Risk Factors for RhD Immunisation Despite Antenatal and Postnatal Anti-D Prophylaxis

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Despite routine antenatal and postnatal administration of anti-D immunoglobulin (Ig) during pregnancy and delivery in a previous pregnancy, 0.1% to 0.3% of women are found to have Rhesus D (RhD) antibodies in their next pregnancy. The primary aim of this case-control study was to identify causative risk factors for rhesus D (RhD) immunization in the next pregnancy among women who had received adequate antenatal and postnatal anti-D prophylaxis in the previous pregnancy. A second aim was to evaluate the preventive effect of additional administration of anti-D Ig in such women with risk factors. Data obtained from the nationwide Dutch antenatal anti- D-prophylaxis program identified 42 new cases of RhD-immunized parae-1, detected with first-trimester screening, despite documented evidence of adequate antenatal and postnatal prophylaxis during the previous pregnancy. The controls were 339 parae-1 without red cell antibodies. Data on risk factors and other information was provided by the obstetric care worker and/or telephone interviews with the women. The primary study outcome measures were risk factors for RhD immunization. Multivariate analysis showed that statistically significant independent risk factors for RhD immunization were postmaturity (≥42 weeks of completed gestation) (odds ratio [OR], 3.07; 95% confidence interval [CI], 1.02-9.02), nonspontaneous delivery (assisted vaginal delivery or cesarean section) (OR, 2.23; 95% CI, 1.04-4.74), and age (OR, 0.89/yr; 95% CI, 0.80-0.98). Pregnancy-related red blood cell transfusion was almost significant; the OR was 3.51, with a 95% CI of 0.97 to 12.7. A condition related to increased feto-maternal hemorrhage and/or insufficient levels of anti-D Ig was observed in at least half of the failures of anti-D Ig prophylaxis. These findings provide direct evidence of causative risk factors for RhD immunization in the next pregnancy of women who had received adequate antenatal and postnatal anti-D prophylaxis in their previous pregnancy. The data show that RhD immunization may be further reduced by routine administration of extra anti-D Ig in these women.