Racial Difference in Incidence of ABO Hemolytic Disease KATHLEEN A. BUCHER,* BA, ABRAM M. PATTERSON, JR.,t MD, ROBERT C. ELSTON,* PHD, CAROLINE A. JONES,t AND HENRY N. KIRKMAN, JR.,t MD
Abstract: In this review of 7,464 consecutive infants born at North Carolina Memorial Hospital, hemolytic disease from ABO incompatibility was found to be two to three times as common in black infants as in white infants. The statistical significance of the difference remained high as more restrictive criteria for ABO hemolytic disease were applied. ABO disease, serious enough to cause an indirect serum bilirubin of 15 mg/lOOml or higher, had an incidence in black newborns as great as the incidence of Rh hemolytic disease
in whites. In contrast, the general prevalence and severity of hyperbilirubinemia was not found to be higher in black newborns than in white infants. The difference cannot be attributed to differences in the prevalence of ABO blood groups between the two races. Policies of early discharge of newborns could be affected by the finding that ABO erythroblastosis is two to three times as common in black infants as in white infants. (Am. J. Public Health 66:854-858, 1976)
Introduction
women is not routinely possible, however, for ABO hemolytic disease. In addition, the disorder can affect first-born infants without necessarily affecting subsequent infants.' Studies on South African populations by Brink,8 Ford,9 and Farrell10 suggest racial differences in the frequency and severity of ABO hemolytic disease. The purpose of the present study was to determine whether such differences exist in the newborns of this country. We believe that this information will be of value in the identification of pregnancies at risk for ABO disease.
Over 98 per cent of cases of iso-immune hemolytic disease of the newborn (erythroblastosis) result from maternalfetal incompatibility for either the rhesus (Rh) factor or the ABO blood group.1' 2 Hemolytic disease from ABO incompatibility is about twice as common as that from Rh incompatibility.' Moreover, the current practice of administering anti-D IgG to Rh negative, post-partum women is decreasing the occurrence of Rh disease1' 2 and thereby raising the ratio of ABO disease to Rh disease still higher. Of the two disorders, ABO hemolytic disease is generally the milder, but either can result in mental retardation, athetosis, or death.3-5 A neurosensory impairment in hearing, resulting in disabilities in learning, can occur without other neurological defects.5 6 These outcomes are preventable by exchange transfusion1 or, especially in the less severe cases of ABO disease, by phototherapy. 1 7 The management of hemolytic disease of the newborn is made easier whenever the disorder can be anticipated. Rising anti-Rh titers or a history of prior sensitization in an Rh negative pregnant woman allows anticipation of Rh disease. Comparable serological monitoring of group 0 pregnant From the University of North Carolina, Chapel Hill, NC 27514: *Department of Biostatistics, School of Public Health; tDepartment of Pediatrics, School of Medicine, and Child Development Institute. Dr. Patterson's present address is PO Box 10, South Boston, VA 24592. Address reprint requests to Professor Robert C. Elston. This paper, submitted to the Journal February 4, 1976, was revised and accepted for publication April 22, 1976.
854
Patients and Methods The infants born at North Carolina Memorial Hospital share a common nursery room. Newborns, both black and white, are under the care of the same house officers and attending physicians. Although approximately 10 per cent of the infants came under the care of two of us, most members of the pediatric staff were unaware of the present study and preliminary findings. The term Coombs reaction shall be used to denote the direct Coombs test1' with Spectra antiglobulin serum. It is the policy for the blood type of each mother to be recorded on the infant's chart and for umbilical cord blood to be stored for possible typing and Coombs test. These determinations on the infant's blood are performed if the mother is Rh negative. Blood types and results of the Coombs test are obtained on the stored umbilical blood of the infant when jaundice appears in the first day or is more than slightly perceptible. In addition, blood samples are takAJPH September, 1976, Vol. 66, No. 9
ABO HEMOLYTIC DISEASE
en from the infant at the time of jaundice, for determination of serum bilirubin. At intervals over a period of five years, hospital charts were reviewed for infants coded as having ABO hemolytic disease, hyperbilirubinemia, or an unspecified hemolytic disease (other than Rh) and born at this hospital during the period from October, 1965, to March, 1973. In addition, the last digit of the chart number was used to select randomly the charts of approximately one-tenth of the infants born at this hospital over the same period of time, regardless of their diagnosis. From both groups of charts the following data were extracted: race, sex, birth weight, approximate age at onset of jaundice, maximum indirect serum bilirubin (mg/I00 ml), age at which maximum bilirubin levels were observed, age at exchange transfusion (if done), and the Rh and ABO blood types of mother and infant. During this period, a total of 7,464 infants weighing 2.5 kg or more, were born at this hospital. Of these, 3,584 (48.02 per cent) were black, 3,831 (51.33 per cent) were white, and 49 (0.65 per cent) were of other races. An infant was considered as possibly having ABO hemolytic disease only if the criteria in Table 1 were met. Similarly, data from the randomly selected charts were used to compare the frequency and severity of hyperbilirubinemia in the two races only when conditions 1 through 4 of Table I were satisfied. The sex ratio and prevalence of the different ABO blood groups were determined from the randomly selected charts. Gene frequencies were estimated from these data by the method of Bernstein.12 Differences between blacks and whites were tested for statistical significance with the function Z = (fw - fb)/[t (I -) (nw-1 + nb-)] where fw and fb are fractions of whites and blacks affected and nw and nb are the total number of whites and blacks. The
expression = (nwfw + nbfb)/(nw + nb) = total number affected/total number, represents a pooled estimate of incidence based on the null hypothesis of no difference between blacks and whites. Z has a standard normal distribution and is considered highly significant if IZI - 2.58 (P _ 0.01) and significant if IZI- 1.96
(P
Abstract: In this review of 7,464 consecutive infants born at North Carolina Memorial Hospital, hemolytic disease from ABO incompatibility was found to be two to three times as common in black infants as in white infants. The statistical significance of the difference remained high as more restrictive criteria for ABO hemolytic disease were applied. ABO disease, serious enough to cause an indirect serum bilirubin of 15 mg/lOOml or higher, had an incidence in black newborns as great as the incidence of Rh hemolytic disease
in whites. In contrast, the general prevalence and severity of hyperbilirubinemia was not found to be higher in black newborns than in white infants. The difference cannot be attributed to differences in the prevalence of ABO blood groups between the two races. Policies of early discharge of newborns could be affected by the finding that ABO erythroblastosis is two to three times as common in black infants as in white infants. (Am. J. Public Health 66:854-858, 1976)
Introduction
women is not routinely possible, however, for ABO hemolytic disease. In addition, the disorder can affect first-born infants without necessarily affecting subsequent infants.' Studies on South African populations by Brink,8 Ford,9 and Farrell10 suggest racial differences in the frequency and severity of ABO hemolytic disease. The purpose of the present study was to determine whether such differences exist in the newborns of this country. We believe that this information will be of value in the identification of pregnancies at risk for ABO disease.
Over 98 per cent of cases of iso-immune hemolytic disease of the newborn (erythroblastosis) result from maternalfetal incompatibility for either the rhesus (Rh) factor or the ABO blood group.1' 2 Hemolytic disease from ABO incompatibility is about twice as common as that from Rh incompatibility.' Moreover, the current practice of administering anti-D IgG to Rh negative, post-partum women is decreasing the occurrence of Rh disease1' 2 and thereby raising the ratio of ABO disease to Rh disease still higher. Of the two disorders, ABO hemolytic disease is generally the milder, but either can result in mental retardation, athetosis, or death.3-5 A neurosensory impairment in hearing, resulting in disabilities in learning, can occur without other neurological defects.5 6 These outcomes are preventable by exchange transfusion1 or, especially in the less severe cases of ABO disease, by phototherapy. 1 7 The management of hemolytic disease of the newborn is made easier whenever the disorder can be anticipated. Rising anti-Rh titers or a history of prior sensitization in an Rh negative pregnant woman allows anticipation of Rh disease. Comparable serological monitoring of group 0 pregnant From the University of North Carolina, Chapel Hill, NC 27514: *Department of Biostatistics, School of Public Health; tDepartment of Pediatrics, School of Medicine, and Child Development Institute. Dr. Patterson's present address is PO Box 10, South Boston, VA 24592. Address reprint requests to Professor Robert C. Elston. This paper, submitted to the Journal February 4, 1976, was revised and accepted for publication April 22, 1976.
854
Patients and Methods The infants born at North Carolina Memorial Hospital share a common nursery room. Newborns, both black and white, are under the care of the same house officers and attending physicians. Although approximately 10 per cent of the infants came under the care of two of us, most members of the pediatric staff were unaware of the present study and preliminary findings. The term Coombs reaction shall be used to denote the direct Coombs test1' with Spectra antiglobulin serum. It is the policy for the blood type of each mother to be recorded on the infant's chart and for umbilical cord blood to be stored for possible typing and Coombs test. These determinations on the infant's blood are performed if the mother is Rh negative. Blood types and results of the Coombs test are obtained on the stored umbilical blood of the infant when jaundice appears in the first day or is more than slightly perceptible. In addition, blood samples are takAJPH September, 1976, Vol. 66, No. 9
ABO HEMOLYTIC DISEASE
en from the infant at the time of jaundice, for determination of serum bilirubin. At intervals over a period of five years, hospital charts were reviewed for infants coded as having ABO hemolytic disease, hyperbilirubinemia, or an unspecified hemolytic disease (other than Rh) and born at this hospital during the period from October, 1965, to March, 1973. In addition, the last digit of the chart number was used to select randomly the charts of approximately one-tenth of the infants born at this hospital over the same period of time, regardless of their diagnosis. From both groups of charts the following data were extracted: race, sex, birth weight, approximate age at onset of jaundice, maximum indirect serum bilirubin (mg/I00 ml), age at which maximum bilirubin levels were observed, age at exchange transfusion (if done), and the Rh and ABO blood types of mother and infant. During this period, a total of 7,464 infants weighing 2.5 kg or more, were born at this hospital. Of these, 3,584 (48.02 per cent) were black, 3,831 (51.33 per cent) were white, and 49 (0.65 per cent) were of other races. An infant was considered as possibly having ABO hemolytic disease only if the criteria in Table 1 were met. Similarly, data from the randomly selected charts were used to compare the frequency and severity of hyperbilirubinemia in the two races only when conditions 1 through 4 of Table I were satisfied. The sex ratio and prevalence of the different ABO blood groups were determined from the randomly selected charts. Gene frequencies were estimated from these data by the method of Bernstein.12 Differences between blacks and whites were tested for statistical significance with the function Z = (fw - fb)/[t (I -) (nw-1 + nb-)] where fw and fb are fractions of whites and blacks affected and nw and nb are the total number of whites and blacks. The
expression = (nwfw + nbfb)/(nw + nb) = total number affected/total number, represents a pooled estimate of incidence based on the null hypothesis of no difference between blacks and whites. Z has a standard normal distribution and is considered highly significant if IZI - 2.58 (P _ 0.01) and significant if IZI- 1.96
(P
