• BJOG · Jun 2002

    Multicenter Study

    Combined ultrasound and biochemical screening for Down's syndrome in the first trimester: a Scottish multicentre study.

    • Jennifer A Crossley, David A Aitken, Alan D Cameron, Elizabeth McBride, and J Michael Connor.
    • Institute of Medical Genetics, Yorkhill NHS Trust, Glasgow, UK.
    • BJOG. 2002 Jun 1; 109 (6): 667-76.

    ObjectiveTo evaluate the use of ultrasound measurements of fetal nuchal translucency (NT) obtained in a routine antenatal clinic setting in combination with appropriate biochemical markers as a first trimester screening test for Down's Syndrome.DesignMulticentre observational study.SettingFifteen Scottish maternity units.PopulationPregnant women (n = 17,229) attending routine antenatal clinics at 10-14 weeks of gestation.MethodsNT measurements were attempted in all women along with the measurement of maternal serum free beta human chorionic gonadotrophin (F beta hCG) and pregnancy-associated plasma protein-A (PAPP-A). All results were converted to multiples of the appropriate gestational median (MoM) and using a statistical model the risk of an affected pregnancy was derived. No results were given to participating women but all were offered routine second trimester biochemical screening. All cases of Down's Syndrome within the study group were ascertained and the detection rate for each marker was estimated.Main Outcome MeasuresSuccess rate of obtaining NT measurements and overall effectiveness of ultrasound and biochemical markers individually and in combination for the detection of Down's Syndrome pregnancies.ResultsNT measurements were obtained in 72.9% of women and blood samples in 98.4%. Forty-five cases of Down's Syndrome were ascertained (2.6/1,000). NT measurements were obtained in 37 cases (median NT 1.65 MoM), blood samples in 42 cases and both NT and blood in 34 cases. In combination with the a priori maternal age risk, observed detection rates at a 5% false positive rate were 20/37 (54%) for NT, 23/42 (55%) for F beta hCG and PAPP-A and 28/34 (82%) for a combination of NT, F beta hCG and PAPP-A using a cutoff risk of 1:250. The effect of failing to obtain NT measurements in all cases reduces the overall detection rate to 62% (i.e. 28/45) if the entire series of affected pregnancies within the study group is considered.ConclusionsNT in combination with appropriate serum markers has the potential to detect over 80% of Down's Syndrome fetuses in early pregnancy. However, NT measurement is highly operator-dependent. It requires training, external quality control and adequate time to allow accurate measurement, otherwise suboptimal performance will result.

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