Advances in the Prenatal Diagnosis of Hematologic Diseases By Blanche P. Alter for the WHO International Registry for Prenatal Monitoring of Hereditary Anemias

T HE MODERN ERA ofprenatal testing for hematologic diseases began in 1974. Prior to that time, the only test available consisted of determination of fetal sex following amniocentesis in cases at risk for sex-linked disorders, such as the hemophilias. Methods for obtaining fetal blood in utero in ongoing pregnancies were initiated in 1974, and these developments led to the possibility of prenatal diagnosis of any blood disorder that was expressed in utero and for which the assay could be miniaturized. The first group of diseases for which such testing was utilized was the hemoglobinopathies. Recent advances in molecular biology have now resulted in a return to the use of amniocentesis for many of these prenatal tests (see Orkin’ for a recent review), although sampling of fetal blood remains the method of choice for detection of hematologic diseases in utero for which deoxyribonucleic acid (DNA) probes are not yet available. The World Health Organization (WHO) supports an International Registry for Prenatal Monitoring of Hereditary Anemias, which attempts to document all cases examined in utero by fetal blood or DNA studies for hematologic diseases. This Registry is maintained on PROPHET, a computer resource sponsored by the Division of Research Resources of the National Institutes of Health. Analyses of the Registry data are complete for the period of June 1974 through December 1982 and will be referred to here. Prenatal diagnosis of hemoglobinopathies was last reviewed two years ago,2 and relevant references may be found there, as well as in a detailed chapter.3 The previous review cited data from the Registry that ended in March 1981 and included 1,856 cases that had been studied by fetal blood analysis because of the risk of hemoglobinopathies. The current Registry includes 4,1 33 cases studied for hemoglobinopathies, or more than 2,000 additional cases, as well as more than 300 cases investigated for other hematologic disorders. A total of 4,47 1 prenatal studies were reported through December 1982. The centers participating in the Registry are listed in Table 1 , and the physicians of record at each center are listed in the Acknowledgment section. All but the Scandinavian centers began with examination of fetal blood in cases at risk for thalassemia. Several have now begun to examine the DNA in such cases, which is obtained currently by amniocentesis and, in the near future, will be obtained from chorionic villi. Some centers have also extended their studies of fetal blood to include disorders other than hemoglobinopathies. This review will summarize the major techniques and results reported to the Registry.