Effectiveness and costs of non-invasive foetal RHD genotyping in rhesus-D negative mothers: a French multicentric two-arm study of 850 women

Meryl Darlington, Bruno Carbonne, Agnès Mailloux, Yves Brossard, Annie Levy-Mozziconacci, Anne Cortey, Hassani Maoulida, Tabassome Simon, Alexandra Rousseau, Isabelle Durand-Zaleski, GENIFERH1 Study Group, Bruno Carbonne, Lionel Carbillon, Olivier Chanelles, Aurélie Revaux, Marc Dommergues, Anne-Florence Naime-Alix, Danièle Vauthier Brouzes, Christine Rouillac-Le Sciellour, Patrick Rozenberg, Valérie Serazin, Véronique Houfflin-Debarge, Stéphane Bezieau, Olivier Pape, Norbert Winer, Anne Cortey, Yves Brossard, Nelly Da Silva, Agnès Mailloux, Vassilis Tsatsaris, Sophie Omnès, Laurent Gavard, Laurent Mandelbrot, Claude d'Ercole, Raoul Desbrière, Jean-Baptiste Haumonté, Nathalie Lesavre, Annie Levy-Mozziconacci, Constance Borie, Aude Recoules-Arché, Yves Colin, Pascal Auquier, Cécile Fortanier, Sandrine Loubière, Abdel Benamar, Elodie Drouet, Mehdi Khadefi, Josiane Ngomlong, Alexandra Rousseau, Tabassome Simon, Sétareh Zarrabian, Meryl Darlington, Isabelle Durand-Zaleski, Hassani Maoulida, Meryl Darlington, Bruno Carbonne, Agnès Mailloux, Yves Brossard, Annie Levy-Mozziconacci, Anne Cortey, Hassani Maoulida, Tabassome Simon, Alexandra Rousseau, Isabelle Durand-Zaleski, GENIFERH1 Study Group, Bruno Carbonne, Lionel Carbillon, Olivier Chanelles, Aurélie Revaux, Marc Dommergues, Anne-Florence Naime-Alix, Danièle Vauthier Brouzes, Christine Rouillac-Le Sciellour, Patrick Rozenberg, Valérie Serazin, Véronique Houfflin-Debarge, Stéphane Bezieau, Olivier Pape, Norbert Winer, Anne Cortey, Yves Brossard, Nelly Da Silva, Agnès Mailloux, Vassilis Tsatsaris, Sophie Omnès, Laurent Gavard, Laurent Mandelbrot, Claude d'Ercole, Raoul Desbrière, Jean-Baptiste Haumonté, Nathalie Lesavre, Annie Levy-Mozziconacci, Constance Borie, Aude Recoules-Arché, Yves Colin, Pascal Auquier, Cécile Fortanier, Sandrine Loubière, Abdel Benamar, Elodie Drouet, Mehdi Khadefi, Josiane Ngomlong, Alexandra Rousseau, Tabassome Simon, Sétareh Zarrabian, Meryl Darlington, Isabelle Durand-Zaleski, Hassani Maoulida

Abstract

Background: The determination of foetal Rhesus D (RHD) status allows appropriate use of IgRh prophylaxis by restricting its use to cases of RHD feto-maternal incompatibilities. There is a degree of uncertainty about the cost-effectiveness of foetal RHD determination, yet screening programs are being introduced into clinical practice in many countries. This paper evaluates the impact of non-invasive foetal Rhesus D (RHD) status determination on the costs of managing RHD-negative pregnant women and on the appropriate use of anti-D prophylaxis in a large sample of RHD-negative pregnant women using individual prospectively collected clinical and economic data.

Methods: A prospective two-armed trial of RHD negative pregnant women was performed in 11 French Obstetric Departments. Non-invasive foetal RHD genotyping was performed before 26 weeks' gestation in the experimental arm whereas the control arm participants received usual care. The costs associated with patient management in relation to their RHD negative status (biological tests, anti-D prophylaxis and visits) were calculated from inclusion to the end of the postpartum period. The costs of hospital admissions during pregnancy and delivery were also determined.

Results: A total of 949 patients were included by 11 centres between 2009 and 2012, and 850 completed follow-up, including medical and biological monitoring. Patients were separated into two groups: the genotyping group (n=515) and the control group (n=335). The cost of the genotyping was estimated at 140 euros per test. The total mean cost per patient was estimated at €3,259 (SD ± 1,120) and €3,004 (SD ± 1,004) in the genotyping and control groups respectively. The cost of delivery represented three quarters of the total cost in both groups. The performance of managing appropriately RHD negative anti-D prophylaxis was 88% in the genotyping group, versus 65% in the control group. Using the costs related to RHD status (biological tests, anti-D immunoglobulin injections and visits) the incremental cost-effectiveness ratio (ICER) was calculated to be €578 for each percentage gain in women receiving appropriate management.

Conclusion: Early knowledge of the RHD status of the foetus using non-invasive foetal RHD genotyping significantly improved the management of RHD negative pregnancies with a small increase in cost.

Trial registration: Clinical trials registry- NCT00832962 -13 January 2009 - retrospectively registered.

Keywords: Anti-D immunoglobulin; Cost evaluation; Cost-effectiveness; Non-invasive foetal RHD genotyping.

Conflict of interest statement

Ethics approval and consent to participate

The ethics committee (Comité de protection des personnes) approved the study. All participants signed an informed consent form. The study was declared to the national committee of computerised records and liberty (Commission Nationale de l’Informatique et des Libertés) before data collection began.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study flow chart
Fig. 2
Fig. 2
Cost-effectiveness plane. Scatter plot on the cost-effectiveness plane showing the difference in costs (pertaining to RHD negative status) and performance from GENIFERH1 data using 1000 bootstrap replicates. The genotyping arm cost of resources per patient was on average €139 more expensive than the control arm. The genotyping arm was more performant with an increase in effectiveness of 24%
Fig. 3
Fig. 3
Cost-effectiveness acceptability curve showing the probability that foetal RHD genotyping is cost-effective compared to usual care based on the uncertainty in cost and effect differences shown in Fig. 2

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