Sources of prenatal samples.- The most common source of cytogenetic samples for prenatal testing is(are) the program(s) for screening for Down's syndrome or other aneuploidies, which in some countries have become standard for all pregnancies in the health services. In the past, maternal age was the only established risk factor, and amniocentesis was the only or the preferred diagnostic test for fetal aneuploidies. Therefore, amniocentesis was offered routinely to mothers over 35. The screening programs aim at minimising the number of amnocentesis procedures while extending the scrutiny in principle to all pregnancies.

The fortuitous finding that alpha-fetoprotein levels in maternal serum drop to about 75% of the normal mean in most aneuploid pregnancies was made by I.R. Merkatz in 1984. Considerable expansions on this were made subsequently, with the inclusion of other maternal serum biochemical markers of aneuploid pregnancies, and improved predictive value by corrections for the more precise dating of the pregnancy. This body of research has culminated in the now widely used 'Triple test' for screening pregnancies for high risk of chromosomal aneuploidies. A very comprehensive review of many technical aspects of these programs can be seen under the entry 'Antenatal Screening for Down's Syndrome', by Wald NJ, Kennard A, Hackshaw A, and McGuire A (1998), 2(1), available in full from the Health Technology Assessment (UK) website. NOTICE. This site contains a large table. Select 'Publications' and go to the table heading 'Diagnostic Technologies and screening', and then select the document mentioned above. You will need Acrobat Reader.

The triple test has produced very considerable ethical debate that can not be ignored. Mention should be made here of some points;

• The screening value of the tests, which means that it is not intended as diagnostic, but only as an estimator of risk. Cytogenetics (after amniocentesis or cvs) remains the diagnostic test.
• Its relatively wide parameters (rate of false positives and false negatives, (see technical description above)), which are of relatively less importance in a screening test than in a diagnostic test, but which can cause considerable and unnecessary parental anxiety.
• Its intended widespread use.
• Its strictly quantitative and economic approach, and its reliance on a high number of terminations to render the screening program economically viable. This would seem to disregard other values that parents may attach to a pregnancy.
• Its apparent disregard of the considerable medical progress that continues to improve the quality of life of these patients. See any of the patients groups mentioned in the 'Constitutional Abnormalities' section for a contrast between the detached approach of the health planner versus a more involved parental approach.

Cell origin and the problem of mosaicism. The main problem confronting prenatal diagnosis is mosaicism, i.e. when more that one karyotype is found in the sample, is this a reflection of genuine mosaicism in the fetus, or does it result from contamination of the sample with other non-fetal tissue? The extent of the problem, relevant definitions and approximate solutions to this problem can be read here.