Discussion
In this article, the authors present the case of a pregnant woman who
met all of the diagnostic criteria for mirror syndrome or Ballantyne
syndrome. This syndrome is associated with intrauterine foetal death in
35.7% of cases; therefore, it is especially important to identify its
cause to reduce possible adverse gestational events. The usual reasons
for consultation in affected patients are maternal oedema (up to
89.3%), increased blood pressure (60.7%) and headache and visual
disturbances (14.3%). In analytical studies, mild anaemia with
haemodilution is a characteristic sign, in contrast with anaemia and
haemoconcentration, which can be present in other entities, such as
preeclampsia. Proteinuria, elevated liver enzymes and uric acid are also
frequent.5,11 Our patient presented the vast majority
of the signs and symptoms previously described in the literature and
associated findings in laboratory tests.
Regarding the precipitating causes of this condition, a systematic
review conducted by Braun et al.5 in 2010 analysed 56
cases compatible with this syndrome . A total of 28.6% of the cases
were associated with foetal-maternal isoimmunization, 17.9% with
multiple pregnancies, 6.1% with viral infections and the remaining
37.5% with foetal malformations, arrhythmias and foetal or placental
tumours. In the cases described in the literature, the symptoms
disappeared an average of 8.9 days after the pregnancy
ended.5 In the particular case of our patient, the
cause of the syndrome was isoimmunization resulting in foetal hydrops
due to severe foetal anaemia, and the patient’s symptoms reversed 7 days
after the end of pregnancy.
At present, less than 10% of cases of hydrops fetalis have an immune
cause. The origin of its pathophysiology is the presence of maternal
antibodies against foetal erythrocyte surface antigens. This
isoimmunization usually originates during pregnancy or in cases of
previous transfusions.10,12 Our patient did not report
previous transfusions but had a previous pregnancy that progressed
normally.
In our environment, gestational screening for irregular antibodies is
usually performed using an indirect Coombs test. The panels used in
maternal screening studies are capable of detecting the majority of
clinically significant isoimmunizations13; however,
they rarely include very low frequency erythrocyte antigens, such as
Kpa, which are present in less than 2% of the Caucasian population and
are even less common in other ethnic groups. This is the why our patient
was not identified with a high-risk pregnancy by the gestational
screening tests for isoimmunization.
Regarding isoimmunization with causes other than RhD, those involving
other Rh group antigens (C, c, E, e) stand out for their frequency and
clinical importance. Isoimmunization against Kell group antigens,
including the Kpa antigen, is also clinically significant in pregnancy.
The anti-K antibody is particularly important because it can lead to
neonatal haemolytic disease with enormous clinical severity. The
anti-Kpa antibody can be difficult to identify with routine screening
tests, as occurred in our patient.12
In a high proportion of cases, foetal anaemia can be diagnosed by
measuring the maximum systolic peak of the middle cerebral artery (MCA).
According to a systematic review published in 2019 that included 12
studies and 696 foetuses, MCA measurement presented a diagnostic
sensitivity of 86%, with a specificity of 71% for predicting
moderate-severe foetal anaemia.14 The anaemia that
develops in foetuses affected by antibodies to erythrocyte antigens is
mainly caused by the suppression of erythropoiesis and, to a lesser
extent, the haemolysis of foetal erythrocytes. For this reason, some
articles suggest that foetal assessment by ultrasound measurement of the
MCA may not be a good predictor of foetal anaemia. This decreased
diagnostic sensitivity in cases of isoimmunization could explain the
presence of moderate and severe foetal anaemia with normal MCA values,
as occurred in our case.15
Within the Kell system, there are also antibodies that rarely cause
erythroblastosis fetalis. Among them is anti-Kpa. In the literature,
there are only seven previous cases of perinatal involvement and three
cases of foetal hydrops (Table 1). We therefore present the first case
of mirror syndrome with foetal hydrops caused by anti-Kpa to be
described in the literature.
Finally, regarding the perinatal management of mirror syndrome,
termination of pregnancy if the maternal condition worsens, since 21.4%
of cases develop serious maternal complications, such as acute lung
oedema. In some reported cases of immune hydrops associated with this
condition, intrauterine red blood cell transfusion has been performed,
and maternal symptoms have disappeared after the correction of foetal
anaemia.11,16