Age-adjusted ultrasound risk assessment for fetal Down's syndrome during the second 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 ultrasound findings.

DESIGN: A case-control study of 142 fetuses with Down's syndrome was compared with 930 control fetuses with normal karyotype. All patients underwent second-trimester ultrasound at a single institution 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, with 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: structural 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 or more ultrasound markers were identified in 68.3% (97) of fetuses with Down's syndrome compared to 12.5% of fetuses with normal karyotype. Among fetuses 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 with Down's syndrome were identified, including 61.5% (24 of 39) from women aged less than 35 years, 67.2% (45 of 67) from women aged 35-39 years inclusively, and 100% (36 of 36) from women aged 40 years or older. AAURA of 930 fetuses with normal karyotype showed an overall false-positive rate of 14.7%, including 4% (21 of 519) from women aged less than 35 years, 12.5% (42 of 337) from women aged 35-39 years inclusively, and 100% from women aged 40 years or older.

CONCLUSIONS: AAURA permits improved individual counselling regarding the risk of fetal Down's syndrome following a second-trimester sonogram. For low-risk women under age 35 years, ultrasound assessment can identify over half of the affected fetuses with Down's syndrome with an acceptable false-positive rate (4%). For women aged 35-39 years, a normal ultrasound can substantially reduce the risk of unnecessary amniocentesis (12.5% from 100%) but will also miss approximately one-third of affected fetuses. Biochemical screening of maternal serum is also suggested for this group. Based on their high a priori risk, women aged 40 years or more should consider genetic amniocentesis regardless of a normal ultrasound.