Diagnostic accuracy of routine antenatal determination of fetal RHD status across gestation: population based cohort study

Chitty, Lyn S.; Finning, Kirstin; Wade, Angela; Soothill, Peter; Martin, Bill; Oxenford, Kerry; Daniels, Geoff; Massey, Edwin

doi:10.1136/bmj.g5243

Cited by 83 publications

(100 citation statements)

References 14 publications

(20 reference statements)

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“…All the studies were prospective studies and were conducted in European countries. Four studies were conducted in England,12,[17][18][19] three of which were based in Bristol. 12,17,18 The sample size (number of patients/samples analysed) of studies ranged from 282 to 18,383 …”

Section: Results: Assessment Of Diagnostic Accuracymentioning

confidence: 99%

“…Only three studies stated that their diagnostic threshold was prespecified during the conduct of the screening programme. 12,17,20 None of the studies reported whether or not there were any adverse events from the index test or reference standard. Two studies 19,21 were judged as having a high risk of bias.…”

Section: Risk Of Bias Of the Included Studiesmentioning

confidence: 99%

“…10,11 However, a recent UK cohort study found that fetal RhD genotyping was more accurate for the prediction of RhD status if it was performed after, rather than before, 11 weeks' gestation. 12 In this assessment we aim to investigate findings of high-throughput NIPT from a number of subgroups, such as those based on different gestational ages and different ethnicities as well as on the usage of different exons of RHD, if data are available.…”

Section: Identification Of Important Subgroupsmentioning

confidence: 99%

“…We conducted sensitivity analyses (SAs) to explore: l the impact of including and excluding undetermined or uninterpretable NIPT results on the pooled test accuracy estimates l test accuracy in UK (Bristol)-based studies 12,17,18 only.…”

Section: Sensitivity Analysesmentioning

confidence: 99%

“…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.…”

Section: Number Of Studies Includedmentioning

confidence: 99%

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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

Saramago

Yang

Llewellyn

et al. 2018

Health Technol Assess

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Background High-throughput non-invasive prenatal testing (NIPT) for fetal rhesus (D antigen) (RhD) status could avoid unnecessary treatment with routine anti-D immunoglobulin for RhD-negative women carrying a RhD-negative fetus, although this may lead to an increased risk of RhD sensitisations. Objectives To systematically review the evidence on the diagnostic accuracy, clinical effectiveness and implementation of high-throughput NIPT and to develop a cost-effectiveness model. Methods We searched MEDLINE and other databases, from inception to February 2016, for studies of high-throughput NIPT free-cell fetal deoxyribonucleic acid (DNA) tests of maternal plasma to determine fetal RhD status in RhD-negative pregnant women who were not known to be sensitised to the RhD antigen. Study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) and A Cochrane Risk of Bias Assessment Tool: for Non-Randomised Studies of Interventions (ACROBAT-NRSI). Summary estimates of false-positive rates (FPRs) and false-negative rates (FNRs) were calculated using bivariate models. Clinical effectiveness evidence was used to conduct a simulation study. We developed a de novo probabilistic decision tree-based cohort model that considered four alternative ways in which the results of NIPT could guide the use of anti-D immunoglobulin antenatally and post partum. Sensitivity analyses (SAs) were conducted to address key uncertainties and model assumptions. Results Eight studies were included in the diagnostic accuracy review, seven studies were included in the clinical effectiveness review and 12 studies were included in the review of implementation. Meta-analyses included women mostly at or post 11 weeks’ gestation. The pooled FNR (women at risk of sensitisation) was 0.34% [95% confidence interval (CI) 0.15% to 0.76%] and the pooled FPR (women needlessly receiving anti-D) was 3.86% (95% CI 2.54% to 5.82%). SAs did not materially alter the overall results. Data on clinical outcomes, including sensitisation rates, were limited. Our simulation suggests that NIPT could substantially reduce unnecessary use of antenatal anti-D with only a small increase in the risk of sensitisation. All large implementation studies suggested that large-scale implementation of high-throughput NIPT was feasible. Seven cost-effectiveness studies were included in the review, which found that the potential for the use of NIPT to produce cost savings was dependent on the cost of the test. Our de novo model suggested that high-throughput NIPT is likely to be cost saving compared with the current practice of providing routine antenatal anti-D prophylaxis to all women who are RhD negative. The extent of the cost saving appeared to be sufficient to outweigh the small increase in sensitisations. However, the magnitude of the cost saving is highly sensitive to the cost of NIPT itself. Limitations There was very limited evidence relating to the clinical effectiveness of high-throughput NIPT, with no evidence on potential adverse effects. The generalisability of the findings to non-white women and multiple pregnancies is unclear. Conclusions High-throughput NIPT is sufficiently accurate to detect fetal RhD status in RhD-negative women from 11 weeks’ gestation and would considerably reduce unnecessary treatment with routine anti-D immunoglobulin, potentially resulting in cost savings of between £485,000 and £671,000 per 100,000 pregnancies if the cost of implementing NIPT is in line with that reflected in this evaluation. Future work Further research on the diagnostic accuracy of NIPT in non-white women is needed. Study registration This study is registered as PROSPERO CRD42015029497. Funding The National Institute for Health Research Health Technology Assessment programme.

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