Precise gaussian distribution functions of maternal serum ⍺-fetoprotein and free β-subunit of human chorionic gonadotropin for trisomy 21 screening: Improved accuracy for patient counseling - 11/09/11
Abstract |
OBJECTIVE: Gaussian equation curves are used to generate baseline curves against which a priori maternal age Down syndrome risks are adjusted to develop likelihood ratios for individual patients. We sought to evaluate the accuracy of these calculations, minimize the affects of outliers, and to make improvements.
STUDY DESIGN: Gaussian distribution functions were used to investigate the best model for ⍺-fetoprotein and free β-human chorionic gonadotropin multiples of the median with use of nonlinear regressions. Parameters from distribution functions can be used to compute a more precise likelihood ratio for the decision logic for trisomy 21. A total of 58,297 normal cases and 348 cases of trisomy 21 were computed.
RESULTS: Log normal distribution functions generated by nonlinear regression produced excellent but exaggerated goodness of fit R 2 to the frequency distributions of the data. For normal cases values were as follows (in mean, SD, and R 2, respectively): log ⍺-fetoprotein –0.07199, 0.15681, and 0.9970; log β-human chorionic gonadotropin –0.15203, 0.24284, and 0.9987. For trisomy 21 cases the values were (in mean, SD, and R 2, respectively) for log ⍺-fetoprotein –0.19303, 0.15802, and 0.9828 and for log β-human chorionic gonadotropin 0.19996, 0.29760, and 0.9669. Distributions reconstructed with use of statistical means and SDs generated goodness of fit R 2 from 0.585 to 0.914. Use of means and SDs derived from distribution functions increased the R 2 to 0.855 and 0.999. The change in the model produces, at a 5% false-positive rate, a sensitivity of 57.18% (199/348). A 1 in 113 cutoff point risk is obtained and is tighter than the 1 in 251 without the distribution functions, as versus 1 in 270 by age calculations alone.
CONCLUSIONS: Our data suggest that (1) normality of log transforms of ⍺-fetoprotein and normality of log transforms of β-human chorionic gonadotropin are reasonable models, (2) distribution functions can minimize the effect of outliers, which produces more realistic risk estimates, and (3) the effect of distribution functions versus standard mean and SDs cannot automatically be extrapolated to other parameters, which must be tested individually. (Am J Obstet Gynecol 1997;177:882-6.)
Le texte complet de cet article est disponible en PDF.Keywords : Gaussian distribution, trisomy 21 screening, ⍺-fetoprotein, human chorionic gonadotropin
Plan
 | From the Departments of Obstetrics and Gynecology,aMolecular Medicine and Genetics,bPathology,cWayne State University, and the Department of Clinical Biochemistry, Oldchurch Hospital.d |
| Reprint requests: Mark I. Evans, MD, Division of Reproductive Genetics, Department of Obstetrics and Gynecology, Hutzel Hospital/Wayne State University, 4707 St. Antoine, Detroit MI 48201. |
 | 0002-9378/97 $5.00 + 0 6/6/84563 |
Vol 177 - N° 4
P. 882-886 - octobre 1997 Retour au numéro
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