Objective To assess the clinical and financial impact, and identify the problems, of providing routine antenatal RhD immunoglobulin prophylaxis for Rhesus D negative nulliparae.Design A retrospective (198G1986) and prospective (1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996) comparison between two similar populations, one population with nulliparae offered routine RhD immunoglobulin 500 IU prophylaxis at 28 and 34 weeks of gestation part way through the study period, and the other population not offered prophylaxis at any time.Setting Obstetric units in two counties (three health districts) with similar annual numbers of matemities and the Regional Blood Transfusion Service antenatal serology laboratory.Participants Non-sentisitised Rhesus D negative pregnant nulliparae.Interventions Intramuscular RhD immunoglobulin 500 IU at 28 and 34 weeks of gestation to eligible women booked for confinement in one county; the intervention not offered in the other county.Main outcome measures 1. Rhesus D sensitised second pregnancy rate; 2. success in providing prophylaxis to eligible women; 3. serology laboratory activity changes; 4. potential savings from the prophylaxis programme.Prophylaxis significantly reduced iso-immunisation in the next pregnancy when compared with historical (OR 0.28, CI 0,14453; P < 0.0001) and contemporary controls (OR 0.43, CI 0.22486; P = 0.02). However, success at achieving comprehensive prophylaxis was disappointing, with only 89% of eligible women receiving the first injection, 74% both injections, and for only 29% were both at the correct gestation. Fifty-two percent of women delivered after 40 weeks of gestation, beyond the period of adequate prophylaxis protection. The savings in antenatal interventions, neonatal care and possible long term ill-health that result from very preterm birth should be considerable.Routine prophylaxis for nulliparae significantly reduces the incidence of sensitised next pregnancies with consequent savings, and its adoption nationwide should be encouraged. A programme offering antenatal prophylaxis for all Rhesus D negative women is unlikely to be economic. Improvement in uptake of prophylaxis is needed; alternative administration strategies should be explored.

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The relation between maternal anti-D concentrations, measured against the British working standard, and outcome of rhesus-sensitised pregnancies was studied.There is a clear relation between increasing anti-D concentrations and the chance of a severely affected baby. Of those pregnancies (78) where serial anti-D concentrations remained below 4 IUI/ml, no baby had a cord haemoglobin below 10 g/dl and three had exchange transfusions. In contrast, of those mothers (106) with anti-D concentrations above 4 IU/ml, 23 had babies with a cord haemoglobin below 10 g/dl and 79 babies had exchange transfusions. It is suggested that those pregnancies where anti-D concentrations remain below 4 IUT/ml represent a relatively safe group in which amniocentesis may be avoided.

Reported here is the first example of a partial D antigen stimulating the production of anti-D: stimulation was of fetal origin. During her second pregnancy, anti-D developed in the serum of a D-negative mother who had received Rh immunoglobulin after the birth of her first D-positive child. Her second baby had moderate neonatal jaundice and was successfully treated by phototherapy. Subsequently the red cells of the father and of the first child were shown to carry a partial D antigen of category DVa type. Six available batches of Rh immunoglobulin reacted with DVa cells.

In a 2-year period 667 sera from approximately 70000 (0.95%) antenatal patients were found to contain 726 atypical red blood cell antibodies. Overall, 66% of the immunized mothers were rhesus (D) positive. Apart from four antibody specificities to rhesus system antigens, knowledge of the rhesus (D) group gave no guide to the ability of the patients to form any of the remaining 21 specificities encountered. Of the 726 antibodies 221 (30%) were not detected in the initial sample tested and 50 of the 92 patients who produced antibodies during pregnancy had not developed detectable antibody when they were sampled at 28 weeks. The significance of these late onset antibodies is discussed both in relation to the risk of haemolytic disease in the newborn and transfusion reactions in the mother. An optimum protocol for testing is defined which takes account of antibody production during the pregnancy and use of this protocol constitutes an attempt to combine maximum clinical safety with minimal consumption of resources.The Regional Blood Transfusion Centre, John Radcliffe Hospital, Headington, Oxford OX3 9DU specificity and potency, and the corresponding blood type of the consort.