Is routine anti-D prophylactic needed?

Administration of antenatal anti-D immunoglobulin to Rhesus (Rh)-negative women without anti-D antibodies may help reduce the incidence of RhD alloimmunization. More research is needed, however, to understand the potential benefits, harms, and cost-effectiveness of routine antenatal anti-D prophylaxis in non-sensitized women, according to authors of a paper published in Cochrane Database of Systematic Reviews.

In their search for studies to include in the review, the investigators identified only two trials that met the selection criteria of having a randomized design and comparing anti-D immunoglobulin administration at 28 weeks or more of gestation versus no treatment, placebo, or a different regimen of anti-D. The two studies, one from France and one from the United Kingdom, included more than 4500 women, and both compared anti-D immunoglobulin given at 28 and 34 weeks’ gestation against no treatment.

Prespecified primary outcomes were incidence of RhD alloimmunization during pregnancy, postpartum (at birth of Rh-positive infant and at follow-up up to 12 months), and in a subsequent pregnancy. The review found that among Rh-negative women carrying a Rh-positive baby, anti-D administration at 28 and 34 weeks’ gestation reduced the risk of RhD-alloimmunization during pregnancy or postpartum from about 1% to about 0.2%. In statistical analyses, however, there were not clear differences between the treated and no treatment groups, and neither study investigated the incidence of RhD alloimmunization in a subsequent pregnancy.

The incidences of a positive Kleihauer test at 32 to 35 weeks’ gestation and at birth of a Rh-positive infant were investigated as a secondary outcome, but assessed in only one trial that found a statistically significant, 40% risk reduction with antenatal anti-D administration. Neonatal morbidity (eg., jaundice, anemia, kernicterus) in current or subsequent pregnancies and adverse events attributable to anti-D treatment were also prespecified secondary outcomes. Data on neonatal jaundice were reported in both studies included in the analysis that found no clear difference in the risk comparing the infants born to mothers who received anti-D immunoglobulin versus controls. Neither trial reported on adverse events associated with anti-D treatment.

The quality of the evidence relating to the prespecified outcomes was assessed using the Grades of Recommendation, Assessment, Development and Evaluation approach and judged to be low or very low. In addition, the included studies were assessed for risk of bias using criteria included in the Cochrane Handbook for Systematic Review of Interventions, and both were considered to be at moderate to high risk of bias.

The authors stated that although the benefit of postpartum anti-D prophylaxis for reducing the incidence of alloimunization after administration and in a subsequent pregnancy is established, it was important to determine the benefits and harms of routine or universal antenatal anti-D prophylaxis because occult or ‘silent’ sensitizing events are thought to constitute the majority of Rh sensitizations.

Based on their findings, they concluded that such a policy generally will not confer benefit or improve outcome in the current pregnancy, but fewer women are likely to have RhD antibodies in any subsequent pregnancy. The authors noted adoption of a policy of routine or universal antental anti-D prophylaxis should consider the costs of prophylaxis versus the costs of care for women who become sensitized and their affected infants along with the adequacy of the local supply of anti-D immunoglobulin. They stated further studies with robust design are needed to investigate the effect of antenatal anti-D on subsequent pregnancies. Other areas for future research include the cost-effectiveness of routine antenatal anti-D administration and what constitutes an optimal regimen in terms of timing, number of treatments, and dosage.