BACKGROUND: Postnatal and antenatal anti-D prophylaxis have dramatically reduced 
maternal sensitisations and cases of rhesus disease in babies born to women with 
RhD negative blood group. Recent scientific advances mean that non-invasive 
prenatal diagnosis (NIPD), based on the presence of cell-free fetal DNA in 
maternal plasma, could be used to target prophylaxis on "at risk" pregnancies 
where the fetus is RhD positive. This paper provides the first assessment of 
cost-effectiveness of NIPD-targeted prophylaxis compared to current policies.
METHODS: We conducted an economic analysis of NIPD implementation in England and 
Wales. Two scenarios were considered. Scenario 1 assumed that NIPD will be only 
used to target antenatal prophylaxis with serology tests continuing to direct 
post-delivery prophylaxis. In Scenario 2, NIPD would also displace postnatal 
serology testing if an RhD negative fetus was identified. Costs were estimated 
from the provider's perspective for both scenarios together with a threshold 
royalty fee per test. Incremental costs were compared with clinical 
implications.
RESULTS: The basic cost of an NIPD in-house test is £16.25 per sample (excluding 
royalty fee). The two-dose antenatal prophylaxis policy recommended by NICE is 
estimated to cost the NHS £3.37 million each year. The estimated threshold 
royalty fee is £2.18 and £8.83 for Scenarios 1 and 2 respectively. At a £2.00 
royalty fee, mass NIPD testing would produce no saving for Scenario 1 and 
£507,154 per annum for Scenario 2. Incremental cost-effectiveness analysis 
indicates that, at a test sensitivity of 99.7% and this royalty fee, NIPD 
testing in Scenario 2 will generate one additional sensitisation for every 
£9,190 saved. If a single-dose prophylaxis policy were implemented nationally, 
as recently recommended by NICE, Scenario 2 savings would fall.
CONCLUSIONS: Currently, NIPD testing to target anti-D prophylaxis is unlikely to 
be sufficiently cost-effective to warrant its large scale introduction in 
England and Wales. Only minor savings are calculated and, balanced against this, 
the predicted increase in maternal sensitisations may be unacceptably high. 
Reliability of NIPD assays still needs to be demonstrated rigorously in 
different ethnic minority populations. First trimester testing is unlikely to 
alter this picture significantly although other emerging technologies may.