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.