ABO Hemolytic Disease of the Newborn SAU-YEE ANN CHAN-SHU, M.D., B.S., AND OLGA BLAIR, B.S.
THE TWO MOST common causes of hemolytic disease of the newborn are (1) ABO incompatibility between the mother and the infant and (2) Rh sensitization of the mother. Since the introduction of routine prophylactic administration of anti-Rho (D) immunoglobulin to Rh-negative women in the immediate postpartum period, there was a sharp drop in the number of sensitized mothers. 5 The incidence of ABO hemolytic disease had not changed. In fact, as more studies were made, 2,3,6 there was evidence that ABO hemolytic disease was more prevalent in blacks. The present report is a retrospective study of infants born at Kings County Hospital Center during a twoyear period. Materials and Methods
the blood bank for blood group and type and a direct Coombs' test. When the direct Coombs' test was positive, a heat eluate was prepared by the method of Landsteiner and Miller and reacted against A cells, B cells, and two screening O cells. 1 When there was reaction with both A cells and B cells, the antibody was called anti-A,B. When there was positive reaction with the screening O cells, further antibody identification was carried out by means of commercially available reagent erythrocytes according to standard methods. 1 Maternal Blood
Samples
Routinely, a clotted and an anticoagulated (EDTA) blood sample was taken from the patient at her first antenatal visit. For patients who had not attended the antenatal clinic, the same type of blood specimen was obtained at the time of delivery. The blood group and type and antibody screening were done on all patients. Whenever the antibody screening was positive, the specificity of the antibody(ies) was identified by standard methods. 1 The results of the maternal blood sample were cross-checked with the results on the cord blood. Results
All the infants in the present study were born during the period from January 1, 1975, to December 31, 1976, at Kings County Hospital Center. Records of each infant's name, hospital number, sex, blood group and type, and results for the direct Coombs' test were obtained from the blood bank. Charts on infants with positive direct Coombs' test were obtained from Medical Records and reviewed. Cord Blood
The Blood Bank, Kings County Hospital Center, Brooklyn, New York
Samples
Routinely, an anticoagulated (EDTA) cord blood sample was taken at the time of delivery and sent to Received November 11, 1977; received revised manuscript and accepted for publication May 12, 1978. Address reprint requests to Dr. Chan-Shu: Kings County Hospital Center, 451 Clarkson Avenue, Brooklyn, New York 11203.
There were 8,007 infants born at Kings County Hospital Center during the period from January 1, 1975, to December 31, 1976. Four hundred eighteen infants had positive direct Coombs' test. Three hundred ninety-nine cases were due to ABO incompatibility between the mother and the infant; 19 cases were due to maternal Rh antibodies, the majority due to antiRho (D). We were able to locate 271 charts from Medical Records, and only 233 cases were used for the present study. The other cases were excluded for one of the following reasons: (1) the birth weight was less than 2,500 g; (2) the mother's blood was not group O; (3) there was more than one antibody in the maternal circulation, such as anti-A and anti-Rho (D); (4) there was insufficient blood for elution studies. Group A or B
0002-9173/79/0600/0677 $00.65 © American Society of Clinical Pathologists
677
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Chan-Shu, Sau-yee Ann, and Blair, Olga: ABO hemolytic disease of the newborn. Am J Clin Pathol 71: 677-679,1979. The charts of newborn infants with positive direct Coombs' test were studied. Only cases in which the mother's blood was group O and the infant's group A or group B were studied. There was no difference between group A and group B infants in the frequency and severity of the hemolytic process caused by maternal antibodies. In group B infants, monospecific antibodies (anti-B) were associated with more severe hemolytic process than cross-reacting antibodies (anti-A,B). In group A infants there was no difference in the severity of the disease between monospecific antibodies (anti-A) and cross-reacting antibodies (anti-A,B). Even though there was no significant difference in the sex distribution of affected infants, there was a higher number of boys in the more severely affected group. (Key words: ABO hemolytic disease of the newborn.)
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CHAN-SHU AND BLAIR
Table I. Blood Group Distribution of All Newborn Infants
Number Percentage
Group A
Group B
Group A,B
Group O
Total
2,339 30%
1.477 18%
269 3%
3,905 49%
8,007 100%
change transfusions fell into this group. There were 14 infants who needed exchange transfusions because of hyperbilirubinemia or anemia, or both. There were eight male infants and six female infants. Nine infants had group A blood, and five infants had group B blood. All tolerated the exchange transfusion(s) well. All the infants in the present study survived and were well at the time of discharge from the hospital. Table 1 shows the blood group distribution of all the infants born during that period. There was a greater discrepancy in the distribution of blood groups among our patients than in that reported by Wiener.11 This difference is probably due to the ethnic origins of the patient populations; our patients were mainly black or Hispanic. Table 2 shows the numbers of infants of blood group O mothers with group A and group B bloods that had positive direct Coombs' tests; the serologic specificities of the antibodies eluted from their cord blood erythrocytes, and the sex distribution of the affected infants. The ratio of all blood group A infants to all blood group B infants born during the period was 1.67:1. For all infants with positive direct Coombs' tests the ratio of group A blood to group B blood was 1.5:1; this difference was not significant (P = 0.05). When the ratios between infants with group A blood and group B blood in the three groups were calculated and compared with that of all infants born during the period, there was no significant difference (P = 0.05 for all groups). When only the infants who needed exchange transfusions were compared with the general infant population there was also no significant difference (P > 0.05). Our results suggest that infants with blood group A were as liable to be affected by ABO hemolytic disease of the newborn as were those with blood group B. The ratio of infant boys to infant girls born at Kings County Hospital Center during the period was 1.05:1.
Table 2. Sex Distribution and Serologic Specificities of Antibodies Eluted from Erythrocytes of Infants of Blood Group O Mothers with Positive Direct Coombs' Tests Blood Group A Infants
Serum bilirubin level Group I ( 0.05 for all three groups). Discussion
related to the type of antibodies eluted from the erythrocytes. In our present study, no attempt was made to distinguish between group A, and group A2. It remains to be determined whether the antibodies coating the erythrocytic surfaces of bloods of subgroup A are of the same specificity. A prospective study will be needed to verify this point. In infants with blood group B there was a progressive increase in the ratio of anti-B to anti-A,B from Group I to Group III. In Group III, the ratio of anti-B to anti-A,B was 5:1, suggesting that monospecific antibodies eluted from the erythrocytes were associated with greater severity of the hemolytic process (P = 0.005). Grundbacher4 showed that more girls were affected by ABO hemolytic disease of the newborn than boys. Our study showed no significant difference in the incidences among the affected infants (P > 0.05 for all groups). When only patients in Group III were considered, there was a slight excess of male infants. Thus, while there was no significant difference in the incidences by sex of infants with ABO hemolytic disease, boys seemed to be more severely affected than girls. References 1. American Association of Blood Banks: Technical Methods and Procedures. Sixth edition, 1974 2. Bucher KA, Patterson AM, Elston RC, et al: Racial difference in incidence of ABO hemolytic disease. Public Health 66: 854-858, 1976 3. Farrell AGW: ABO incompatibility and hemolytic disease of the newborn. S Afr Med J 44:211-213, 1970 4. Grundbacher FJ: ABO hemolytic disease of the newborn: A family study with emphasis on the strength of the A antigen. Pediatrics 35:916-924, 1965 5. Huestis DW, Bove JR, Busch S: Practical Blood Transfusion. Second edition. Boston, Little, Brown and Company, 1976, pp 313-318 6. Kirkman HN: Further evidence for a racial difference in frequency of ABO hemolytic disease. J Pediatr, 90: 717-721, 1977 7. Mollison PL: Blood Transfusion in Clinical Medicine. Fifth edition. Oxford, Blackwell Scientific Publications, 1972, pp 661-663 8. Nathan DG, Oski FA: Hematology of Infancy and Childhood, Philadelphia, W. B. Saunders, 1974, pp 280-314 9. Rosenfield RE, Ohno G: A.B. hemolytic disease of the newborn. Rev Hematol 10:231-235, 1955 10. Voak D: The serologic specificity of the sensitizing antibodies in ABO heterospecific pregnancy of the group-0 mother. Vox Sang 14:271-281, 1968 11. Wiener AS: Problems and pitfalls in blood grouping tests for nonparentage. Am J Clin Pathol 51:9-14, 1969 12. Zuelzer WW, Cohen F, Robinson AR: Specific and crossreacting antibodies in ABO heterospecific twin pregnancy. Blood 12:883-906, 1957
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Studies of Caucasian populations tend to show a low incidence of hemolytic disease of the newborn from ABO incompatibility. Mollison7 stated that the incidence was about one in 150 births, and he estimated that when exposed to the appropriate antibody an infant whose blood group was A would be more likely to be affected than a blood group B infant. Bucher and associates2 and Kirkman6 showed that ABO hemolytic disease was two to three times more common in black than in white people. Farrel3 had shown a higher incidence of ABO hemolytic disease in South African blacks and that infants with blood group B were more severely affected than those with blood group A. Most of our patients are black or Hispanic. In the present study, the incidence of ABO hemolytic disease was about 2%, which was higher than that reported by Mollison and more in agreement with the incidence reported by Bucher, Kiriman, and Farrel, whose work had been mainly with black people. The incidence of positive direct Coombs' tests in our study was about 5%, and this coincided with that reported by Chown,7 even though his patients were of a different ethnic origin. From the present study, the distribution of infants with blood group A and those with blood group B in the three affected groups showed no significant difference from that in the general population. Thus, contrary to reports by Mollison and Farrel, an infant whose blood group was A was as likely to be affected by ABO hemolytic disease of the newborn as a blood group B infant. The maternal antibodies that cross the placenta in ABO hemolytic disease are IgG immunoglobulins, which may be monospecific or cross-reacting, or both.1012 Rosenfield had shown that the cord blood of infants born to mothers with blood group O frequently contained cross-reacting antibodies.9 Table 2 shows the serologic specificities of the antibodies eluted from the erythrocytes. There were more monospecific antibodies (anti-A or anti-B) eluted from the erythrocytes than cross-reacting ones. In infants with blood group A the severity of hemolytic disease was not
679
THE TWO MOST common causes of hemolytic disease of the newborn are (1) ABO incompatibility between the mother and the infant and (2) Rh sensitization of the mother. Since the introduction of routine prophylactic administration of anti-Rho (D) immunoglobulin to Rh-negative women in the immediate postpartum period, there was a sharp drop in the number of sensitized mothers. 5 The incidence of ABO hemolytic disease had not changed. In fact, as more studies were made, 2,3,6 there was evidence that ABO hemolytic disease was more prevalent in blacks. The present report is a retrospective study of infants born at Kings County Hospital Center during a twoyear period. Materials and Methods
the blood bank for blood group and type and a direct Coombs' test. When the direct Coombs' test was positive, a heat eluate was prepared by the method of Landsteiner and Miller and reacted against A cells, B cells, and two screening O cells. 1 When there was reaction with both A cells and B cells, the antibody was called anti-A,B. When there was positive reaction with the screening O cells, further antibody identification was carried out by means of commercially available reagent erythrocytes according to standard methods. 1 Maternal Blood
Samples
Routinely, a clotted and an anticoagulated (EDTA) blood sample was taken from the patient at her first antenatal visit. For patients who had not attended the antenatal clinic, the same type of blood specimen was obtained at the time of delivery. The blood group and type and antibody screening were done on all patients. Whenever the antibody screening was positive, the specificity of the antibody(ies) was identified by standard methods. 1 The results of the maternal blood sample were cross-checked with the results on the cord blood. Results
All the infants in the present study were born during the period from January 1, 1975, to December 31, 1976, at Kings County Hospital Center. Records of each infant's name, hospital number, sex, blood group and type, and results for the direct Coombs' test were obtained from the blood bank. Charts on infants with positive direct Coombs' test were obtained from Medical Records and reviewed. Cord Blood
The Blood Bank, Kings County Hospital Center, Brooklyn, New York
Samples
Routinely, an anticoagulated (EDTA) cord blood sample was taken at the time of delivery and sent to Received November 11, 1977; received revised manuscript and accepted for publication May 12, 1978. Address reprint requests to Dr. Chan-Shu: Kings County Hospital Center, 451 Clarkson Avenue, Brooklyn, New York 11203.
There were 8,007 infants born at Kings County Hospital Center during the period from January 1, 1975, to December 31, 1976. Four hundred eighteen infants had positive direct Coombs' test. Three hundred ninety-nine cases were due to ABO incompatibility between the mother and the infant; 19 cases were due to maternal Rh antibodies, the majority due to antiRho (D). We were able to locate 271 charts from Medical Records, and only 233 cases were used for the present study. The other cases were excluded for one of the following reasons: (1) the birth weight was less than 2,500 g; (2) the mother's blood was not group O; (3) there was more than one antibody in the maternal circulation, such as anti-A and anti-Rho (D); (4) there was insufficient blood for elution studies. Group A or B
0002-9173/79/0600/0677 $00.65 © American Society of Clinical Pathologists
677
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
Chan-Shu, Sau-yee Ann, and Blair, Olga: ABO hemolytic disease of the newborn. Am J Clin Pathol 71: 677-679,1979. The charts of newborn infants with positive direct Coombs' test were studied. Only cases in which the mother's blood was group O and the infant's group A or group B were studied. There was no difference between group A and group B infants in the frequency and severity of the hemolytic process caused by maternal antibodies. In group B infants, monospecific antibodies (anti-B) were associated with more severe hemolytic process than cross-reacting antibodies (anti-A,B). In group A infants there was no difference in the severity of the disease between monospecific antibodies (anti-A) and cross-reacting antibodies (anti-A,B). Even though there was no significant difference in the sex distribution of affected infants, there was a higher number of boys in the more severely affected group. (Key words: ABO hemolytic disease of the newborn.)
678
CHAN-SHU AND BLAIR
Table I. Blood Group Distribution of All Newborn Infants
Number Percentage
Group A
Group B
Group A,B
Group O
Total
2,339 30%
1.477 18%
269 3%
3,905 49%
8,007 100%
change transfusions fell into this group. There were 14 infants who needed exchange transfusions because of hyperbilirubinemia or anemia, or both. There were eight male infants and six female infants. Nine infants had group A blood, and five infants had group B blood. All tolerated the exchange transfusion(s) well. All the infants in the present study survived and were well at the time of discharge from the hospital. Table 1 shows the blood group distribution of all the infants born during that period. There was a greater discrepancy in the distribution of blood groups among our patients than in that reported by Wiener.11 This difference is probably due to the ethnic origins of the patient populations; our patients were mainly black or Hispanic. Table 2 shows the numbers of infants of blood group O mothers with group A and group B bloods that had positive direct Coombs' tests; the serologic specificities of the antibodies eluted from their cord blood erythrocytes, and the sex distribution of the affected infants. The ratio of all blood group A infants to all blood group B infants born during the period was 1.67:1. For all infants with positive direct Coombs' tests the ratio of group A blood to group B blood was 1.5:1; this difference was not significant (P = 0.05). When the ratios between infants with group A blood and group B blood in the three groups were calculated and compared with that of all infants born during the period, there was no significant difference (P = 0.05 for all groups). When only the infants who needed exchange transfusions were compared with the general infant population there was also no significant difference (P > 0.05). Our results suggest that infants with blood group A were as liable to be affected by ABO hemolytic disease of the newborn as were those with blood group B. The ratio of infant boys to infant girls born at Kings County Hospital Center during the period was 1.05:1.
Table 2. Sex Distribution and Serologic Specificities of Antibodies Eluted from Erythrocytes of Infants of Blood Group O Mothers with Positive Direct Coombs' Tests Blood Group A Infants
Serum bilirubin level Group I ( 0.05 for all three groups). Discussion
related to the type of antibodies eluted from the erythrocytes. In our present study, no attempt was made to distinguish between group A, and group A2. It remains to be determined whether the antibodies coating the erythrocytic surfaces of bloods of subgroup A are of the same specificity. A prospective study will be needed to verify this point. In infants with blood group B there was a progressive increase in the ratio of anti-B to anti-A,B from Group I to Group III. In Group III, the ratio of anti-B to anti-A,B was 5:1, suggesting that monospecific antibodies eluted from the erythrocytes were associated with greater severity of the hemolytic process (P = 0.005). Grundbacher4 showed that more girls were affected by ABO hemolytic disease of the newborn than boys. Our study showed no significant difference in the incidences among the affected infants (P > 0.05 for all groups). When only patients in Group III were considered, there was a slight excess of male infants. Thus, while there was no significant difference in the incidences by sex of infants with ABO hemolytic disease, boys seemed to be more severely affected than girls. References 1. American Association of Blood Banks: Technical Methods and Procedures. Sixth edition, 1974 2. Bucher KA, Patterson AM, Elston RC, et al: Racial difference in incidence of ABO hemolytic disease. Public Health 66: 854-858, 1976 3. Farrell AGW: ABO incompatibility and hemolytic disease of the newborn. S Afr Med J 44:211-213, 1970 4. Grundbacher FJ: ABO hemolytic disease of the newborn: A family study with emphasis on the strength of the A antigen. Pediatrics 35:916-924, 1965 5. Huestis DW, Bove JR, Busch S: Practical Blood Transfusion. Second edition. Boston, Little, Brown and Company, 1976, pp 313-318 6. Kirkman HN: Further evidence for a racial difference in frequency of ABO hemolytic disease. J Pediatr, 90: 717-721, 1977 7. Mollison PL: Blood Transfusion in Clinical Medicine. Fifth edition. Oxford, Blackwell Scientific Publications, 1972, pp 661-663 8. Nathan DG, Oski FA: Hematology of Infancy and Childhood, Philadelphia, W. B. Saunders, 1974, pp 280-314 9. Rosenfield RE, Ohno G: A.B. hemolytic disease of the newborn. Rev Hematol 10:231-235, 1955 10. Voak D: The serologic specificity of the sensitizing antibodies in ABO heterospecific pregnancy of the group-0 mother. Vox Sang 14:271-281, 1968 11. Wiener AS: Problems and pitfalls in blood grouping tests for nonparentage. Am J Clin Pathol 51:9-14, 1969 12. Zuelzer WW, Cohen F, Robinson AR: Specific and crossreacting antibodies in ABO heterospecific twin pregnancy. Blood 12:883-906, 1957
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
Studies of Caucasian populations tend to show a low incidence of hemolytic disease of the newborn from ABO incompatibility. Mollison7 stated that the incidence was about one in 150 births, and he estimated that when exposed to the appropriate antibody an infant whose blood group was A would be more likely to be affected than a blood group B infant. Bucher and associates2 and Kirkman6 showed that ABO hemolytic disease was two to three times more common in black than in white people. Farrel3 had shown a higher incidence of ABO hemolytic disease in South African blacks and that infants with blood group B were more severely affected than those with blood group A. Most of our patients are black or Hispanic. In the present study, the incidence of ABO hemolytic disease was about 2%, which was higher than that reported by Mollison and more in agreement with the incidence reported by Bucher, Kiriman, and Farrel, whose work had been mainly with black people. The incidence of positive direct Coombs' tests in our study was about 5%, and this coincided with that reported by Chown,7 even though his patients were of a different ethnic origin. From the present study, the distribution of infants with blood group A and those with blood group B in the three affected groups showed no significant difference from that in the general population. Thus, contrary to reports by Mollison and Farrel, an infant whose blood group was A was as likely to be affected by ABO hemolytic disease of the newborn as a blood group B infant. The maternal antibodies that cross the placenta in ABO hemolytic disease are IgG immunoglobulins, which may be monospecific or cross-reacting, or both.1012 Rosenfield had shown that the cord blood of infants born to mothers with blood group O frequently contained cross-reacting antibodies.9 Table 2 shows the serologic specificities of the antibodies eluted from the erythrocytes. There were more monospecific antibodies (anti-A or anti-B) eluted from the erythrocytes than cross-reacting ones. In infants with blood group A the severity of hemolytic disease was not
679
