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Background and Objectives: A successful routine RBC alloantibody screening programme should not lead to unnecessary emotional burden during pregnancy due to inadequate counselling on the risk of severe haemolytic disease of the foetus and the newborn (HDFN). Rareness of this disease may result in insufficient knowledge and subsequent inadequate information transfer to women, diagnosed with RBC antibodies. We investigated the current knowledge, views and experiences of Dutch obstetric care providers regarding RBC alloimmunization during pregnancy., Materials and Methods: We performed a quantitative cross-sectional study, using a structured digital questionnaire to measure knowledge, attitude and practices (KAP) regarding maternal RBC alloimmunization among Dutch obstetric care providers in 2016., Results: About 10% of obstetric care providers completed the questionnaire. A sufficient level of knowledge was found in 7% of all participants (N = 329). Knowledge about RhD immunisation and prophylaxis was sufficient in 60% of the responders. Knowledge gaps were found concerning the relevance of non-RhD RBC antibodies, the indications for giving extra RhD prophylaxis and the interpretation of laboratory test results. Healthcare providers estimated their own level of knowledge 'sufficient' (primary/secondary care) to 'good' (tertiary care), and all participants considered their professional role important within the screening programme., Conclusion: Dutch obstetric care providers showed a lack of knowledge regarding maternal RBC immunization. Awareness of the lack of knowledge is necessary to help obstetric care providers to be careful in giving information and even to decide to contact the expert centre before counselling the patient., (© 2019 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Background: Hemolytic disease of the fetus and newborn (HDFN) is caused by maternal antibodies against fetal red blood cell antigens, most often anti-D, -K, or -c. ABO incompatibility between mother and child and anti-D immunoprophylaxis (RhIG) are known to reduce the risk of D immunization and subsequent HDFN. However, no immunoprophylaxis has been developed to prevent non-D immunizations., Study Design and Methods: We evaluated whether ABO incompatibility has a preventive effect on formation of non-D alloantibodies, by performing a case-control study including pregnant women with newly detected non-D antibodies, identified within a nationwide data set, immunized during their first pregnancy and/or delivery. Subsequently, we assessed a possible protective effect of RhIG in a subgroup with non-Rh antibodies only. The proportions of previous ABO incompatibility and of RhIG administrations of these women were compared to the known rate of 19.4% ABO incompatibility and 9.9% RhIG administrations (D- women carrying a D+ child) in the general population of pregnant women., Results: A total of 11.9% of the 232 included immunized women had a possible ABO incompatibility in their first pregnancy (vs. expected 19.4%; 95% confidence interval [CI], 7.3-18.8; p = 0.036). Furthermore, 1.0% women with non-Rh antibodies were D-, delivered a D+ child, and had therefore received RhIG, whereas 9.9% was expected (95% CI, 0.18-5.50; p = 0.003)., Conclusion: We found that ABO incompatibility and RhIG reduce the risks not only for D, but also for non-Rh immunizations, suggesting that antibody-mediated immune suppression in this condition is not antigen specific., (© 2018 AABB.)

Objective: To identify risk factors for Rhesus D (RhD) immunisation in pregnancy, despite adequate antenatal and postnatal anti-D prophylaxis in the previous pregnancy. To generate evidence for improved primary prevention by extra administration of anti-D Ig in the presence of a risk factor., Design: Case-control study., Setting: Nation-wide evaluation of the Dutch antenatal anti-D-prophylaxis programme., Cases: 42 RhD-immunised parae-1, recognised by first-trimester routine red cell antibody screening in their current pregnancy, who received antenatal and postnatal anti-D Ig prophylaxis (gifts of 1000 iu) in their first pregnancy., Controls: 339 parae-1 without red cell antibodies., Methods: Data were collected via obstetric care workers and/or personal interviews with women., Main Outcome Measure: Significant risk factors for RhD immunisation in multivariate analysis., Results: Independent risk factors were non-spontaneous delivery (assisted vaginal delivery or caesarean section) (OR 2.23; 95% CI:1.04-4.74), postmaturity (>or=42 weeks of completed gestation: OR 3.07; 95% CI:1.02-9.02), pregnancy-related red blood cell transfusion (OR 3.51; 95% CI:0.97-12.7 and age (OR 0.89/year; 95% CI:0.80-0.98). In 43% of cases, none of the categorical risk factors was present., Conclusions: In at least half of the failures of anti-D Ig prophylaxis, a condition related to increased fetomaternal haemorrhage (FMH) and/or insufficient anti-D Ig levels was observed. Hence, RhD immunisation may be further reduced by strict compliance to guidelines concerning determination of FMH and accordingly adjusted anti-D Ig prophylaxis, or by routine administration of extra anti-D Ig after a non-spontaneous delivery and/or a complicated or prolonged third stage of labour.

Objective: To identify risk factors for the presence of non-rhesus D (RhD) red blood cell (RBC) antibodies in pregnancy. To generate evidence for subgroup RBC antibody screening and for primary prevention by extended matching of transfusions in women <45 years., Design: Case-control study., Setting: Nationwide evaluation of screening programme for non-RhD RBC antibodies., Cases: consecutive pregnancies (n=900) with non-RhD immunisation identified from 1 September 2002 to 1 June 2003 and 1 October 2003 to 1 July 2004; controls (n=968): matched for obstetric caregiver and gestational age., Methods: Data collection from the medical records and/or from the respondents by a structured phone interview., Main Outcome Measures: Significant risk factors for non-RhD immunisation in multivariate analysis., Results: Significant independent risk factors: history of RBC transfusion (OR 16.7; 95% CI: 11.4-24.6), parity (para-1 versus para-0: OR 1.3; 95% CI: 1.0-1.7; para-2 versus para-0: OR 1.4; 95% CI: 1.0-2.0; para >2 versus para-0: OR 3.2; 95% CI: 1.8-5.8), haematological disease (OR 2.1; 95% CI: 1.0-4.2), history of major surgery (OR 1.4; 95% CI: 1.1-1.8). For the clinically most important antibodies, anti-K, anti-c and other Rh-nonD-antibodies RBC transfusion was the most important risk factor, especially for anti-K (OR 96.4; 95%-CI: 56.6-164.1); 83% of the K-sensitised women had a history of RBC transfusion. Pregnancy-related risk factors were a prior male child (OR 1.7; 95% CI: 1.2-2.3) and caesarean section (OR 1.7; 95% CI: 1.1-2.7)., Conclusions: RBC transfusion is by far the most important independent risk factor for non-RhD immunisation in pregnancy, followed by parity, major surgery and haematological disease. Pregnancy-related risk factors are a prior male child and caesarean section. Subgroup screening for RBC antibodies, with exclusion of RhD-positive para-0 without clinical risk factors, is to be considered. This approach will be equally sensitive in detecting severe Haemolytic Disease of the Fetus and Newborn compared with the present RBC antibody screening programme without preselection. Primary prevention by extending preventive matching of transfusions in women younger than 45 will prevent more than 50% of pregnancy immunisations.

Background: Since July 1998 all Dutch women (+/- 200,000/y) are screened for red cell antibodies, other than anti-RhesusD (RhD) in the first trimester of pregnancy, to facilitate timely treatment of pregnancies at risk for hemolytic disease of the fetus and newborn (HDFN). Evidence for benefits, consequences and costs of screening for non-RhD antibodies is still under discussion. The screening program was evaluated in a nation-wide study. As a part of this evaluation study we investigated, according to the sixth criterium of Wilson and Jüngner, the acceptance by pregnant women of the screening program for non-RhD antibodies., Methods: Controlled longitudinal survey, including a prenatal and a postnatal measurement by structured questionnaires., Main Outcome Measures: information satisfaction, anxiety during the screening process (a.o. STAI state inventory and specific questionnaire modules), overall attitude on the screening program. Univariate analysis was followed by standard multivariate analysis to identify significant predictors of the outcome measures., Participants: 233 pregnant women, distributed over five groups, according to the screening result., Results: Satisfaction about the provided information was moderate in all groups. All screen- positive groups desired more supportive information. Anxiety increased in screen- positives during the screening process, but decreased to basic levels postnatally. All groups showed a strongly positive balance between perceived utility and burden of the screening program, independent on test results or background characteristics., Conclusion: Women highly accept the non-RhD antibody screening program. However, satisfaction about provided information is moderate. Oral and written information should be provided by obstetric care workers themselves, especially to screen-positive women.

Background: The objective was the evaluation of the effect of the Dutch national routine antenatal RhIG (anti-D) immunization prevention (RAADP) program comprising one single dose of 200 microg (1000 IU) of RhIG in the 30th week of pregnancy, restricted to women without a living child., Study Design and Methods: A nationwide historic control study was performed. All newly detected anti-D-immunized para-1 in 1999, 2002, and 2004 were included and classified on the basis of received prophylaxis during the first pregnancy: antenatal and postnatal versus only postnatal RhIG. The numbers of D- parae-1 who delivered a D+ first child before the introduction (control group) or after the introduction (intervention group) of the RAADP were calculated from Vital Birth Statistics (8,700 and 12,000, respectively)., Results: Fifty-eight newly detected anti-D immunizations in the first trimester were observed in the control group and 39 in the intervention group, which resulted in a significant reduction of the prevalence of new anti-D immunizations from 0.67 percent (95% confidence interval [CI], 0.50%-0.84%) to 0.31 percent (95% CI, 0.21%-0.41%). No reduction was observed in anti-D immunizations newly detected at the 30th-week screening (0.25%). A nonsignificant risk reduction of the risk of severe hemolytic disease of the fetus and newborn (HDFN) was found (0.23% vs. 0.10%). The numbers needed to treat to prevent one anti-D-immunized pregnancy and one case of subsequent severe HDFN were 357 and 1255, respectively., Conclusions: RAADP of one single dose of 200 microg of RhIG in addition to postnatal RhIG (200 microg) halves the risk of anti-D immunization and subsequent severe HDFN.

Background: Hemolytic disease of the fetus and newborn (HDFN) is a severe disease, resulting from maternal red cell (RBC) alloantibodies directed against fetal RBCs. The effect of a first-trimester antibody screening program on the timely detection of HDFN caused by antibodies other than anti-D was evaluated., Study Design and Methods: Nationwide, all women (1,002 in 305,000 consecutive pregnancies during 18 months) with alloantibodies other than anti-D, detected by a first-trimester antibody screen, were included in a prospective index-cohort study. In a parallel-coverage validation study, patients with HDFN caused by antibodies other than anti-D, that were missed by the screening program, were retrospectively identified., Results: The prevalence of positive antibody screens at first-trimester screening was 1,232 in 100,000; the prevalence of alloantibodies other than anti-D was 328 in 100,000, of which 191 of 100,000 implied a risk for occurrence of HDFN because the father carried the antigen. Overall, severe HDFN, requiring intrauterine or postnatal (exchange) transfusions, occurred in 3.7 percent of fetuses at risk: for anti-K in 11.6 percent; anti-c in 8.5 percent; anti-E in 1.1 percent; Rh antibodies other than anti-c, anti-D, or anti-E in 3.8 percent; and for antibodies other than Rh antibodies or anti-K, in none of the fetuses at risk. All affected children, where antibodies were detected, were promptly treated and healthy at the age of 1 year. The coverage validation study showed a sensitivity of the screening program of 75 percent. Five of 8 missed cases were caused by anti-c, with delay-induced permanent damage in at least 1., Conclusion: First-trimester screening enables timely treatment of HDFN caused by antibodies other than anti-D, however, with a sensitivity of only 75 percent. A second screening at Week 30 of c- women will enhance the screening program. Severe HDFN, caused by antibodies other than anti-D, is associated with anti-K, anti-c, and to a lesser extent with other Rh-alloantibodies.