Improved parameters for risk estimation in Down's syndrome screening

Cuckle, Howard

doi:10.1002/pd.1970151111

Cited by 67 publications

(40 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6.1 statistical program. Briefly, using the observed population parameters for ADAM 12 and those for AFP and free β-hCG from (Cuckle, 1995), a series of random MoM were selected from the distributions in unaffected and affected pregnancies. These values were then used to calculate likelihood ratios for the combinations.…”

Section: Methodsmentioning

confidence: 99%

ADAM 12 as a second‐trimester maternal serum marker in screening for Down syndrome

et al. 2007

View full text Add to dashboard Cite

Background ADAM 12 is a placenta-derived glycoprotein that is involved in growth and differentiation. The maternal serum concentration of ADAM 12 is a potential first-trimester maternal serum marker of Down syndrome (DS). Here we examine the potential of ADAM 12 as a second-trimester maternal serum marker of DS. Materials and MethodsThe concentration of ADAM 12 was determined in gestational week 14-19 in 88 DS pregnancies and 341 matched control pregnancies. Medians of normal pregnancies were established by polynomial regression and the distribution of log 10 MoM ADAM 12 values in DS pregnancies and controls determined. Correlations with alpha-fetoprotein (AFP) and free β-human chorionic gonadotrophin (free β-hCG) were established and used to model the performance of maternal serum screening with ADAM 12 in combination with other second-trimester serum markers. ResultsThe ADAM 12 maternal serum concentration was significantly increased with a median MoM of 1.85 and a mean log 10 MoM (SD) of 0.268 (0.2678) compared to a mean log 10 MoM (SD) of 0.013 (0.4318) in controls. ADAM 12 correlated with maternal weight and ethnicity (with the serum concentration increased in Afro-Caribbeans), but neither with maternal age nor gestational age, and only marginally with AFP (r(DS) = 0.078, r(controls) = 0.093) and free β-hCG (r(DS) = 0.073, r(controls) = 0.144. The increase in detection rate-for a false positive rate of 5%-by adding ADAM 12 to the double test (AFP + free β-hCG) was 4%, similar to that of adding uE3 to the double test.Conclusion ADAM 12 is an efficient second-trimester marker for DS. Further studies should be conducted to determine whether it may be a useful additonal or alternative marker to those currently used in the secondtrimester.

show abstract

Section: Methodsmentioning

confidence: 99%

ADAM 12 as a second‐trimester maternal serum marker in screening for Down syndrome

et al. 2007

View full text Add to dashboard Cite

show abstract

“…This methodology is based on the observed variance of measurements in the unaffected population. 11 Parameters for NT measurements are also taken from the Serum, Urine and Ultrasound Screening Study (SURUSS) study (logarithmic mean, standard deviation of 0.2922, 0.2313 and 0.000, 0.1329 in …”

Section: Resultsmentioning

confidence: 99%

“…9 The parameters describing these distributions were taken from the literature, 10 but the standard deviations and correlation coefficients were modified, on the basis of the distribution of unaffected pregnancies observed in the present study, using a published methodology. 11 These modified parameters allow the calculation of likelihood ratios specific to the characteristics of dried blood spots and fresh sera. These likelihood ratios were then multiplied by the ageassociated risk to generate an individual Down syndrome risk.…”

Section: Modeling Down Syndrome Screening Performancementioning

confidence: 99%

Estimating first-trimester combined screening performance for Down syndrome in dried blood spots versus fresh sera

Palomaki

Neveux

Knight

et al. 2007

Genetics in Medicine

View full text Add to dashboard Cite

Purpose: The study purpose was to examine the consequences of using dried blood spots rather than fresh sera in first-trimester Down syndrome screening. Methods: We collected and compared human chorionic gonadotropin and pregnancy-associated plasma protein-A results from clients providing dried blood spots (Cohort 1) and from other clients providing fresh sera (Cohort 2). Inclusion and exclusion criteria aimed at ensuring the two cohorts were similar. Results: The average concentrations of human chorionic gonadotropin and pregnancy-associated plasma protein-A are significantly different for the two cohorts. When the results are converted to multiples of the median and weight-adjusted, the variances for human chorionic gonadotropin and pregnancy-associated plasma protein-A in Cohort 1 are greater by 25% and 14%, respectively. Modeling the impact of this increased variance shows that Down syndrome detection is expected to be lower in Cohort 1 (83% vs. 85% at a 5% false-positive rate) or the false-positive rate is expected to be higher (3.9% vs. 3.0% at an 80% detection rate). Conclusions: This study of two closely matched cohorts provides indirect evidence that dried blood spots will result in slightly lower Down syndrome screening performance. Studies should be undertaken to confirm and further quantify differences in assigned risks by a direct comparison using matched serum and dried blood spots collected from the same Virtually all prenatal screening protocols for Down syndrome use measurements made in maternal serum, sometimes with the inclusion of first-trimester ultrasound determination of nuchal translucency (NT) thickness. In a few reports, these serum markers have been measured by using dried blood spots rather than fresh sera. 1-4 Collection of blood spots is less invasive than drawing blood and is sometimes more convenient for office personnel and the patient because referral to a phlebotomy station is not required. Also, some analytes can be more stable in blood spots than in whole blood or serum when shipping and handling occurs under conditions such as elevated temperature (e.g., the free ␤-subunit of human chorionic gonadotropin [hCG]). 5 There is limited information concerning possible differences introduced by the choice of sample type. To our knowledge, no study has made a direct (matched) comparison of the screening performance of maternal Down syndrome markers using measurements obtained from a dried blood spot and maternal serum collected from the same women. Matched studies have been undertaken for other analytes, such as newborn screening markers 6 and prostate-specific antigen. 7 Although not as powerful as a matched study, a cohort study design can yield information on the relative performance of the two sample types when results are compared from women screened who provided blood spots with those screened who provided maternal serum. The current study was undertaken to determine whether any meaningful differences attributable to collection method are observed between two similar cohorts o...

show abstract

“…Correlation coefficients between log 10 -transformed MoMs were calculated after excluding values Ͼ3 SD from the mean (20 ). For affected pregnancies, it was assumed that established differences in the variances and covariances between affected and unaffected pregnancies could be directly added to the values obtained for the unaffected pregnancies (21 ). With the statistical parameter sets for each laboratory, we simulated the results for sets of affected and unaffected pregnancies tested in the 2 laboratories.…”

Section: Methodsmentioning

confidence: 99%

“…SDs of log 10 MoMs were estimated from the median absolute deviation function in S-Plus, which is considered to provide a robust estimate by minimizing the effect of outliers. Correlation coefficients between log 10 -transformed MoMs were calculated after excluding values Ͼ3 SD from the mean (20 ). For affected pregnancies, it was assumed that established differences in the variances and covariances between affected and unaffected pregnancies could be directly added to the values obtained for the unaffected pregnancies (21 ).…”

Section: Methodsmentioning

confidence: 99%

Reproducibility of Risk Figures in 2nd-Trimester Maternal Serum Screening for Down Syndrome: Comparison of 2 Laboratories

et al. 2006

View full text Add to dashboard Cite

Background: Analytical error affects 2nd-trimester maternal serum screening for Down syndrome risk estimation. We analyzed the between-laboratory reproducibility of risk estimates from 2 laboratories. Methods: Laboratory 1 used Bayer ACS180 immunoassays for ␣-fetoprotein (AFP) and human chorionic gonadotropin (hCG), Diagnostic Systems Laboratories (DSL) RIA for unconjugated estriol (uE3), and DSL enzyme immunoassay for inhibin-A (INH-A). Laboratory 2 used Beckman immunoassays for AFP, hCG, and uE3, and DSL enzyme immunoassay for INH-A. Analyte medians were separately established for each laboratory. We used the same computational algorithm for all risk calculations, and we used Monte Carlo methods for computer modeling.Results: For 462 samples tested, risk figures from the 2 laboratories differed >2-fold for 44.7%, >5-fold for 7.1%, and >10-fold for 1.7%. Between-laboratory differences in analytes were greatest for uE3 and INH-A. The screen-positive rates were 9.3% for laboratory 1 and 11.5% for laboratory 2, with a significant difference in the patients identified as screen-positive vs screennegative (McNemar test, P <0.001). Computer modeling confirmed the large between-laboratory risk differences. Conclusion: Differences in performance of assays and laboratory procedures can have a large effect on patientspecific risks. Screening laboratories should minimize

show abstract

Improved parameters for risk estimation in Down's syndrome screening

Cited by 67 publications

References 23 publications

ADAM 12 as a second‐trimester maternal serum marker in screening for Down syndrome

ADAM 12 as a second‐trimester maternal serum marker in screening for Down syndrome

Estimating first-trimester combined screening performance for Down syndrome in dried blood spots versus fresh sera

Reproducibility of Risk Figures in 2nd-Trimester Maternal Serum Screening for Down Syndrome: Comparison of 2 Laboratories

Contact Info

Product

Resources

About