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Cost-effectiveness of various strategies used for the evaluation of pregnancies complicated by elevated maternal serum alpha-fetoprotein (MSAFP)
$88
SPO Abstracts
J a n u a r y 1997 A m J Obstet Gynecol
285
COST-EFFECTIVENESS OF VARIOUS STRATEGIES USED FOR THE EVALUATION OF PREGNANCIES COMPLICATED BY ELEVATED MATERNAL SERUM ALPHA-FETOPROTEIN (MSAFP). A. Nadel, M. Natron, L. Wilkins-Haug. Dept. Ob/Gyn, Brigham and Women's Hospital, Boston, MA. OBJECTIVE: We compared the cost-effectiveness of 3 protocols at two different cut-otis of MSAFP, 2.0 and 2.5 muhiples of the median (MOM) : 1) "targeted " ultrasound 2) amniocentesis tor alpha~fetoprotein and acetylcholinesterase, and 3) amniocentesis for alpba-fetoprotein, acetylcholinesterase and fetal kmyotype. STUDY DESIGN: Data fi'om our own institution and published reports were used to deternfine the prevalence of the relevant anomalies, the sensitivity and specificity of MSAFP, and the sensitivity, specificity, cost, and safety of targeted ultrasound and amniocentesis. RESULTS: In a hypothetical cohort of 100,000 singleton pregnancies, a strategy of targeted ultrasound for MSAFP -->2.0 MOM detects 94 abnormal fetuses (90 structural abnormalities and 4 autosomal aneuploidies) without iatrogenic fetal loss at a cost of $5,400 per anomalous fetus detected. A strategy of anmiocentesis with karyotype for MSAFP ->2.5 MOM detects only 11 additional abnormal fetuses (87 structural abnormalities, 10 autosomal and 8 sex chromosomal abnormalities) with 9 iatrogenic fetal losses at a cost of $11,500 per anomalous flatus detected. CONCLUSIONS: A policy of offering targeted ultrasound to women whose MSAFP is ->2.0 MOM is more cost-effective than one which offers amniocentesis to women whose MSAFP is ->2.5 MOM.
287
ANEUPLOIDY: IS CYTOGENETIC EVALUATION INDICATED FOR UNEXPLAINED ELEVATED MATERNAL SERUM ALPHA-FETOPROTEIN? Hiett AK, Brown HL, Callaghan C~P, Golichowski AM, Heerma N A ~. Dept. Ob/Gyn, Indiana Univ, Indianapolis, IN. OBJECTIVE: The purpose of this study was to examine the value of fetal karyotyping in pregnancies complicated by unexplained elevated maternal serum alpba-ti~toprotein. METHODS: 58,162 obstetrical ultrasounds performed at Indiana University Prenatal Diagnostic Center from July 1988 to March 1996 for various indications were reviewed using a computerized database. Fetuses with maternal serum alpha-fetoprotein MOM -->2.5 and normal extensive ultrasounds were identified. Maternal demograpbic data and fetal karyotype were obtained. Statistical analysis was performed using the Chi square test. RESULTS: 790 patients received ultrasounds for evaluation of elevated maternal serum alpha-fetoprotein. Of the 595 patients with normal scans, 189 (31.8%) underwent anmiocentesis and cytogenetic evaluation. Two chromosomal abnormalities were detected (1.1%) including an inversion in the long arm of the number 9 chromosome and a balanced translocadon, 46XX,t(7;8),(q34;q23.1). This was not statistically significant (p - 0.317) compared to the theoretical risk of chromosomal anomalies in this sample population based solely on maternal age (0.3%). CONCLUSION: The prevalence of karyotypic abnormalities in our patients with unexplained elevated maternal serum alpha-fetoprotein values and a normal targeted ultrasound examination was not significantly elevated. Of the abnormalities detected, none were life threatening or associated with significant perinatal morbidity. Our results suggest that routine kap/otype analysis in this group of patients is of limited value.
286
MATERNAL SERUM ANALYTE LEVELS IN FETAL DOWN SYNDROME PREGNANCIES DUE T O TRANSLOCATIONS. DNSallerJr,,1jACanick2X LHKellner 3x , NCRose 4,JGarza ix , CAFrench ix , RAMooney 1x. 1Univ of Rochester, Strong Mere Hos~, Rochester, NY; 2Brown Univ, Women & Infants Hosp Providence, RI; Albert Einstein Coll of Med, Montefiore Med Center, Bronx, NY; 4Unlv of PA, Phila, PA OBJECTIVE: To determine whether pregnancies affected by fetal Down syndrome (DS) due to Robertsonian translocations (RT) are associated with second trimester maternal serum analyte levels different from those associated with fetal trisomy 21 (T21). S T U D Y DESIGN: Pregnancies with DS due to RT were identified through the cytogenetic labs at the participating institutions. Those with maternal serum screening (MSS) values between 15-20 weeks were further studied. RESULTS: Analyte values are in muhiples of the median (MoM).
288
PRECISE BIVARIANT NORMAL DISTRIBUTIONS OF MATERNAL SERUM AFP AND FREE bHCG FOR TRISOMY 21 (T21) BIOCHEMICAL SCREENING. L Chik, ~ K Spencer/MPJohnson, M Ayoub, x E Kfivchenia/ M P Dombrowski, M I E v a n s . Depts. of Ob/Gyn, Molecular Med. & Genetics, and Patbology, WSU, Detroit; Dept. of Clin Biochem, Oldchurch Hosp, Romford, England 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 outliners, and to make intprovements. STUDY DESIGN: Cumulative distribution functions (CDE) were used to investigate the best model for AFP, and free-bHCG MOMs. Within limits, normal distributions would be the preferred choice. Parameters from CDF can be used to compute a more precise likelihood ratio for the decision logic for o'isomy 21. 58,297 cases with 348 T21 were computed using non-linear regressions. RESULTS: Normal distributions using existing curves generated r-values o1 approximately 0.87. Our statistical modifications increase the r 2 to .999 for CDF.
+~
Karyotype
46,XY, t (14;21) 46,XY, t (14;21) 46,XY, t(I 4;21) 46,XX, t(14;21) 46,XY, t (14;21) 46,XY, t(21;21) 46,XX,t(21;21) 46,XY, t(21;21) 46,XY, t(21;21) 46,XX, t(21;21) 46,XX,t(21;21) RT DS Median
28 28 28 31 35 22 28 31 31 32 34 31
16 16 15 15,5 15,6 17,6 15,2 18,1 17,6 16 17,0 16
0.72 1.07 0.62 0.98 0.83 0.68 0.59 0.45 0.53 0.53 1.28 0.68
---0.84 0.71 1.05 1.23 0.63 0.50 0.21 0.44 0.67
1.33 2.18 3.43 3.38 3.56 2.83 2.93 1.51 1.68 10.15 1.21 2.83
1:760 1:500 1:50 1:90 1:14 1:530 1:820 1:50 1:20 1:>2 1:420 1:90
+ + + + + +
Age - maternal age at EDC. Risk - Adjusted second trimester DS Risk Previously published medians (fi-om metaanalysis) for T21 DS are: T21 Median
0.73
0.71
2.04
CONCLUSIONS: These data suggest that DS due to RT is associated with second trimester maternal serum analyte levels similar to those associated with T21 and will be detected in a similar percentage of cases.
Normals T21
log AFP log bHCG log AFP log bHCG
.02793 .01990 - . 15781 .38255
.16807 .26327 .17550 .29977
.9999 .9997 .9989 .9987
The change in the model produces at a 5% false positive rate, a sensitivity" of 57.76% (201 out of 348). A 1 in 243 cutoff point risk is obtained, and is tighter than the 1 in 251 without the CDF, as versus 1 in 270 by age calculations alone. CONCLUSIONS: Our data suggest 1) Normality of log transforms of AFP and bHCG are reasonable models; 2) CDF can minimize the effect of outliners, which produces more realistic risk estimates; 3) The effect of CDF versus standard mean and standard deviations cannot automatically be extrapolated to other parameters which must be tested individually.
SPO Abstracts
J a n u a r y 1997 A m J Obstet Gynecol
285
COST-EFFECTIVENESS OF VARIOUS STRATEGIES USED FOR THE EVALUATION OF PREGNANCIES COMPLICATED BY ELEVATED MATERNAL SERUM ALPHA-FETOPROTEIN (MSAFP). A. Nadel, M. Natron, L. Wilkins-Haug. Dept. Ob/Gyn, Brigham and Women's Hospital, Boston, MA. OBJECTIVE: We compared the cost-effectiveness of 3 protocols at two different cut-otis of MSAFP, 2.0 and 2.5 muhiples of the median (MOM) : 1) "targeted " ultrasound 2) amniocentesis tor alpha~fetoprotein and acetylcholinesterase, and 3) amniocentesis for alpba-fetoprotein, acetylcholinesterase and fetal kmyotype. STUDY DESIGN: Data fi'om our own institution and published reports were used to deternfine the prevalence of the relevant anomalies, the sensitivity and specificity of MSAFP, and the sensitivity, specificity, cost, and safety of targeted ultrasound and amniocentesis. RESULTS: In a hypothetical cohort of 100,000 singleton pregnancies, a strategy of targeted ultrasound for MSAFP -->2.0 MOM detects 94 abnormal fetuses (90 structural abnormalities and 4 autosomal aneuploidies) without iatrogenic fetal loss at a cost of $5,400 per anomalous fetus detected. A strategy of anmiocentesis with karyotype for MSAFP ->2.5 MOM detects only 11 additional abnormal fetuses (87 structural abnormalities, 10 autosomal and 8 sex chromosomal abnormalities) with 9 iatrogenic fetal losses at a cost of $11,500 per anomalous flatus detected. CONCLUSIONS: A policy of offering targeted ultrasound to women whose MSAFP is ->2.0 MOM is more cost-effective than one which offers amniocentesis to women whose MSAFP is ->2.5 MOM.
287
ANEUPLOIDY: IS CYTOGENETIC EVALUATION INDICATED FOR UNEXPLAINED ELEVATED MATERNAL SERUM ALPHA-FETOPROTEIN? Hiett AK, Brown HL, Callaghan C~P, Golichowski AM, Heerma N A ~. Dept. Ob/Gyn, Indiana Univ, Indianapolis, IN. OBJECTIVE: The purpose of this study was to examine the value of fetal karyotyping in pregnancies complicated by unexplained elevated maternal serum alpba-ti~toprotein. METHODS: 58,162 obstetrical ultrasounds performed at Indiana University Prenatal Diagnostic Center from July 1988 to March 1996 for various indications were reviewed using a computerized database. Fetuses with maternal serum alpha-fetoprotein MOM -->2.5 and normal extensive ultrasounds were identified. Maternal demograpbic data and fetal karyotype were obtained. Statistical analysis was performed using the Chi square test. RESULTS: 790 patients received ultrasounds for evaluation of elevated maternal serum alpha-fetoprotein. Of the 595 patients with normal scans, 189 (31.8%) underwent anmiocentesis and cytogenetic evaluation. Two chromosomal abnormalities were detected (1.1%) including an inversion in the long arm of the number 9 chromosome and a balanced translocadon, 46XX,t(7;8),(q34;q23.1). This was not statistically significant (p - 0.317) compared to the theoretical risk of chromosomal anomalies in this sample population based solely on maternal age (0.3%). CONCLUSION: The prevalence of karyotypic abnormalities in our patients with unexplained elevated maternal serum alpha-fetoprotein values and a normal targeted ultrasound examination was not significantly elevated. Of the abnormalities detected, none were life threatening or associated with significant perinatal morbidity. Our results suggest that routine kap/otype analysis in this group of patients is of limited value.
286
MATERNAL SERUM ANALYTE LEVELS IN FETAL DOWN SYNDROME PREGNANCIES DUE T O TRANSLOCATIONS. DNSallerJr,,1jACanick2X LHKellner 3x , NCRose 4,JGarza ix , CAFrench ix , RAMooney 1x. 1Univ of Rochester, Strong Mere Hos~, Rochester, NY; 2Brown Univ, Women & Infants Hosp Providence, RI; Albert Einstein Coll of Med, Montefiore Med Center, Bronx, NY; 4Unlv of PA, Phila, PA OBJECTIVE: To determine whether pregnancies affected by fetal Down syndrome (DS) due to Robertsonian translocations (RT) are associated with second trimester maternal serum analyte levels different from those associated with fetal trisomy 21 (T21). S T U D Y DESIGN: Pregnancies with DS due to RT were identified through the cytogenetic labs at the participating institutions. Those with maternal serum screening (MSS) values between 15-20 weeks were further studied. RESULTS: Analyte values are in muhiples of the median (MoM).
288
PRECISE BIVARIANT NORMAL DISTRIBUTIONS OF MATERNAL SERUM AFP AND FREE bHCG FOR TRISOMY 21 (T21) BIOCHEMICAL SCREENING. L Chik, ~ K Spencer/MPJohnson, M Ayoub, x E Kfivchenia/ M P Dombrowski, M I E v a n s . Depts. of Ob/Gyn, Molecular Med. & Genetics, and Patbology, WSU, Detroit; Dept. of Clin Biochem, Oldchurch Hosp, Romford, England 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 outliners, and to make intprovements. STUDY DESIGN: Cumulative distribution functions (CDE) were used to investigate the best model for AFP, and free-bHCG MOMs. Within limits, normal distributions would be the preferred choice. Parameters from CDF can be used to compute a more precise likelihood ratio for the decision logic for o'isomy 21. 58,297 cases with 348 T21 were computed using non-linear regressions. RESULTS: Normal distributions using existing curves generated r-values o1 approximately 0.87. Our statistical modifications increase the r 2 to .999 for CDF.
+~
Karyotype
46,XY, t (14;21) 46,XY, t (14;21) 46,XY, t(I 4;21) 46,XX, t(14;21) 46,XY, t (14;21) 46,XY, t(21;21) 46,XX,t(21;21) 46,XY, t(21;21) 46,XY, t(21;21) 46,XX, t(21;21) 46,XX,t(21;21) RT DS Median
28 28 28 31 35 22 28 31 31 32 34 31
16 16 15 15,5 15,6 17,6 15,2 18,1 17,6 16 17,0 16
0.72 1.07 0.62 0.98 0.83 0.68 0.59 0.45 0.53 0.53 1.28 0.68
---0.84 0.71 1.05 1.23 0.63 0.50 0.21 0.44 0.67
1.33 2.18 3.43 3.38 3.56 2.83 2.93 1.51 1.68 10.15 1.21 2.83
1:760 1:500 1:50 1:90 1:14 1:530 1:820 1:50 1:20 1:>2 1:420 1:90
+ + + + + +
Age - maternal age at EDC. Risk - Adjusted second trimester DS Risk Previously published medians (fi-om metaanalysis) for T21 DS are: T21 Median
0.73
0.71
2.04
CONCLUSIONS: These data suggest that DS due to RT is associated with second trimester maternal serum analyte levels similar to those associated with T21 and will be detected in a similar percentage of cases.
Normals T21
log AFP log bHCG log AFP log bHCG
.02793 .01990 - . 15781 .38255
.16807 .26327 .17550 .29977
.9999 .9997 .9989 .9987
The change in the model produces at a 5% false positive rate, a sensitivity" of 57.76% (201 out of 348). A 1 in 243 cutoff point risk is obtained, and is tighter than the 1 in 251 without the CDF, as versus 1 in 270 by age calculations alone. CONCLUSIONS: Our data suggest 1) Normality of log transforms of AFP and bHCG are reasonable models; 2) CDF can minimize the effect of outliners, which produces more realistic risk estimates; 3) The effect of CDF versus standard mean and standard deviations cannot automatically be extrapolated to other parameters which must be tested individually.