Rhesus disease and non-immune hydrops

Abstract

Hippocrates first documented the condition of ‘fetal hydrops’ in 400 BC. There was recognition of jaundice of the newborn in the 17th century, but it was not until 1909 that Buchan established a link between some cases of newborn jaundice and anaemia, and 1932 before Diamond described the condition of erythroblastosis fetalis. Between 1938 and 1941, the identification of maternal red cell antibodies, the Rhesus antigen and blood group inheritance were established. In 1947, Diamond first described post-natal treatment utilizing transfusion, with exchange transfusion being described by Mollison in 1952. Intra-uterine therapy was not established until 1963 when Liley first published the use of intraperitoneal transfusion. The last 40 years have seen rapid advances in the understanding, assessment and therapy of Rhesus disease and non-immune hydrops. We have seen exploration of: amniotic fluid bilirubin levels, to determine whether a fetus is at risk of haemolytic disease of the newborn (Freda and Liley); plasmapheresis (Powell), aiming to reduce the maternal circulating antibody levels; fetal blood sampling, to establish a diagnosis; and intraperitoneal or intravascular transfusion, as methods of direct therapy, the latter initially using fetoscopy and then using an ultrasound-guided approach to fetal vessels. Stem-cell therapy has been explored and, more recently, non-invasive methods to assess fetal anaemia have been introduced using the mean range on a computerized cardiotocograph (CTG) and middle cerebral artery maximum flow velocity. In cases where the partner is heterozygous for a particular red cell antigen, the potential for determining fetal group by identification of fetal cells in the maternal circulation for testing has also become a possibility. Approximately 20% of cases of non-immune hydrops remain ‘idiopathic’, the remainder either being a result of a cardiac structural anomaly, arrhythmia or a metabolic disorder. Twinning accounts for approximately 6% of cases of non-immune hydrops. This article aims to give an overview of what is happening today and a glimpse of what might be possible in the future.