LONDON, SATURDAY 29 JULY 1978
MEDICAL Preventing Rh haemolytic disease Henry VIII was happily married to Catherine of Aragon for 19 years, and most historians agree that he would have remained married to her for the rest of his life had she borne him a son. Apart from a single surviving daughter, Mary, she had several miscarriages and premature labours and produced five babies who died within days or weeks of delivery. It has been suggested' that this appalling obstetric history could be explained by Rh incompatibility if Catherine had already been sensitised by her first husband, who was Henry's brother Arthur. If this hypothesis is correct, then had Rh immunoglobulin been invented the course of English history would have been very different. The tragic saga of Henry's future wives would have been averted. The Church of England might not have been formed, Queen Elizabeth the First would not have been born, we would have been spared mad "Farmer George," with his possible porphyria -and hence we might have retained our American colonies and so saved the NHS from its present financial predicament. Nevertheless, Rh immunoglobulin is now with us,' albeit a little late, and undoubtedly the incidence of Rh haemolytic disease has been greatly reduced.'-5 Between 1968 and 1975 the stillbirth rate from rhesus haemolytic disease in England and Wales fell from 0 52 to 0 16 per 1000 live births (430 to 100 stillbirths) and the infant mortality rate fell from 019 to 0-06 per 1000 live births (158 to 36 postnatal deaths).6 About a quarter of these deaths were due to sensitisation before the introduction of Rh immunoglobulin, and some of them were associated with sensitised women with bad obstetric histories coming to Britain for treatment. In practical terms the disease may now be said to be controlled; and Tovey et al3 have recently suggested that the incidence of severely affected babies could be reduced to one or two cases a year in a population of three to four million. The reduction in cases is not solely due to Rh immunoglobulin, because there has also been a significant fall in the incidence of haemolytic disease in babies born to women with previously affected infants. Probably many sensitised women are avoiding further pregnancies. Rhesus haemolytic disease still occurs: Tovey et al3 noted 134 cases in 1976, though many of these cases were mild, and there were no deaths; nevertheless, exchange transfusion was required in several cases. Why do cases still occur ? Could we reduce the incidence of rhesus haemolytic disease further or even eliminate it completely ? Cases occurring in women sensitised before the introduction of Rh immunoglobulin should gradually disappear, and many women with bad obstetric histories are being advised against further pregnancies. Administrative failure, in which Rh immunoglobulin had not been given to women at risk, caused 14 cases in the same series. The crucial preventive step is for (© BRITISH MEDICAL JOURNAL 1978. All reproduction rights reserved.
all Rh-negative unsensitised women to receive Rh immunoglobulin after the birth of an Rh-positive infant. This is so important that it is a valid reason why all Rh-negative women should be delivered in hospital, where facilities for testing cord blood are readily available. Furthermore, some doctors still seem unaware that women may be sensitised after abortion; all Rh-negative women should be protected with Rh immunoglobulin after termination of pregnancy or spontaneous miscarriage. Rh sensitisation from this source is unlikely to be eliminated completely, however, because many early abortions are not detected clinically and are simply passed over as a menstrual irregularity. Finally, Rh immunoglobulin given after delivery does not provide absolute protection: Tovey and his colleagues3 recorded a failure rate of 0 90 0. The present highly successful preventive policy is based on the idea that most cases of sensitisation are due to transplacental bleeds caused by placental trauma at delivery. 8 A few women, however, are sensitised by transplacental bleeds during pregnancy. The initial stages of sensitisation are not always detectable serologically, and most of the treatment failures are caused by giving Rh immunoglobulin after delivery, when the sensitisation process has already been initiated and cannot be reversed. Some Rh-negative primiparae have detectable antibody in the first pregnancy, probably owing to sensitisation very early in pregnancy or to a preceding abortion which may have been subclinical. There are therefore good reasons for suggesting that the incidence of rhesus haemolytic disease could be reduced further by giving an additional dose of Rh immunoglobulin during pregnancy. This does not harm the fetus, and the results of clinical trials in Canada have been promising.9 Antenatal treatment on these lines, however, would entail the use of much larger quantities of Rh immunoglobulin. This would present serious logistic problems, and the extra effort is probably not worth while, as the national death rate is already so low. 1
Maclennan, H, Medical History, 1967, 11, 66. 2Clarke, C A, and Finn, R, American Journal of Obstetrics and Gynecology,
1977, 127, 538. 3Tovey, L A D, et al, British Medical3Journal, 1978, 2, 106. 4Tovey, L A D, Health Trends, 1976, 8, 25. Freda, V J, Gorman, J G, and Pollack, W, American 7ournal of Obstetrics and Gynecology, 1977, 28, 456. 6 Office of Population Censuses and Surveys, Mortality Statistics: Childhood, 1975, London, HMSO, 1978. 7Knox, E G, British Jrournal of Preventive and Social Medicine, 1976, 30,
163. 8 Finn, R, et al, Transfusion (Philadelphia), 1963, 3, 114. 9 Bowman, J M, et al, Canadian Medical Association Journal, 1978,
118, 623.
NO 6133 PAGE 307
MEDICAL Preventing Rh haemolytic disease Henry VIII was happily married to Catherine of Aragon for 19 years, and most historians agree that he would have remained married to her for the rest of his life had she borne him a son. Apart from a single surviving daughter, Mary, she had several miscarriages and premature labours and produced five babies who died within days or weeks of delivery. It has been suggested' that this appalling obstetric history could be explained by Rh incompatibility if Catherine had already been sensitised by her first husband, who was Henry's brother Arthur. If this hypothesis is correct, then had Rh immunoglobulin been invented the course of English history would have been very different. The tragic saga of Henry's future wives would have been averted. The Church of England might not have been formed, Queen Elizabeth the First would not have been born, we would have been spared mad "Farmer George," with his possible porphyria -and hence we might have retained our American colonies and so saved the NHS from its present financial predicament. Nevertheless, Rh immunoglobulin is now with us,' albeit a little late, and undoubtedly the incidence of Rh haemolytic disease has been greatly reduced.'-5 Between 1968 and 1975 the stillbirth rate from rhesus haemolytic disease in England and Wales fell from 0 52 to 0 16 per 1000 live births (430 to 100 stillbirths) and the infant mortality rate fell from 019 to 0-06 per 1000 live births (158 to 36 postnatal deaths).6 About a quarter of these deaths were due to sensitisation before the introduction of Rh immunoglobulin, and some of them were associated with sensitised women with bad obstetric histories coming to Britain for treatment. In practical terms the disease may now be said to be controlled; and Tovey et al3 have recently suggested that the incidence of severely affected babies could be reduced to one or two cases a year in a population of three to four million. The reduction in cases is not solely due to Rh immunoglobulin, because there has also been a significant fall in the incidence of haemolytic disease in babies born to women with previously affected infants. Probably many sensitised women are avoiding further pregnancies. Rhesus haemolytic disease still occurs: Tovey et al3 noted 134 cases in 1976, though many of these cases were mild, and there were no deaths; nevertheless, exchange transfusion was required in several cases. Why do cases still occur ? Could we reduce the incidence of rhesus haemolytic disease further or even eliminate it completely ? Cases occurring in women sensitised before the introduction of Rh immunoglobulin should gradually disappear, and many women with bad obstetric histories are being advised against further pregnancies. Administrative failure, in which Rh immunoglobulin had not been given to women at risk, caused 14 cases in the same series. The crucial preventive step is for (© BRITISH MEDICAL JOURNAL 1978. All reproduction rights reserved.
all Rh-negative unsensitised women to receive Rh immunoglobulin after the birth of an Rh-positive infant. This is so important that it is a valid reason why all Rh-negative women should be delivered in hospital, where facilities for testing cord blood are readily available. Furthermore, some doctors still seem unaware that women may be sensitised after abortion; all Rh-negative women should be protected with Rh immunoglobulin after termination of pregnancy or spontaneous miscarriage. Rh sensitisation from this source is unlikely to be eliminated completely, however, because many early abortions are not detected clinically and are simply passed over as a menstrual irregularity. Finally, Rh immunoglobulin given after delivery does not provide absolute protection: Tovey and his colleagues3 recorded a failure rate of 0 90 0. The present highly successful preventive policy is based on the idea that most cases of sensitisation are due to transplacental bleeds caused by placental trauma at delivery. 8 A few women, however, are sensitised by transplacental bleeds during pregnancy. The initial stages of sensitisation are not always detectable serologically, and most of the treatment failures are caused by giving Rh immunoglobulin after delivery, when the sensitisation process has already been initiated and cannot be reversed. Some Rh-negative primiparae have detectable antibody in the first pregnancy, probably owing to sensitisation very early in pregnancy or to a preceding abortion which may have been subclinical. There are therefore good reasons for suggesting that the incidence of rhesus haemolytic disease could be reduced further by giving an additional dose of Rh immunoglobulin during pregnancy. This does not harm the fetus, and the results of clinical trials in Canada have been promising.9 Antenatal treatment on these lines, however, would entail the use of much larger quantities of Rh immunoglobulin. This would present serious logistic problems, and the extra effort is probably not worth while, as the national death rate is already so low. 1
Maclennan, H, Medical History, 1967, 11, 66. 2Clarke, C A, and Finn, R, American Journal of Obstetrics and Gynecology,
1977, 127, 538. 3Tovey, L A D, et al, British Medical3Journal, 1978, 2, 106. 4Tovey, L A D, Health Trends, 1976, 8, 25. Freda, V J, Gorman, J G, and Pollack, W, American 7ournal of Obstetrics and Gynecology, 1977, 28, 456. 6 Office of Population Censuses and Surveys, Mortality Statistics: Childhood, 1975, London, HMSO, 1978. 7Knox, E G, British Jrournal of Preventive and Social Medicine, 1976, 30,
163. 8 Finn, R, et al, Transfusion (Philadelphia), 1963, 3, 114. 9 Bowman, J M, et al, Canadian Medical Association Journal, 1978,
118, 623.
NO 6133 PAGE 307
