Targeted Routine Antenatal Anti-D Prophylaxis in the Prevention of RhD Immunisation - Outcome of a New Antenatal Screening and Prevention Program

Eleonor Tiblad,Magnus Westgren,Agneta Taune Wikman,Elisabeth Nordlander,Bibi Shassti Holländer,Gunilla Ajne,Agneta Blanck,Yvonne Jansson,Anita Karlsson,Claire Thorne

doi:10.1371/journal.pone.0070984

Eleonor Tiblad, Magnus Westgren + Show 8 more

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https://doi.org/10.1371/journal.pone.0070984

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Abstract

ObjectiveTo estimate the incidence of RhD immunisation after implementation of first trimester non-invasive fetal RHD screening to select only RhD negative women carrying RHD positive fetuses for routine antenatal anti-D prophylaxis (RAADP).Materials and MethodsWe present a population-based prospective observational cohort study with historic controls including all maternity care centres and delivery hospitals in the Stockholm region, Sweden. All RhD negative pregnant women were screened for fetal RHD genotype in the first trimester of pregnancy. Anti-D immunoglobulin (250–300 µg) was administered intramuscularly in gestational week 28–30 to participants with RHD positive fetuses. Main outcome measure was the incidence of RhD immunisation developing during or after pregnancy.ResultsDuring the study period 9380 RhD negative women gave birth in Stockholm. Non-invasive fetal RHD genotyping using cell-free fetal DNA in maternal plasma was performed in 8374 pregnancies of which 5104 (61%) were RHD positive and 3270 (39%) RHD negative. In 4590 pregnancies with an RHD positive test the women received antenatal anti-D prophylaxis. The incidence of RhD immunisation in the study cohort was 0.26 percent (24/9380) (95% CI 0.15–0.36%) compared to 0.46 percent (86/18546) (95% CI 0.37 to 0.56%) in the reference cohort. The risk ratio (RR) for sensitisation was 0.55 (95% CI 0.35 to 0.87) and the risk reduction was statistically significant (p = 0.009). The absolute risk difference was 0.20 percent, corresponding to a number needed to treat (NNT) of 500.ConclusionsUsing first trimester non-invasive antenatal screening for fetal RHD to target routine antenatal anti-D prophylaxis selectively to RhD negative women with RHD positive fetuses significantly reduces the incidence of new RhD immunisation. The risk reduction is comparable to that reported in studies evaluating the outcome of non selective RAADP to all RhD negative women. The cost-effectiveness of this targeted approach remains to be studied.

Highlights

Alloimmunisation against the Rhesus D (RhD) red cell antigen is still the most common cause of severe hemolytic disease of the fetus and newborn (HDFN). [1,2] Affected pregnancies require close surveillance in order to detect fetal anemia in a timely manner, and the neonates often require treatment for hyperbilirubinemia and anemia
Using first trimester non-invasive antenatal screening for fetal RHD to target routine antenatal anti-D prophylaxis selectively to RhD negative women with RHD positive fetuses significantly reduces the incidence of new RhD immunisation
The risk reduction is comparable to that reported in studies evaluating the outcome of non selective routine antenatal anti-D prophylaxis (RAADP) to all RhD negative women

Summary

Introduction

Alloimmunisation against the Rhesus D (RhD) red cell antigen is still the most common cause of severe hemolytic disease of the fetus and newborn (HDFN). [1,2] Affected pregnancies require close surveillance in order to detect fetal anemia in a timely manner, and the neonates often require treatment for hyperbilirubinemia and anemia. The discovery of cellfree fetal DNA in maternal plasma has led to the development of non-invasive methods to determine the fetal RHD genotype.[12,13,14] Several studies have confirmed the safety and high diagnostic accuracy of this approach.[15,16,17,18,19] This enables administration of RAADP selectively to RhD negative women with an RHD positive fetus and avoids giving it to women who are not at risk This strategy has recently been introduced to Danish and Dutch screening programs, but no study has yet been published of the effectiveness of this approach in reducing the incidence of new RhD immunisation. This strategy has recently been introduced to Danish and Dutch screening programs, but no study has yet been published of the effectiveness of this approach in reducing the incidence of new RhD immunisation. [20]

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