AGE-ADJUSTED ULTRASOUND RISK ASSESSMENT FOR FETAL DOWNS-SYNDROME DURING THE 2ND-TRIMESTER - DESCRIPTION OF THE METHOD AND ANALYSIS OF 142 CASES

Objective To describe and test a method of individual risk assessment for fetal Down's syndrome based on maternal age and second-trimester u ltrasound findings. Design A case-control study of 142 fetuses with Do wn's syndrome was compared with 930 control fetuses with normal karyot ype. All patients underwent second-trimester ultrasound at a single in stitution with a standardized ultrasound protocol without knowledge of fetal karyotype. Age adjusted ultrasound risk assessment (AAURA) for Down's syndrome was performed by multiplying the a priori risk, based on maternal age, wish likelihood ratios resulting from the presence or absence of specific ultrasound findings for each patient. Individual ultrasound findings were assigned likelihood ratios (LR) as follows: s tructural abnormality (LR 25), nuchal thickening (LR 18.6), echogenic bowel (LR 5.5), shortened humerus (LR 2.5), shortened femur (LR 2.2), echogenic intracardiac focus (LR 2), and renal pyelectasis (LR 1.6). A normal ultrasound was assigned a LR of 0.4. Results One ol more ultra sound markers were identified in 68.3% (97) of fetuses with Down's syn drome compared to 12.5% of fetuses with normal karyotype, Among fetuse s with positive ultrasound, 31% of those with Down's syndrome and 80% of those with normal karyotype showed a single non-structural finding. Using AAURA and a threshold of 1 :200, 74% (105 of 142) of fetuses wi th Down's syndrome were identified including 61.5% (24 of 39) from wom en aged less than 35 years, 67.2% (45 of 67) from women aged 35-39 yea rs inclusively, and 100% (36 of 36) from women aged 40 years or older. AAURA of 930 fetuses with normal karyotype showed and overall false-p ositive rate of 14.7%, including 4% (21 of 519) from women aged less t han 35 years, 12.5% (42 of 337) from women aged 35-39 years inclusivel y, and 100% from women aged 40 years or older. Conclusions AAURA permi ts improved individual counselling regarding the risk of fetal Down's syndrome following a second-trimester sonogram. For low-risk women und er age 35 years, ultrasound assessment can identify over half of the a ffected fetuses with Down's syndrome with an acceptable false-positive rate (4%). For women aged 35-39 years, a normal ultrasound can substa ntially reduce the risk of unnecessary amniocentesis (12.5% from 100%) but will also miss approximately one-third of affected fetuses. Bioch emical screening of maternal serum is also suggested for this group. B ased oz their high a priori risk, women aged 40 years or more should c onsider genetic amniocentesis regardless of a normal ultrasound.