ABO  lncompatibility and Parity Effects

on Perinatal Mortality

C. T. Gualtieri, R. E. Hicks, and J. P. Mayu,
Social Biology, 1985

Biological Sciences Research Center
University of North Carolina
Chapel Hill, North Carolina

Abstract
The perinatal mortality rate is known to increase with parity (pregnancies increase). This high parity effect is shown in be steepest for "O"-type mothers, compared to mothers with blood groups  A, B or AB. Thus, there is a heightened parity effect in mothers who are likeliest to be antigenically dissimilar from their fetuses. This model may also be germane to other clinical conditions where negative parity effects are observed. Maternal-fetal immunoreactivity is a likely explanation for parity effects on perinatal mortality attribuable to ABO incompatibility and may also contribute in the occurrence of negative parity effects in other conditions. The paradox of pregnancy is that cir­culating maternal antibodies against the histocompatibility antigens of the fetus develop simultaneously with the specific inhibition of immune reactivity against the fetus as a graft (Simmons, 1971). However, there are instances where mechanisms of fetal immunoprotection break down. Maternal immune attack upon the fetus plays a central role in pathologic conditions like Rh disease, runt disease, autoimmune thrombocytopenia and hemolytic anemia,  myasthenia gravis and thyroiditis (13rent, 1971). Spontaneous abortion and peri­natal death may also be consequences of maternal-fetal immunoreactivity. It is our contention that maternal­-fetal immunoreactivity may also contribute to other pathologic conditions in which a "negative parity effect" is ob­served. The development of maternal antibodies to fetal antigens increases with successive pregnancies (Doughty and Gelsthrope, 197C), and maternal immunoreactivity rnay therefore be expected in certain circumstances, to exert deleterious effects upon the course or the outcome of successive pregnancies. Negative parity effects, i.e., an in­creased likehood of untoward outcome with increasing birth order, have been described in connection with stillbirth and perinatal mortality (Niswander and Gordon, 1972), mental retardation (Belmont et al., 1972),  specific Iearning disabilities (Nichols and Chen, l981), in­fant characteristics (Waldrop and Bell, 1966), height ( (Belmont et al., 1975), birth weight and placenta size (Vernier, 1975), and IQ (Belmont and Marulla, l973). Maternal-fetal ABO incompatibility is known to occasion inci­dence of fetal wastage (Cohen, 1970). Since it is likely that phenomena has immunoreactive basis, we thought that perinatal mortality as a consequence of ABO incompatibility might be a good model for demonstrat­ing how maternal-fetal immunoreactiv­ity may have manifested as a negative par­ity effect. Since it is already known that relative parity effect exists for still­birth and perinatal mortality (Niswan­der and Gordon, 1972), the demonstra­tion would require that the parity effect for antigenically incompatible matings should be demonstrably stronger. With respect to ABO incompatibility, the idea would be supported by the demon­stration of a greater parity effect on peri­natal mortality in children of 0-type mothers.The data are from the British Perina­tal Study (Butler and Bonhan, 963). The perinatal mortality rate for a sample of 14,732 pregnancies was related to ma­ternal ABO type and parity (sec Table l). It is found that within each maternal blood group, the perinatal mortality rate increased with parity. As predicted, the slope of the mortality/parity regres­sion line is substantially steeper for O mothers than for A, B, or AB mothers (sec Figure 1). The significance of this difference was tested by analysis of variance with orthogonal polynomial decomposition (unweighted means). The interac­tion, birth order (linear) x maternal ABO status (O vs. A, B, and AB) x perinatal mortality rate was significant (F (1,14730] = 4.30, P < 0. 05). Parity effects on perinatal mortality are most strongly felt by O mothers, who are also most prone to develop an immune reaction to fetal blood group antigens. Heightened maternal-fetal im­munoreactivity is thus manifest in a sharper parity effect.
Since fetal ABO status was not avail­able in the data base from the British Perinatal Study, it was not possible to perform a more incisive analysis of maternal-fetal ABO incompatibility rel­ative to parity effects and perinatal mor­tality. Nevertheless, the fact that maternal-fetal incompatibility can con­tribute to and be demonstrated in the slope of the negative parity effect may be useful to research in other pathologic conditions where negative parity effects are known to exist. It is conceivable that maternal-fetal immunoreactivity may play a role in their development as well.

p.s. par un phénomène magique, la parité n'aggrave les risques que dans les situations spécifiques d'incompatibilité sanguine RH ou ABO, mais non pas en immunologie générale où la mère tend à développer des mécanismes d'adaptation, à l'égard du foetus mi-greffon, et surtout du garçon. CJ