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.

Urinary gonadotropin peptide levels in preeclamptic and normotensive pregnant women. Results from a pilot case-control study.

OBJECTIVE: Elevated maternal serum human chorionic gonadotropin (hCG) is an important marker of Down syndrome. Notably, women with unexplained elevated serum hCG in the second trimester experience a 2- to 5-fold increase risk of preeclampsia. Urinary gonadotropin peptide (UGP), thought to be a metabolite of hCG that is excreted into urine, has recently been shown to be elevated in Down syndrome pregnancies. We sought to examine urinary UGP levels in preeclamptic and normotensive pregnant women. METHODS: We measured UGP levels in urine collected during the third trimester from 18 women with preeclampsia and 20 normotensive controls. UGP levels were determined using enzyme immunoassay and were corrected for dilution using urinary creatinine. Statistical significance testing was done using the Wilcoxon-Mann-Whitney Rank Sum test and Student t test statistics. RESULTS: There was a statistically significant elevation in urinary UGP levels among preeclamptic cases as compared to normotensive control subjects (p = 0.013). Mean urinary UGP levels were 80.7 and 31.3 pmol/mg creatinine for preeclampsia cases and controls, respectively. Elevations in UGP levels among women with preeclampsia as compared with normotensive control subjects persisted after adjustments for possible confounding factors. CONCLUSION: These early findings suggest that elevations in urinary UGP may be a risk marker for preeclampsia. Prospective studies should further clarify the relation between urinary UGP levels and adverse pregnancy outcomes. These results are consistent with results suggesting a role of placental hypoperfusion in the etiology of preeclampsia.

Eugenic considerations in the theory and practice of genetic counseling.

Is genetic counseling a form of eugenics? To some extent, the answer depends upon how the terms "eugenics" and "genetic counseling" are defined. This paper reviews the eugenic implications of four models of genetic counseling. The complexities of slapping the eugenic label on genetic counseling are illustrated with three cases drawn from clinical practice. However, even though genetic counseling is not always a eugenic activity, genetic counselors work in a medical/financial setting that has the net eugenic effect of, and profits from, reducing the number of people with genetic disorders.