[Prenatal diagnosis. Review, personal and prospective studies]

1. In a review of methods developed for the identification of fetal malformations, the technique, risks and results of amniocentesis are presented. 2. Large series already published have demonstrated the relative simplicity and feasibility of the procedure as well as current indications for its utilization. These include the detection of chromosomal anomalies, the determination of sex (in certain sex-linked disorders), documentation of enzymatic and metabolic deficiencies, and the demonstration of open lesions of the neural tube by appropriate techniques. 3. Experience with over 500 cases personally tested by the authors entirely confirms the major indications for and benefits of this modern method for the detection and prevention of severe congenital anomalies during early pregnancy. 4. The identification of chromosomal alterations is currently the major objective of the method. Increased risks are associated with pregnancies involving a maternal age of 35 years or older (which account for 1-3% of aneuploidies), the birth of a previous infant with free trisomy 21 (1% recurrence risk) or secondary to a parental chromosome translocation (as much as 10% risk of aneuploidy). Fetal karyotyping for determination of sex, in cases where the mother is a carrier of an X-linked recessive gene (on average, 50% of male offspring will be affected), is an inadequate method of diagnosis to be utilized only until alternative techniques render possible specific diagnosis of the anomalies under consideration (hemophilias A and B, muscular dystrophy, etc). 5. Several of these techniques are now nearing development through the advent of fetoscopy and advanced ultrasound methodology, and have already been applied to the detection of certain sex-linked disorders and also for diagnosis of hemoglobinopathies (thalassemias, sickel cell anemia) and other conditions requiring the obtaining of fetal blood for diagnosis. Technology allowing direct examination of fetal parts by means of optical instruments is particularly useful in cases where a severe fetal morphologic malformation cannot currently be identified by indirect visualization (ultrasound) or by analysis of cytogenetic or molecular markers. 6. Pathological accumulations of alpha-fetoprotein which are associated with diverse feto-placental abnormalities (particularly open malformations of the neural tube) can be detected in the amniotic fluid and/or maternal blood. In extension of this approach, it is foreseeable that conditions existing prenatally will be diagnosed in a growing number of cases from the study of fetal cells and molecules which can be isolated from the venous blood of pregnant women. This will become feasible as a result of some well-developed techniques which allow separation of fetal from maternal cells and metabolites, and also to some extremely fine analytic techniques, notably examination of the DNA itself by means of restriction enzymes.