Discussion
In this study, we systematically assessed the possibility that group O mothers would give birth to non-group-O infants and the incidence of an infant actually developing haemolytic disease due to ABO incompatibility. Depending on the genotype frequencies, the likelihood of ABO incompatibility between a mother and her infant was 13.28%, but the occurrence rate of ABO HDN was 6.03%. There was no significant difference in severity between O-A and O-B incompatibility groups, and the frequency of maternal-foetal blood group mismatch in O-A and O-B was almost equal. The DAT positive neonates were more prone to haemolysis and led to even lower Hb. Moreover, we found that the later the postnatal age of admission, the higher the peak TSB level, whether a newborn develops severe hyperbilirubinemia.
Disparities between regions and ethnicities are conspicuous factors affecting the prevalence of haemolytic diseases. Our data showed that 13.28% of newborns have a major ABO incompatibility with mothers, while haemolytic disease was observed in only 6.03% of newborns, which is different to the incidence of HDN due to ABO incompatibility in Singapore [16]. In Caucasians, ABO incompatibility between the neonate and mother occurs in 10-25% of pregnancies and only 1-2.5% of infants are complicated by haemolytic disease [12, 17]. The reason for this discrepancy may be that A and B antigens are expressed at different frequencies and strengths in different populations. The results of Sebija Izetbegovic et al. [18] from Sarajevo showed an ABO incompatibility in 15% of pregnancies an ABO HDN of 0.67% in all newborns included in the study.
The variance in the incidence of blood group incompatibility and haemolytic disease can be attributed to the weak expression of major blood group antigens A and B on foetal erythrocytes; blood group antigens A and B are also expressed in other tissues, to which antibodies could bind. In addition, the immunoglobulin subclasses each have differing biological properties affecting their pathogenic potency. IgG3 has more effective transported across the placenta [19], compared with other subclasses of IgG, which may be responsible for whether the disease is present.
The American Academy of Pediatrics has reported blood group incompatibility with positive DAT as one of the most important risk factors for severe hyperbilirubinemia [15]. Clinically observable ABO HDN is usually diagnosed by severe jaundice within the first few days of life, followed by a positive laboratory test. DAT as a screening test for incomplete antibodies present on an individual’s RBCs has poor sensitivity (50%) in identifying neonates that will develop clinically significant jaundice [15] and does not determine the specificity of the antibody attached to red blood cells. The eluate test is performed if DAT results are negative in our institution, which makes up for the defects of the DAT test in HDN identification caused by ABO antibody. We observed that DAT-positive neonates with haemolytic disease had lower Hb concentrations, so even at lower sensitivity, DAT was an invaluable screening tool for HDN. As other studies show, ABO incompatibility with positive DAT infants is at increased risk of receiving phototherapy and invasive treatment when compared with DAT-negative infants [20], and the increasing strength of DAT positivity is associated with phototherapy need [21].
The results of this study showed that the frequencies of O–A and O–B incompatibility and the severity of haemolysis between group A and group B were almost the same, as also observed in the study of Y. R. Bhat et al. [6]. Many investigators in Western countries suggest that O-A blood group incompatibility has a higher morbidity and forms a majority of the ABO HDN, but haemolysis due to IgG anti-B is more severe [20, 22]. This divergence may be due to the difference in the distribution of blood type phenotypes between the other regions and ours [23]. However, the higher incidence of positive DAT in O-A blood group incompatibility that we observe is similar to the results of Kaplan, M. et al. [21]. Michael Kaplan et al. [22] conducted a retrospective study of the incidence of hyperbilirubinemia in neonates who were DAT-positive, ABO incompatible and compared O-A and O-B groups; the condition was more prevalent in the group B neonates and hyperbilirubinemia developed in more O-B newborns than O-A newborns at <24 hours.
Hyperbilirubinemia in the first week of life occurs in more than 60% of otherwise healthy infants and usually resolves within 7–10 days of age [5, 24]. In our research, the peak TSB levels increased gradually with the prolonging of postnatal age of admission and a good correlation was observed. The onset of hyperbilirubinemia caused by ABO incompatibility was most likely to occur prior to 72 hours of age and is associated with increased bilirubin production [5]. A study conducted by R. D. Christensen et al. [25] found that group A and B neonates, born to O (+) mothers, had higher peak TSB levels during the first 10 days after birth than did group O neonates. Due to the immature liver function of newborns, the level of bilirubin is markedly elevated with the duration of jaundice. Moreover, among ABO HDN newborns with severe hyperbilirubinemia, the age at admission was significantly higher than that of newborns without severe hyperbilirubinemia, which indicated that early admission might reduce the risk of severe hyperbilirubinemia for infants with ABO incompatibility, although the sample size needs to be larger for confirmation of this result.
Although we recognize that A, B, or AB mothers can deliver neonates with ABO haemolytic disease, those incompatibilities very infrequently have any clinical significance. The probability of ABO incompatibility, which represents the possibility of an O-type mother giving birth to a non-O-type baby, has been calculated using genetic frequencies from the 8 5590 blood donors in the Affiliated Hospital of Qingdao University in northern China. With respect to the prevalence of ABO HDN, an estimate of the incidence in northern China would be 1 in 6 live births (471 in 7 810 over the 3-year study period). It is anticipated that any infant born in the Affiliated Hospital of Qingdao University complicated by haemolytic disease due to ABO incompatibility would be referred to a doctor for treatment. However, some newborns may go to other hospitals or even no hospital. The estimate of 1 in 6 live births is likely conservative given that this is based on hospital medical records.
Neonatal haemolytic disease caused by ABO incompatibility of mother and infant is not infrequent in northern China. Although not all neonates develop neonatal haemolytic disease and the disease process is usually benign, it can be devastating if left untreated. For DAT positive newborns with ABO incompatibility, timely monitoring is advised, because early hospitalization and appropriate interventions, if necessary, can reduce the risk of severe hyperbilirubinemia.