Haemoglobinopathies in pregnancy.

The haemoglobinopathies are a heterogenous group of disorders which have highly variable clinical manifestations. At one end of the spectrum there is incompatibility with life and, at the other end, the patient under a stress, such as pregnancy, may experience some deterioration in her normal healthy state. Outside this wide range lie the symptomless carrier states which may demand obstetric action only because of problems connected with genetic counselling or antenatal diagnosis. It must be instantly apparent that the possible pathology to be expected during the pregnant state will vary from one clearly defined genetic entity to another. On top of this, even within one clearly defined disease process, eg, sickle-cell anaemia, there are widely varying degrees of clinical severity. Some women with sickle-cell anaemia appear to have child after child effortlessly, whilst others are racked with crisis after crisis during their first pregnancy until, at some point (often around the time of delivery), they eventually succumb. Some of the extenuating factors are becoming understood but in many cases the different clinical course run by the same genetic disease is quite inexplicable. An understanding of the underlying pathologywhich leads on to an attempt to rationalize obstetric management-depends upon a basic knowledge of protein structure and simple Mendelian genetics. Once these are understood, the classification of the haemoglobinopathies is easily comprehended. In the haemoglobinopathies, the anaemia is due to lack of the normal protein globin, which is an essential part of the haemoglobin molecule, and the red cells produced have a shortened life span, causing a chronic haemolytic anaemia. This lack of normal globin may be due to either: (1) the manufacture within the developing red cell of an abnormal globin which, when combined with haem, results in an abnormal haemoglobin; (2) failure of the developing red cell to produce enough globin (thalassaemia). In this case, the affected gene produces either an inadequate amount of globin or no globin at all. Both the abnormal haemoglobins and the thalassaemias give rise to health problems of immense proportions. The World Health Organization estimate that each year 80000 children die (mainly in central Africa) of sickle-cell anaemia and 100000 children die of ,B thalassaemia major. Whilst / thalassaemia major remains a lethal childhood disease, better medical care now permits many patients with sickle-cell anaemia to live long enough to become pregnant and conceive children. Because of large-scale immigration, many doctors in the United Kingdom now have first-hand experience of both these disorders and it is with sickle-cell haemoglobin and 3 thalassaemia that this article is mainly concerned.