3.3.3 Rh isoimmunization

Rh isoimmunization is a type of haemolytic disease of the fetus and newborn (HDFN). Specifically, it is the development of antibodies against the Rh antigens on the surface of red blood cells of another individual (i.e. one’s own fetus) (123).

Rationale

A systematic review assessed the effect of routine anti-D administration among unsensitized Rh-negative individuals undergoing an abortion. There are few studies examining Rh isoimmunization in unsensitized Rh-negative individuals seeking abortion before 12 weeks of gestation. Only two studies, conducted in Israel and the USA, met the inclusion criteria for the review, both published in 1972 (124, 125). A summary of the evidence is presented in Supplementary material 2, EtD framework on Rh isoimmunization.

The evidence on the effectiveness of the intervention may favour the intervention, because fewer women in the intervention group (anti-D administration) had antibody formation after the initial pregnancy compared to the women in the comparison group (no anti-D), and no harms (undesirable effects) of the intervention were noted. However, after consideration of the resources required, cost-effectiveness and feasibility of administering anti-D, as well as the very low certainty of the evidence on effectiveness, the expert panel concluded that overall, the evidence does not favour the intervention and decided to recommend against it for gestational ages < 12 weeks, rather than < 9 weeks, as mentioned in the 2012 guidance (19). The justification for this new recommendation is outlined in the following points: (i) The presence of fetal blood in Rh-negative women at early gestational ages does not necessarily correlate with development of Rh alloimmunization and if we apply the results of an experimental study to this scenario, then theoretically there is zero chance of antibody formation if the Rh negative woman is exposed to the Rh-antigen of the fetal blood cells (126); (ii) A study comparing Rh alloimmunization rates in two countries demonstrated the safety of not treating Rh-negative women with spontaneous abortion under 10 weeks of gestation (127); (iii) WHO only recommends antenatal prophylaxis with anti-D immunoglobulin in non-sensitized Rh-negative pregnant women at 28 and 34 weeks of gestation to prevent RhD alloimmunization in the context of rigorous research (128).