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A preliminary prospective evaluation of biochemical markers for fetal trisomies
POSTER ABSTRACTS
phosphorylation was accompanied by an increase in the affinity of PDE for CaM and Ca2.. Analysis of the complex regulatory properties of PDE has led to the suggestion that fluxes of cAMP and Ca2÷ during cell activation are closely coupled, and that PDE plays a key role in the signalcoupling phenomenon. (Supported by the Heart and Stroke Foundation of Saskatchewan).
Comparison of the predictive performance of biochemical markers and mean arterial pressure f o r p r e - e c l a m p s i a Mass~, J., Forest, J-C., Moutquin, J.M., Marcoux, S., Brideau, N.A. and B61anger, M. D~partements de Biochimie, Obst6trique-Gyn6cologie, M6Aecine Sociale et Pr6ventive, Facult6 de M6Aecine, Universit6 Laval, Cit6 Universitaire, Qu6bec, G1K 7P4, Canada We prospectively evaluated the predictive performance of several potential biochemical markers of pre-eclampsia readily available in the clinical setting. We measured these markers (n = 27) on three occasions during pregnancy (814, 15-24, 25-34 weeks of gestation) in 1,366 nulliparous women. After delivery, women were classified into three categories: normal, pre-eclampsia, transient hypertension. The predictive performance of the tests, either used alone or in combination (stepwise multiple logistic regression), was assessed and compared to that of the mean arterial pressure. Pre-eelampsia developed in 109 of the pregnant women. Significant difference in the mean value of the tests between the normal and pre-eclamptic women, after Bonferroni correction, was only observed for three biochemical variables: progesterone, mean corpuscular volume and haptoglobin. Multiple logistic regression models were developed using the biochemical and clinical variables. Their predictive performance was compared with that of the mean arterial pressure using a cut-off value at a given specificity of 80%. The sensitivity, positive and negative predictive values for mean arterial pressure were respectively 46.6%, 23.5%, 92.0% at the second visit and 52.5%, 26.0% and 92.6% at the third visit. A logistic model for the second visit that included the mean arterial pressureshowed a sensitivity of 57.1%, a positive predictive value of 26.9% and a negative predictive value of 93.7%. For the model developed for the third visit, the corresponding values were 66.1%, 30.0% and 94.6%. Combination of the tests in a stepwise multiple regression model offered little advantages over the single use of mean arterial pressure.
CLINICALBIOCHEMISTRY,VOLUME 26, APRIL 1993
-ffq
A preliminary prospective evaluation of
b i o c h e m i c a l m a r k e r s f o r fetal t r i s o m i e s Forest, J-C., Mass6, J., Rousseau, F., Moutquin, J.M., Brideau, N.A., B61anger, M. and Bastide, A. D6partements de Biochimie et Obst~trique-Gyn6cologie, Facult~ de M6Aecine, Universit6 Laval, Cit6 Universitaire, Qu6bec, G1K 7P4, Canada We are currently measuring three markers (alphafetoprotein, estriol, choriogonadotropin) in pregnant women of all ages to determine their value in screening for fetal trisomies. Our study population consists of 9,000 women who attended the perinatal clinics of six hospitals and had signed a consent form. A blood specimen was obtained between 10 and 19 weeks gestation and the serum was stored at -20°C. Alphafetoprotein and choriogonadotropin were rrleasured with Enzymun-Test R enzymeimmunoassays (Boehringer Mannheim Canada). Unconjugated estriol was assayed with an ultrasensitive radioimmunometric assay (DSL Canada). Random samples from unaffected pregnancies were used to determine the distribution of results at each week. The maternal agespecific risk (a priori odds) was determined using published results (Br J Obstet G~aecol 1987; 94:387-402). The woman's multiples of median for each marker were used to calculate a likelihood ratio using the distribution parameters derived from our population. The posteriori odds were obtained by multiplying the a priori odds by the likelihood ratios. The results were considered positive if the calculated risk was equal to or higher than that of women of 35 years. Thirteen cases of singleton trisomy 21 occurred. Using age in combination with the three biochemical markers, 53.8% of these cases have been detected. No cases that happened in women 35 years or older would have been missed. These results confirm the sensitivity published by other groups. The application of this screening strategy in the older women does not appear to affect detection of a trisomic foetus while obviating a number of unnecessary amniocenteses. II
METHOD AND INSTRUMENT EVALUATION
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A t i m e - s t u d y a n a l y s i s to e v a l u a t e a l b u m i n c a r b a m y l a t i o n in vitro Balion, C.M., Caines, P.S.M., Draisey, T.F. and Thibert, g.J. Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, N9B 3P4, Canada
135
phosphorylation was accompanied by an increase in the affinity of PDE for CaM and Ca2.. Analysis of the complex regulatory properties of PDE has led to the suggestion that fluxes of cAMP and Ca2÷ during cell activation are closely coupled, and that PDE plays a key role in the signalcoupling phenomenon. (Supported by the Heart and Stroke Foundation of Saskatchewan).
Comparison of the predictive performance of biochemical markers and mean arterial pressure f o r p r e - e c l a m p s i a Mass~, J., Forest, J-C., Moutquin, J.M., Marcoux, S., Brideau, N.A. and B61anger, M. D~partements de Biochimie, Obst6trique-Gyn6cologie, M6Aecine Sociale et Pr6ventive, Facult6 de M6Aecine, Universit6 Laval, Cit6 Universitaire, Qu6bec, G1K 7P4, Canada We prospectively evaluated the predictive performance of several potential biochemical markers of pre-eclampsia readily available in the clinical setting. We measured these markers (n = 27) on three occasions during pregnancy (814, 15-24, 25-34 weeks of gestation) in 1,366 nulliparous women. After delivery, women were classified into three categories: normal, pre-eclampsia, transient hypertension. The predictive performance of the tests, either used alone or in combination (stepwise multiple logistic regression), was assessed and compared to that of the mean arterial pressure. Pre-eelampsia developed in 109 of the pregnant women. Significant difference in the mean value of the tests between the normal and pre-eclamptic women, after Bonferroni correction, was only observed for three biochemical variables: progesterone, mean corpuscular volume and haptoglobin. Multiple logistic regression models were developed using the biochemical and clinical variables. Their predictive performance was compared with that of the mean arterial pressure using a cut-off value at a given specificity of 80%. The sensitivity, positive and negative predictive values for mean arterial pressure were respectively 46.6%, 23.5%, 92.0% at the second visit and 52.5%, 26.0% and 92.6% at the third visit. A logistic model for the second visit that included the mean arterial pressureshowed a sensitivity of 57.1%, a positive predictive value of 26.9% and a negative predictive value of 93.7%. For the model developed for the third visit, the corresponding values were 66.1%, 30.0% and 94.6%. Combination of the tests in a stepwise multiple regression model offered little advantages over the single use of mean arterial pressure.
CLINICALBIOCHEMISTRY,VOLUME 26, APRIL 1993
-ffq
A preliminary prospective evaluation of
b i o c h e m i c a l m a r k e r s f o r fetal t r i s o m i e s Forest, J-C., Mass6, J., Rousseau, F., Moutquin, J.M., Brideau, N.A., B61anger, M. and Bastide, A. D6partements de Biochimie et Obst~trique-Gyn6cologie, Facult~ de M6Aecine, Universit6 Laval, Cit6 Universitaire, Qu6bec, G1K 7P4, Canada We are currently measuring three markers (alphafetoprotein, estriol, choriogonadotropin) in pregnant women of all ages to determine their value in screening for fetal trisomies. Our study population consists of 9,000 women who attended the perinatal clinics of six hospitals and had signed a consent form. A blood specimen was obtained between 10 and 19 weeks gestation and the serum was stored at -20°C. Alphafetoprotein and choriogonadotropin were rrleasured with Enzymun-Test R enzymeimmunoassays (Boehringer Mannheim Canada). Unconjugated estriol was assayed with an ultrasensitive radioimmunometric assay (DSL Canada). Random samples from unaffected pregnancies were used to determine the distribution of results at each week. The maternal agespecific risk (a priori odds) was determined using published results (Br J Obstet G~aecol 1987; 94:387-402). The woman's multiples of median for each marker were used to calculate a likelihood ratio using the distribution parameters derived from our population. The posteriori odds were obtained by multiplying the a priori odds by the likelihood ratios. The results were considered positive if the calculated risk was equal to or higher than that of women of 35 years. Thirteen cases of singleton trisomy 21 occurred. Using age in combination with the three biochemical markers, 53.8% of these cases have been detected. No cases that happened in women 35 years or older would have been missed. These results confirm the sensitivity published by other groups. The application of this screening strategy in the older women does not appear to affect detection of a trisomic foetus while obviating a number of unnecessary amniocenteses. II
METHOD AND INSTRUMENT EVALUATION
[]
A t i m e - s t u d y a n a l y s i s to e v a l u a t e a l b u m i n c a r b a m y l a t i o n in vitro Balion, C.M., Caines, P.S.M., Draisey, T.F. and Thibert, g.J. Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, N9B 3P4, Canada
135