Multiple Marker Screening Research Articles

Effect of adjustment of maternal serum ?-fetoprotein levels in insulin-dependent diabetes mellitus

Our objective was to determine the effect of the 20% upward adjustment of maternal serum alphafetoprotein (MSAFP) in patients with insulin-dependent diabetes mellitus (IDDM) on the number of patients that would be classified at increased risk for pregnancy complicated by either Down syndrome (DS) or neural tube defect (NTD). We retrospectively evaluated a database containing 63,110 patients who underwent multiple serum marker screening between 14 and 22 weeks gestation; 620 patients with IDDM had measurements of MSAFP of which 479 also had measurements of beta-HCG, allowing calculation of DS risk. Increased NTD risk was defined as MSAFP >2.5 MOM while increased DS risk was defined as a calculated risk > or =1/270. One IDDM patient delivered an infant with a NTD; it was not detected on serum screening. No infants were born with DS. Of the 620 patients with MSAFP determinations, 9 had values >2.5 MOM before adjustment. After upward adjustment, 7 additional patients were identified. Sixteen patients were identified at increased risk for DS before and after adjustment. Our data suggest that the 20% upward adjustment of MSAFP increases by 78%, the number of patients who would require further evaluation for NTD's. Although we were able to identify 620 women with IDDM who underwent serum screening for NTD, the low prevalence of NTD's did not allow us to demonstrate an increased detection rate. The effect of upward adjustment of MSAFP on the number of patients categorized at increased DS risk appears to be minimal.

Effect of adjustment of maternal serum α‐fetoprotein levels in insulin‐dependent diabetes mellitus

Our objective was to determine the effect of the 20% upward adjustment of maternal serum alphafetoprotein (MSAFP) in patients with insulin-dependent diabetes mellitus (IDDM) on the number of patients that would be classified at increased risk for pregnancy complicated by either Down syndrome (DS) or neural tube defect (NTD). We retrospectively evaluated a database containing 63,110 patients who underwent multiple serum marker screening between 14 and 22 weeks gestation; 620 patients with IDDM had measurements of MSAFP of which 479 also had measurements of β-HCG, allowing calculation of DS risk. Increased NTD risk was defined as MSAFP >2.5 MOM while increased DS risk was defined as a calculated risk ≥1/270. One IDDM patient delivered an infant with a NTD; it was not detected on serum screening. No infants were born with DS. Of the 620 patients with MSAFP determinations, 9 had values >2.5 MOM before adjustment. After upward adjustment, 7 additional patients were identified. Sixteen patients were identified at increased risk for DS before and after adjustment. Our data suggest that the 20% upward adjustment of MSAFP increases by 78%, the number of patients who would require further evaluation for NTD's. Although we were able to identify 620 women with IDDM who underwent serum screening for NTD, the low prevalence of NTD's did not allow us to demonstrate an increased detection rate. The effect of upward adjustment of MSAFP on the number of patients categorized at increased DS risk appears to be minimal. Am. J. Med. Genet. 75:176–178, 1998. © 1998 Wiley-Liss, Inc.

Significance of a False-Positive Trisomy 18 Multiple-Marker Screening Test

Objective: To determine if a false-positive trisomy 18 multiple-marker screening test (all three analytes low: maternal serum alpha-fetoprotein [AFP] at most 0.75 multiples of the median [MoM], unconjugated estriol at most 0.60 MoM, and hCG at most 0.55 MoM) indicates increased risk for obstetric complications or is related to maternal weight.Methods: We accessed our genetic database to obtain multiple-marker screening test results, fetal karyotypes, and pregnancy outcomes from all patients with a normal multiple-marker screening test (n = 3900) and from all patients with a positive trisomy 18 screening test (n = 103) seen in the prenatal diagnosis clinic from 1992 to 1996. During this period, only maternal serum AFP was adjusted for maternal weight.Results: A positive trisomy 18 screen identified five of 12 trisomy 18 fetuses. Women with a false-positive trisomy 18 screen were heavier (175.6 ± 43.8 lb versus 159.9 ± 37.9 lb, P < .001) and younger (29.7 ± 6.5 years versus 32.3 ± 6.5 years, P < .001) than women with a normal multiple-marker screening test, but were not at increased risk for pregnancy complications. Weight-adjusting all three analytes reduced the false-positive trisomy 18 screen rate by 42% (from 1.9% to 1.1%) but did not change the trisomy 18 detection rate.Conclusion: A false-positive trisomy 18 screening test does not indicate increased risk to develop pregnancy complications and may be related to inadequate correction for increased maternal weight.

α-Fetoprotein, free β-human chorionic gonadotropin, and dimeric inhibin A produce the best results in a three-analyte, multiple-marker screening test for fetal Down syndrome

Objective: The purpose of this study was to determine, among six second-trimester maternal serum analytes, the best three-analyte combination for fetal Down syndrome detection. Study Design: With use of commercially available assay kits, medians for free β-human chorionic gonadotropin, CA 125, and dimeric inhibin A were established in stored sera from 45 to 50 euploid pregnancies at each week of gestation from 14 to 22 weeks and from 33 Down syndrome pregnancies. Maternal serum α-fetoprotein, unconjugated estriol, and intact human chorionic gonadotropin levels measured in each sample before storage were retrieved. All 20 possible three-analyte combinations were evaluated in the multiple-marker screening test for Down syndrome. Results: The mean maternal age of the study population was 35.6 ± 5.3 years. The best three-analyte combination was maternal serum α-fetoprotein, free β-human chorionic gonadotropin, and dimeric inhibin A: 97% of Down syndrome cases were detected at a false-positive rate of 16%. At a slightly higher false-positive rate (18%) maternal serum α-fetoprotein, estriol, and intact human chorionic gonadotropin detected only 79% of cases. Conclusions: Of six second-trimester maternal serum analytes, the best three-analyte combination for fetal Down syndrome detection was maternal serum α-fetoprotein, free β-human chorionic gonadotropin, and dimeric inhibin A. This retrospective analysis should now be confirmed prospectively.

Elevated second-trimester dimeric inhibin A levels identify Down syndrome pregnancies

Objective: Our purpose was to determine whether second-trimester dimeric inhibin A levels distinguish Down syndrome pregnancies from euploid pregnancies. Study Design: With use of a commercially available enzyme-linked immunosorbent assay (Serotec, Oxford) inhibin A medians were established in stored sera from 40 to 50 euploid pregnancies at each week of gestation from 14 to 20 weeks and from 33 Down syndrome pregnancies. Maternal serum α-fetoprotein, unconjugated estriol, and human chorionic gonadotropin levels measured in each sample before storage were retrieved. The performance of inhibin A in the multiple-marker screening test was evaluated. Results: The mean inhibin A multiple of the median was significantly higher in the Down syndrome group than in the euploid group (2.84 ± 2.0 vs 1.22 ± 1.0, p = 0.0001). An inhibin A level ≥1.6 multiples of the median identified 70% of all Down syndrome pregnancies at a false-positive rate of 22%. Replacing estriol with inhibin A in the multiple-marker screening test resulted in a higher Down syndrome detection rate at a lower screen-positive rate. Conclusion: Elevated second-trimester maternal serum inhibin A levels identify Down syndrome pregnancies; replacing estriol with inhibin A in the multiple-marker screening test improves test performance.

Pregnancy outcomes following false-positive multiple marker screening tests.

Pregnancy outcomes in women with a false-positive midtrimester multiple marker screening test (MMST) were reviewed. A genetic database was used to identify all women > or = age 30 who had a MMST at 15-20 weeks of gestation, a targeted ultrasound, and amniocentesis, and complete pregnancy outcome data. All patients with an abnormal fetal ultrasound (US) or karyotype were excluded. The incidence of adverse outcomes (defined as fetal death, preterm delivery, or a birth weight less than the 10th percentile for gestational age), in those women with a positive MMST (risk of Down's syndrome > or = 1:190) was compared to the incidence of adverse outcomes in control women with negative MMST. Chi-square analysis and Fisher's exact tests were used for comparisons as appropriate. Complete data was available from 1135 women. Seventy-seven percent were over age 35. Two hundred and forty-six women (22%) had a positive multiple marker test. No significant differences in outcomes were discovered after comparisons to controls: fetal death 1 of 246 (0.4%) versus 12 of 889 (1.3%), p = 0.32; preterm delivery 32 of 246 (13.0%) versus 147 of 889 (16.5%), p = 0.17; birth weight less than the 10th percentile, 9 of 246 (3.7%) versus 30 of 889 (3.4%), p = 0.83. Our data suggest that women > or = age 30 with a false-positive MMST and a normal midtrimester obstetrical sonogram are not at an increased risk for adverse pregnancy outcomes in later gestation.

Free β-hCG Subunit Versus Intact hCG in Down Syndrome Screening

Objective: To assess the ability of second-trimester maternal serum free β-hCG to detect fetal Down syndrome and to compare free β-hCG to intact hCG in the multiple-marker screening test for Down syndrome.Methods: From our bank of stored maternal sera, we selected 40–50 samples from euploid pregnancies at each week of gestation from 14 to 20 weeks and 31 samples from Down syndrome pregnancies. Free β-hCG was measured by enzyme-linked immunosorbent assay, and week-specific multiples of the median (MoM) were derived. The free β-hCG Down syndrome detection and false-positive rates were determined. Free β-hCG was then substituted for intact hCG in the multiple-marker screening test, and the Down syndrome detection and false-positive rates at various risk cutoffs were compared.Results: The mean (± standard deviation) maternal age of all study samples was 35.6 ± 5.3 years. The mean Down syndrome free β-hCG MoM was significantly higher than the mean euploid MoM (2.4 ± 1.1 versus 1.2 ± 1.0; P < .001). A free β-hCG level of at least 1.7 MoM identified 68% of Down syndrome pregnancies at a false-positive rate of 20%. When intact hCG was replaced with free β-hCG in the multiple-marker screening test, a higher Down syndrome detection rate was achieved at a lower false-positive rate at each of several screen positive risk cutoffs.Conclusion: Elevated free β-hCG levels identify Down syndrome pregnancies. Replacing intact hCG with free β-hCG in the multiple-marker screening test results in a higher Down syndrome detection rate at a lower false-positive rate.

PRENATAL DIAGNOSIS OF A DELETION OF 18q IN A FETUS ASSOCIATED WITH MULTIPLE-MARKER SCREEN POSITIVE RESULTS

We report here the observations of positive maternal serum screening tests for Down syndrome, cytogenetic and molecular analysis, and dysmorphic fetal features in a pregnancy with 18q-syndrome. A 33-year-old primigravida was referred for genetic counselling because of multiple-marker screen positive results. At 14 weeks' gestation, the woman had a Down syndrome risk of 1:107 calculated from a maternal serum alpha-fetoprotein (MSAFP) level of 1.49 multiples of the median (MOM), a total human chorionic gonadotrophin (hCG) level of 2.42 MOM, and a serum unconjugated oestriol (uE3) level of 0.55 MOM. At 17 weeks' gestation, a repeat test showed a Down syndrome risk of 1:10 calculated from an MSAFP level of 1.09 MOM and a free beta-hCG level of 12.3 MOM. Genetic amniocentesis revealed a de novo deletion of 18q22.2-qter. Intrauterine fetal death occurred at 21 weeks' gestation. At birth, the fetus manifested clinical findings of the 18q-syndrome. The phenotype was correlated with the extent of the deletion. Linkage analysis of the family confirmed the extent and paternal origin of the deletion.

Second-trimester maternal serum CA-125 versus estriol in the multiple-marker screening test for Down syndrome: Wenstrom K.D.; Owen J.; Boots L. USA Obstet Gynecol 1997 89/3 (359–363)

International Journal of Gynecology & ObstetricsVolume 57, Issue 3 p. 345-345 Citations from the literature (including the russian literature) trisomy Second-trimester maternal serum CA-125 versus estriol in the multiple-marker screening test for Down syndrome Wenstrom K.D.; Owen J.; Boots L. USA Obstet Gynecol 1997 89/3 (359–363) First published: 15 December 1997 https://doi.org/10.1016/S0020-7292(97)89953-5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume57, Issue3June 1997Pages 345-345 RelatedInformation

Second-trimester maternal serum CA-125 versus estriol in the multiple-marker screening test for down syndrome

To determine the ability of second-trimester maternal serum CA-125 levels to detect fetal Down syndrome. From stored, second-trimester maternal serum analyzed previously with the multiple-marker screening test for fetal Down syndrome, we selected 306 samples from euploid pregnancies and 22 samples from Down syndrome pregnancies at 14-20 weeks' gestation. CA-125 levels were measured by enzyme-linked immunosorbent assay and converted to gestational week-specific multiples of the median (MoM). The mean maternal age (+/- standard deviation) of the study population was 35.5 +/- 5.3 years. The Down syndrome group CA-125 mean MoM was significantly higher than the euploid group mean MoM (1.47 +/- 0.51 MoM versus 1.05 +/- 0.44 MoM; P < .001). CA-125 at or above 1.5 MoM identified 10 of 22 (45%) Down syndrome cases. Substituting CA-125 for estriol (E3) in the multiple-marker screening test resulted in a lower screen-positive rate (67 of 328, 20% [95% confidence interval {CI} 16, 25] versus 91 of 328, 28% [95% CI 23, 33]) with a similar Down syndrome detection rate (18 of 22, 82%). Alternatively, when the screen-positive rate was held constant, the Down syndrome detection rate improved (20 of 22, 91% [95% CI 71, 99] versus 18 of 22, 82% [95% CI 60, 95]). Down syndrome pregnancies have higher second-trimester maternal serum CA-125 levels than euploid pregnancies. CA-125 may be superior to E3 in the multiple-marker screening test for fetal Down syndrome.

Optimizing the multiple marker screening test for fetal down syndrome using a pentavariate gaussian algorithm

Optimizing the multiple marker screening test for fetal down syndrome using a pentavariate gaussian algorithm

Free beta HCG subunit versus intact HCG in the multiple marker screening test for fetal down syndrome

Free beta HCG subunit versus intact HCG in the multiple marker screening test for fetal down syndrome

Alphafetoprotein (AFP), free beta human chorionic gonadotrophin (FβhCG), and dimeric inhibin a (IH-A) produce the best results in a three-analyte multiple marker screening test for fetal down syndrome

Alphafetoprotein (AFP), free beta human chorionic gonadotrophin (FβhCG), and dimeric inhibin a (IH-A) produce the best results in a three-analyte multiple marker screening test for fetal down syndrome

The effect of inaccurate gestational age estimation on the multiple marker screening test (MMST) for fetal down syndrome (DS)

The effect of inaccurate gestational age estimation on the multiple marker screening test (MMST) for fetal down syndrome (DS)

Choroid plexus cysts and trisomy 18: Risk modification based on maternal age and multiple-marker screening

Choroid plexus cysts are more common in fetuses with chromosomal aneuploidies, particularly trisomy 18. Although it is accepted that the risk of karyotypic abnormality justifies amniocentesis when associated abnormalities are present, disagreement continues as to the risk of trisomy 18 in a fetus with an isolated choroid plexus cyst. We propose consideration of maternal age and multiple-marker screening for chromosomal aneuploidy in the assessment of risk. Bayesian statistical modeling was used to calculate the risk of trisomy 18 from age-related risk figures for trisomy 18 and the incidence of isolated choroid plexus cysts in fetuses with trisomy 18. The risk was further modified on the basis of the ability of multiple-marker screening to detect fetuses with trisomy 18. From risk estimates calculated across maternal ages 20 to 45 years, the risk of trisomy 18 does not approach that of amniocentesis until a maternal age of ≥37 years. Therefore in the presence of an isolated choroid plexus cyst and normal multiple-marker screen results amniocentesis is justified only in the patient with advanced maternal age. (Am J Obstet Gynecol 1996;175:1493-7.)

Empirical validation of risk screening for Down's syndrome.

To validate individual risk estimates in antenatal serum screening for Down's syndrome. Women screened for Down's syndrome using maternal serum alpha fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotrophin (hCG) with maternal age (the triple test) or AFP, uE3, free beta subunit and free alpha subunit of hCG with maternal age (the quadruple test) were grouped according to their predicted risk of having an affected pregnancy. The mean predicted risk in each category was then compared with the observed prevalence based on the number of affected and unaffected pregnancies in each category. About 100,000 pregnant women screened for Down's syndrome from 1989 to 1995. There was close agreement between the predicted term risk and the prevalence at birth for both the triple test and the quadruple test. For example, with the quadruple test the predicted risk in the highest risk group was 1 in 3.3 and the prevalence was 1 in 2.6; in the lowest risk group these were 1 in 3000 and 1 in 2300 respectively. Risk estimates based on multiple marker screening for Down's syndrome are accurate. The technique used to demonstrate this is simple and offers a useful empirical check on screening performance.

Effect of parity correction on Down syndrome detection by the multiple-marker screening test

OBJECTIVE: Our purpose was to determine whether maternal parity affects analyte levels in the multiple-marker screening test for Down syndrome and to derive a correction factor and determine its effect on Down syndrome detection and screen-positive rates. STUDY DESIGN: Our database consisted of 3039 multiple-marker screening test results and corresponding fetal karyotypes (2983 euploid and 56 Down syndrome). Cases were grouped by maternal parity as follows: 0 (n = 848), 1 (n = 1140), or ≥2 (n = 1051). The mean multiple of the median of maternal serum α-fetoprotein, estriol, and human chorionic gonadotropin was determined for each group. A correction factor was derived for each parity group and applied to the database. Parity-corrected Down syndrome detection rates and screen-positive rates were determined. RESULTS: Parity significantly affected the mean multiple of the median of human chorionic gonadotropin levels (p = 0.0001) but did not affect the values for estriol or maternal serum α-fetoprotein. Application of a parity correction factor for human chorionic gonadotropin increased the Down syndrome detection rate in women who had two or more pregnancies from 71% to 82% without increasing the overall screen-positive rate. CONCLUSION: Human chorionic gonadotropin levels are significantly lower in multiparous women. Correcting human chorionic gonadotropin for maternal parity increases Down syndrome detection for women who had two or more pregnancies without affecting the overall screen-positive rate. (Am J Obstet Gynecol 1996;175:1004-7.)

Pre‐screening education in multiple marker screening programs: The effect on patient anxiety and knowledge

Previous studies have shown that unexplained deviations in maternal serum multiple marker screening (MMS) generate considerable anxiety during the remainder of pregnancy. While the role of education in decreasing anxiety is documented, to date there has been no prospective evaluation of which educational practices might minimize this emotional stress. In a pilot study, we prospectively examined the effects on anxiety and knowledge by providing information about MMS (1) by genetic counselor, (2) by pamphlet, and (3) by primary physician. Women randomized to one of these three modalities were administered the Spielberger State- Trait Anxiety Inventory [STAI] and knowledge questionnaires at their initial obstetrics visit, at their second visit after educational intervention and 1-2 weeks after MMS results were provided to patients. Education resulted in an increase in knowledge and post-education knowledge was different between educational modalities. Anxiety declined in patients educated through genetic counseling or a pamphlet.

Second trimester maternal serum CA-125 is superior to estriol in the multiple marker screening test for down syndrome.

Second trimester maternal serum CA-125 is superior to estriol in the multiple marker screening test for down syndrome.

Logistic regression generated probability estimates for trisomy 21 outcomes from serum alpha fetoprotein and beta human chorionic gonadotrophin: simplification with increased specificity.

Traditional Gaussian approaches to biochemical screening make calculations very cumbersome. We have sought to develop a logistic regression mathematical model for the calculation of risk for trisomy 21 in multiple marker screening that would be more "user friendly." Biochemical screening data from 15,444 patients with confirmed normal outcomes and 28 with trisomy 21 were analyzed by logistic regression analysis (LRA) to produce a direct mathematical approach to risk calculation that combines the improvements in sensitivity and specificity already demonstrated by us with extreme value cumulative function surface fittings, but which can be extended for other exploratory variables. LRA yields a 71.4% sensitivity with a 95% specificity which is comparable to our previously published discriminant aneuploidy detection (DADs) approach; both are an improvement over the commonly used Gaussian approach of risk assessment. In our study population, LRA performed as well as DADs; both performed better than the Gaussian method, and LRA is a simpler approach.