Exclusion of chromosomal mosaicism in amniotic fluid cultures: Efficacy of in situ versus flask techniques

Accurate diagnosis of mosaicism in amniotic fluid cell cultures represents a major problem. If insufficient cells are analysed, true fetal mosaicism may go undetected. False-positive diagnosis is also possible since a second cell line may arise in vitro and not reflect the true fetal genetic constitution. These difficulties apply to both flask and in situ culture techniques, to varying degrees. The relative accuracy of flask versus in situ culture techniques in excluding mosaicism was determined by statistical analysis of experimental data from ten pairs of mixed male-female amniotic fluid specimens. The data support the idea that the majority of in situ colonies are independent of one another. The following conclusions are drawn: (1) analysis of a single metaphase from a number of different colonies enhances the confidence for excluding mosaicism; (2) analysis of more than one cell per colony offers little advantage; (3) exclusion of a given level of mosaicism requires analysis of fewer metaphases using the in situ method; (4) the confidence for excluding mosaicism is high with both in situ and flask techniques, using the provided guidelines; and (5) it is shown that the two-stage approach used by many laboratories is currently the most efficient way to exclude mosaicism.     

Maternal serum thyroid antibodies in early pregnancy and fetal Down's syndrome

Thyroid antibodies were measured in mid-trimester antenatal serum samples from 77 pregnancies affected by fetal Down's syndrome and 385 unaffected control pregnancies. Using a haemagglutination technique, thyroglobulin antibodies were detected in 5·2 per cent of cases (4) and 2·9 per cent of controls (11), and thyroid microsomal antibodies were detected in 22 per cent (17) and 15 per cent (59), respectively. Using an enzyme-linked immunosorbent assay (ELISA) for thyroglobulin antibodies and a cut-off level of 50 KIU/1, positive results were found in 25 per cent of cases (19) and 22 per cent of controls (84). Using an ELISA for thyroid microsomal antibodies and the same cut-off level, the proportions were 52 per cent (40) and 39 per cent (149), respectively. While not statistically significant, the differences were consistent with the previously reported increased levels of thyroid antibody found in nonpregnant women who had had pregnancies associated with Down's syndrome.