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

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.

High-throughput non-invasive prenatal testing for fetal rhesus D status in RhD-negative women not known to be sensitised to the RhD antigen: a systematic review and economic evaluation

“…20,26 One study 26 compared patients undergoing NIPT with routine management with no NIPT and routine postnatal anti-D prophylaxis only (historical control). The other comparative study 20 reported data on anti-D compliance in a small subgroup of participants from one region in Denmark, comparing participants receiving NIPT with those receiving no NIPT.…”

“…After initial screening of titles and abstracts, 227 were considered to be potentially relevant and were ordered for full-text paper screening. In total, eight studies 12,[17][18][19][20][21][22][23] were included in the diagnostic review of high-throughput NIPT, seven studies 18,20,22,[24][25][26][27] were included in the clinical effectiveness review and 12 studies 13,17,18,[20][21][22][23][24][25][26][27][28] were included in the review of implementation of high-throughput NIPT (with some overlap between studies). Figure 1 shows a flow diagram outlining the screening process with reasons for exclusion of full-text papers.…”

“…In summary, both studies had significant limitations. Tiblad et al 26 was considered as having a serious risk of bias, primarily owing to concerns about patient selection, confounding and missing data. Banch Clausen et al 20 was considered as having a critical risk of bias across all outcomes because of concerns about patient selection and lack of adjustment for potential confounders.…”

“…Tiblad et al 26 compared targeted routine antenatal anti-D in the first trimester with routine care (postnatal anti-D only, historical control) in the Stockholm region, Sweden. The study reported that the incidence of RhD sensitisation in the cohort that underwent high-throughput NIPT was 0.26% (95% CI 0.15% to 0.36%, n = 8347), compared with 0.46% (95% CI 0.37% to 0.56%, n = 18,546) in the historical control cohort.…”

“…Seven studies reported on uptake rates of NIPT screening. 18,20,22,[25][26][27] Uptake rates ranged from 70% to > 95% across the studies. In the pilot study conducted by Soothill et al 18 in three maternity services in the south west of England, only 70% of eligible women joined the study in the initial 6 months.…”