Evaluation of the clinical effect of a nationwide implementation of targeted routine antenatal anti-D prophylaxis in Denmark

Background: In 2010, Denmark was the first country to implement a targeted routine antenatal anti-D prophylaxis (tRAADP) program, offering fetal RHD genotyping to all nonimmunized D negative pregnant women. The program represented a shift from only postnatal prophylaxis to a combined antenatal and postnatal prophylaxis. This study aimed to evaluate the clinical effect of tRAADP in Denmark.

Study design and methods: This nationwide registry-based cohort study included all D negative women who gave birth between 2004-2020, identified through the National Medical Birth Register and the Departments of Clinical Immunology in Denmark. The clinical effect of tRAADP was assessed by comparing the incidence of new D immunization between 2004-2009 (non-tRAADP-cohort) and 2011-2018 (tRAADP-cohort).

Results: A total of 282 women were D immunized during pregnancy between 2004-2009 (non-tRAADP-cohort), and 167 between 2011-2018 (tRAADP-cohort). The incidence of new D immunization decreased from 0.46% (95% CI 0.41-0.52) in the non-tRAADP-cohort to 0.22% (95% CI 0.19-0.25) in the tRAADP-cohort. The risk reduction was statistically significant p < 0.001. Notably, in the tRAADP cohort 0.1% (95% CI 0.08-0.12) of new D immunizations occurred before the time of antenatal prophylaxis.

Discussion: tRAADP significantly reduced the incidence of new D immunization by more than half, thus demonstrating the expected effect. However, even with full adherence to the current program, some women with early fetomaternal hemorrhage (FMH) were still at risk. Future studies may evaluate the impact of administering an additional tRAADP dose earlier in the second trimester to prevent this.