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BMJ No 7121 Volume 315 Editorial Saturday 6 December 1997
Preventing RhD haemolytic disease of the newbornGive anti-rhesus(D) immunoglobulin to all pregnant women who are Rh negativeIn 1994 we saw the 25th anniversary year of the worldwide introduction of anti-rhesus (D) immunoglobulin prophylaxis, one of the most successful prophylactic programmes in medical history. In 1977, 110 cases of stillbirth or neonatal death due to RhD haemolytic disease were registered in Britain; by 1992, this figure seemed to have dropped to nine cases.(1) In this issue of the BMJ, however, Whitfield and colleagues show that this is a serious underestimation (p 1504).(2) Extrapolation of their Scottish figures suggests that there are 50 deaths a year due to RhD haemolytic disease in Britain. They conclude that the discrepancy is due to underreporting because deaths due to early abortion (before 24 weeks) and late neonatal death (second to fourth week of life) are not included in official figures.The policy introduced in 1969 was to give anti-D immunoglobulin to RhD negative women only after the birth of a RhD positive infant or after a sensitising event in pregnancy, such as antepartum haemorrhage. The question now is whether the policy should be extended so that all pregnant women who are RhD negative receive an antenatal dose of anti-D immunoglobulin. More than half the deaths in Whitfield's study were due to sensitisation of the mother between the 28th and 40th week of her first pregnancy. Routine antenatal prophylaxis with anti-D immunoglobulin would largely have prevented sensitisation in the first pregnancy, and neonatal death after a subsequent pregnancy. Another paper in this issue reports that introducing a programme of antenatal prophylaxis in Derbyshire reduced the sensitisation rate from 1.12% of women at risk to 0.28%, a finding that is consistent with previous work.(3-5) This paper also shows that the shift from hospital to community based antenatal care did not reduce the programme's success. The lower incidence of sensitisation might also have been due to a heightened awareness among general practitioners of the need to give anti-D immunoglobulin to women with antepartum haemorrhage; the number of such events doubled during the period under study. There are two reasons why RhD immunisation and sensitisation of pregnant women still occurs. Firstly, because not all women receive anti-D immunoglobulin when they should, and, secondly, because small, undetected leaks of fetal blood into the maternal circulation can occur during the third trimester of pregnancy. Both issues were extensively discussed in April during a consensus conference organised by the Royal College of Physicians of Edinburgh and the Royal College of Obstetricians and Gynaecologists. Contributors were worried that current guidelines for prophylaxis with anti-D immunoglobulin were not being followed.(6,7) Potentially sensitising events during pregnancy such as blunt abdominal trauma and antepartum haemorrhage require that the mother is protected by an injection of anti-D immunoglobulin, preferably after a Kleihauer test or equivalent to asses the size of the fetomaternal bleed. Kleihauer tests may be difficult to perform and standardise,(8) but health professionals should at least recognise sensitising events and consider giving anti-D immunoglobulin "blind" if testing is not available. Pregnant women who are RhD negative should also be educated about the condition, so that they recognise the need for treatment should a sensitising event occur. The conference agreed that the second cause of RhD immunisation - fetomaternal bleeding during the last trimester - would be largely eliminated by giving anti-D immunoglobulin antenatally in one of two possible dose schedules: two doses of 500 IU, one at 28 weeks and the other at 34 weeks, or one dose of 1000 IU given between 28 and 30 weeks. Both options are effective.(3)(9) Antenatal programmes are cost effective if reserved for women in their first pregnancy, as they were in the Derbyshire study.(10,11) Although the conference consensus panel considered that this restriction could not be justified on ethical or economic grounds, it seems that the tremendous global shortage of anti-D immunoglobulin may prevent extension of antenatal prophylaxis to all pregnant women at risk. The shortage of anti-D immunoglobulin from voluntary RhD negative donors is a major concern worldwide. The risk of transmitting viruses with the immunising RhD positive red cells cannot be completely eliminated and has caused the withdrawal of many voluntary donors.(12) Most countries now accept immunoglobulin preparations from commercial sources, prepared from paid donors' blood, and these seem to be safe. Once human monoclonal anti-D immunoglobulin is available, shortage will be a thing of the past; but, while it is being developed and tested, the need for immunised donors will continue well into the next century, and the debate about how best to use this scarce resource will continue. Bob van Dijk
Consultant in blood transfusion
References
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2 Whitfield C R, Raafat A, Urbaniak S J. Underreporting of
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8 Duguid J K M. Antenatal serological testing and prevention of
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12 Crespigny L de, Davison G. Anti-D administration in early
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