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Down's syndrome screening: a controversial test, with more controversy to come!
  1. N J Sebire
  1. Department of Histopathology, St Mary's Hospital, Paddington, London W2, UK
    1. T M Reynolds
    1. Department of Clinical Chemistry, Queen's Hospital, Belvedere Road, Burton upon Trent, Staffordshire DE13 0RB, UK

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      Recently, Professor Reynolds eloquently highlighted some of the current controversies surrounding the provision of Down's syndrome screening, primarily from a biochemical standpoint,1 and most of those involved in this field would certainly agree with the last part of the title. Nevertheless, there are several issues raised in the article, which require some further clarification to achieve a balanced discussion. First, the issue of intrauterine lethality and detection of affected fetuses that may spontaneously abort is one that potentially affects all forms of prenatal diagnosis and screening, not just ultrasound screening for nuchal translucency thickness (NT), as implied. Second, this issue only becomes important, in terms of evaluating detection rates, if those fetuses that are destined to abort spontaneously are preferentially detected by the screening test. In a study on this issue using data from individual pregnancies, rather than epidemiological models, there is indeed a significant increase in intrauterine lethality, but only when the NT thickness is considerably raised (which accounts for only a small proportion of fetuses with trisomy 21), resulting in only a small impact of the lethality issue on screening efficiency, with an estimated reduction in live birth rate of about 70% for an 80% detection rate at 12 weeks.2 Third, and by far most importantly, an ultrasound scan at 11–14 weeks has many other benefits for antenatal care, allowing the accurate assessment of gestational age, the detection of multiple pregnancy, the detection of most major structural defects, the detection of markers for major cardiac defects, all in addition to the measurement of NT thickness for the assessment of risk for trisomy 21,3 with or without the addition of first trimester biochemical assays to improve detection rates. At the time of the scan, the findings and risks can be discussed with the patient and questions answered without delay to allow the parents to decide about further invasive testing. From a political point of view, a national screening policy makes sense, but only if it makes the best use of resources (which might be used not just for Down's syndrome screening, but to improve all aspects of integrated antenatal care), and is welcomed by the “clients”, most of whom choose to have a first trimester ultrasound examination if given the option, with early diagnostic testing if appropriate.

      I declare the following personal and family interests in Down's syndrome screening: (1) patents, none; (2) grants, none; (3) software, none; (4) consultancies, none; (5) medicolegal, none.


      The author replies

      Dr Sebire is absolutely correct about the apparent benefits of early antenatal ultrasound assessment, not least the ability to measure nuchal translucency (NT), thereby indicating that it is necessary to carry out earlier diagnostic tests, to allow earlier “therapeutic” intervention. Here of course it is possible to raise the level of controversy about antenatal screening by querying who benefits from the intervention. However, once one accepts that screening should be carried out, the truth remains that although the trials of NT screening appear convincing, they can be criticised as flawed. They do not allow a true comparison with second trimester biochemical screening programmes because immediate intervention prevents the assessment of natural intrauterine lethality. Second trimester testing was introduced into a relatively virgin field in which there was no established regimen of care. Despite the many potential advantages of NT screening, it has to break into an already occupied medical niche, meaning that extra momentum is required to change what has already become firmly engrained practice.

      In an ideal world, we would carry out a trial that ignored significant first trimester results until a comparator test could be carried out in the second trimester. Clearly, however, given what we know about NT this would be completely unethical, and we are permanently reduced to debating the effect of intrauterine lethality in an attempt to identify comparable first and second trimester detection rates. If in the fullness of time early ultrasound is more advantageous than second trimester screening it will take over, and biochemical screening will justifiably disappear. The ethics of screening for cystic fibrosis are already being queried because the CFTR gene has been sequenced and a possible cure is expected. Who knows whether the human genome project will make trisomy 21 a treatable condition? We can only wait and see.

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