ABSTRACTS
16th Annual Meeting of the Society of Perinatal Obstetricians
February 4 - 10, 1996 Kamuela, Hawaii
450_____
FIRST TRIMESTER SEROLOGIC SCREENING: ADDITIONAL DETECTION OF TRISOMIES 18 AND 13.
D. Krantz1, B. Brambati2, L. Tului2, T. Hallahan1, P. Buchanan3, J. Larsen4, J. Macri1. 1NTD Laboratories, Inc., Huntington Station, NY, 2First Institute of OB/GYN, Univ. Of Milan, Italy, 3GeneCare Medical Genetics Center, Chapel Hill, NC, 4George Washington Univ. Med. Ctr., Washington, DC.
OBJECTIVE: To determine if Trisomy 18 (T-18) and Trisomy 13 (T-13) can be detected within the scope of a first trimester Down syndrome (DS) screening protocol using free Beta hCG (FB) and PAPP-A.
STUDY DESIGN: First trimester samples from 1355 unaffected, 59 DS, 9 T-18, and 3 T-13 cases were evaluated retrospectively. Day-specific multiples of the median (MOM) were calculated for analytes. DS detection efficiency was determined by modeling observed likelihood ratios with the U.S. live birth age distribution. T-18 and T-13 detection and false positive rates were determined by atypical combinations of levels of both analytes. An atypicality index based on Mahalanobis' Squared Distance of >9.21 with each analyte MOM value ,2.0 was used as the decision criteria.
RESULTS: In DS, the median FB and PAPP-A MOM was 1.0 and 0.5 respectively. At a 5% false positive rate, detection efficiency for DS was 60%. In T-18, median FB and PAPP-A MOM was 0.12 and 0.5 respectively. A trisomy 18 detection efficiency of 89% (8 of 9 cases) at a 0.4% false positive rate was achieved. In T-13 median FB and PAPP-A MOM was 0.19 and 0.67 respectively. One case of T-13 was detectable.
CONCLUSION: First trimester screening with FB and PAPP-A may detect a medically significant number of cases of DS and T-18. The value of this method for T-13 remains uncertain.
463_____
SECOND-TRIMESTER MATERNAL SERUM SCREENING FOR DOWN'S SYNDROME: COMPARISON OF FREE BETA-hCG
AND ALPHA-FETOPROTEIN WITH TOTAL hCG, ALPHA-FETOPROTEIN AND UNCONJUGATED ESTRIOL.
Ph. Extermann, P. Bischof, F. Beguin. Dept. Of Ob/Gyn, Univ. Of Geneva, Geneva, Switzerland.
OBJECTIVE: To compare two protocols for second-trimester maternal serum screening for Down's syndrome in the same serum samples, using a triple test (total hCG, alpha-fetoprotein, unconjugated estriol) and a double test (free beta-hCG, alpha-fetoprotein).
STUDY DESIGN: Eighteen singleton pregnancies with fetal Down's syndrome and 2522 pregnant women receiving routine antenatal care in Geneva were the subjects of this study.
RESULTS: Among the 18 affected cases, at a cut-off risk of 1:380, the detection rate of Down's syndrome was higher with the double test (94%; 17/18) than with the triple test (67%; 12/18) (p > 0.05). In the cohort of 2522 pregnant women screened between 15 and 18 week's gestation, for a statistically similar detection rate of affected cases, the double test achieved a significant reduction (p < 0.0001) in the number of false positive cases among patients under 35 years of age, irrespective of the cut-off risk selected (from 1:190 to 1:380).
CONCLUSIONS: Compared to total hCG, alpha-fetoprotein and unconjugated estriol, use of free beta-hCG and alpha-fetoprotein represents a better second-trimester screening test for Down's syndrome, because it significantly decreases the false positive rate at a lower running cost.
1627_____AMNIOTIC FLUID AFP AND AChE RESULTS IN EARLY AND LATE GESTATION. TW Hallahan1, JW Larsen2, PD Buchanan3, DA Krantz1, JN Macri1. 1NTD Laboratories, Inc., Huntington Station, NY, 2George Washington University Medical Center, Washington DC, 3GeneCare Medical Genetics Center, Chapel Hill, NC.
Amniotic fluid biochemical testing for open neural tube defect is conducted between 14 and 22 weeks of pregnancy. We analyzed amniotic fluid samples drawn prior to 14 (early) and after 22 weeks (late) gestation for both AFP and acetylcholinesterase (AChE). Early amniotic fluid AFP medians determined on 338 negative AChE samples were:
| GA: | 9 | 10 | 11 | 12 | 13 |
| N | 0 | 6 | 24 | 61 | 247 |
| AFP(KIU/ml) | -- | 16.4 | 12.8 | 15.0 | 16.0 |
| Regressed | 12.2 | 13.1 | 14.0 | 15.0 | 16.0 |
Four (1.2%) of these cases had AFP levels greater than 2.0 MOM. In three early cases with positive AChE we observed 2 fetal demise at 9 weeks (13.0 and 4.8 MOM) and 1 acrania at 13 weeks (51.1 MOM). Late GA AFP medians determined on 572 negative AChE samples ranged from 3.8 to 0.2 KIU/ml between 23 and 38 weeks. AFP in 82 (14.3%) of these cases was at or above 2.0 MOM. AFP MOMs in 24 late GA cases with positive AChE included 10 open spina bifida cases (median MOM 4.62), 2 anencephalic (27.0 and 56.9 MOM), 2 VWD (30.8 and 53.6 MOM). 7 other defects with elevated AFP (median MOM 18.4). 1 ONTD normal for AFP (0.54 MOM) and 2 weak atypical positive AChE with elevated AFP (42.5 MOM, gastroschisis and 70.6 MOM, fetal demise). No false positive AChE (early or late) were observed. Based on this data, AChE appears to be effective at all GA's while AFP appears to be a better marker in early rather than late amniotic fluid.
451_____DIMERIC INHIBIN-A IN SECOND TRIMESTER DOWN SYNDROME SCREENING. T. Hallahan1, J. Larsen2, P. Buchanan3, D. Krantz1, J. Macri1. 1NTD Laboratories, Inc., Huntington Station, NY, 2George Washington University Medical Center, Washington, DC, 3GeneCare Medical Genetics Center, Chapel Hill, NC.
OBJECTIVE: To determine if second trimester serologic levels of dimeric inhibin-A (DIA) are elevated in Down syndrome (DS).
STUDY DESIGN: DIA, free Beta hCG (FB) and AFP in maternal serum samples from 19 cases of DS,each matched with 3 unaffected controls for gestational age in menstrual weeks (GA), maternal age and length of freezer storage time were evaluated. Multiples of the GA-specific medians (MoM's) were determined for each analyte. Detection efficiency and false positive rates were estimated by modeling observed likelihood ratios with the age distribution of live births.
RESULTS: The GA-specific medians for DIA were:
| GA |
14 |
15 |
16 |
17 |
18 |
19 |
20 |
| Controls | 156 | -- | 149 | 233 |
| Controls(Number) | 3 | 12 | 24 | 9 | 0 | 6 | 3 |
| DS(pg/ml) | 451 | 297 | 334 | 402 | -- | 420 | 363 |
| DS(Number) | 1 | 4 | 8 | 3 | 0 | 2 | 1 |
An insignificant association of DIA with GA was observed (r = 0.216, P = .107). Overall median MoM's of DS cases for DIA, FB and AFP were 2.14, 2.89 and 0.79, respectively. Correlation of DIA with FB was 0.344 in DS cases and 0.349 in controls. Correlation of DIA with AFP was 0.425 in DS cases and 0.307 in controls. At a 5% false positive rate, individuals detection efficiency for DIA, FB, and AFP was 44%, 64% and 31%, respectively.
CONCLUSIONS: DIA is elevated in cases of DS. Additional data will determine if DIA, when combined with the current second trimester protocol of free beta hCG and AFP, will enhance detection of DS.
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46th Annual Meeting of The American Society of Human Genetics
October 29 - November 2, 1996 San Francisco, California
1846_____
DETECTION OF MOLAR PREGNANCIES WITHIN A DOWN SYNDROME SCREENING PROTOCOL USING FREE-BETA
hCG AND AFP. P. Buchanan1, D. Krantz2
, T. Hallahan3, J. Larsen
3, J. Macri2.
1GeneCare Medical Genetics, Chapel Hill, NC and
2NTD Laboratories, Inc., Huntington Station, NY,
3George Washington University, Washington, DC.
To determine if hydatidiform mole (HM) can be detected in second trimester screening we identified seven such cases including one of a twin pair. Free-Beta (hCG) and AFP values were available from initial screening. PAPP-A levels were determined using in-house ELISA. Analyte MoM values were:
| SAMPLE | GA(LMP WEEKS) | FREE-BETA | AFP | PAPP-A |
|---|
| 1 | 19 | 1.15 | 0.00 | 0.03 |
| 2 | 16 | 5.28 | 0.04 | 0.21 |
| 3 | 16 | 19.90 | 0.02 | 0.29 |
| 4 | 16 | 39.50 | 0.04 | 0.23 |
| 5 | 16 | 1.33 | 0.12 | 0.23 |
| 6 | 16 | 69.40 | 0.07 | ---- |
| Median Mom | 0.23 |
| Twin with HM | 16 | 22.00 | 1.02 | 1.68 |
Free-Beta was either normal or very high in HM, possibly distinguishing different subtypes of moles. AFP was similar to that seen in non-pregnant females. PAPP-A values were low in all samples tested. All six HM pregnancies would have been identified at increased risk for Down syndrome using the free-Beta/AFP protocol. Free-Beta combined with PAPP-A is an effective first trimester Down syndrome screening protocol and could potentially provide an earlier identification of HM as well.
1876_____CORRELATION OF MATERNAL BLOOD AND MATERNAL URINARY FREE-BETA hCG USING DRIED SPECIMEN TECHNOLOGY. T. Hallahan1, R. Anderson1, B. Brambati2, L. Tului2, D. Krantz1, J. Larsen3, P. Buchanan4 F. Orlandi5, J. Macri1. 1NTD Laboratories, Inc. Huntington Station, NY, 2First Institute of OB/GYN, University of Milan, Italy, 3George Washington Univ., Washington Univ., Washington, DC, 4GeneCare Medical Genetics Center, Chapel Hill, NC, 5Prenatal Diagnosis Center, Cervello Hospital, Palermo, Italy.
Free-Beta hCG is the only maternal serum marker for Down Syndrome discriminatory in both the first and second trimester. Recently, free-Beta hCG and it's primary metabolic product beta-core hCG have been demonstrated to be potentially effective in a maternal urine Down Syndrome screening protocol. We have now developed a novel dried urine collection protocol for use in Down Syndrome screening. Our liquid serum ELISA was modified first for dried blood and then for dried urine, all using the same antibody sandwich pair which has been observed in a liquid non-competitive format to have the following cross reactivity: free Beta 100%, beta-core hCG 0.2%, free alpha 0.23% and beta LH 0.28%. The limit of detection for free-Beta in dried urine was 0.050 mg/L.
Matched maternal blood and urine specimens were then collected using dried specimen technology from 100 patients between 9 and 18 weeks gestation. All urinary free-beta values were normalized against creatinine levels determined using a modified Jaffe reagent assay. The correlation between dried blood and dried urinary free-Beta hCG levels was 0.6.
The strong correlation with dried blood specimens suggests that maternal urine free-Beta hCG screening using dried specimen technology may have utility in prenatal screening. The advantages of dried urine technology include; a simple non-invasive collection protocol, enhanced safety in specimen handling, specimen preservation, no precipitate formation, no centrifugation and ease of shipping and storage.
1890_____PRENATAL SCREENING OF CONSECUTIVE PREGNANCIES IN THE SAME PATIENT. J. Larsen1, D. Krantz2, T. Hallahan2, P. Buchanan3, J. Macri2. 1George Washington University, Washington, DC, 2NTD Laboratories, Inc. Huntington Station, NY, 3GeneCare Medical Genetics Center, Chapel Hill, NC.
We identified 3,509 white, non-insulin dependent diabetic patients in which two unaffected singleton pregnancies were screened for open neural tube defects (AFP) and Down Syndrome (free-Beta hCG & AFP). All MoM values were weight adjusted. The correlation coefficient between consecutive pregnancies was 0.399 for free-Beta and 0.322 for AFP. The table shows screening results on prior and subsequent pregnancies. Since maternal age is a factor, DS risk for the subsequent pregnancy was adjusted by setting maternal age equal to that of the prior pregnancy.
| Result in Prior Pregnancy | Result in Subsequent Pregnancy |
| | Normal | DS Risk | DS Risk Adjusted | ONTD Risk |
| Normal | 3311 (94.4%) | 3018 (91.2%) | 229 (6.9%) | 145 (4.4%) | 64 (1.9%) |
| DS Risk | 103 (2.9%) | 71 (68.9%) | 29 (28.2%) | 23 (22.3%) | 3 (2.9%) |
| ONTD Risk | 95 (2.7%) | 83 (87.4%) | 3 (3.2%) | 2 (2.1%) | 9 (9.5%) |
A prior pregnancy at increased risk result in a 5 fold increase in the odds of a second pregnancy being at risk for the same anomaly. This information could be included when counseling patients who have had previous results outside of normal range, however, more data is required to formulate a valid risk adjustment factor.
1891_____EARLY AMNIOCENTESIS - 1988 - 1995. C.H. Laundon*, A. Boutcher, R. Scherer, L. Springstead, P. Buchanan. GeneCare Medical Genetics Center, 120 Conner Drive, Chapel Hill, NC 27514.
Early amniocentesis (EA) has been offered by our Center for the past 7 years to couples who have pregnancies at risk for a chromosome abnormality and other anomalies. EA refers to an amniocentesis performed at 10 -14 weeks gestation. Amniotic fluid was cultured by the in situ method on glass coverslips. On average, 4 slips were set on EA's from 10.0 - 11.9 weeks gestation and 6 slips on EA's from 12.0 - 14.9 weeks. The average number of days to first harvest was 6 and average days to final diagnosis was 8. EA accurately diagnosed all 64 (2.8%) chromosome abnormalities. Acetylcholinesterase and alpha-fetoprotein accurately detected all 5 open neural tube defects and 4 IUFDs. Only three spontaneous abortions out of 2260 EAs (1 out of 753) occurred within 2 weeks of the procedure which is less than the possible 1/200 risk of traditional amniocentesis (TA).
Advantages of EA to the laboratory include: 1) specimens blend nicely into flow of established cytogenetics lab; 2) enough specimen available for 4-6 coverslips; 3) in situ clonal analysis; 4) tissue culture growth of EA equal to TA; 5) high quality chromosome preparations with 550 - 850 bands; and 7) technician time is the same as TA and about half that of chorionic villus sampling (CVS). Advantages to patients include: 1) early testing; 2) testing for chromosome and open neural tube defects; and 3) safety of EA equal to TA. EA has many advantages for both the patient and the laboratory.
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46th Annual Meeting of The American Society of Human Genetics
October 29 - November 2, 1996 San Francisco, California
First Trimester References
1844_____FIRST-TRIMESTER DOWN SYNDROME SCREENING WITH FREE BETA AND PAPP-A: OBSERVATIONS IN MULTIPLE PREGNANCIES. B.Brambati1, L. Tului1, F. Orlandi2, G. Damiani2, D. Krantz3, T. Hallahan3, J. Macri3. 1First Institute of OB/GYN, Univ. Of Milan, Italy, 2Prenatal Diagnosis Service, Cervello Hospital, Palermo, Italy, 3NTD Laboratories, Inc., Huntington Station, NY.
Free Beta hCG combined with PAPP-A has been retrospectively demonstrated as an effective first-trimester Down syndrome (DS) screening protocol. We demonstrate here results of this first-trimester protocol with multiple pregnancies. Values are expressed as median multiples of the singleton median.
| Outcome | N | free-Beta | PAPP-A |
| Twins (dichorionic) | 32 | 2.08 | 1.44 |
| Twins (monochorionic) | 4 | 1.62 | 1.53 |
| Triplets | 4 | 3.72 | 3.96 |
| Twins - 1IUD | 2 | 1.18 | 1.59 |
| Twins - 1DS | 3 | 2.48 | 1.03 |
| Triplet - 1 Reduction | 10 | 2.38 | 2.16 |
| Triplet - 1 Spontaneous Abortion | 1 | 0.64 | 1.30 |
|
| Triplet - 2 Reduction | 3 | 3.82 | 2.77 |
| Triplet - 1IUD, 1Reduction | 3 | 1.82 | 1.70 |
Both free-Beta and PAPP-A levels are raised approximately in proportion with increasing multiplicity. Furthermore, a proportionate decrease in analyte levels is observed in cases of twins with one spontaneous fetal reduction and triplets with one elective reduction. Proportionality in triplets with other permutations of fetal reduction was not observed in this small data set. This data may be used to establish reference values for normal multiple pregnancies. As in second trimester screening, however, more affected case data is needed to determine the detection efficiency of first-trimester screening for multiple pregnancy.
1888_____PROSPECTIVE FIRST-TRIMESTER DOWN SYNDROME SCREENING: FREE-BETA / PAPP-A ANALYSIS UTILIZING DRIED BLOOD TECHNOLOGY. D. Krantz1, F. Orlandi2, C. Rossi2, B. Brambati3, L. Tului3, J. Larsen4, R. Anderson1, T. Hallahan1, J. Macri1. 1NTD Laboratories, Inc., Huntington Station, NY. 2Prenatal Diagnosis Service, Cervello Hospital, Palermo, Italy, 3First Institute of OB/GYN, Univ. Of Milan, Italy, 4George Washington University, Washington, DC.
Dried blood samples from 854 patients between 8-13 weeks gestation were analyzed prospectively to determine Down syndrome risk based on free-Beta, PAPP-A and maternal age. A DS risk cut-off of 1/380 at term was used.
| <35 Years | 35 Years |
| Total Screened | 554 | 310 |
| Median Age | 29 | 39 |
| Increased DS Risk | 33 | 34 |
| False Positive Rate | 5.8% | 9.3% |
| Yield* | 1/33 | 1/7 |
*Overall 3 cases of DS were detected (1 under and 2 over the age of 35). No cases of DS were missed. In addition, in the over 35 group, 1 Fetal Demise and 2 cases of Long-Y chromosome were detected. The three cases of Down syndrome had DS risks after screening of 1/53, 1/93, and 1/5.
An atypicality index based on Mahalanobis' Squared Distance was used to identify patients at risk for other adverse outcomes. Overall, 16 cases had atypical levels with both free Beta and PAPP-A being low. In this group were 4 Affected (1 fetal demise, 1 anencephaly, 1 T-13, and 1, 69XXX) for a yield of 1/4.
The yields obtained in this trial so far are comparable to current second-trimester protocols. As larger databases of normative data are developed, false positive rates should improve.
1904_____FIRST-TRIMESTER PRENATAL SCREENING UTILIZING DRIED BLOOD TECHNOLOGY: EFFECT OF MATERNAL WEIGHT ON FREE-BETA/PAPP-A. F. Orlandi1, M. Jakil1, D. Krantz2, T. Hallahan2, J. Macri2. Prenatal Diagnosis Service, Cervello Hospital, Palermo, Italy, 2NTD Laboratories, Inc. Huntington Station, NY.
Six hundred fifty seven first-trimester dried blood spot specimens in which maternal weight was available were analyzed for free-Beta hCG and PAPP-A. Both analytes demonstrated a small negative correlation with maternal weight (Free-Beta,
r = 0.232; PAPP-A, r = 0.228). Weight adjustment formulas developed were:
free-Beta (Adj) = free Beta/EXP ( 0.7815 *Log (weight Kgs) + 3.1786)
PAPP-A (Adj) = PAPP-A/EXP ( 0.8363*Log (weight Kgs) + 3.4273)
Weight adjustment of the normal analyte values lowered the standard distributions (LOGe MoM) of free-Beta and PAPP-A and reduced the correlation.
| Analyte | Unadjusted | Adjusted |
| free-Beta SD | 0.5033 | 0.4866 |
| PAPP-A SD | 0.5468 | 0.5273 |
| Correlation | 0.303 | 0.264 |
Prior to weight adjustment 42 patients were at increased risk for Down syndrome and 14 patients were at increased risk based on an atypicality index. After weight adjustment, one additional case was at risk for Down syndrome and one additional case was at increased risk based on atypicality. Two Down syndrome cases were at increased risk for DS before and after adjustment. One case each of Fetal Demise, 69XXX, Trisomy-13 and anencephaly were at atypicality risk before and after weigh adjustment. One case of turner syndrome was within normative range before weight adjustment and in the atypical risk after weight adjustment.
The use of a weight adjustment factor may potentially enhance the detection efficiency of first-trimester screening because of the decrease in the width of the normal distribution curve but it has little effect on false positive rates.
1931_____Effect of Maternal Weight and Smoking on First-Trimester Down Syndrome Screening with Maternal Serum free-Beta/PAPP-A. L. Tului1, B. Brambati1, D. Krantz2, T. Hallahan2, J. Macri2. 1First Institute of OB/GYN, Univ of Milan, Italy, 2NTD Laboratories, Inc. Huntington Station, NY.
A retrospective study of 740 first-trimester maternal serum samples in which maternal weight and smoking status was available were analyzed for free-Beta hCG and PAPP-A. Of the 740 patients in the study, 89 smoke cigarettes. Both analytes demonstrated a small negative correlation with maternal weight (Free-Beta, r = 0.143; PAPP-A, r = 0.221). Weight adjustment formulas developed were:
free-Beta = EXP ( 0.6439 * Loge (weight) + 2.6466)
PAPP-A = EXP( 0.8390 * Loge (weight) + 3.4771)
Patients were divided into two groups (smokers and non-smokers). Differences in the median analyte levels were tested using the Wilcoxon test.
| Analyte | Wt. Adj. | Non-Smokers (n-651) | Smokers | P Value |
| free-Beta | No | 0.99 | 0.95 | .9486 |
| Yes | 0.97 | 0.93 | .9703 |
| PAPP-A | No | 1.01 | 0.98 | .5414 |
| Yes | 1.01 | 0.97 | .4666 |
The use of a weight adjustment factor may potentially enhance the efficiency of first-trimester screening. Maternal smoking status does not appear to have a significant impact on screening.
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17th Annual Meeting of the Society of Perinatal Obstetricians
January 20 - 25, 1997 Anaheim, California
293_____SECOND-TRIMESTER DETECTION OF TRISOMY 18 USING FREEBETA HCG AND AFP. D. Krantz1X, T. Hallahan1, P. Buchanan2, J. Larsen3, J. Macri1. 1NTD Laboratories, Inc. Huntington Station, NY, 2GeneCare Medical Genetics Center, Chapel Hill, NC, 3George Washington Univ. Washington, DC.
OBJECTIVE: To compare whether an atypicality index or a patient specific trisomy 18 risk calculation gives better screening efficiency for trisomy 18.
STUDY DESIGN: As part of routine prospective second-trimester Down syndrome screening with freeBeta hCG and AFP, 31 trisomy 18 cases were identified. A total of 3100 unaffected matched controls (100/T-18 case) were evaluated. For each sample, an atypicality index based on the Mahalanobis Squared distance and a patient specific trisomy 18 risk were calculated. Modeling was based on age distribution of live births and observed likelihood ratios.
RESULTS: Population parameters and weight adjusted screening results follow:
| Sample | Mean | AFP MoM Median, SD | FB MoM Median, SD | r |
| Age | GA |
| Controls | 27.4 | 16.6 | 0.99(0.370) | 1.01 (0.661) | 0.044 |
| Cases | 33.1 | 16.2 | 0.68 (0.513) | 0.20 (0.740) | -.246 |
The calculated false positive and detection rates are as follows:
| Method | Observed | Modeled |
| FP | DE | FP | DE |
| Atypicality: 9.21 | 0.7% | 45% | 0.7% | 45% |
| T18 Risk: 1/100 | 0.3% | 55% | 0.3% | 50% |
| T18 Risk: 1/150 | 0.4% | 61% | 0.4% | 54% |
| T18 Risk: 1/200 | 0.6% | 65% | 0.6% | 58% |
CONCLUSION: Using the freeBeta/AFP protocol, patient specific risk estimation gives better detection of trisomy 18 than an atypicality index.
300_____MATERNAL URINE SCREENING USING DRIED SPECIMEN TECHNOLOGY: COMPARISON OF FREE-BETA HCG AND BETA CORE FRAGMENT.T. Hallahan1X, D. Krantz1, B. Brambati2 L. Tului2, P. Buchanan3, F. Orlandi4, V. Klein5, J. Larsen6, J. Macri1. 1NTD Laboratories, Inc. Huntington Station, NY, 2First Institute OB/GYN, Univ. Of Milan, Italy, 3GeneCare Medical Genetics Center, Chapel Hill, NC, 4Prenatal Diagnosis Service, Cervello Hospital, Palermo, Italy, 5North Shore Univ. Hospital, Manhasset, NY, 6George Washington Univ., Washington, DC.
OBJECTIVE: To compare the effectiveness of free-Beta hCG and Beta Core hCG in a dried urine Down syndrome screening protocol.
STUDY DESIGN: We analyzed dried maternal urine specimens from 164 control, 9 Down syndrome affected and 4 trisomy 18 affected pregnancies between 8-25 weeks for free-Beta hCG and Beta Core hCG (UGF, Toagosei, Inc.). Creatinine was used to normalize values. Gestational age specific medians and Multiples of the Median (MoMs) were calculated for each analyte.
RESULTS: Free-Beta and Beta-core hCG values were closely correlated in controls and affected cases (r=0.61 and 0.95, respectively).
| Analyte | Control Percentiles | Ctrl SD LOGe | DS MoM | DS Detection |
| 10 | 50 | 90 | | | 5% | 10% |
| free-Beta | 0.37 | 1.03 | 2.21 | .697 | 2.42 | 22% | 56% |
| beta-core | 0.28 | 0.96 | 2.67 | .897 | 2.40 | 33% | 44% |
In the four cases of Trisomy 18 the free-Beta hCG median MoM was 0.35 while that of Beta Core hCG was 0.51.
CONCLUSIONS:This study confirms an earlier report of Spencer et al. in which urinary free-Beta and beta-core showed similar elevations in DS cases. Urinary free-Beta MoMs in DS cases are similar to those found in serum, however, the wider distributions observed in urine may decrease screening efficiency. Beta core values in DS cases appear to be more similar to free-Beta than seen in other small series. Additional evaluation of assay specificities are required to determine the cause of observed discrepancies among studies.
26_____ALPHAFETOPROTEIN (AFP), FREE BETA HUMAN CHORIONIC GONADOTROPHIN (F hCG), AND DIMERIC INHIBIN A (IH-A) PRODUCE THE BEST RESULTS IN A THREE-ANALYTE MULTIPLE MARKER SCREENING TEST FOR FETAL DOWN SYNDROME. K.D. Wenstrom, J. Owen, D.C. ChuX, L. BootsX. Dept. Of Ob/Gyn., Univ. of Alabama at Birmingham, AL.
OBJECTIVE: To determine the best three-analyte combination of six potential maternal serum markers in the multiple marker screening test (MMST) for fetal Down syndrome (DS).
STUDY DESIGN: From our bank of second trimester maternal serum stored at -70 for 2 years, we randomly selected 313 samples from euploid pregnancies at 14 to 20 weeks' gestation (mean maternal age = 35.6 %B1 5.2) and 33 samples from DS pregnancies. AFP, unconjugated estriol (E3), and Intact hCG (IhCG) levels had been determined prior to storage; after thawing, CA-125, F hCG, and IH-A levels were determined by ELISA and converted to week-specific multiples of the median (MoM). Various combinations of three analytes were used in the MMST and the screen positive rates (DS risk 1:190) and DS detection rates were compared to those of the traditional MMST (AFP, E3, IhCG).
RESULTS: Combinations including E3 and IhCG were rejected as a result of suboptimal performance. Other combinations included:
| Analytes | Screen Positive % | DS Detection % |
| AFP, E3, ihCG | 28 | 85 |
| F hCG, CA-125 | 20 | 84 |
| AFP, CA-125, IH-A | 20 | 85 |
| AFP, F hCG, IH-A | 18 | 90 |
*High SP% reflect the high mean maternal age of the study population.
CONCLUSION: The best combination of 3 analytes in the MMST appears to be AFP, F hCG, and IH-A, resulting in the lowest screen positive rate (18%) and the highest DS detection rate (90%). This combination should be evaluated prospectively.
Abstracts Continued
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