Routine administration of Anti-D: the ethical case for offering pregnant women fetal RHDgenotyping and a review of policy and practice

Abstract

BackgroundSince its introduction in the 1960s Anti-D immunoglobulin (Anti-D Ig) has been highly successful in reducing the incidence of haemolytic disease of the fetus and newborn (HDFN) and achieving improvements to maternal and fetal health. It has protected women from other invasive interventions during pregnancy and prevented deaths and damage amongst newborns and is a technology which has been adopted worldwide. Currently about one third of pregnant women with the blood group Rhesus D (RhD) negative in the UK (approximately 40,000 women per year in England and Wales), receive antenatal Anti-D Ig in pregnancy when they do not require it because they are carrying a RhD negative fetus. Since 1997, a test using cell free fetal DNA (cffDNA) in maternal blood has been developed to identify the genotype of the fetus and can be used to predict the fetal RhD blood group.DiscussionThis paper considers whether it is ethically acceptable to continue administering antenatal Anti-D Ig to all RhD negative women when fetal RHD genotyping using maternal blood could identify those women who do not need this product.SummaryThe antenatal administration of Anti-D Ig to a third of RhD negative pregnant women who carry a RhD negative fetus and therefore do not need it raises important ethical issues. If fetal RHD genotyping using maternal blood was offered to all RhD negative pregnant women it would assist them to make an informed choice about whether or not to have antenatal Anti-D Ig.

Use of cffDNA to avoid administration of anti‐D to pregnant women when the fetus is RhD‐negative: implementation in the NHS

“…Irrespective of the financial costs, it has been argued that it is ethically unacceptable to continue administering antenatal anti‐D Ig to all RhD‐negative women when a fetal RHD genotyping test using maternal blood could identify those women who do not need this product . Each dose of anti‐D is prepared from multiple blood donations from many donors.…”

“…A NIHR‐funded multi‐centre (Bristol was one centre) study investigated the performance of this test at different gestational ages and demonstrated the test is reliable after 11 weeks’ gestation . This has led to the suggestion that the continuing practice of giving a blood product pooled from multiple donors to healthy pregnant women is ethically unreasonable . National fetal RhD testing programmes to direct antenatal anti‐D prophylaxis have been introduced successfully in other countries, but (with the exception of the Netherlands) these were in countries which did not previously have an antenatal anti‐D administration programme and were therefore considering the issues from a different starting point.…”

Usefulness of Non-Invasive Fetal RHD Genotyping towards Immunoprophylaxis Optimization

“…On the other hand, it has been recently discussed that routine administration of biological products, such as IgRH, would not be ethically acceptable when molecular methodologies for fetal RHD genotyping are available to identify those women that do not need their administration [10]. …”

“…Thus, the assessment of the risk of HDFN by determining the RHD genotype from the cell-free fetal DNA (cffDNA) in maternal blood implicates an improvement in IgRH prophylaxis, only comparable to that of the introduction of the prophylaxis itself at that time. Therefore, non-invasive genotyping of fetal RHD status by analyzing cffDNA in maternal plasma has already been incorporated into routine clinical practice of many countries, causing a great impact on management protocols of D-negative pregnant women [10]. In Belgium, since 2002, fetal RHD genotyping has been used during the follow-up of D-negative pregnant women for an accurate indication of prophylaxis, and, in parallel, prevention policies have been implemented, allowing to avoid IgRH injection in 39% of the women who carry D-negative fetuses [11].…”

Genetic and molecular cell technologies in diagnostics Rh Factor fetus in pregnant women with Rh-negative blood

“…В то же время сфера не-инвазивной пренатальной диагностики не ограни-чивается диагностикой генетических особенностей и анеуплоидий плода. Одно из активно развиваю-щихся направлений -неинвазивное генетическое определение резус-фактора плода у женщин с резус-отрицательной принадлежностью крови [1][2][3][4]. До настоящего времени преемственность результатов исследований неинвазивной пренатальной диагно-стики и клинической практики была довольно огра-ничена.…”