Rh disease prevention: the European Perspective

Toly-Ndour, Cécile; Huguet-Jacquot, Stéphanie; Mailloux, Agnès; Delaby, Hélène; Canellini, Giorgia; Olsson, Martin L.; Wikman, Agneta; Koelewijn, Joke M.; Minon, Jean‐Marc; Legler, Tobias J.; Clausen, Frederik Banch; Lambert, Mark; Ryan, Helen; Bricl, Irena; Hasslund, Sys; Orzińska, Agnieszka; Guz, Katarzyna; Uhrynowska, Małgorzata; Matteocci, Antonella; Nogués, Núria; Muñiz‐Díaz, Eduardo; Sainio, Susanna; Haas, Masja de; Schoot, C. Ellen van der

doi:10.1111/voxs.12617

Cited by 9 publications

(7 citation statements)

References 32 publications

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“…In addition to the 5000 doses of RhIg saved thanks to the fetal genotyping carried out over all these years, by applying our algorithm (Figure 1) to explore the discordant results, 90 additional RhIg doses could be saved: 3 incorrectly identified as RhD negative women, 45 women with weak variant type 1, 2 and 3 and 42 women with isolated amplification of one or two exons. To these numbers, we also have to add the doses potentially administered in case of feto‐maternal hemorrhage due to trauma, invasive procedure, etc 1 …”

Section: Discussionmentioning

confidence: 99%

“…It is well established that non-invasive fetal RHD genotyping is an efficient tool to predict fetal RhD blood group and to adequately manage pregnancy in terms of RhIg prophylaxis and blood transfusion 1,20 that is, it allows to spare RhD negative blood which, around the world, is rarer than RhD positive blood. There is abundance of articles where authors performed fetal RHD genotyping in different cohorts of pregnant women and presented the diagnostic performances of the test.…”

Section: 1%)mentioning

confidence: 99%

“…In many European countries, the first step of anti-D allo-immunized pregnant women management is to perform non-invasive fetal RHD genotyping as early as 12th week of gestation. In Belgium, this fetal genotyping is also provided to all nonimmunized RhD negative pregnant women so Rh antenatal prophylaxis is only applied to those carrying a D positive fetus as in other European countries where the fetal genotyping is implemented on a national scale and the costs are covered by governments 1,2 (i.e. : Denmark, Sweden, Norway, Finland, The Netherlands, Germany, Slovenia, Iceland and England).…”

Section: Introductionmentioning

confidence: 99%

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Investigation of discrepancies obtained during 15 years of non‐invasive fetal RHD genotyping in apparent serologic RhD‐negative pregnant women

et al. 2022

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Objectives In some European countries, non‐invasive fetal RHD genotyping is the first step of anti‐D allo‐immunized pregnant women management but presence of RHD variant alleles may interfere with the results accuracy. We developed an algorithm allowing solving discordant results (due to the presence of RHD variant) in fetal RHD genotyping assay. Method This study gathered the results of fetal RHD genotyping performed between 2006 and 2020 in the Medicine Laboratory of CHR Liège. Exons 4, 5 and 10 of the fetal RHD were profiled in maternal plasma using real time polymerase chain reaction (PCR). When the results were discrepant, maternal RHD variant was further explored by sequence‐specific primer PCR on maternal buffy coat. Results A total of 11,630 pregnant women (mainly of both Caucasian and African origins) were tested during the study period and RHD variant alleles were detected in 247 women. The most frequent variant was RHD*08N.01 found in 66 women mainly of Black African origin. We identified 45 women with weak RHD variant type 1, 2 or 3. Conclusion Women with weak RHD variant type 1, 2 or 3 can safely be considered as RhD positive in terms of RhIg prophylaxis and/or transfusion of blood components. Therefore, identification of RHD allele variants in women with discordant fetal RHD genotyping results contributes to save RhIg prophylaxis and RhD negative blood components.

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Section: Discussionmentioning

confidence: 99%

Section: 1%)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Investigation of discrepancies obtained during 15 years of non‐invasive fetal RHD genotyping in apparent serologic RhD‐negative pregnant women

et al. 2022

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“…This is, however, not mandatory. In some countries, a KBT is routinely performed after delivery or in the case of risk factors related to increased FMH 2,35 . In some prophylaxis programmes, a higher dose of RhIg of 1500 IU is routinely used to reduce the risk of RhD immunisation.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for RhD immunisation in a high coverage prevention programme of antenatal and postnatal RhIg: a nationwide cohort study

Slootweg

Zwiers

Koelewijn

et al. 2022

BJOG

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Objective: To evaluate which risk factors for RhD immunisation remain, despite adequate routine antenatal and postnatal RhIg prophylaxis (1000 IU RhIg) and additional administration of RhIg. The second objective was assessment of the current prevalence of RhD immunisations. Design: Prospective cohort study.Setting: The Netherlands.Population: Two-year nationwide cohort of alloimmunised RhD-negative women.Methods: RhD-negative women in their first RhD immunised pregnancy were included for risk factor analysis. We compared risk factors for RhD immunisation, occurring either in the previous non-immunised pregnancy or in the index pregnancy, with national population data derived from the Dutch perinatal registration (Perined). Results:In the 2-year cohort, data from 193 women were eligible for analysis.Significant risk factors in women previously experiencing a pregnancy of an RhDpositive child (n = 113) were: caesarean section (CS) (OR 1.7, 95% CI 1.1-2.6), perinatal death (OR 3.5, 95% CI 1.1-10.9), gestational age >42 weeks (OR 6.1, 95% CI 2.2-16.6), postnatal bleeding (>1000 ml) (OR 2.0, 95% CI 1.1-3.6), manual removal of the placenta (MRP) (OR 4.3, 95% CI 2.0-9.3); these factors often occurred in combination. The miscarriage rate was significantly higher than in the Dutch population (35% versus 12.-5%, P < 0.001). Conclusion:Complicated deliveries, including cases of major bleeding and surgical interventions (CS, MRP), must be recognised as a risk factor, requiring estimation of fetomaternal haemorrhage volume and adjustment of RhIg dosing. The higher miscarriage rate suggests that existing RhIg protocols need adjustment or better compliance.

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“…21 Prevention strategies in Europe differ, especially for indications to quantify FMH in PSEs or at delivery, and with regard to the evaluation of national prevention programs. 22 Intriguing proposals for reducing remaining anti-D immunizations by administering an additional anti-D immunoglobulin dose after non-spontaneous delivery or prolonged third stage, or repeating RAADP at term to ensure detectable anti-D at delivery, have been made. 11,23 While reasons for prophylaxis failures are unclear, changes in current practices should be considered carefully.…”

Section: Discussionmentioning

confidence: 99%

Time points and risk factors for RhD immunizations after the implementation of targeted routine antenatal anti‐D prophylaxis: A retrospective nationwide cohort study

Jernman

Isaksson

Haimila

et al. 2021

Acta Obstet Gynecol Scand

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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.

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Rh disease prevention: the European Perspective

Cited by 9 publications

References 32 publications

Investigation of discrepancies obtained during 15 years of non‐invasive fetal RHD genotyping in apparent serologic RhD‐negative pregnant women

Investigation of discrepancies obtained during 15 years of non‐invasive fetal RHD genotyping in apparent serologic RhD‐negative pregnant women

Risk factors for RhD immunisation in a high coverage prevention programme of antenatal and postnatal RhIg: a nationwide cohort study

Time points and risk factors for RhD immunizations after the implementation of targeted routine antenatal anti‐D prophylaxis: A retrospective nationwide cohort study

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