UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10-14 weeks of gestation. Fetal Medicine Foundation First Trimester Screening Group.
BACKGROUND
Prenatal diagnosis of trisomy 21 currently relies on assessment of risk followed by invasive testing in the 5% of pregnancies at the highest estimated risk. Selection of the high-risk group by a combination of maternal age and second-trimester maternal serum biochemistry gives a detection rate of about 60%. We investigated assessment of risk by a combination of maternal age and fetal nuchal-translucency thickness, measured by ultrasonography at 10-14 weeks of gestation.


METHODS
The risk of trisomy 21 was estimated for 96127 women of median age 31 years (range 14-49) with singleton pregnancies. Ultrasonography was done by 306 appropriately trained sonographers in 22 centres. Risk of trisomy 21 was calculated from the maternal age and gestational-age-related prevalence, multiplied by a likelihood ratio depending on the deviation from normal in nuchal-translucency thickness for crown-rump length. The distribution of risks was investigated and the sensitivity of a cut-off risk of 1 in 300 was calculated. Phenotype was assessed by fetal karyotyping or clinical examination of liveborn infants.


RESULTS
The estimated trisomy-21 risk, from maternal age and fetal nuchal-translucency thickness, was 1 in 300 or higher in 7907 (8.3%) of 95476 normal pregnancies, 268 (82-2%) of 326 with trisomy 21, and 253 (77.9%) of 325 with other chromosomal defects. The 5% of the study population with the highest estimated risk included 77% of trisomy-21 cases.


CONCLUSIONS
Selection of the high-risk group for invasive testing by this method allows the detection of about 80% of affected pregnancies. However, even this method of risk assessment requires about 30 invasive tests for identification of one affected fetus.
Snijders
R J
RJ
Harris Birthright Research Centre for Fetal Medicine, Department of Obstetrics and Gynaecology, King's College School of Medicine and Dentistry, London, UK.
Noble
P
P
Sebire
N
N
Souka
A
A
Nicolaides
K H
KH
D000293:Adolescent; D000328:Adult; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D018568:Crown-Rump Length; D004314:Down Syndrome / Q000175:diagnosis* / Q000000981:diagnostic imaging; D005260:Female; D005333:Fetus / Q000033:anatomy & histology*; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D007621:Karyotyping; D016013:Likelihood Functions; D008423:Maternal Age; D008875:Middle Aged; D009333:Neck / Q000000981:diagnostic imaging / Q000196:embryology*; D010641:Phenotype; D011237:Predictive Value of Tests; D011247:Pregnancy; D011256:Pregnancy Outcome; D037841:Pregnant People; D015995:Prevalence; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016216:Ultrasonography, Prenatal; D006113:United Kingdom