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

Abstract

Objective To identify risk factors for Rhesus D (RhD) immunisation in pregnancy, despite adequate antenatal and postnatal anti-D prophylaxis in the previous pregnancy. To generate evidence for improved primary prevention by extra administration of anti-D Ig in the presence of a risk factor.Design Case-control study.Setting Nation-wide evaluation of the Dutch antenatal anti-D-prophylaxis programme.Population Cases: 42 RhD-immunised parae-1, recognised by first-trimester routine red cell antibody screening in their current pregnancy, who received antenatal and postnatal anti-D Ig prophylaxis (gifts of 1000 iu) in their first pregnancy. Controls: 339 parae-1 without red cell antibodies.Methods Data were collected via obstetric care workers and/or personal interviews with women.Main outcome measure Significant risk factors for RhD immunisation in multivariate analysis.Results Independent risk factors were non-spontaneous delivery (assisted vaginal delivery or caesarean section) (OR 2.23; 95% CI:1.04-4.74), postmaturity ( ‡42 weeks of completed gestation: OR 3.07; 95% CI:1.02-9.02), pregnancy-related red blood cell transfusion (OR 3.51; 95% CI:0.97-12.7 and age (OR 0.89/year; 95% CI:0.80-0.98). In 43% of cases, none of the categorical risk factors was present.Conclusions In at least half of the failures of anti-D Ig prophylaxis, a condition related to increased fetomaternal haemorrhage (FMH) and/or insufficient anti-D Ig levels was observed. Hence, RhD immunisation may be further reduced by strict compliance to guidelines concerning determination of FMH and accordingly adjusted anti-D Ig prophylaxis, or by routine administration of extra anti-D Ig after a non-spontaneous delivery and/or a complicated or prolonged third stage of labour.

Single dose v two‐dose antenatal anti‐D prophylaxis: a randomised controlled trial

“…Despite the increased volume of distribution of administered anti‐D in heavier women and the consequently lower circulating levels achieved with equivalent doses, protection against sensitisation depends on the total amount of anti‐D, not its blood concentration; heavier women should not be at greater risk of sensitisation, as the concentration of fetal red blood cells in maternal blood will also be reduced. This interpretation is supported by the results of a case–control study (42 cases, 339 controls) that found no association between weight and sensitisation …”

Antigen specificity determines anti‐red blood cell IgG‐Fc alloantibody glycosylation and thereby severity of haemolytic disease of the fetus and newborn

“…Patient samples and clinical data from the prospective OPZI study (Detection and Prevention of Pregnancy Immunisation) were included after informed consent (Koelewijn et al , , ). The OPZI study included all Dutch pregnant women with clinically relevant non‐D RBC antibodies, detected at first trimester screening, from 1 Sept 2002–1 June 2003 and from 1 Oct 2003–1 July 2004 ( n = 230) and 964 controls and antigen‐negative children (Koelewijn et al , , ). None of the affected cases received intravenous immunoglobulin therapy.…”

ABO incompatibility and RhIG immunoprophylaxis protect against non‐D alloimmunization by pregnancy

“…By not including women who developed D antibodies, part of the D– population (of which a considerable proportion might be “high‐responders,” very prone to develop additional antibodies) was excluded. This exclusion did not affect the found preventive effect of RhIG on the development of non‐Rh antibodies, as we previously found that in primiparous women with newly detected D antibodies and without a previous blood transfusion, non‐Rh antibodies in addition to D antibodies are rarely developed …”