Ar~n~s of
Arch Gynecol Obstet (1991) 248:175-180
Gynecology and Obstetrics
© Springer-Verlag199t
Haemolytic disease of the newborn infant. Long term efficiency of the screening and the prevention of alloimmunization in the mother: thirty years of experience P. Moncharmont, F. Juron Dupraz, M. Vignal, D. Rigal, F. Meyer, and P. Debeaux C.R.T.S. de Lyon-Beynost BP 401, F-01704 Beynost Cedex, France Received April 6, 1990/Accepted October 10, 1990
Summary. During the last thirty years, the diagnosis, management and prevention of haemolytic disease of the newborn infant (HDN) have improved. From 1959 to 1988, 3004 HDN (ABO excluded) have been collected. The percentage of HDN with anti-D alloimmunization decreased significantly (98.4% from 1959 to 1968, 93.5% from 1969 to 1978 and 68.1% from 1979 to 1988). The anti-D HDN with exchange transfusion (ET) fell significantly between the first and second periods (577 versus 970; Z~ = 19.92; P < 0.001). On the other hand, the number of HDN other than anti-D increased during these three periods, but the percentage of these HDN which needed ET decreased. Our study shows the long term efficiency of the prevention of anti-D alloimmunization (since 1970) and of the irregular antibodies screening among all pregnant women (since 1979). Key words: Alloimmunization - Haemolytic disease - Newborn Introduction Since the initial discovery of the Rhesus (D) blood group by Levine and Stetson (1939), many other red blood cell antigens have been found. Some of them are involved in the haemolytic disease of the newborn infant (HDN). Among HDN cases (ABO antigens excepted), the anti-D alloimmunization of the mother remains the most frequently observed. In France, since 1962, in order to detect an anti-D alloimmmlization in the mother during pregnancy, ABO Rhesus blood group of all pregnant women has been performed at the time of their first antenatal visit. When the mother's blood group is Rh (D) negative, her serum is tested for irregular anti red blood cell antibodies. At this time, the mothers, whose blood group was Rh (D) positive, were not, or only occasionally, tested for irregular antibodies. After the study of Finn et al. (1961), Clarke et al. Offprint requests to: D r P Moncharmont (address see above)
176
P. Moncharmont et al.
(1963), Freda et al. (1964) and Woodrow and Donohoe (1968), it has been well established that anti-D sensitization of an Rh (D) negative mother by erythrocytes of her Rh (D) positive newborn infant could be prevented by using anti-D immunoglobulins just after the delivery. In Lyon, since 1970, this prevention has been performed with intravenous anti-D immunoglobulins. During the same period, determination of the Liley index on the amniotic fluid (Liley 1961) was introduced. Since 1979, the screening of anti-erythrocytes irregular antibodies in all pregnant woman has been used in Lyon. Screening was not introduced all over the country until 1985. During these thirty last years, we have observed a considerable decrease of HDN with anti-D alloimmunization of the mother, particularly during the seventies. On the contrary, the number of HDN with an alloimmunization other than anti-D has increased. The percentage of anti-D HDN with ET decreased as did the percentage of HDN with alloimmunization other than anti-D which required ET.
Material and methods Patients In Lyon, from 1959 to 1988, most HDN have been detected, managed and treated by the Regional Blood Transfusion Center. Diagnosis of HDN is established when the direct anti-human globulin test (DAT) on cord blood is positive, the red blood cells of the newborn have the antigen which the mother lacks and alloantibodies against this antigen are present in the mother's serum. The majority of the mother's alloimmunizations which have induced an HDN were also detected by the Regional Blood Transfusion Center. Some samples collected in pregnant women were found, after the screening, positive for anti-erythroeytes alloantibodies by other laboratories. In aim to confirm the positivity and obtain the specificity of the anti-erythrocytes alloantibodies, these samples were send to our laboratory. The survey of the mother's alloimmtmization during the pregnancy until the delivery was performed by ourselves. Few HDN were detected by other laboratories, but the determination of the specifity of the antibodies, the survey and treatment of the newborn were carried out by the Regional Blood Transfusion Center. Determination of the Liley index on amniotic fluid is also performed by the Blood Transfusion Center as is the management of anti-D aUoimmunization prevention. Lastly, the ET of the newborn infants are carried out by our department.
Methods During these years, red blood cell typing and detection of anti red blood celt irregular antibodies have been performed with standard technics (anti-human globulin test, enzyme treated red blood cells, polybren auto analyzer) (AABB 1977). Improvements in one or more technics are quickly introduced. The Liley method has been used for the amniotic fluid analysis (Liley 1961).
Statistical analysis The Z2 test has been used.
Efficiency of alloimmunization screening and prevention
177
Results
As shown decreased. 1988), the 93.5% and
in Table 1, the number of anti-D HDN cases has significantly During the three periods studied (1959-1968; 1969-1978; 1979percentages of HDN with anti-D alloimmunization were 98.4%, 68.1% respectively (Table 2). On the other hand, the number of
Table 1. Haemolytic disease of the newborn infant (HDN) observed during the thirty years (1959-
1968; 1969-1978; 1979-1988). Prevention of Rh (D) alloimmunization of all pregnant women introduced in 1970 and screening of irregular antibodies in all pregnant women in 1979 1959
1960
1961
1962
1963
1964
1965
1966
1967
1968
Number of deliveries
18449 b 18599
19548
19997
21332
22346
22380
22314
21917
22491
Anti-D with ET a without ET Total
57 20 77
89 21 110
83 33 116
116 54 170
122 48 170
103 57 160
112 49 161
104 63 167
120 47 167
1 1 2
1 0 1
2 1 3
3 3 6
0 1 1
1 1 2
1 1 2
3 2 5
64 27 91
Other with ET without ET Total 1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
Number of deliveries
22826
22939
23975
23864
23657
22087
20852
20831
21377
21500
Anti-D with ET without ET Total
92 52 144
84 55 139
89 50 139
95 53 148
72 31 103
40 49 89
33 13 46
26 23 49
24 23 47
22 21 43
Other with ET without ET Total
5 1 6
3 0 3
7 1 8
4 3 7
4 2 6
3 2 5
5 2 7
1 4 5
2 8 10
3 6 9
1979
1980
1981
1982
1983
1984
1985
1986
1987
1988
Number of deliveries
22145
23674
24116
23981
22466
22579
23209
23510
22974
24126
Anti D with ET without ET Total
40 20 60
27 17 44
19 12 31
26 10 36
27 20 47
21 19 40
25 16 41
20 18 38
25 8 33
13 12 25
Other with ET without ET Total
6 7 13
5 8 13
6 7 13
3 11 14
5 20 25
5 18 23
4 18 22
3 19 22
2 13 15
7 18 25
a ET = Exchange transfusion; b For each year, the number of deliveries was kindly given by the "Institut National de la Statistique et des Etudes Economiques"
178
P. Moncharmont et al.
H D N cases with an alloimmunization other than anti-D detected, has increased. As seen in Table 3, among anti-D HDN, the number of H D N with ET decreased significantly between the first two periods (577 versus 970; g 2 = 19.92; P < 0.001). The percentages of H D N with ET also decreased between these periods (60.9% versus 69.8%). Despite the decrease of the anti-D H D N cases, the percentages of the H D N which needed ET remained stable during the last two periods (60.9% versus 69.8%). Despite the decrease of the anti-D H D N cases, the percentages of the H D N which needed ET remained stable during the last two periods (60.9% and 61.5% respectively). On the contrary, during the first two periods, percentages of H D N cases with alloimmunization other than anti-D and which have needed ET were similar (54.5% and 56.0% respectively). The number of the H D N other than anti-D detected increased significantly between the second and the third period when the screening of irregular alloantibodies was introduced for all pregnant women. Despite this increase, the percentages of the H D N cases with ET therapy decreased from 56.0% to 24.9% (Table 3). The distribution of the alloantibodies specificity other than anti-D detected in all the H D N observed during these thirty years is shown in Table 4. The anti-c and anti-E alloantibodies were the most frequently observed. Table 2. Number of haemolytic disease of the newborn infant with anti-D and non anti-D alloimmunization (ABO excepted) in the mother during thirty years 1959-1968 Anti-D Non anti-D
1389 22
Total
1411
1969-1978 947a 66 1013
1979-1988
Total
395 b 185
2731 273
580
3004
a Comparison between the first two periods (1959-1968 and 1969-1978) )~2 = 41.33 P < 0.001; b comparison between the last two periods (1969-1978 and 1979-1988) X2 = 178.94 P < 0.00t Table 3. Number of haemolytic disease of the newborn infant with or without exchange transfusion (ET) in anti-D and non anti-D aUoimmunized mother (ABO excluded) 1959-1968
1969-1978
1979-1988
Total
Anti-D with ET without ET Total
970 419 1389
577 ~ 370 947
243 b 152 395
1699 1032 2731
Non anti-D with ET without ET Total
12 10 22
37~ 29 66
46~ 139 185
95 178 273
A n t i - D : a comparison between the first two periods (1959-1968 and 1969-1978) ?(2= 19.92 P < 0.001;
b comparison between the last two periods (1969-1978 and 1979-1988) X2 = 0.04 P non significant. N o n anti-D: c comparison between the first two periods (1959-1968 and 1969-1978) ~2 = 0.02 Pnon significant; a c o m p a r i s o n b e t w e e n t h e l a s t t w o p e r i o d s ( 1 9 6 9 _ 1 9 7 8 a n d 1 9 7 9 _ 1 9 8 8 ) ~ 2 = 2 1 . 4 8 P < 0 . 0 0 1
Efficiency of alloimmunization screening and prevention
179
Tabelle 4. Specificity of the allo antibodies other than anti-D among haemolytic disease of the newborn infant (ABO excluded) detected over thirty years Specificity
with ET ~
Anti-c Anti-E Anti-C Anti-e
72 12 1
80 45 2 5
152 57 3 5
Anti-K Anti-k
3 2
16 1
19 3
Anti-Fya Anti-Jka Anti-Jkb Anti-s
1 1
6 6 2 2
7 7 2 2
5 1 2 1 1 1 1 1
5 3 2 1 1 1 I 1 1
178
273
Anti-c + K Anti-c + Fya Anti-c + S Anti-E + C Anti-E + K Anti-E + Fya Anti-C + K Anti-C + Jka Anti-Wra Total
2
without ET
1
95
Total
a ET = Exchange transfusion
Discussion
Administration of anti-D immunoglobulins immediately after the delivery in a Rh (D) negative mother who gave birth to a Rh (D) positive baby and the improvements of the HDN management before delivery, significantly reduce the alloimmunization of the mother and the number of HDN with perinatal death (Clarke et al. 1985, Bowmann 1978, Bennebroeck Gravenhorst 1988). In our study, since 1970, the number of HDN has constantly decreased. Nevertheless, among HDN, anti-D altoimmunization remained the most frequently observed at the beginning of the eighties (Table 1). In 1988, for the first time, the number of anti-D and non anti-D HDN were similar (Table 1). During the second period (1969-1978), with the decrease of all anti-D HDN, we also observed a decrease of anti-D HDN with ET. But the percentage of anti-D HDN which needed ET did not fall between 1979 and 1988. In their study, Pepperell et al. (1977) have observed a reduction of the incidence of the anti-D alloimmunization among mothers after the introduction of the prevention with anti-D immunoglobulins. They have estimated that the incidence of irregular antibodies in pregnant women is about 1.3%. In their group of 1,437 patients with irregular antibodies, 479 (33.3%) had an alloimmunization with an antibody other than anti-D. During the thirty years studied, 10.0% of the HDN
180
P. Moncharmont et al.
were induced by an irregular antibody other than anti-D. But, after the beginning of the screening of irregular allo antibodies in all pregnant women in 1979, this percentage particularly increased (31.9% versus 3.6% between 1959 and 1978). In our study, the screening of irregular antibodies in all pregnant women is efficient. The detection of HDN other than anti-D was improved and the management of these HDN was easier. Nevertheless, we observed a slight increase of the non anti-D HDN which needed ET (46 cases between 1979 and 1988 versus 37 cases between 1969 and 1978) with a decrease of the percentage from 56.0% during the second period to 24.9% during the third (Table 3). This observation probably means that HDN other than anti-D which did not require therapy, are before the screening, not or occasionally detected after the delivery. In conclusion, this study performed during the last thirty years shows that the number of HDN with an anti-D alloimmunization in the mother has significantly decreased particularly since 1970, when the anti-D immunoglobulins have been used. Nevertheless the percentage of anti-D HDN with ET remains stable. Furthermore, during this period, an increase of the number of HDN other than anti-D detected is observed. This increase was particularly marked when the screening of irregular antibodies in all pregnant women was introduced. Thus, the screening and prevention of the alloimmunization in the mother have a long term efficiency.
References 1. American Association of Blood Bank (1977) Technical manual, 7th ed. Washington 2. Bennebroeek Gravenhorst J (1988) Management of serious alloimmunization in pregnancy. Vox Sang 55:1-8 3. Bowman JM (1978) The management of Rh-isoimmunization. Obstet Gyneco152:1-16 4. Clarke CA, Donohoe WTA, Me Connel RB, Woodrow JC, Finn R, Krevans JR, Kulke W, Lehane D, Sheppard PM (1963) Further experimental studies on the prevention of Rh haemolytic disease. Br Med J 1:979-984 5. Clarke CA, Mollison PL, Whitfietd AGW (1985) Deaths from rhesus haemolytic disease in England and Wales in 1982 and 1983. Br Med J 291:17-19 6. Finn R, Clarke CA, Donohoe WTA, Mc Connell RB, Sheppard PM, Lehane D, Kulke W (1961). Experimental studies on the prevention of Rh haemolytic disease. Br Med J 1:14861490 7. Freda VJ, Gorman JG, Pollack W (1964) Successftd prevention of experimental Rh sensitization in man with an anti-Rh gammas-globulin antibody preparation: a preliminary report. Transfusion 4:26-32 8. Levine P, Stetson RE (1939) An unusual case ofintra-group agglutination. JAMA 113:126-127 9. Liley AW (1961) Liquor amnii analysis in the management of the pregnancy complicated by rhesus sensitization. Am J Obstet Gynecot 82:1359-1370 10. Pepperell RJ, Barrie JV, Fliegner JR (1977) Significance of red cell irregular antibodies in the obstetric patient. Med J Aust 2:453-456 11. Woodrow JC, Donohoe WTA (1968) Rh-immunization by pregnancy: results of a survey and their relevance to prophylactic therapy. Br Med J 4:139-144
Arch Gynecol Obstet (1991) 248:175-180
Gynecology and Obstetrics
© Springer-Verlag199t
Haemolytic disease of the newborn infant. Long term efficiency of the screening and the prevention of alloimmunization in the mother: thirty years of experience P. Moncharmont, F. Juron Dupraz, M. Vignal, D. Rigal, F. Meyer, and P. Debeaux C.R.T.S. de Lyon-Beynost BP 401, F-01704 Beynost Cedex, France Received April 6, 1990/Accepted October 10, 1990
Summary. During the last thirty years, the diagnosis, management and prevention of haemolytic disease of the newborn infant (HDN) have improved. From 1959 to 1988, 3004 HDN (ABO excluded) have been collected. The percentage of HDN with anti-D alloimmunization decreased significantly (98.4% from 1959 to 1968, 93.5% from 1969 to 1978 and 68.1% from 1979 to 1988). The anti-D HDN with exchange transfusion (ET) fell significantly between the first and second periods (577 versus 970; Z~ = 19.92; P < 0.001). On the other hand, the number of HDN other than anti-D increased during these three periods, but the percentage of these HDN which needed ET decreased. Our study shows the long term efficiency of the prevention of anti-D alloimmunization (since 1970) and of the irregular antibodies screening among all pregnant women (since 1979). Key words: Alloimmunization - Haemolytic disease - Newborn Introduction Since the initial discovery of the Rhesus (D) blood group by Levine and Stetson (1939), many other red blood cell antigens have been found. Some of them are involved in the haemolytic disease of the newborn infant (HDN). Among HDN cases (ABO antigens excepted), the anti-D alloimmunization of the mother remains the most frequently observed. In France, since 1962, in order to detect an anti-D alloimmmlization in the mother during pregnancy, ABO Rhesus blood group of all pregnant women has been performed at the time of their first antenatal visit. When the mother's blood group is Rh (D) negative, her serum is tested for irregular anti red blood cell antibodies. At this time, the mothers, whose blood group was Rh (D) positive, were not, or only occasionally, tested for irregular antibodies. After the study of Finn et al. (1961), Clarke et al. Offprint requests to: D r P Moncharmont (address see above)
176
P. Moncharmont et al.
(1963), Freda et al. (1964) and Woodrow and Donohoe (1968), it has been well established that anti-D sensitization of an Rh (D) negative mother by erythrocytes of her Rh (D) positive newborn infant could be prevented by using anti-D immunoglobulins just after the delivery. In Lyon, since 1970, this prevention has been performed with intravenous anti-D immunoglobulins. During the same period, determination of the Liley index on the amniotic fluid (Liley 1961) was introduced. Since 1979, the screening of anti-erythrocytes irregular antibodies in all pregnant woman has been used in Lyon. Screening was not introduced all over the country until 1985. During these thirty last years, we have observed a considerable decrease of HDN with anti-D alloimmunization of the mother, particularly during the seventies. On the contrary, the number of HDN with an alloimmunization other than anti-D has increased. The percentage of anti-D HDN with ET decreased as did the percentage of HDN with alloimmunization other than anti-D which required ET.
Material and methods Patients In Lyon, from 1959 to 1988, most HDN have been detected, managed and treated by the Regional Blood Transfusion Center. Diagnosis of HDN is established when the direct anti-human globulin test (DAT) on cord blood is positive, the red blood cells of the newborn have the antigen which the mother lacks and alloantibodies against this antigen are present in the mother's serum. The majority of the mother's alloimmunizations which have induced an HDN were also detected by the Regional Blood Transfusion Center. Some samples collected in pregnant women were found, after the screening, positive for anti-erythroeytes alloantibodies by other laboratories. In aim to confirm the positivity and obtain the specificity of the anti-erythrocytes alloantibodies, these samples were send to our laboratory. The survey of the mother's alloimmtmization during the pregnancy until the delivery was performed by ourselves. Few HDN were detected by other laboratories, but the determination of the specifity of the antibodies, the survey and treatment of the newborn were carried out by the Regional Blood Transfusion Center. Determination of the Liley index on amniotic fluid is also performed by the Blood Transfusion Center as is the management of anti-D aUoimmunization prevention. Lastly, the ET of the newborn infants are carried out by our department.
Methods During these years, red blood cell typing and detection of anti red blood celt irregular antibodies have been performed with standard technics (anti-human globulin test, enzyme treated red blood cells, polybren auto analyzer) (AABB 1977). Improvements in one or more technics are quickly introduced. The Liley method has been used for the amniotic fluid analysis (Liley 1961).
Statistical analysis The Z2 test has been used.
Efficiency of alloimmunization screening and prevention
177
Results
As shown decreased. 1988), the 93.5% and
in Table 1, the number of anti-D HDN cases has significantly During the three periods studied (1959-1968; 1969-1978; 1979percentages of HDN with anti-D alloimmunization were 98.4%, 68.1% respectively (Table 2). On the other hand, the number of
Table 1. Haemolytic disease of the newborn infant (HDN) observed during the thirty years (1959-
1968; 1969-1978; 1979-1988). Prevention of Rh (D) alloimmunization of all pregnant women introduced in 1970 and screening of irregular antibodies in all pregnant women in 1979 1959
1960
1961
1962
1963
1964
1965
1966
1967
1968
Number of deliveries
18449 b 18599
19548
19997
21332
22346
22380
22314
21917
22491
Anti-D with ET a without ET Total
57 20 77
89 21 110
83 33 116
116 54 170
122 48 170
103 57 160
112 49 161
104 63 167
120 47 167
1 1 2
1 0 1
2 1 3
3 3 6
0 1 1
1 1 2
1 1 2
3 2 5
64 27 91
Other with ET without ET Total 1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
Number of deliveries
22826
22939
23975
23864
23657
22087
20852
20831
21377
21500
Anti-D with ET without ET Total
92 52 144
84 55 139
89 50 139
95 53 148
72 31 103
40 49 89
33 13 46
26 23 49
24 23 47
22 21 43
Other with ET without ET Total
5 1 6
3 0 3
7 1 8
4 3 7
4 2 6
3 2 5
5 2 7
1 4 5
2 8 10
3 6 9
1979
1980
1981
1982
1983
1984
1985
1986
1987
1988
Number of deliveries
22145
23674
24116
23981
22466
22579
23209
23510
22974
24126
Anti D with ET without ET Total
40 20 60
27 17 44
19 12 31
26 10 36
27 20 47
21 19 40
25 16 41
20 18 38
25 8 33
13 12 25
Other with ET without ET Total
6 7 13
5 8 13
6 7 13
3 11 14
5 20 25
5 18 23
4 18 22
3 19 22
2 13 15
7 18 25
a ET = Exchange transfusion; b For each year, the number of deliveries was kindly given by the "Institut National de la Statistique et des Etudes Economiques"
178
P. Moncharmont et al.
H D N cases with an alloimmunization other than anti-D detected, has increased. As seen in Table 3, among anti-D HDN, the number of H D N with ET decreased significantly between the first two periods (577 versus 970; g 2 = 19.92; P < 0.001). The percentages of H D N with ET also decreased between these periods (60.9% versus 69.8%). Despite the decrease of the anti-D H D N cases, the percentages of the H D N which needed ET remained stable during the last two periods (60.9% versus 69.8%). Despite the decrease of the anti-D H D N cases, the percentages of the H D N which needed ET remained stable during the last two periods (60.9% and 61.5% respectively). On the contrary, during the first two periods, percentages of H D N cases with alloimmunization other than anti-D and which have needed ET were similar (54.5% and 56.0% respectively). The number of the H D N other than anti-D detected increased significantly between the second and the third period when the screening of irregular alloantibodies was introduced for all pregnant women. Despite this increase, the percentages of the H D N cases with ET therapy decreased from 56.0% to 24.9% (Table 3). The distribution of the alloantibodies specificity other than anti-D detected in all the H D N observed during these thirty years is shown in Table 4. The anti-c and anti-E alloantibodies were the most frequently observed. Table 2. Number of haemolytic disease of the newborn infant with anti-D and non anti-D alloimmunization (ABO excepted) in the mother during thirty years 1959-1968 Anti-D Non anti-D
1389 22
Total
1411
1969-1978 947a 66 1013
1979-1988
Total
395 b 185
2731 273
580
3004
a Comparison between the first two periods (1959-1968 and 1969-1978) )~2 = 41.33 P < 0.001; b comparison between the last two periods (1969-1978 and 1979-1988) X2 = 178.94 P < 0.00t Table 3. Number of haemolytic disease of the newborn infant with or without exchange transfusion (ET) in anti-D and non anti-D aUoimmunized mother (ABO excluded) 1959-1968
1969-1978
1979-1988
Total
Anti-D with ET without ET Total
970 419 1389
577 ~ 370 947
243 b 152 395
1699 1032 2731
Non anti-D with ET without ET Total
12 10 22
37~ 29 66
46~ 139 185
95 178 273
A n t i - D : a comparison between the first two periods (1959-1968 and 1969-1978) ?(2= 19.92 P < 0.001;
b comparison between the last two periods (1969-1978 and 1979-1988) X2 = 0.04 P non significant. N o n anti-D: c comparison between the first two periods (1959-1968 and 1969-1978) ~2 = 0.02 Pnon significant; a c o m p a r i s o n b e t w e e n t h e l a s t t w o p e r i o d s ( 1 9 6 9 _ 1 9 7 8 a n d 1 9 7 9 _ 1 9 8 8 ) ~ 2 = 2 1 . 4 8 P < 0 . 0 0 1
Efficiency of alloimmunization screening and prevention
179
Tabelle 4. Specificity of the allo antibodies other than anti-D among haemolytic disease of the newborn infant (ABO excluded) detected over thirty years Specificity
with ET ~
Anti-c Anti-E Anti-C Anti-e
72 12 1
80 45 2 5
152 57 3 5
Anti-K Anti-k
3 2
16 1
19 3
Anti-Fya Anti-Jka Anti-Jkb Anti-s
1 1
6 6 2 2
7 7 2 2
5 1 2 1 1 1 1 1
5 3 2 1 1 1 I 1 1
178
273
Anti-c + K Anti-c + Fya Anti-c + S Anti-E + C Anti-E + K Anti-E + Fya Anti-C + K Anti-C + Jka Anti-Wra Total
2
without ET
1
95
Total
a ET = Exchange transfusion
Discussion
Administration of anti-D immunoglobulins immediately after the delivery in a Rh (D) negative mother who gave birth to a Rh (D) positive baby and the improvements of the HDN management before delivery, significantly reduce the alloimmunization of the mother and the number of HDN with perinatal death (Clarke et al. 1985, Bowmann 1978, Bennebroeck Gravenhorst 1988). In our study, since 1970, the number of HDN has constantly decreased. Nevertheless, among HDN, anti-D altoimmunization remained the most frequently observed at the beginning of the eighties (Table 1). In 1988, for the first time, the number of anti-D and non anti-D HDN were similar (Table 1). During the second period (1969-1978), with the decrease of all anti-D HDN, we also observed a decrease of anti-D HDN with ET. But the percentage of anti-D HDN which needed ET did not fall between 1979 and 1988. In their study, Pepperell et al. (1977) have observed a reduction of the incidence of the anti-D alloimmunization among mothers after the introduction of the prevention with anti-D immunoglobulins. They have estimated that the incidence of irregular antibodies in pregnant women is about 1.3%. In their group of 1,437 patients with irregular antibodies, 479 (33.3%) had an alloimmunization with an antibody other than anti-D. During the thirty years studied, 10.0% of the HDN
180
P. Moncharmont et al.
were induced by an irregular antibody other than anti-D. But, after the beginning of the screening of irregular allo antibodies in all pregnant women in 1979, this percentage particularly increased (31.9% versus 3.6% between 1959 and 1978). In our study, the screening of irregular antibodies in all pregnant women is efficient. The detection of HDN other than anti-D was improved and the management of these HDN was easier. Nevertheless, we observed a slight increase of the non anti-D HDN which needed ET (46 cases between 1979 and 1988 versus 37 cases between 1969 and 1978) with a decrease of the percentage from 56.0% during the second period to 24.9% during the third (Table 3). This observation probably means that HDN other than anti-D which did not require therapy, are before the screening, not or occasionally detected after the delivery. In conclusion, this study performed during the last thirty years shows that the number of HDN with an anti-D alloimmunization in the mother has significantly decreased particularly since 1970, when the anti-D immunoglobulins have been used. Nevertheless the percentage of anti-D HDN with ET remains stable. Furthermore, during this period, an increase of the number of HDN other than anti-D detected is observed. This increase was particularly marked when the screening of irregular antibodies in all pregnant women was introduced. Thus, the screening and prevention of the alloimmunization in the mother have a long term efficiency.
References 1. American Association of Blood Bank (1977) Technical manual, 7th ed. Washington 2. Bennebroeek Gravenhorst J (1988) Management of serious alloimmunization in pregnancy. Vox Sang 55:1-8 3. Bowman JM (1978) The management of Rh-isoimmunization. Obstet Gyneco152:1-16 4. Clarke CA, Donohoe WTA, Me Connel RB, Woodrow JC, Finn R, Krevans JR, Kulke W, Lehane D, Sheppard PM (1963) Further experimental studies on the prevention of Rh haemolytic disease. Br Med J 1:979-984 5. Clarke CA, Mollison PL, Whitfietd AGW (1985) Deaths from rhesus haemolytic disease in England and Wales in 1982 and 1983. Br Med J 291:17-19 6. Finn R, Clarke CA, Donohoe WTA, Mc Connell RB, Sheppard PM, Lehane D, Kulke W (1961). Experimental studies on the prevention of Rh haemolytic disease. Br Med J 1:14861490 7. Freda VJ, Gorman JG, Pollack W (1964) Successftd prevention of experimental Rh sensitization in man with an anti-Rh gammas-globulin antibody preparation: a preliminary report. Transfusion 4:26-32 8. Levine P, Stetson RE (1939) An unusual case ofintra-group agglutination. JAMA 113:126-127 9. Liley AW (1961) Liquor amnii analysis in the management of the pregnancy complicated by rhesus sensitization. Am J Obstet Gynecot 82:1359-1370 10. Pepperell RJ, Barrie JV, Fliegner JR (1977) Significance of red cell irregular antibodies in the obstetric patient. Med J Aust 2:453-456 11. Woodrow JC, Donohoe WTA (1968) Rh-immunization by pregnancy: results of a survey and their relevance to prophylactic therapy. Br Med J 4:139-144
