The aim of this dissertation was to identify gaps in knowledge and room for improvements in certain aspects of the current system of prevention and care regarding RBC alloimmunization in pregnancy.... Show moreThe aim of this dissertation was to identify gaps in knowledge and room for improvements in certain aspects of the current system of prevention and care regarding RBC alloimmunization in pregnancy. The focus in this thesis was to evaluate the performance of new measures in the prevention program, the follow-up with laboratory monitoring in alloimmunized pregnancies and the counseling of pregnant women and their partners, in cases of RBC alloimmunization. Show less
Slootweg, Y.M.; Zwiers, C.; Koelewijn, J.M.; Schoot, E. van der; Oepkes, D.; Kamp, I.L. van; Haas, M. de 2022
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... Show moreObjective 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 RhD-positive 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. Show less
Slootweg, Y.M.; Walg, C.; Koelewijn, J.M.; Kamp, I.L. van; Haas, M. de 2019
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... Show moreBackground 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. Show less
Koelewijn, J.M.; Slootweg, Y.M.; Folman, C.; Kamp, I.L. van; Oepkes, D.; Haas, M. de 2019
BACKGROUND Pregnant women are routinely screened for red blood cell (RBC) antibodies early in pregnancy. If RBC-alloantibodies are detected, repeated laboratory testing is advised to timely... Show moreBACKGROUND Pregnant women are routinely screened for red blood cell (RBC) antibodies early in pregnancy. If RBC-alloantibodies are detected, repeated laboratory testing is advised to timely identify pregnancies at high risk for severe hemolytic disease of the fetus and newborn (HDFN). We assessed for RBC alloantibodies, other than anti-D or anti-K, cut-offs for the titer and the antibody dependent cellular cytotoxicity (ADCC) test to select high-risk cases. To advise on test repeat intervals, and to avoid unnecessary testing, we evaluated the chance for exceeding the cut-offs for Rh antibodies other than anti-D, Jk, Fy, and S/s antibodies. STUDY DESIGN AND METHODS Diagnostic value of antibody titer and ADCC test was determined with data from a prospective index-cohort study, conducted in 2002-2004. Laboratory test outcomes were from a recent observational cohort (2015-2016). RESULTS A titer cut-off of >= 16 showed a sensitivity of 100% (95% CI:73-100%) and a positive predictive value (PPV) of 17% (95% CI:14%-20%). The percentage of pregnancies reaching a titer above the cut-off of >= 16 varied from 0% for anti-Jk(a)/Jk(b) (n = 38) to 36% for anti-c (n = 97). The ADCC test showed no cut-off with a 100% sensitivity. However, in cases with a titer >= 16 and an ADCC test >= 30% a PPV of 38% was obtained to detect severe HDFN. CONCLUSION A titer cut-off of >= 16 is adequate to detect all cases at risk for severe HDFN; the ADCC test may add a more accurate risk estimation. Repeated testing is recommended in pregnancies with anti-c. In pregnancies with other Rh antibodies a repeated test in the third trimester is recommended. Show less
Koelewijn, J.M.; Slootweg, Y.M.; Folman, C.; Kamp, I.L. van; Oepkes, D.; Haas, M. de 2019
BACKGROUND Pregnant women are routinely screened for red blood cell (RBC) antibodies early in pregnancy. If RBC-alloantibodies are detected, repeated laboratory testing is advised to timely... Show moreBACKGROUND Pregnant women are routinely screened for red blood cell (RBC) antibodies early in pregnancy. If RBC-alloantibodies are detected, repeated laboratory testing is advised to timely identify pregnancies at high risk for severe hemolytic disease of the fetus and newborn (HDFN). We assessed for RBC alloantibodies, other than anti-D or anti-K, cut-offs for the titer and the antibody dependent cellular cytotoxicity (ADCC) test to select high-risk cases. To advise on test repeat intervals, and to avoid unnecessary testing, we evaluated the chance for exceeding the cut-offs for Rh antibodies other than anti-D, Jk, Fy, and S/s antibodies. STUDY DESIGN AND METHODS Diagnostic value of antibody titer and ADCC test was determined with data from a prospective index-cohort study, conducted in 2002-2004. Laboratory test outcomes were from a recent observational cohort (2015-2016). RESULTS A titer cut-off of >= 16 showed a sensitivity of 100% (95% CI:73-100%) and a positive predictive value (PPV) of 17% (95% CI:14%-20%). The percentage of pregnancies reaching a titer above the cut-off of >= 16 varied from 0% for anti-Jk(a)/Jk(b) (n = 38) to 36% for anti-c (n = 97). The ADCC test showed no cut-off with a 100% sensitivity. However, in cases with a titer >= 16 and an ADCC test >= 30% a PPV of 38% was obtained to detect severe HDFN. CONCLUSION A titer cut-off of >= 16 is adequate to detect all cases at risk for severe HDFN; the ADCC test may add a more accurate risk estimation. Repeated testing is recommended in pregnancies with anti-c. In pregnancies with other Rh antibodies a repeated test in the third trimester is recommended. Show less
Slootweg, Y.M.; Lindenburg, I.T.; Koelewijn, J.M.; Kamp, I.L. van; Oepkes, D.; Haas, M. de 2018
Objective: To evaluate the effect of red blood cell (RBC) antibody screening in the 27th week of pregnancy in Rhc-negative women, on detection of alloimmunisation, undetected at first trimester... Show moreObjective: To evaluate the effect of red blood cell (RBC) antibody screening in the 27th week of pregnancy in Rhc-negative women, on detection of alloimmunisation, undetected at first trimester screening ('late' alloimmunisation), and subsequent haemolytic disease of the fetus and newborn (HDFN), to assess risk factors for late alloimmunisation.Design: Prospective cohort and nested case-control study.Setting: The Netherlands.Population: Two-year nationwide cohort.Methods: Prospective inclusion of Rhc-negative women with negative first trimester screening and of screen-negative controls. Assessment of incidence and numbers needed to screen (NNS) of late alloimmunisation and HDFN; logistic regression analysis to establish risk factors for late alloimmunisation.Main outcome measures: Late alloimmunisation, HDFN.Results: Late alloimmunisation occurred in 99 of 62 096 (0.159%) Rhc-negative women; 90% had c/E antibodies and 10% non-Rhesus antibodies. Severe HDFN (fetal/neonatal transfusion) occurred in two of 62 096 (0.003%) of Rhc-negative women and 2% of late alloimmunisations; moderate HDFN (phototherapy) occurred in 20 children [22.5%; 95% confidence interval (CI), 13.8-31.1%]. Perinatal survival was 100%. The NNS to detect one HDFN case was 2823 (31 048 for severe, 3105 for moderate HDFN). Significant risk factors were former blood transfusion [odds ratio (OR), 10.4; 95% CI, 1.14-94.9], parity (P-1: OR, 11.8; 95% CI, 3.00-46.5; P > 1: OR, 7.77; 95% CI, 1.70-35.4) and amniocentesis/chorionic villus sampling during current pregnancy (OR, 9.20; 95% CI, 1.16-72.9).Conclusions: Additional screening of Rhc-negative women improved the detection of late alloimmunisation and HDFN, facilitating timely treatment, with a NNS of 2823. Independent risk factors for late alloimmunisation were blood transfusion, parity and chorionic villus sampling/amniocentesis in the current pregnancy. The occurrence of most factors before the current pregnancy suggests a secondary immune response explaining most late alloimmunisations. Show less
