Replacing the paternal blood test stage of England’s antenatal sickle cell and thalassaemia screening programme with non-invasive prenatal testing (NIPT) would substantially increase costs while resolving more pregnancies with a definite diagnosis, according to a modelling study published in Diagnostic and Prognostic Research. The exploratory analysis, built around the 2019/2020 English screening cohort of 616,573 pregnancies, estimates that introducing NIPT for the screen-positive sickle cell disease population would add £7,584,551 in testing costs compared with the current standard of care, which cost £296,338 against £7,880,889 for the NIPT pathway.
The current NHS Sickle Cell and Thalassaemia Screening Programme, recommended by the UK National Screening Committee, offers pregnant women a carrier blood test. In areas of high sickle cell prevalence, all women are offered a full blood count followed by high performance liquid chromatography or capillary electrophoresis; elsewhere, a family origin questionnaire helps determine who needs further testing. When a woman screens positive as a carrier, the biological father is offered a blood test. If he is also a carrier, or if his result is unavailable, the woman is counselled and offered invasive prenatal diagnosis, performed by chorionic villus sampling or amniocentesis, to establish whether the fetus is affected.
NIPT analyses cell-free DNA from the placenta circulating in the maternal bloodstream, which in most cases reflects the fetal genome. Exploratory studies suggest the technique may be able to identify pregnancies at risk of sickle cell disease and thalassaemia, but it has not been proven accurate enough for diagnosis and cannot currently replace invasive prenatal diagnosis. Its proposed role in the modelled pathway is therefore to replace the paternal blood test: all women with a positive maternal carrier result would be offered NIPT, and only those with a high-risk NIPT result would be offered invasive prenatal diagnosis. The researchers note this could improve equity and risk stratification for the 24% of screen-positive women whose baby’s biological father is unavailable for testing, and could speed up decision-making.
The team, led by Vittoria Vardanega, built a deterministic decision tree model in Microsoft Excel from the perspective of NHS England, informed by the 2019/2020 screening report, literature inputs, cost data from a 2016 cost analysis, and two stakeholder workshops involving the screening programme, the UK National Screening Committee, clinicians and researchers. Because stakeholders noted that NIPT is not currently diagnostically feasible for thalassaemia in a clinical setting, the published analysis focuses on the sickle cell disease population, with combined and thalassaemia results reported as supplementary material. The model allowed women to decline testing at any stage, with those women treated as lost to follow-up.
In the modelled standard-of-care arm, 6216 women screened positive as carriers. Of these, 4051 had a negative paternal carrier blood test and required no further testing, and 2165 were offered prenatal diagnosis; 276 of these invasive tests were performed, with 1995 women declining. The pathway produced 76 true positive and 1 false negative diagnoses, with a positive predictive value of 97.46% and overall accuracy of 99.00%. In the NIPT arm, all 6216 screen-positive women were offered NIPT; 5639 initial tests were performed, and accounting for an 8% test failure rate that required repeats, 6090 NIPTs were carried out in total. Following positive NIPT results, 543 prenatal diagnoses were performed, yielding 213 true positives and 235 false positives, with a pathway positive predictive value of 47.55% and accuracy of 95.67%, assuming NIPT sensitivity of 96.0% and specificity of 88.5%.
The cost differences were stark. The cost per case detected rose from £3901 in the standard-of-care pathway to £37,059 with NIPT, an incremental £33,158 per case detected, while the cost per accurate diagnosis rose by £368, from £1088 to £1457. A threshold analysis calculated that NIPT would need to cost just £45.21 per test performed to match the standard of care on cost per case detected, and up to £875.90 to match it on cost per accurate diagnosis. No feasible value of NIPT specificity or sensitivity alone, at the modelled test price, would achieve cost parity. A scenario analysis assuming better NIPT performance, with a maximum of two false negatives per year and 99.0% sensitivity, still produced an incremental cost of £32,137 per case detected and required a NIPT price of £45.89 per case detected for parity.
The model was anchored to minimally acceptable criteria developed in a parallel publication to inform a future diagnostic accuracy study of NIPT, since real-world accuracy data for NIPT in this pathway do not yet exist. The base case assumed a maximum of nine false negative diagnoses following NIPT before prenatal diagnosis and an overall positive predictive value of 25%, matching the proportion of pregnancies where both parents are sickle cell carriers. The authors caution that the modelled positive predictive value is likely less desirable than would be expected in clinical practice, because false-positive NIPT results can be corrected by the subsequent offer of invasive diagnosis if accepted.
Scenario and sensitivity analyses showed how the results shift with real-world assumptions. Reducing NIPT uptake from 90.71% to 80% or 40% cut the number of tests to 5371 or 2685 and lowered total pathway costs, but left more women without a final diagnosis. Varying the uptake of follow-up prenatal diagnosis after a positive NIPT result from 63% to 30%, 70% or 90% changed total costs only modestly, but had a large effect on false positives, which fell from 438 at 30% uptake to 191 at 70% and 68 at 90%. Using a lower NIPT cost of £1100, representing the molecular test alone without transport and counselling, reduced the NIPT pathway cost to £7,253,589, still £6,957,251 above the standard of care. For the combined sickle cell and thalassaemia population, the incremental cost rose to £16,131,619.
Beyond economics, the model suggested the NIPT pathway could reduce uncertainty for pregnant women. It produced 5002 more true negative and 137 more true positive diagnoses than the standard of care, although the authors note this must be weighed against the 4051 pregnancies resolved as not at risk by a negative paternal blood test in the current pathway. Overall, there were 5484 fewer pregnancies lost to follow-up, meaning without a final positive or negative diagnosis, in the NIPT pathway. The modelled NIPT pathway was 3.33% less accurate than the standard of care in detecting sickle cell disease.
The authors emphasise that this is an exploratory analysis with important limitations. Diagnostic accuracy inputs for NIPT came from literature and stakeholder judgement rather than clinical data, the real-world failure rate is unknown and depends on gestational age, body mass index and sample quality, and the model excluded downstream costs of care following diagnosis. It also assumed no time dependency, likely overestimating NIPT uptake since screening acceptance falls as pregnancy progresses. Because no willingness-to-pay threshold exists for NIPT in this setting, the team used a threshold approach rather than a full cost-effectiveness analysis. They conclude that the cost-effectiveness of the NIPT pathway cannot be definitively stated, and that research into NIPT’s diagnostic accuracy, alongside better cost data, is needed before the model can be repopulated to inform any decision on introducing NIPT into the English sickle cell screening pathway.
Subject of Research: A decision tree model of the cost-effectiveness of replacing paternal blood testing with non-invasive prenatal testing in the English sickle cell and thalassaemia antenatal screening pathway
Article Title: Modelling the cost-effectiveness of non-invasive prenatal testing in the English sickle cell and thalassaemia screening pathway
Article References: Vardanega, V., Bobrowska, A., Ruban-Fell, B., Doorbar, J. A., Lombardo, S., Seedat, F., Hogan, A., Leeflang, M. M. G., Mann, K., Schuh, A., & Marshall, J. (2026). Modelling the cost-effectiveness of non-invasive prenatal testing in the English sickle cell and thalassaemia screening pathway. Diagnostic and Prognostic Research, 10(1), Article 17. https://doi.org/10.1186/s41512-025-00212-9
Image Credits: AI Generated
DOI: 10.1186/s41512-025-00212-9
Keywords: non-invasive prenatal testing, sickle cell disease, thalassaemia, antenatal screening, cost-effectiveness, NHS England, decision tree model, prenatal diagnosis, paternal blood testing, cell-free DNA, screening programme, health economics
News Source: Ophelia Keating. (October 29, 2026). Model suggests replacing father blood tests with NIPT would raise England’s sickle cell screening costs. Scienmag.
