Improving first trimester screening by combining rapid MF-PCR of PAP smears with nuchal ultrasound scanning

基因缺陷是胚胎和胎儿死亡的主要原因，也是造成儿童残疾的主要原因。虽然目前澳大利亚每年进行的约50,000次产前检查发现了许多方法，但这些方法只提供给高危母亲，因为它们是侵入性的(约1%的流产风险)，而且-或昂贵。因此，一种快速、低成本、侵入性较小和更安全的替代产前诊断方法，如PAP涂片，可以提供给所有母亲，而不考虑风险，因此对母亲和卫生保健系统都具有巨大价值。这项建议通过改进PAP涂片的产前诊断来加强早期妊娠筛查。虽然通常是用来检测癌症的，但这些涂片含有大量的胎儿细胞。我们将调查：获得这些细胞的最佳方式和时间，从任何污染中清除这些细胞的最佳方法，使用一种名为MF-PCR的技术改进这些细胞的基因诊断，该技术正在迅速革新传统的产前诊断。通过自动化这些程序，它们将变得更便宜，而且无论风险如何，所有母亲都更容易获得这些程序。我们还将比较这些程序与替代的早期妊娠筛查技术，如颈部半透明，以确定两种测试的单独和联合的价值。这项研究应该提供一种安全、可靠和准确的方法，使所有孕妇都可以进行廉价的产前筛查。使用这一新测试的一般筛查方案，特别是如果与颈部半透明方案相结合，将大大减少受影响的婴儿，对家庭和卫生保健系统产生重大影响。

Genetic defects are the major cause of embryonic and foetal death as well as being responsible for a large proportion of childhood disabilities. Although many are detected by the ~50,000 prenatal tests currently performed annually in Australia, these methods are only offered to high risk mothers because they are invasive (~1% risk of miscarriage), and-or expensive. A rapid, low cost, less invasive and safer alternative prenatal diagnostic method such as PAP smears that could be offered to all mothers regardless of risk is therefore of immense value both to mothers and to the health care system. This proposal enhances first trimester screening by improving prenatal diagnosis from PAP smears. Although normally taken to detect cancer, these smears contain significant numbers of foetal cells. We will investigate: the best way and time to obtain these cells, the best way to remove the cells from any contamination, improvements in genetic diagnosis of these cells using a technique known as MF-PCR which is rapidly revolutionising conventional prenatal diagnosis. By automating these procedures, they will become less expensive and more accessible to all mothers regardless of risk. We will also compare these procedures with alternative first trimester screening techniques such as nuchal translucency to determine the value of both tests singly and in combination. This research should provide a safe, reliable and accurate method allowing inexpensive prenatal screening to be available for all pregnancies. General screening programmes using this new test, particularly if combined with nuchal translucency programmes, would result in a dramatic reduction in affected babies with major implications to families and the health care system.