Increased nuchal translucency, hydrops fetalis or hygroma colli - A new test strategy for early fetal aneuploidy detection

Objectives: Nuchal translucency measurement of 3 mm or more (greater than o r equal to 95th centile for gestation age), hydrops feta lis or hygroma col li between the 11th and 14th weeks of gestation is associated with a higher risk of fetal Down syndrome and other aneuploidies. So far, chromosome pre paration of chorionic villi samplings (CVS) after shortterm (or direct) cul ture is the on ly valid, reliable and rapid method of choice for the early detection of chromosomal aberrations. However, because of the placental mos aicisms detected after short-term culture, CVS has to be confirmed by a sec ond method. Moreover, short-term villi preparation does not always provide a sufficient quantity a nd quality of metaphases to enable cytogenetic anal ysis. Unfortunately, a predicative cytogenetic result will be available onl y after long-term cultivation (usually after 1-2 weeks). An alternative rap id method, inexpensive and suitable for diagnosing autosomal trisomies, is the quantitative fluorescence polymerase reaction (OF-PCR) using different polymorphic small tandem repeats (STRs) on CVS-DNA. Therefore, it was the a im of the study to evaluate whether a new CVS test strategy could be employ ed in early pregnancies at high risk after the rapid detection of fetal chr omosomal abnormalities by QF-PCR for chromosomes 13, 18 or 21 and sexing in conjunction with short-term chromosome analysis. Materials: Nineteen CVS w ere chosen for OF-PCR detection of trisomy 21, 18 or 13 after an increased nuchal translucency measurement (greater than or equal to 95th centile for gestation age), a hydrops fetalis or a hygroma colli. The amelogenin locus of chromosomes X and Y (AMXY) were used for sexing. The OF-PCR results were com pared with routine karyotyping after short- and/or longterm cultivatio n of CVS cells. Results: An informative result was demonstrated in all anal ysed specimens. Nine CVS were diagnosed as a OF-PCR trisomy either for chro mosome 21, 18 and 13. The pathological samples also included 4 cases of mos aicism where the normal cell line was not identified by QF-PCR. In 1 additi onal case with a normal OF-PCR result, short-term CVS chromosome analysis s howed a mosaic trisomy 13, whereas long-term CVS culture revealed a normal karyotype. The malformed aborted fetus showed no clinical signs of trisomy 13, confirming the normal results obtained by OF-PCR and long-term CVS chro mosome analysis. One pregnancy with a Turner syndrome was not identified by molecular analysis. Conclusions: This study showed that all early pregnanc ies with a clinically relevant autosomal trisomy could be detected prenatal ly in routine practice by OF-PCR, The combined use of both rapid methods - QF-PCR and short-term chromosome analysis - optimise the results by minimis ing the possibility of false-positive or false-negative findings. We believ e that after verification of a pathological result obtained by two independ ent methods (QF-PCR and short-term CVS chromosome analysis), long-term vill i cultivation is no longer necessary. However, in all cases with discrepanc ies, especially in samples with mosaic findings at short-term CVS cultivati on, further studies are still necessary. Copyright (C) 2001 S. Karger AG. B asel.