Objective: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) results from maternal platelet-directed antibodies which can cause severe intracranial haemorrhage (ICH) in fetuses and new-borns. Screening for human platelet antigen-1a (HPA-1a) directed antibodies during pregnancy could allow for timely intervention with antenatal treatment and prevent the occurrence of ICH. We aim to assess the cost-effectiveness of adding screening for anti-HPA-1a to the prenatal screening program. Design: A decision analysis model was developed. Setting: The Netherlands. Population: 171,713 pregnant women. Methods: Lifetime costs and effects of antenatal anti-HPA-1a screening with subsequent diagnostic and treatment interventions were compared to the current situation without screening in the Netherlands. Model parameters were based on literature and expert opinions. One-way-sensitivity analysis and probabilistic sensitivity analysis were performed. Main Outcome Measures: Incremental cost-effectiveness ratio (ICER). Results: Adding screening for HPA-1a antibodies to the current antenatal screening program of the Netherlands will lead to an additional cost of 4.7 million euro and a gain of 226 Quality-Adjusted Life Years (QALY) per year, indicating an ICER of \euro20,782 per QALY gained. One-way sensitivity analysis showed that the uncertainty around the incidence of ICH, lifetime costs of disabled children and the probability of having antibody quantitation >3.0 IU/ml at 20 weeks had the highest effect on the ICER. Conclusion: Antenatal HPA-1a screening might be cost-effective. To obtain more knowledge and thereby reduce the uncertainty on risk stratification, a pilot screening program is warranted. Funding: Sanquin

Objective: To evaluate which risk factors for RhD immunization remain, despite adequate routine antenatal and postnatal RhIg prophylaxis (1000 IU RhIg) and additional administration of RhIg. Assessment of the prevalence of RhD immunizations. Design: Prospective cohort Setting: The Netherlands. Population: Two-year nationwide cohort. Methods: RhD-negative women in their first RhD immunized pregnancy and their foregoing non-immunized pregnancy. Risk factors for RhD immunization were compared with population data. Main outcomes measures: Risk factors for FMH and subsequently RhD immunization, prevalence of RhD immunizations. Results: The prevalence of newly detected RhD immunizations was 0.31% (79/25,170) of all RhD-negative pregnant women in the Netherlands. After exclusion, 193 women remained. Significant risk factors found in the group of 113 parous women (previous pregnancy >16 weeks, RhD positive child) 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 over 42 weeks (OR 6.1, 95% CI 2.2-16.6), postnatal bleeding (>1000mL) (OR 2.0 95% CI 1.1-3.6), surgical removal of the placenta (SRP) (OR 4.3, 95% CI 2.0-9.3). The miscarriage rate in the group of women without a previous RhD positive child was significantly higher than in the Dutch population (35% vs 12.5% p<0.001). Conclusion: Complicated deliveries, including cases of major bleeding and surgical interventions (CS, SRP) need to be recognized as risk factor, requiring determination of FMH volume and adjustment of RhIg dosing. Miscarriage may be an additional risk factor for RhD immunization, requiring further studies. Funding: This research was partly funded by a grant from Sanquin Amsterdam.

OBJECTIVE(S): to evaluate the severity of HDFN in subsequent pregnancies with RhD immunization and to identify predictive factors for severe disease. DESIGN: prospective cohort. SETTING: the Netherlands. POPULATION: nationwide selection of all pregnant women with RhD antibodies. METHODS: women with two subsequent RhD immunized pregnancies with RhD-positive children after antibodies were detected were included. MAIN OUTCOME MEASURE: the severity of HDFN in the first and subsequent pregnancy at risk. RESULTS: 62 RhD immunized women with a total of 150 RhD-positive children were included. The severity of HDFN increased significantly in the subsequent pregnancy (P<.001), although it remained equal or even decreased in 44% of women. When antibodies were already detected at first trimester screening in the first immunized pregnancy, severe HDFN in the next pregnancy was uncommon (22%), especially when no therapy or only non-intensive phototherapy was indicated during the first pregnancy (6%), or if the ADCC result remained <10%. Contrarily, women with antibodies detected during the first pregnancy of a RhD positive child (>= 27th week), most often before they had ever received RhIg prophylaxis, were most prone for severe disease in a subsequent pregnancy (48%). CONCLUSION(S): RhD-mediated HDFN in a subsequent pregnancy is generally more severe than in the first pregnancy at risk and can be estimated using moment of antibody detection and severity in the first immunized pregnancy. Women developing antibodies in their first pregnancy of a RhD-positive child are at highest risk of severe disease in the next pregnancy.