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FETAL NASAL-BONE EXAMINATION COULD IMPROVE ACCURACY OF DOWN'S SYNDROME SCREENING (pp 1658, 1665)

November 14, 2001

A new screening tecnique using ultrasonography to determine the presence or absence of nasal bone in fetuses aged 11-14 weeks could improve the accuracy of Down's syndrome screening, conclude authors of a fast-track study in this week's issue of THE LANCET.

Prenatal diagnosis of Down's syndrome (the identification of three copies of chromosome 21 in the fetus, also known as trisomy 21) requires an invasive test in women regarded as being at high risk after screening. Four screening methods are currently used, which have varying degrees of efficiency (sensitivity): maternal age alone (30% sensitivity); maternal age + maternal blood-testing in the second trimester of pregnancy (60-70%); maternal age + first-trimester fetal nuchal translucency scanning (75%); and maternal age + fetal nuchal translucency + maternal-blood analysis at 11-14 weeks (85%). The lack of efficiency of screening sometimes results in 'false-positive testing', resulting in the unnecessary use of invasive testing for some women with non-trisomy-21 fetuses; false-positive frequency from screening is around 1-5%.

Kypros Nicolaides and colleagues from the Harris Birthright Research Centre for Fetal Medicine, Kings College Hospital School of Medicine, London, UK, did an ultrasound examination of the fetal profile in 701 fetuses at 11-14 weeks' pregnancy. This was done immediately before karyotyping for a possible chromosomal abnormality detected by maternal age and fetal nuchal translucency screening. The presence or absence of a nasal bone was noted.

The nasal bone was absent in 43 of 59 (73%) trisomy 21 fetuses and in three of 603 (0.5%) chromosomally normal fetuses. Fetuses without a nasal bone were estimated to be at around 150 times more likely of having trisomy 21 compared with normal fetuses.

Kypros Nicolaides comments: " Our study suggests that examination of the fetal profile at 11-14 weeks could have major beneficial implications in screening for trisomy 21 by maternal age and fetal nuchal translucency. The increase in sensitivity from 75% to 85% could be achieved with a simultaneous reduction in the false-positive rate from 5% to about 1% and a consequent five-fold reduction in the rate of miscarriage from invasive testing and the cost of invasive testing and analysis."

In an accompanying Commentary (p 1658), Howard Cuckle from the University of Leeds, UK, concludes: "First-trimester screening has obvious benefits over second-trimester screening other than efficiency. These advantages include, for some, an early diagnosis with consequent safer and less traumatic therapeutic abortion, and, for most, an earlier reassuranceso where does this leave the UK Department of Health's forthcoming National Down's Syndrome Screening Programme? Despite a large body of published data on first-trimester markers and growing clinical experience with nuchal translucency, it is being planned as a second- trimester service. The findings on the nasal bone published today demand an urgent rethink of this policy."

Contact: Professor Kypros Nicolaides, Harris Birthright Research Centre for Fetal Medicine, King's College Hospital Medical School, Denmark Hill, London SE5 8RX, UK; T) +44 (0)20 7346 3040; E) fmf@fetalmedicine.com

Professor Howard S Cuckle, Reproductive Epidemiology, Centre for Reproductive Growth and Development, 26 Clarendon Road, Leeds LS2 9NZ, UK; T) +44 (0)113 233 6771; F) +44 (0)113 233 6774; E) h.s.cuckle@leeds.ac.uk

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