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Rh erythroblastosis and ABO incompatibility
Rh erythroblastosis and ABO incompatibility ANDREW F. CAUGHEY, JR., M.D. Detroit, Michigan
roblastosis ( Rh) had a positive direct Coombs test and most of them had severe cases requiring exchange transfusions. Likewise, all normal (control) babies had a negative direct Coombs test and normal hematologic findings. No case selection was permitted except that two cases of erythroblastosis in which it could not be determined whether the cause was Rh or ABO (or both) were not included and that no repeat pregnancies were counted (i.e., all pregnancies reported were from different patients). The results of this study are shown in Table II. It will be seen that the incidence of ABO incompatibility between mother and fetus is much higher in those Rh-negative mothers whose babies were normal. This difference is statistically significant (chi-square 5.15; probability close to 0.02). There are three possible theoretical explanations for this occurrence. 1 First, if an Rh-negative mother, for example, Type 0, has Group A children, Rh-positive, her antibody-making tissues may be too fully occupied in making more anti-A to make antiRh: second, it may be that the A Rh+ cells enter the mother's circulation and are eliminated by her anti-A before they have time to cause Rh sensitization; lastly, the cause may be the elimination of ABO-incompatible
THE fact that ABO incompatibility protects the fetus against erythroblastosis due to Rh has long been recognized by most immunologists but has been ignored by some obstetricians. In 1950 Race and Sanger 1 summarized the work that had been done on this problem and demonstrated the curious fact that mothers of children with hemolytic disease due to Rh incompatibility were more often compatibly mated in regard to the ABO system than were unselected women (i.e., in these cases the husband could be a blood donor to his wife). Hence, the babies also tended to be compatible with their mothers in the ABO system. It is not difficult to calculate the probable ABO type of the infant from the types of the parents; one must merely remember the genotypes of the common types. Type 0 is always "00," A is either "AO" (here A is dominant) or ''AA," B is likewise either "BO" or "BB," and AB is always "AB." Then a square is drawn; for example, the mating of a Type A and Type 0 couple is shown in Table I (ignoring A1 and A2). In the first case, one half of the children are likely to be Type 0, while in the second case all the children will be Type A. Calculations for all possible combinations can thus be easily performed. To verify this assertion that ABO incompatibility protects the Rh-incompatible fetus from erythroblastosis, I investigated Rh .. negative mothers from my own practice (32 cases) and from the files of two Detroit hospitals ( 33 cases). All babies with eryth..
Table I
From the Department of Obstetrics and Gynecology, Highland Park General Hospital.
A
I AO
AO
0
00
00 1.
577
0
0
0
0
I
A
A 2.
September, 1960 ,\m. ]. Ob
578 Caughey
Table II. Relationship of erythroblastosis ( Rh) and ABO incompatibility (all mothers Rh negative)* Fetus ABO ,:L
I
Yes
No
Total
Erythroblastosis (Rh) present Erythroblastosis (Rh) not present
Ill
19
29
Total
14
51
65
*Average parity of mothers of erythroblastotic babies was 1.9 and average parity of mothers of noncrylhroblastotic babies was 4.0.
Table III. Chances of sensitization to Rh ABO compatibility of Husband's =:J'gosity for Rh
Heterozygous Homozygous Zygosity unknown
hus~and Incom- I patible
(%)
I 4-·5
2-3
I ABO
I type
of ': husband ! Compatible I unknown I (%) (%)
3
2
11
9
7-8
5
children, irrespective of Rh groups. Levine' found fewer A children when the mother was 0 and the father A than when the mother was A and the father 0. Fisher1 has suggested that this elimination of ABO-in-
compatible fetuses early in pregnancy would reduce the amount of anti-Rh production. I favor the second explanation which seems to agree with clinical experience. However, regardless of the actual cause of this phenomenon, it may be used by the obstetrician as a guide in prognosis both in the present and in future pregnancies. In their recent book, Allen and Diarnond 2 tabulated the chances of eventual sensitization to Rh by pregnancy alone in the Rh-negative wives of Rh-positive men (Table III\. In their opinion, ABO compatibility doubles the chance of the occurrence of Rh sensitization. Summary
1. An old theory that ABO incompatibility protects (or is associated with) the fetus from Rh sensitization is re-emphasized. 2. Data from my practice and from two hospitals are presented which support this theory. 3. Possible causes for this occurrence are discussed and its prognostic importance emphasized. Besides the Rh-positive husband's zygosity and the previous obstetric history. the ABO compatibility of the husband and wife (or mother and fetus) should be considered.
REFERENCES
1. Race, R. R., and Sanger, R.: Blood Groups in Man, Springfield, IlL, 1954, Charles C Thomas, Publisher, pp. 352-354.
2. Allen, F. H., Jr., and Diamond, L K.: Eryth· roblastosis Foetalis, Boston, 1958, Little, Brown & Co., p. 91.
roblastosis ( Rh) had a positive direct Coombs test and most of them had severe cases requiring exchange transfusions. Likewise, all normal (control) babies had a negative direct Coombs test and normal hematologic findings. No case selection was permitted except that two cases of erythroblastosis in which it could not be determined whether the cause was Rh or ABO (or both) were not included and that no repeat pregnancies were counted (i.e., all pregnancies reported were from different patients). The results of this study are shown in Table II. It will be seen that the incidence of ABO incompatibility between mother and fetus is much higher in those Rh-negative mothers whose babies were normal. This difference is statistically significant (chi-square 5.15; probability close to 0.02). There are three possible theoretical explanations for this occurrence. 1 First, if an Rh-negative mother, for example, Type 0, has Group A children, Rh-positive, her antibody-making tissues may be too fully occupied in making more anti-A to make antiRh: second, it may be that the A Rh+ cells enter the mother's circulation and are eliminated by her anti-A before they have time to cause Rh sensitization; lastly, the cause may be the elimination of ABO-incompatible
THE fact that ABO incompatibility protects the fetus against erythroblastosis due to Rh has long been recognized by most immunologists but has been ignored by some obstetricians. In 1950 Race and Sanger 1 summarized the work that had been done on this problem and demonstrated the curious fact that mothers of children with hemolytic disease due to Rh incompatibility were more often compatibly mated in regard to the ABO system than were unselected women (i.e., in these cases the husband could be a blood donor to his wife). Hence, the babies also tended to be compatible with their mothers in the ABO system. It is not difficult to calculate the probable ABO type of the infant from the types of the parents; one must merely remember the genotypes of the common types. Type 0 is always "00," A is either "AO" (here A is dominant) or ''AA," B is likewise either "BO" or "BB," and AB is always "AB." Then a square is drawn; for example, the mating of a Type A and Type 0 couple is shown in Table I (ignoring A1 and A2). In the first case, one half of the children are likely to be Type 0, while in the second case all the children will be Type A. Calculations for all possible combinations can thus be easily performed. To verify this assertion that ABO incompatibility protects the Rh-incompatible fetus from erythroblastosis, I investigated Rh .. negative mothers from my own practice (32 cases) and from the files of two Detroit hospitals ( 33 cases). All babies with eryth..
Table I
From the Department of Obstetrics and Gynecology, Highland Park General Hospital.
A
I AO
AO
0
00
00 1.
577
0
0
0
0
I
A
A 2.
September, 1960 ,\m. ]. Ob
578 Caughey
Table II. Relationship of erythroblastosis ( Rh) and ABO incompatibility (all mothers Rh negative)* Fetus ABO ,:L
I
Yes
No
Total
Erythroblastosis (Rh) present Erythroblastosis (Rh) not present
Ill
19
29
Total
14
51
65
*Average parity of mothers of erythroblastotic babies was 1.9 and average parity of mothers of noncrylhroblastotic babies was 4.0.
Table III. Chances of sensitization to Rh ABO compatibility of Husband's =:J'gosity for Rh
Heterozygous Homozygous Zygosity unknown
hus~and Incom- I patible
(%)
I 4-·5
2-3
I ABO
I type
of ': husband ! Compatible I unknown I (%) (%)
3
2
11
9
7-8
5
children, irrespective of Rh groups. Levine' found fewer A children when the mother was 0 and the father A than when the mother was A and the father 0. Fisher1 has suggested that this elimination of ABO-in-
compatible fetuses early in pregnancy would reduce the amount of anti-Rh production. I favor the second explanation which seems to agree with clinical experience. However, regardless of the actual cause of this phenomenon, it may be used by the obstetrician as a guide in prognosis both in the present and in future pregnancies. In their recent book, Allen and Diarnond 2 tabulated the chances of eventual sensitization to Rh by pregnancy alone in the Rh-negative wives of Rh-positive men (Table III\. In their opinion, ABO compatibility doubles the chance of the occurrence of Rh sensitization. Summary
1. An old theory that ABO incompatibility protects (or is associated with) the fetus from Rh sensitization is re-emphasized. 2. Data from my practice and from two hospitals are presented which support this theory. 3. Possible causes for this occurrence are discussed and its prognostic importance emphasized. Besides the Rh-positive husband's zygosity and the previous obstetric history. the ABO compatibility of the husband and wife (or mother and fetus) should be considered.
REFERENCES
1. Race, R. R., and Sanger, R.: Blood Groups in Man, Springfield, IlL, 1954, Charles C Thomas, Publisher, pp. 352-354.
2. Allen, F. H., Jr., and Diamond, L K.: Eryth· roblastosis Foetalis, Boston, 1958, Little, Brown & Co., p. 91.