Targeted anti-RhD prophylaxis finds favor in Canada

Findings of a decision analysis conducted by researchers from the University of Calgary, Alberta, support conversion from the current policy of routine antenatal anti-Rhesus D (RhD) prophylaxis in unsensitized RhD-negative pregnant women to a targeted approach based on noninvasive fetal RhD genotyping using maternal blood because it provides benefits without posing harm.

Cost per pregnancy in Canadian dollars was analyzed as the primary outcome and it was found to be reduced almost 6% by switching from the routine program to targeted prophylaxis (71.43 vs. 67.20, respectively). Secondary outcomes analyses showed that targeted prophylaxis would not affect the 0.0012 sensitization rate per RhD-negative pregnancy but would reduce the number of Rh immunoglobulin (RhIG) doses administered over a 1-year period by 4072, representing a decrease of about 20%.

Not reflected by the analysis are the benefits of sparing the large numbers of RhD-negative women with an Rh-D negative fetus the discomfort and risks accompanying an unnecessary blood product injection, said Jo-Ann M. Johnson, MD, senior author and Professor of Obstetrics and Gynecology, University of Calgary.

“We would like to bring Canadian policy on anti-RhD prophylaxis in alignment with the targeted programs that successfully exist in the United Kingdom and countries in northern Europe, and the findings of our study provide evidence to support that transition,” she said.

“At a recent conference attended by representatives from the multiple players affected by this decision, a consensus was reached favoring implementation of a targeted program. We are now writing up the proceedings of that meeting for publication and determining how to leverage existing resources to achieve our goal.”

For the analyses, decision trees to model the cost and benefits of the routine and targeted prophylaxis programs were constructed using clinical and administrative data to set the probabilities of different outcomes and specific costs. The targeted model assumed RhD genotyping would be performed at 12 weeks’ gestation in all RhD-negative women and that RhIG would be given at 28 weeks’ gestation, at any potentially sensitizing event, and postpartum only to women with an Rh-positive fetus.

A series of sensitivity analyses were also conducted that excluded postpartum cord blood analysis from targeted prophylaxis, accounted for a 12% inconclusive rate of the RhD genotyping, and used a higher cost for fetal RhD genotyping.

“Since the fetal genotyping test is not being performed by any labs in Canada yet, the cost set in our primary model was an estimate determined by our molecular genetics team using a published protocol. The results of our sensitivity analyses consistently supported targeted prophylaxis,” said Lisa Teitelbaum, MD, lead author and senior resident in Obstetrics and Gynecology at the University of Calgary.

The researchers noted their findings differ from an earlier published analysis investigating the cost of implementing targeted prophylaxis in the United States that favored maintaining routine antenatal anti-RhD prophylaxis. However, the discrepancy may be accounted for by differences in healthcare costs between the United States and Canada and the decreasing cost of fetal RhD genotyping.

“In the future, we can anticipate there may be even greater cost savings using the targeted prophylaxis as we expect the cost of the test will continue to decline and will also be lowered by economies of scale if targeted prophylaxis is adopted,” said Dr. Teitelbaum.

Amy Metcalfe, PhD, coauthor and Assistant Professor of Obstetrics and Gynecology, University of Calgary, commented about the accuracy of fetal RhD genotyping using maternal blood and the finding that the sensitization rate would not be increased by targeted prophylaxis.

“There is a risk of maternal sensitization because of a false-negative result with the fetal RhD genotyping. It is reassuring to know, however, that sensitization is an extremely rare outcome with both our current program of routine prophylaxis and with targeted prophylaxis,” she said.