Prenatal diagnosis: general introduction, methodology, and review.

Prenatal diagnosis of hematologic disease has been performed in more than 10,000 fetuses since 1974, with the majority at risk for thalassemia. Fetal blood sampling was the initial method, but most centers are now changing to DNA technology, particularly using specimens obtained by chorionic villus sampling. Fetal blood globin chain composition and synthesis is examined using carboxymethyl cellulose columns, electrophoresis, and high performance liquid chromatography. Fetal globin DNA is tested for gene deletions, mutations that affect restriction enzyme cleavage sites, and restriction fragment length polymorphisms, and specific oligonucleotides are used to identify some point mutations. The current trend is for early sampling (by chorionic villus sampling), gene amplification, and specific DNA analyses. The safety of all methods (blood or DNA) is above 96%, and the accuracy more than 99%. The acceptability of these approaches has been high.