Health Policy / Ethics
Cost-Effectiveness of the Management of Rh-Negative Pregnant Women

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Abstract

Objective

The purpose of this study was to determine the most cost-effective option to prevent alloimmunization against the Rh factor.

Methods

A virtual population of Rh-negative pregnant women in Quebec was built to simulate the cost-effectiveness of preventing alloimmunization. The model considered four options: (1) systematic use of anti-D immunoglobulin; (2) fetal Rh(D) genotyping; (3) immunological determination of the father’s Rh type; (4) mixed screening: immunological determination of the father’s Rh type, followed if positive by fetal Rh(D) genotyping. Two outcomes were considered, in addition to the estimated costs: (1) the number of babies without hemolytic disease, and (2) the number of surviving infants.

Results

In a first pregnancy, two options emerged as the most cost-effective options: systematic prophylaxis and immunological Rh typing of the father, with overlapping confidence intervals between them. In a second pregnancy, the results were similar. In all cases (first or second pregnancy or a combination of the two) fetal genotyping was not found to be a cost-effective option.

Conclusion

Routine prophylaxis and immunological Rh typing of the father are the most cost-effective options for the prevention of Rh alloimmunization. Considering that immunological typing of the father would probably not be carried out by the majority of clinicians, routine prophylaxis remains the preferred option. However, this could change if the cost of Rh(D) fetal genotyping fell below $140 per sample.

Résumé

Objectif

Cette étude avait pour objectif d’identifier l’option la plus rentable pour la prévention de l’allo-immunisation contre le facteur Rh.

Méthodes

Une population virtuelle québécoise de femmes enceintes séronégatives pour le facteur Rh a été créée pour simuler la rentabilité de la prévention de l’allo-immunisation. Ce modèle a pris en considération quatre options : (1) l’utilisation systématique d’immunoglobuline anti-D; (2) le génotypage Rh(D) fœtal; (3) la détermination immunologique du type Rh du père; (4) le dépistage mixte : détermination immunologique du type Rh du père, suivie (en présence de résultats positifs) du génotypage Rh(D) fœtal. Deux critères d’évaluation ont été pris en considération, en plus des coûts estimés : (1) le nombre d’enfants nés sans maladie hémolytique et (2) le nombre de nouveau-nés survivants.

Résultats

Dans le cas d’une première grossesse, deux options se sont avérées les plus rentables : la prophylaxie systématique et la détermination immunologique du type Rh du père; leurs intervalles de confiance se chevauchaient. Dans le cas d’une deuxième grossesse, les résultats ont été semblables. Dans tous les cas (première ou deuxième grossesse, ou une combinaison des deux), nous avons constaté que le génotypage fœtal ne constituait pas une option rentable.

Conclusion

La mise en œuvre systématique d’une prophylaxie et la détermination immunologique du type Rh du père constituent les options les plus rentables pour la prévention de l’allo-immunisation contre le facteur Rh. Puisqu’il est peu probable que la détermination immunologique du type Rh du père soit mise en œuvre par la majorité des cliniciens, la prophylaxie systématique demeure l’option à privilégier. Cependant, cela pourrait changer si le coût du génotypage Rh(D) fœtal chutait en deçà de 140 $ par prélèvement.

Section snippets

INTRODUCTION

Despite the availability of prophylactic measures, alloimmunization to the Rh(D) antigen during pregnancy remains the most common cause of hemolytic disease of the newborn (1:1000 newborns).1 Alloimmunization is the occurrence of an immune response to the presence of an antigen (alloantigen) that an individual lacks, but that is present in other individuals of the same species. In humans, this situation is observed only in special circumstances: pregnancy (immunization of an Rh-negative mother

METHODS

We built a virtual population of 10 000 Rh-negative pregnant women. This number was considered sufficient to perform statistically meaningful simulations given that 150 cases of Rh(D) incompatibility would be expected. The model assumed that 55% of women will have a second pregnancy,20 on average 3.15 years after the first.21 The Rh type of the fetus was established based on the probability of the father being either homozygously or heterozygously Rh positive.22

Besides the estimated costs, two

RESULTS

When the development of HDF and neonatal survival at 28 days were considered as clinical outcomes, two options emerged as the most cost-effective: routine prophylaxis and immunological Rh typing of the father in the first pregnancy (Table 3). However, confidence intervals overlapped between these options.

In the second pregnancy, when the outcome of number of babies without HDF was considered, the immunological Rh typing of the father emerged as the most cost-effective option (Table 4). When

DISCUSSION

Our results suggest that the four proposed strategies for prevention and treatment of Rh(D) alloimmunization are similar in terms of effectiveness. This was expected as all the options include giving anti-D IgG prophylaxis to women who need it. Moreover, the specificity and sensitivity of both fetal genotyping and immunological Rh typing of the father are high, which means that women who need prophylaxis are generally properly identified. In addition, all women who refuse testing (30%) either

CONCLUSION

Until automation of Rh(D) fetal genotyping is implemented and the cost of screening falls below $140, immunological Rh typing of the father and routine anti-D IgG prophylaxis are the most cost-effective options. Because routine immunological Rh typing of the father would probably not be adopted by the majority of Canadian clinicians, routine prophylaxis remains the preferred option, as recommended by the Canadian guidelines for the prevention of maternal–fetal Rh alloimmunization.

ACKNOWLEDGEMENTS

The work that led to this manuscript was supported by a grant from the Canadian Institutes for Health Research (grant number CFBA-49658), and also in part by the FQR-S Réseau de médecine génétique appliquée, and the APOGÉE-Net/CanGèneTest Research and Knowledge Network in Genetic health Services, funded by the Canadian Institutes for Health Research (www.cangenetest.org), (grant number ETG-92250). This work also involved the FRSQ/MSSS/CHUQ Research Chair in Technology Assessment and

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      Citation Excerpt :

      Three studies reported on neonatal outcomes such as the number of healthy babies born,20,21,23 number of newborns without HDFN,23 and number of newborns with serious morbidity or who died owing to HDFN20 (Table 1). It is unclear how and why HDFN was modeled and detected in the first (nonalloimmunized) pregnancy in one study.23 The U.K. CEA17 was the only study to estimate the QALYs of the newborn associated with the consequences of HDFN through inclusion of the two health states (a temporary one accounting for minor developmental problems such as myopia or delay in language and fine motor skills, and a lifetime health state associated with major developmental problems such as bilateral deafness or severe neurodevelopmental delay).

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    Competing Interests: None declared.

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