Routine Antenatal Anti-D Prophylaxis in Women Who Are Rh(D) Negative: Meta-Analyses Adjusted for Differences in Study Design and Quality

Turner, Rebecca; Lloyd-Jones, M; Anumba, Dilly; Smith, Gordon C. S.; Spiegelhalter, David; Squires, Hazel; Stevens, John; Sweeting, Michael; Urbaniak, S. J.; Webster, Robert M.; Thompson, Simon G.

doi:10.1371/journal.pone.0030711

Cited by 52 publications

(46 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To inform other parameter estimates for this simulation, we conducted an additional literature search to identify relevant systematic reviews of antenatal anti-D prophylaxis. Four relevant reviews [61][62][63][64] were identified. These reviews provided data on the probability estimates of the events used in the simulation study, including sensitisation and compliance rates.…”

Section: Simulation Study Of Clinical Effectivenessmentioning

confidence: 99%

“…Turner et al 63 Following the publication of the NICE TA156, Turner et al 63 revisited the effectiveness of RAADP for preventing sensitisation in pregnant RhD-negative women. This publication used alternative meta-analytic methods, which allow for the adjustment of both methodological limitations (internal biases) in the set of studies to be combined and differences in study design relative to the research question of interest (external biases).…”

Section: National Institute For Health and Care Excellence Technologymentioning

confidence: 99%

“…62 Subsequent to NICE TA156 a further meta-analysis was performed by Turner et al, 63 which suggests that anti-D immunoglobulin could be marginally more effective if all studies are taken into account, reducing the rate of sensitisation with 'no test and RAADP' from 0.35% to 0.30%. The increased efficacy of RAADP will increase the health costs associated with false-negative results of high-throughput NIPT, as women will have incorrectly forgone a more effective treatment.…”

Section: Sensitivity Analysismentioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

Section: Simulation Study Of Clinical Effectivenessmentioning

confidence: 99%

Section: National Institute For Health and Care Excellence Technologymentioning

confidence: 99%

Section: Sensitivity Analysismentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

show abstract

“…Then, if appropriate, a metaanalysis or qualitative assessment can be conducted, incorporating the information 5 . For example, a UK group combined 6 data from clinical trials with those from cohort studies in a metaanalysis to assess the effectiveness of anti-D, a drug given to some pregnant women to prevent them from producing antibodies against their babies. In this case, potential sources of bias, such as different clinics providing care for the women in cohort studies, were systematically identified, and their impact was minimized.…”

Section: Make Sense Of Health Datamentioning

confidence: 99%

Informatics: Make sense of health data

Elliott

Grimshaw

Altman

et al. 2015

Nature

View full text Add to dashboard Cite

“…2 Late anemia is a recognized complication of HDN regardless of the initial disease severity. 3 Now-a-days HDN is becoming less common, because of introduction of anti D antibodies, early intervention and specialty care centers. In this case report, we present a 24 day old infant born to an Rh negative mother with initial mild jaundice followed by late onset severe anemia.…”

Section: Introductionmentioning

confidence: 99%