal deaths and 100,000 disabilities annually. This apparent failure to take appropriate preventive measures is of great concern. Thus, there is a great need to do much better. We wish to draw attention to the unnecessary continuing burden of Rh disease, to discuss some of the reasons for this failure, and to provide suggestions for a better way forward., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To describe fetomaternal hemorrhage (FMH) during second-trimester dilation and evacuation (D&E) to evaluate if Rhesus-immune globulin (RhIG) 100 mcg (used in the United Kingdom) and 300 mcg (used in the United States) provide adequate prophylaxis., Study Design: We conducted an exploratory prospective descriptive study of women undergoing D&E between 15 weeks 0 days and 23 weeks 6 days of gestation. Enrolled participants had Kleihauer-Betke testing on specimens obtained before and after D&E. We assessed the main outcome measures of FMH in mL suggesting need for more than 100 mcg and 300 mcg RhIG (FMH of 10 mL and 30 mL fetal whole blood, respectively) and association of postprocedure FMH with demographic characteristics and procedure-related variables., Results: The 300 participants had a mean gestational age of 19 weeks 6 days±2 weeks 2 days. The median preprocedure FMH was 0 mL (range 0-50 mL) with 2 (0.67%) women exceeding 10 mL (19 mL and 50 mL). The median postprocedure FMH was 1 mL (range 0-60 mL). Almost all participants had postprocedure FMH <10 mL (n=295, 98.3%) and <30 mL (n=298, 99.3%). All participants under 18 weeks had FMH <10 mL. We found no demographic or procedure-related factors to be predictive of FMH quantity., Conclusions: FMH occurring with routine second-trimester D&E procedures is minimal. Adequate prophylaxis with RhIG 100 mcg and 300 mcg occurred in >98% of women and in all cases <18 weeks of gestation. This study is the first step to potentially reducing the dose and costs of RhIG administration with D&E., Implications: This study is a first step in quantifying fetomaternal hemorrhage with routine dilation and evacuation procedures; larger trials are needed, especially to understand why some women have recognizable hemorrhage preprocedure. If dosing requirements are too high with current guidelines, lower doses will result in resource and cost savings., (Copyright © 2018. Published by Elsevier Inc.)

Background and Objectives: Fetal RHD genotyping of cell-free fetal DNA from RhD-negative pregnant women can be used to guide targeted antenatal and postnatal anti-D prophylaxis for the prevention of RhD immunization. To assure the quality of clinical testing, we conducted an external quality assessment workshop with the participation of 28 laboratories., Materials and Methods: Aliquots of pooled maternal plasma were sent to each laboratory. One sample was positive, and the second sample was negative for fetal RHD, verified by pre-workshop testing using quantitative real-time PCR (qPCR) analysis of RHD exons 4, 5, 7 and 10. Plasma samples were shipped at room temperature. A reporting scheme was supplied for data collection, including questions regarding the methodological setup, results and clinical recommendations. Different methodological approaches were used, all employing qPCR with a total of eight different combinations of RHD exon targets. The samples were tested blindly., Results: Fetal RHD genotyping was performed with no false-negative and no false-positive results. One inconclusive result was reported for the RHD-positive sample, and four inconclusive results were reported for the RHD-negative sample. All clinical conclusions were satisfactory., Conclusion: This external quality assessment workshop demonstrates that despite the different approaches taken to perform the clinical assays, fetal RHD genotyping is a reliable laboratory assay to guide targeted use of Rh prophylaxis in a clinical setting., (© 2019 International Society of Blood Transfusion.)

Objective: To compare the efficacy and costs of three different strategies of antenatal rhesus immune globulin (RhIG) administration in a US population., Methods: A decision tree analysis was undertaken for universal antenatal RhIG administration based on RhD serologic paternity testing, universal administration without paternity, and selective antenatal RhIG administration using cell free fetal DNA (cfDNA) for RHD fetal typing. Rates of alloimmunization were calculated. Charges were determined for laboratory testing and obstetrical and neonatal treatments for the first pregnancy and cases of alloimmunization in the following pregnancy., Results: The largest number of new RhD alloimmunization cases resulted from a strategy of universal RhIG that included paternity. Fewer cases resulted from a selective strategy; the least number of cases were associated with a universal approach that discounted paternity. When the costs of first pregnancies and alloimmunized second pregnancies were combined, a universal strategy that excludes paternity had the least costs followed by a selective strategy followed by a universal strategy that included paternity., Conclusion: The use of cfDNA to determine the selective use of antenatal RhIG would not be cost-effective in the United States. Universal antenatal RhIG without paternity is more effective in preventing new cases of alloimmunization than the current ACOG guideline., (© 2019 John Wiley & Sons, Ltd.)

Background: The determination of foetal Rhesus D (RHD) status allows appropriate use of IgRh prophylaxis by restricting its use to cases of RHD feto-maternal incompatibilities. There is a degree of uncertainty about the cost-effectiveness of foetal RHD determination, yet screening programs are being introduced into clinical practice in many countries. This paper evaluates the impact of non-invasive foetal Rhesus D (RHD) status determination on the costs of managing RHD-negative pregnant women and on the appropriate use of anti-D prophylaxis in a large sample of RHD-negative pregnant women using individual prospectively collected clinical and economic data., Methods: A prospective two-armed trial of RHD negative pregnant women was performed in 11 French Obstetric Departments. Non-invasive foetal RHD genotyping was performed before 26 weeks' gestation in the experimental arm whereas the control arm participants received usual care. The costs associated with patient management in relation to their RHD negative status (biological tests, anti-D prophylaxis and visits) were calculated from inclusion to the end of the postpartum period. The costs of hospital admissions during pregnancy and delivery were also determined., Results: A total of 949 patients were included by 11 centres between 2009 and 2012, and 850 completed follow-up, including medical and biological monitoring. Patients were separated into two groups: the genotyping group (n=515) and the control group (n=335). The cost of the genotyping was estimated at 140 euros per test. The total mean cost per patient was estimated at €3,259 (SD ± 1,120) and €3,004 (SD ± 1,004) in the genotyping and control groups respectively. The cost of delivery represented three quarters of the total cost in both groups. The performance of managing appropriately RHD negative anti-D prophylaxis was 88% in the genotyping group, versus 65% in the control group. Using the costs related to RHD status (biological tests, anti-D immunoglobulin injections and visits) the incremental cost-effectiveness ratio (ICER) was calculated to be €578 for each percentage gain in women receiving appropriate management., Conclusion: Early knowledge of the RHD status of the foetus using non-invasive foetal RHD genotyping significantly improved the management of RHD negative pregnancies with a small increase in cost., Trial Registration: Clinical trials registry- NCT00832962 -13 January 2009 - retrospectively registered.

Background: The successful introduction of prophylaxis with anti-RhD immunoglobulin has resulted in a significant decline of pregnancy-related RhD immunizations but also has decreased the availability of naturally immunized women as (new) anti-D donors. An influx of new donors is necessary to maintain a sufficient pool of anti-D donors. We investigated motivators, barriers, and predictors for anti-D donorship in RhD-immunized women., Study Design and Methods: A mixed-methods design was applied, including focus group discussions and questionnaires. Two focus groups (including 11 women) served as input for the questionnaire., Results: In total, 47.6% of 750 anti-D donors and potential donors completed the questionnaire (50.4% donors; 38% nondonors; 11.6% former donors). Almost 70% of the nondonors would have become donors if they had known about the possibility. Travel time investment was reported as a disadvantage; one-half of donors mentioned no disadvantages. Motivators for anti-D donorship were "doing something in return" (31.2%) and "preventing others having a sick child or losing a child" (33.9%). In multivariable analysis, living single (odds ratio, 5.8; p = 0.02) and living partnered without resident children (odds ratio, 7.9; p = 0.03), compared with living partnered with children, were predictors for anti-D donorship. Not being registered as an organ donor (odds ratio, 0.25; p < 0.001) predicted that the individual would not be an anti-D donor., Conclusion: The main barrier for anti-D donorship was a lack of knowledge. Positive predictors of anti-D donorship were living without resident children, altruism, and being registered as an organ donor. A blood bank should develop targeted recruitment strategies with a focus on spreading knowledge about anti-D donorship among RhD-immunized women., (© 2018 AABB.)

Background/aim: The aim of this study was to assess unnecessary immunization rates and compare the cost-effectiveness of targeted prophylaxis with fetal Rh genotyping with that of traditional management of Rh-Rh incompatibility in a virtual economic model. Materials and methods: This retrospective data analysis was conducted at two tertiary centers between 2011 and 2015. The data of 1135 pregnant women were analyzed. The main outcome measure was to determine the unnecessary immunization rate among the whole Rh-Rh incompatibility group. The second outcome measure was to compare the cost-effectiveness of universal immunization with that of targeted prophylaxis with fetal Rh genotyping in a virtual economic model. Results: Average cost per patient was found as $259.20 with universal prophylaxis and the total cost was $177,344, whereas if targeted prophylaxis had been applied to these patients the total cost would have been $263,392 and cost per patient would have been $385. Universal prophylaxis was more cost-effective than targeted prophylaxis in terms of both total cost and cost per patient (P < 0.0001). Conclusion: Unless the cost of noninvasive fetal Rh genotyping is reduced, a universal approach of anti-D immune globulin prophylaxis is more cost-effective than noninvasive determination of fetal Rh genotyping with targeted prophylaxis.

Objective: To provide guidelines on use of anti-D prophylaxis to optimize prevention of rhesus (Rh) alloimmunization in Canadian women., Outcomes: Decreased incidence of Rh alloimmunization and minimized practice variation with regards to immunoprophylaxis strategies., Evidence: The Cochrane Library and MEDLINE were searched for English-language articles from 1968 to 200 I, relating to the prevention of Rh alloimmunization. Search terms included: Rho(D) immune globulin, Rh iso- or aile-immunization, anti-D, anti-Rh, WinRho, Rhogam, and pregnancy. Additional publications were identified from the bibliographies of these articles. All study types were reviewed. Randomized controlled trials were considered evidence of highest quality, followed by cohort studies. Key individual studies on which the principal recommendations are based are referenced. Supporting data for each recommendation is briefly summarized with evaluative comments and referenced., Values: The evidence collected was reviewed by the Maternal-Fetal Medicine and Genetics Committees of The Society of Obstetricians and Gynaecologists of Canada (SOGC) and quantified using the Evaluation of Evidence guidelines developed by the Canadian Task Force on the Periodic Health Exam., Recommendations: VALIDATION: These guidelines have been reviewed by the MaternalFetal Medicine Committee and the Genetics Committee, with input from the Rh Program of Nova Scotia. Final approval has been given by the Executive and Council of The Society of Obstetricians and Gynaecologists of Canada., Sponsors: The Society of Obstetricians and Gynaecologists of Canada., (Copyright © 2018. Published by Elsevier Inc.)

Objective:  The objective of this study was to compare national guidelines on the prevention of RhD alloimmunization., Study Design:  We performed a review of four national guidelines on prevention of alloimmunization from the American Congress of Obstetricians and Gynecologists, Royal College of Obstetricians and Gynaecologists, Society of Obstetricians and Gynaecologists of Canada, and The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. We compared the indications/contraindications, timing, dosing, formulation and route of anti-D immune globulin, and management of unique circumstances. The references were compared with regard to the number of randomized control trials, Cochrane Reviews, and systematic reviews/meta-analyses cited., Results:  Variation exists in recommendations on the timing and need for consent prior to routine antenatal anti-D immune globulin administration, prophylaxis for unique circumstances (e.g., threatened abortion < 12 weeks, complete molar pregnancy), and the use of cell-free fetal DNA testing for fetal RhD genotype., Conclusion:  These variations in recommendations reflect the heterogeneity of the literature on the prevention of alloimmunization and highlight the need for synthesis of evidence to create an international guideline on prevention of alloimmunization. This may improve safety, quality, optimize outcomes, and stimulate future trials., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Introduction: The aim of this study was to assess the accuracy of the non-invasive fetal RHD test at 24-26 weeks of gestation as part of the national antenatal screening program to target routine antenatal anti-D prophylaxis (RAADP) at 28-30 weeks at women carrying an RhD-positive fetus., Material and Methods: A prospective cohort study involving all maternity care centers and delivery hospitals in Finland between February 2014 and January 2016. Fetal RHD genotyping using cell-free fetal DNA in maternal plasma was performed with real-time polymerase chain reaction in a centralized setting. The results were systematically compared with the serological newborn RhD typing. The main outcome measure was the accuracy of the fetal RHD assay; the secondary variable was compliance with the newly introduced RAADP program., Results: Fetal RHD was screened from 10 814 women. For the detection of fetal RHD, sensitivity was 99.99% [95% confidence interval (CI) 99.92-99.99] and specificity 99.81% (95% CI 99.60-99.92). One false-negative and seven false-positive results were reported by the delivery hospitals in two years. The negative predictive value of the test was 99.97% (95% CI 99.81-99.99). At the end of the study period, over 98% of the RhD-negative women participated in the new screening program., Conclusions: The targeted RAAPD program was implemented effectively in the national maternity care program in Finland. An accurate fetal RHD screening test allows discontinuation of newborn testing without risking the postnatal prophylaxis program. In the future, the main area to investigate will be the clinical effect of RAADP on subsequent pregnancies., (© 2017 Nordic Federation of Societies of Obstetrics and Gynecology.)

Advances in the prevention and treatment of Rh D alloimmunization have been one of the great success stories of modern obstetrics. There is wide variation in prevalence rates of Rh D-negative individuals between regions, for example from 5% in India to 15% in North America (1). However, high birth rates in low prevalence areas means Rh hemolytic disease of the newborn is still an important cause of morbidity and mortality in countries without prophylaxis programs (1). In such countries, 14% of affected fetuses are stillborn and one half of live born infants suffer neonatal death or brain injury (1). The routine use of Rh D immune globulin is responsible for the reduced rate of red cell alloimmunization in more economically developed countries. First introduced in the 1970s, the postpartum administration of Rh D immune globulin reduced the rate of alloimmunization in at-risk pregnancies from approximately 13-16% to approximately 0.5-1.8% (2, 3). The risk was further reduced to 0.14-0.2% with the addition of routine antepartum administration (2, 3). Despite considerable proof of efficacy, there are still a large number of cases of Rh D alloimmunization because of failure to follow established protocols. In addition, there are new data to help guide management, especially with regard to weak D phenotype women. The purpose of this document is to provide evidence-based guidance for the management of patients at risk of Rh D alloimmunization.

Advances in the prevention and treatment of Rh D alloimmunization have been one of the great success stories of modern obstetrics. There is wide variation in prevalence rates of Rh D-negative individuals between regions, for example from 5% in India to 15% in North America (1). However, high birth rates in low prevalence areas means Rh hemolytic disease of the newborn is still an important cause of morbidity and mortality in countries without prophylaxis programs (1). In such countries, 14% of affected fetuses are stillborn and one half of live born infants suffer neonatal death or brain injury (1). The routine use of Rh D immune globulin is responsible for the reduced rate of red cell alloimmunization in more economically developed countries. First introduced in the 1970s, the postpartum administration of Rh D immune globulin reduced the rate of alloimmunization in at-risk pregnancies from approximately 13-16% to approximately 0.5-1.8% (2, 3). The risk was further reduced to 0.14-0.2% with the addition of routine antepartum administration (2, 3). Despite considerable proof of efficacy, there are still a large number of cases of Rh D alloimmunization because of failure to follow established protocols. In addition, there are new data to help guide management, especially with regard to weak D phenotype women. The purpose of this document is to provide evidence-based guidance for the management of patients at risk of Rh D alloimmunization.

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.

Objective: To estimate the cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal versus no routine antenatal anti-D prophylaxis (RAADP) or versus non-targeted RAADP., Design: Model based on a population-based cohort study., Setting: The Swedish health service., Population: Intervention subjects in the underlying cohort study were RhD-negative pregnant women receiving first trimester fetal RHD screening followed by targeted anti-D in 2010-2011 (n = 6723). Historical comparators were RhD-negative women who delivered in 2008-2009 when standard care did not include RAADP (n = 7099)., Methods: Healthcare costs for the three strategies were included for the first and subsequent pregnancies. For the comparison with non-targeted RAADP, the immunisation rate was based on the observed rate for targeted therapy and adjusted downwards by removing the influence of false negatives., Main Outcome Measure: Additional cost per RhD immunisation averted., Results: Compared with RAADP, targeted prophylaxis was associated with fewer immunisations (0.19 versus 0.46% per pregnancy) and lower costs (cost-savings of €32 per RhD-negative woman). The savings were from lower costs during pregnancy and delivery, and lower costs of future pregnancies through fewer immunisations. Non-targeted anti-D was estimated to result in 0.06% fewer immunisations and an additional €16 in cost-savings per mother, compared with targeted anti-D., Conclusion: Based on effect data from a population-based cohort study, targeted prophylaxis was associated with lower immunisation risk and costs versus no RAADP. Based on effect data from theoretical calculations, non-targeted RAADP was predicted to result in lower costs and immunisation risk compared with targeted prophylaxis., Tweetable Abstract: Fetal RHD screening and targeted prophylaxis resulted in lower immunisation risk and costs compared with no RAADP., (© 2015 Royal College of Obstetricians and Gynaecologists.)

Background and Objectives: Determining whether anti-D represents active or passive alloimmunization after RhIg administration is challenging. The objectives were to use antibody reaction strength to differentiate patients who may have become RhD alloimmunized during pregnancy from those manifesting passive anti-D and to investigate which methods work best for this determination., Materials and Methods: Data were collected from patients residing in the Edmonton region of Canada, ≥18 years old, undergoing antibody screening in late pregnancy, who received 300 μg (1500 IU) of RhIg in the preceding 120 days. A total of 1106 tests were performed on 1050 blood samples from 963 patients: 640 by PEG, 156 by gel-card and 310 by solid-phase methodology., Results: PEG was the least sensitive to passive anti-D, with significantly fewer positive results at ≥8 weeks after RhIg compared to the other methods. Strength of reactivity and time since RhIg injection could be used to identify patients at high risk using PEG as a 4+ reaction at any time, ≥3+ at >2 weeks, ≥2+ at >6 weeks and ≥1+ at >14 weeks. Similarly, the gel-card method thresholds were 4+ at >5 weeks, ≥3+ at >10 weeks and ≥2+ at >15 weeks. Reaction strength by solid-phase was too variable to establish useful thresholds by this method. Infant RhD status did not significantly affect results., Conclusion: Patients can be risk stratified for alloimmunization by anti-D reaction strength and time after RhIg administration. The PEG method was the best of those investigated, but the gel-card method can also be used., (© 2015 International Society of Blood Transfusion.)

Objective: To compare the rates of alloimmunization with the use of cell-free DNA (cfDNA) screening to target antenatal rhesus immune globulin (RhIG) prenatally, versus routine administration of RhIG in rhesus D (RhD)-negative pregnant women in a theoretic cohort using a decision-analytic model., Methods: A decision-analytic model compared cfDNA testing to routine antenatal RhIG administration. The primary outcome was maternal sensitization to RhD antigen. Sensitivity and specificity of cfDNA testing were assumed to be 99.8% and 95.3%, respectively. Univariate and bivariate sensitivity analyses, Monte Carlo simulation, and threshold analyses were performed., Results: In a cohort of 10,000 RhD-negative women, 22.6 sensitizations would occur with utilization of cfDNA, while 20 sensitizations would occur with routine RhIG. Only when the sensitivity of the cfDNA test reached 100%, the rate of sensitization was equal for both cfDNA and RhIG. Otherwise, routine RhIG minimized the rate of sensitization, especially given RhIG is readily available in the United States., Conclusions: Adoption of cfDNA testing would result in a 13.0% increase in sensitization among RhD-negative women in a theoretical cohort taking into account the ethnic diversity of the United States' population.

Background: Fetal-maternal hemorrhage is usually spontaneous and goes undetected but can be associated with adverse perinatal outcomes., Case: We describe the detection of a fetal-maternal hemorrhage by abrupt disappearance of prophylactic anti-D on antibody screen in an Rh-negative mother with dichorionic twins admitted for atrial flutter of one twin. Both rosette and Kleihauer-Betke tests were positive. The diagnosis was confirmed by anemia in one twin at birth., Conclusion: Fetal-maternal hemorrhage requires a high index of suspicion for diagnosis. An unexpected sudden decline in Rh immune globulin-related anti-D may be an indication of fetal-maternal hemorrhage.

Aim of the Study: Assess the incidence of spontaneous antepartal RhD alloimmunization in RhD negative pregnant women with an RhD positive fetus., Design: Clinical study., Setting: Department of Obstetrics and Gynecology, Medical School and University Hospital Olomouc., Methods: A total of 906 RhD negative women with an RhD positive fetus and without the presence of anti-Dalloantibodies at the beginning of pregnancy were examined. Always it was a singleton pregnancy, RhD blood group of the pregnant women was assessed in the 1st trimester of pregnancy, RhD status of the fetus was determined after delivery. Screening for irregular antierythrocyte antibodies was performed in all women in the 1st trimester of pregnancy, at 28-32 weeks gestation and immediately prior to delivery at 38-42 weeks gestation. Screening for irregular antierythrocyte antibodies was performed also at 6 months following delivery in all cases of positive antibodies before delivery. Antibody screening was performed using the indirect antiglobulin (LISS/NAT) and enzyme (papain) test with their subsequent identification using a panel of reference erythrocytes by column agglutination method Dia-Med. After delivery, the volume of fetomaternal hemorrhage was assesed in all RhD negative women and RhD alloimmunization prophylaxis was performed by administering the necessary IgG anti-D dose; none of the women were administered IgG anti-D antepartally., Results: During screening for irregular antierythrocyte antibodies at 28-32 weeks gestation, anti-D alloantibodies were diagnosed in 0.2% of the women (2/906); immediately prior to the delivery at 38-42 weeks gestation, anti-D alloantibodies were diagnosed in 2.3% of the women (21/906) and repeatedly even at 6 months following delivery (21/157). In 82.7% of the women (749/906), examination at 6 months following delivery was not performed, therefore in these women spontaneous antepartal RhD alloimmunization cannot reliably be ruled out. Alloimmunization may not be diagnosed yet at term of delivery. If anti-D alloantibodies were not present prior to the delivery, these women were all administered IgG anti-D in a dose of at least 125 μg after delivery., Conclusion: In RhD negative women with an RhD positive fetus, the incidence of spontaneous antepartal RhD alloimmunization was at least 2.3%. Most cases may theoretically be prevented by prophylactic administration of 250 μg of IgG anti-D to all RhD negative women at 28 weeks gestation.

Background: During pregnancy, a Rhesus negative (Rh-negative) woman may develop antibodies when her fetus is Rhesus positive (Rh-positive). These antibodies may harm Rh-positive babies., Objectives: To assess the effects of antenatal anti-D immunoglobulin on the incidence of Rhesus D alloimmunisation when given to Rh-negative women without anti-D antibodies., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved studies., Selection Criteria: Randomised trials in Rh-negative women without anti-D antibodies given anti-D after 28 weeks of pregnancy, compared with no treatment, placebo or a different regimen of anti-D., Data Collection and Analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy., Main Results: We included two trials involving over 4500 women, comparing anti-D prophylaxis with no anti-D during pregnancy in this review. Overall, the trials were judged to be at moderate to high risk of bias. The quality of the evidence for pre-specified outcomes was also assessed using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach.In regards to primary review outcomes, there did not appear to be a clear difference in the risks of immunisation when women who received anti-D at 28 and 34 weeks' gestation were compared with women who were not given antenatal anti-D: risk ratio (RR) for incidence of Rhesus D alloimmunisation during pregnancy was 0.42 (95% confidence interval (CI) 0.15 to 1.17, two trials, 3902 women; GRADE: low quality evidence); at birth of a Rh-positive infant the RR was 0.42 (95% CI 0.15 to 1.17, two trials, 2297 women); and within 12 months after birth of a Rh-positive infant the average RR was 0.39 (95% CI 0.10 to 1.62, two trials, 2048 women; Tau²: 0.47; I²: 39%; GRADE: low quality evidence). Neither of the trials reported on incidence of Rhesus D alloimmunisation in subsequent pregnancies.Considering secondary outcomes, in one trial, women receiving anti-D during pregnancy were shown to be less likely to register a positive Kleihauer test (which detects fetal cells in maternal blood) in pregnancy (at 32 to 25 weeks) (RR 0.60, 95% CI 0.41 to 0.88; 1884 women; GRADE: low quality evidence) and at the birth of a Rh-positive infant (RR 0.60, 95% CI 0.46 to 0.79; 1189 women; GRADE: low quality evidence). No clear differences were seen for neonatal jaundice (RR 0.26, 95% CI 0.03 to 2.30; 1882 infants; GRADE: very low quality evidence). Neither of the trials reported on adverse effects associated with anti-D treatment., Authors' Conclusions: Existing studies do not provide conclusive evidence that the use of anti-D during pregnancy benefits either mother or baby in terms of incidence of Rhesus D alloimmunisation during the pregnancy or postpartum, or the incidence of neonatal morbidity (jaundice) (low to very low quality evidence). However women receiving anti-D may be less likely to register a positive Kleihauer test in pregnancy and at the birth of a Rh-positive infant (low quality evidence). Fewer women who receive anti-D during pregnancy may have Rhesus D antibodies in a subsequent pregnancy, with benefits for the baby, however this needs to be tested in studies of robust design.

Background: The rare amorph Rhnull phenotype is caused by silent alleles at the RH locus and usually arises in consanguineous families. To date, only five molecular backgrounds have been identified in five unrelated families. Subjects with Rhnull red blood cells (RBCs) readily produce alloantibodies to high-prevalence Rh antigens., Study Design and Methods: RBCs from a pregnant woman (G5P3) from Libya, with a positive indirect antiglobulin test were phenotyped by hemagglutination. RHD and RHCE genes were analyzed at the genomic level and mutation inheritance pattern was assessed in the patient's family., Results: Hemagglutination testing showed a D-C-E-c-e- phenotype in the proposita associated with the presence of a high titer anti-Rh29 (4096). Molecular analysis revealed a deletion of RHD and presence of a novel RHCE allele with a 7-bp duplication in Exon 7. This duplication is predicted to introduce a frameshift after His350, a new C-terminal sequence, and a premature stop codon resulting in shortened predicted protein with only 402 amino acids. The mutated allele was found at homozygous state in the proposita and heterozygous state in her parents and one brother., Conclusion: This report describes a novel RHCE mutation causing the loss of RhCE antigen expression in association with RHD deletion, leading to an amorph Rhnull phenotype., (© 2014 AABB.)

Purpose: 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., Summary: 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., Conclusion: 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., (Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Objective: Non-invasive fetal Rhesus (Rh) D genotyping, using cell-free fetal DNA (cffDNA) in the maternal blood, allows targeted antenatal anti-RhD prophylaxis in unsensitized RhD-negative pregnant women. The purpose of this study was to determine the cost and benefit of this approach as compared to routine antenatal anti-RhD prophylaxis for all unsensitized RhD-negative pregnant women, as is the current policy in the province of Alberta, Canada., Methods: This study was a decision analysis based on a theoretical population representing the total number of pregnancies in Alberta over a 1-year period (n = 69 286). A decision tree was created that outlined targeted prophylaxis for unsensitized RhD-negative pregnant women screened for cffDNA (targeted group) vs routine prophylaxis for all unsensitized RhD-negative pregnant women (routine group). Probabilities at each decision point and costs associated with each resource were calculated from local clinical and administrative data. Outcomes measured were cost, number of women sensitized and doses of Rh immunoglobulin (RhIG) administered., Results: The estimated cost per pregnancy for the routine group was 71.43 compared with 67.20 Canadian dollars in the targeted group. The sensitization rates per RhD-negative pregnancy were equal, at 0.0012, for the current and targeted programs. Implementing targeted antenatal anti-RhD prophylaxis would save 4072 doses (20.1%) of RhIG over a 1-year period in Alberta when compared to the current program., Conclusions: These data support the feasibility of a targeted antenatal anti-RhD prophylaxis program, at a lower cost than that of the existing routine prophylaxis program, with no increased risk of sensitization., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Background: The purpose of this scoping review was to review the literature on healthcare provider provision of anti-D prophylaxis to RhD negative pregnant women in appropriate clinical situations in various healthcare settings., Methods: A scoping review framework was used to structure the process. The following databases were searched: CINAHL (EBSCO), EBM Reviews (OvidSP), Embase (OvidSP), Medline (OvidSP), and Web of Science (ISI). In addition, hand searching of article references was conducted. The search yielded 301 articles. Thirty-five articles remained for review after screening. Two team members reviewed each article using a detailed data collection sheet. A third reviewer was utilized if discrepancies occurred amongst reviewers., Results: The review process yielded 18 included articles. The majority of the studies were conducted in the United Kingdom. Of the 18 studies, 15 were retrospective studies. The articles were largely conducted in one institution. The articles with a focus on routine antenatal provision of anti-D immunoglobulin found that it was given 80 to 90% of the time. Postpartum provision of anti-D immunoglobulin had significantly higher results of 95-100%. The review found that the delivery of anti-D immunoglobulin to RhD negative pregnant women during situations of potential sensitizing events was suboptimal., Conclusions: The included articles examine the management of RhD negative pregnancies in various countries with existing national guidelines. The existing evidence indicates an opportunity for quality improvement in situations where potential sensitizing events are not at routine times in pregnancy, such as miscarriage or fetal demise early in pregnancy. Routine care for the prevention of RhD alloimmunization in pregnancy and postpartum appears to be fairly consistent. The paucity of recent literature in this area leads to a recommendation for further research.

Rhesus (Rh) antigens are not expressed on platelets but residual red cells carry the risk of anti-D iso-immunization in transfusion recipients of platelet concentrates (PC). The main theoretical risk associated with this reaction relates to female subjects due to potential obstetrical situations of maternal-foetal Rh incompatibility. Isogroup PC transfusion in this system is therefore advised. However, logistical constraints impose frequent Rh-incompatible transfusions that require the recommendation of anti-Rh immunoglobulin in a girl of childbearing age in this situation. This recommendation, already restricted to a group of patients deserves to be questioned over a decade after being issued. Data from published reports are difficult to interpret because of the heterogeneity of the few series (CP type, immune status, timing of biological tests) but the current techniques for preparing products and most common use of CP apheresis limited the risk of immunization. Moreover, platelet transfusions are particularly relevant to immunocompromised populations which, to what extent (heavy chemotherapy and/or hematopoietic stem cells recipients) seems to be protected from this risk. It is noteworthy that the clinical consequences that may be expected from such immunization are not reported. Although some authors emphasize significant isoimmunization rates (maximum 19%), the heterogeneous conditions and the lack of evidence of clinical consequence suggest evaluating the recommendations or revising them towards more targeted indications of seroprophylaxis., (Copyright © 2014. Published by Elsevier SAS.)

Objective: To analyze the timing of Rhesus D (RhD) immunization in pregnancy and the consequences for the index pregnancy and for subsequent pregnancies to be able to optimize the design of antenatal screening and prevention programs., Design: Retrospective cohort study., Setting: Stockholm county, Sweden., Population: All RhD immunized pregnant women 1990-2008 before the introduction of routine antenatal anti-D prophylaxis., Methods: Data were collected from transfusion medicine registers and databases, medical records, the Swedish Medical Birth Register and the National Perinatal Quality Register and entered into a standardized database before analysis., Main Outcome Measures: The order of pregnancy and trimester when immunization occurred and treatment of hemolytic disease of the fetus and newborn., Results: A total of 290 RhD immunized women were included in the study. In 147/290 (51%) of the women, sensitization occurred with their first-born child and in 96/290 (33%) it occurred with their second-born child. Anti-D antibodies developed during the second or third trimester in 212/290 (73%) and in 61/290 (21%) at term or after delivery. In subsequent pregnancies 56% (144/259) of the neonates required treatment for hemolytic disease of the fetus and newborn., Conclusions: Based on our study, at least half of the cases could potentially have been avoided by routine antenatal anti-D prophylaxis in the beginning of the third trimester. To optimize the beneficial effects of new prevention programs, we propose providing anti-D prophylaxis in gestational week 28-30 selectively to all RhD-negative women with RhD-positive fetuses., (© 2013 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To examine the cost and clinical outcomes of noninvasive RhD typing with cell-free fetal DNA to selectively deliver antenatal and postnatal prophylaxis with anti-D immune globulin for prevention of alloimmunization in RhD-negative women., Methods: We developed a decision tree to compare the costs and clinical outcomes of three strategies in an RhD-negative nonalloimmunized population as follows: 1) routine antenatal anti-D immune globulin prophylaxis and postpartum prophylaxis guided by cord blood typing (the current approach in most of the United States); 2) noninvasive fetal RhD typing with prophylaxis guided by test results; and 3) no screening or prophylaxis. Costs were estimated for testing and treatment algorithms using hospital billing records and information from the manufacturer of the fetal RhD genotyping test. Probability estimates were derived from published literature. The decision tree and sensitivity analyses were constructed and performed with Microsoft Excel., Results: We estimated the cost of the current approach to prevention of alloimmunization to be $351 per pregnancy, and we estimated the cost of noninvasive determination of fetal RhD status to be $682. Assuming essentially perfect test performance, threshold analysis found the cost must decrease to $119 to break even. The gap widened in favor of routine prophylaxis in most other circumstances (increased false-negative test rate and decreasing prevalence of RhD negativity)., Conclusion: Unless the cost of noninvasive fetal RhD typing is reduced substantially, routine antenatal anti-D immune globulin prophylaxis with postpartum prophylaxis guided by cord blood typing is less costly than noninvasive determination of fetal RhD status.

Objective: To estimate the incidence of RhD immunisation after implementation of first trimester non-invasive fetal RHD screening to select only RhD negative women carrying RHD positive fetuses for routine antenatal anti-D prophylaxis (RAADP)., Materials and Methods: We present a population-based prospective observational cohort study with historic controls including all maternity care centres and delivery hospitals in the Stockholm region, Sweden. All RhD negative pregnant women were screened for fetal RHD genotype in the first trimester of pregnancy. Anti-D immunoglobulin (250-300 µg) was administered intramuscularly in gestational week 28-30 to participants with RHD positive fetuses. Main outcome measure was the incidence of RhD immunisation developing during or after pregnancy., Results: During the study period 9380 RhD negative women gave birth in Stockholm. Non-invasive fetal RHD genotyping using cell-free fetal DNA in maternal plasma was performed in 8374 pregnancies of which 5104 (61%) were RHD positive and 3270 (39%) RHD negative. In 4590 pregnancies with an RHD positive test the women received antenatal anti-D prophylaxis. The incidence of RhD immunisation in the study cohort was 0.26 percent (24/9380) (95% CI 0.15-0.36%) compared to 0.46 percent (86/18546) (95% CI 0.37 to 0.56%) in the reference cohort. The risk ratio (RR) for sensitisation was 0.55 (95% CI 0.35 to 0.87) and the risk reduction was statistically significant (p = 0.009). The absolute risk difference was 0.20 percent, corresponding to a number needed to treat (NNT) of 500., Conclusions: Using first trimester non-invasive antenatal screening for fetal RHD to target routine antenatal anti-D prophylaxis selectively to RhD negative women with RHD positive fetuses significantly reduces the incidence of new RhD immunisation. The risk reduction is comparable to that reported in studies evaluating the outcome of non selective RAADP to all RhD negative women. The cost-effectiveness of this targeted approach remains to be studied.

Objective: The purpose of this study was to determine the most cost-effective option to prevent alloimmunization against the Rh factor., Methods: A virtual population of Rh-negative pregnant women in Quebec was built to simulate the cost-effectiveness of preventing alloimmunization. The model considered four options: (1) systematic use of anti-D immunoglobulin; (2) fetal Rh(D) genotyping; (3) immunological determination of the father's Rh type; (4) mixed screening: immunological determination of the father's Rh type, followed if positive by fetal Rh(D) genotyping. Two outcomes were considered, in addition to the estimated costs: (1) the number of babies without hemolytic disease, and (2) the number of surviving infants., Results: In a first pregnancy, two options emerged as the most cost-effective options: systematic prophylaxis and immunological Rh typing of the father, with overlapping confidence intervals between them. In a second pregnancy, the results were similar. In all cases (first or second pregnancy or a combination of the two) fetal genotyping was not found to be a cost-effective option., Conclusion: Routine prophylaxis and immunological Rh typing of the father are the most cost-effective options for the prevention of Rh alloimmunization. Considering that immunological typing of the father would probably not be carried out by the majority of clinicians, routine prophylaxis remains the preferred option. However, this could change if the cost of Rh(D) fetal genotyping fell below $140 per sample.

Objective: To highlight the errors associated with the use of anti-D immunoglobulin in RhD antigen-negative women, and their resultant clinical impact during and after pregnancy, and to suggest strategies to reduce these errors., Design: Retrospective review of cumulative reporting to the UK confidential haemovigilance scheme, Serious Hazards of Transfusion (SHOT), between 1996 and 2011., Setting: Obstetric departments in the UK., Population: Mothers who require anti-D immunoglobulin to prevent RhD sensitisation during pregnancy or after birth., Methods: Hospital transfusion teams reported adverse events to the SHOT database., Main Outcome Measures: Reported number of events and their causes, and morbidity and mortality associated with errors., Results: In 15 years of reporting, SHOT haemovigilance has shown a total of 1211 errors related to the administration of anti-D immunoglobulin, particularly regarding omission or late administration (157/249 or 63% reported in 2011). Anti-D immunoglobulin errors comprised 13.7% (249/1815) of all SHOT reports in 2011. Failure to recognise women who already have RhD sensitisation occurred in 19 cases, and was followed by suboptimal monitoring of the pregnancy. Nine of the infants suffered haemolytic disease of the fetus and newborn (HDFN): one resulted in neonatal death and three required red cell transfusion., Conclusions: Babies as well as their mothers remain at risk from avoidable errors. More active attention at national and local levels to further education and training, particularly for midwives, is an absolute necessity. We recommend the use of a SHOT-devised anti-D administration flowchart, adapted locally into a checklist, to help reduce errors., (© 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.)

Objectives: To evaluate the prevention of fetomaternal rhesus-D allo-immunization between 2008 and 2010. This evaluation was a part of the continuous medical evaluation (CME) that is compulsory in French hospitals. It was carried out using the tools recommended by the Haute Autorité de santé. We followed the national guidelines for the prevention of fetomaternal rhesus-D allo-immunization as outlined in 2005 by the national French college of Obstetrics and Gynecology., Materials and Methods: We audited 3926 consultations in the first four months of 2008. Based on the results of the audit, actions were implemented to improve care. In 2009, we audited 4021 consultations to look for improvement, and another 3932 consultations in 2010., Results: In 2008, 14% of the patients had an overall optimal prevention. After actions were taken, 44% of patients in 2009 and 58% of patients in 2010 demonstrated optimal prevention (P<0,05). Especially, the prevention of fetomaternal allo-immunization has been explained for 43% of the patients in 2008 and to 90% of them in 2010. And immunoprophylaxia has been prescribed to 70% of the patients in 2008 and to 93% of them in 2010., Conclusion: This CME has resulted in a statistically significant improvement of the prevention of allo-immunization., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Events following which immunoglobulin (Ig) G anti-D should be given to all RhD negative women with no anti-D alloantibodies: First trimester indications (IgG anti-D sufficient dose of 50 μg*) - termination of pregnancy, spontaneous abortion followed by instrumentation, ectopic pregnancy, chorionic villus sampling, partial molar pregnancy; Second and third trimester indications (IgG anti-D sufficient dose of 100 μg*) - amniocentesis, cordocentesis, other invasive prenatal diagnostic or therapeutic procedures, spontaneous or induced abortion, intrauterine fetal death, attempt at external cephalic version of a breech presentation, abdominal trauma, obstetric hemorrhage; Antenatal prophylaxis at 28th weeks of gestation (IgG anti-D sufficient dose of 250 μg*); Delivery of an RhD positive infant** (IgG anti-D sufficient dose of 100 μg*); Minimal dose*: before 20 weeks gestation - 50 μg (250 IU), after 20 weeks gestation*** - 100 μg (500 IU); Timing: as soon as possible, but no later than 72 hours after the event. In cases where prevention of RhD alloimmunization is not performed within 72 hours of a potentially sensitising event, it is still reasonable to administer IgG anti-D within 13 days, and in special cases, administration is still recommended up to a maximum interval of 28 days postpartum; Legend: *administration of a higher dose of IgG anti-D is not a mistake, ** also if the D type is not known, *** simultaneous assessment of the volume of fetomaternal hemorrhage (FMH) to specify the dose is suitable; The FMH volume assessment - If the volume of fetal erythrocytes (red bood cells, RBCs) which entered maternal circulation is assessed, intramuscular administration of IgG anti-D in a dose of 10 μg per 0.5 mL of fetal RBCs or 1 mL of whole fetal blood is indicated. IgG anti-D in a dose of 10 μg administered intramuscularly should cover 0.5 mL of fetal RhD positive RBCs or 1mL of whole fetal blood. FMH is the fetal RBC volume; fetal blood volume is double (expected fetal hematocrit is 50%).