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