scholarly journals Serum marker truncation limits in first trimester antenatal screening for trisomy 18

2018 ◽  
Vol 25 (4) ◽  
pp. 169-173
Author(s):  
Jonathan P Bestwick ◽  
Wayne J Huttly ◽  
Nicholas J Wald
Keyword(s):  
Risk Estimation ◽  
False Positive Rate ◽  
Protein A ◽  
First Trimester ◽  
Trisomy 18 ◽  
Antenatal Screening ◽  
Screening Performance ◽  
Combined Test ◽  
Probability Plots ◽  
Β Hcg

Objective To assess whether the accuracy of risk estimation in antenatal screening for trisomy 18 using the Combined test can be improved by revising the truncation limits of two serum markers. Methods In an audit of data from 420 trisomy 18 and 573,754 unaffected singleton pregnancies screened at the Wolfson Institute of Preventive Medicine, London (March 2003 to June 2017), the accuracy of risk estimation was assessed by inspection of a validation plot (the median predicted late first trimester Combined test risk plotted against observed prevalence within categories of predicted risk estimates). Using validation and probability plots, we assessed whether the revised pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotrophin (free β-hCG) truncation limits led to more accurate risk estimation and improved screening performance. Results With the lower truncation limits currently used for PAPP-A and free β-hCG (0.15 and 0.30 multiples of the median [MoM], respectively), risk was underestimated. Revised lower truncation limits of 0.05 MoM for both PAPP-A and free β-hCG led to greater accuracy, with an increase in the number of trisomy 18 pregnancies detected (from 85.4% to 90.2%) for a small increase in the false-positive rate (from 0.20% to 0.29%) at a 1 in 100 late first trimester risk cut-off. Conclusion The revised truncation limits for PAPP-A and free β-hCG increase the accuracy of trisomy 18 risk estimation and improve screening performance using the Combined test. Validation and probability plots are useful in setting screening marker truncation limits.

First trimester Down's syndrome screening marker values and cigarette smoking: new data and a meta-analysis on free β human chorionic gonadotophin, pregnancy-associated plasma protein-A and nuchal translucency

2008 ◽  
Vol 15 (4) ◽  
pp. 204-206 ◽  
Author(s):  
Jonathan P Bestwick ◽  
Wayne J Huttly ◽  
Nicholas J Wald
Keyword(s):  
Meta Analysis ◽  
False Positive Rate ◽  
Protein A ◽  
First Trimester ◽  
Nuchal Translucency ◽  
Screening Performance ◽  
Combined Test ◽  
Positive Rate ◽  
Trimester Screening ◽  
Β Hcg

Objectives To examine the effect of smoking on three first trimester screening markers for Down's syndrome that constitute the Combined test, namely nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A) and free β human chorionic gonadotophin (free β-hCG) and to use the results to determine which of these markers need to be adjusted for smoking and by how much. Methods The difference in the median multiple of the median (MoM) values in smokers compared to non-smokers was determined for NT, PAPP-A and free β-hCG in 12,517 unaffected pregnancies that had routine first trimester Combined test screening. These results were then included in a meta-analysis of published studies and the effect of adjusting for smoking on screening performance of the Combined test was estimated. Results The results using the routine screening data were similar to the summary estimates from the meta-analysis of all studies. The results from the meta-analysis were; median MoM in smokers compared to non-smokers: 1.06 NT (95% confidence interval 1.03 to 1.10), 0.81 PAPP-A (0.80 to 0.83) and 0.94 free β-hCG (0.89 to 0.99). The effect of adjusting for smoking on the Combined test is small, with an estimated less than half percentage point increase in the detection rate (the proportion of affected pregnancies with a positive result) for a 3% false-positive rate (the proportion of unaffected pregnancies with a positive result) and less than 0.2 percentage point decrease in the false-positive rate for an 85% detection rate. Conclusion Adjusting first trimester screening markers for smoking has a minimal favourable effect on screening performance, but it is simple to implement and this paper provides the adjustment factors needed if a decision is made to make such an adjustment.

scholarly journals Pregnancy-associated plasma protein-A truncation limits in antenatal screening for trisomy 18

2017 ◽  
Vol 25 (1) ◽  
pp. 47-48 ◽  
Author(s):  
JP Bestwick ◽  
WJ Huttly ◽  
NJ Wald
Keyword(s):  
Detection Rate ◽  
False Positive Rate ◽  
Protein A ◽  
Trisomy 18 ◽  
Screening Tests ◽  
Antenatal Screening ◽  
Percentage Point Increase ◽  
Point Increase ◽  
Positive Rate ◽  
Singleton Pregnancies

Upper and lower truncation limits are commonly applied to quantitative markers used in medical screening tests. We here examine data on 375 trisomy 18 and 522,081 unaffected singleton pregnancies, to determine if the lower truncation limit should be set below the previously specified 0.2 multiples of the median. A lower truncation limit of 0.15 would reduce the underestimation of the risk of having a trisomy 18 pregnancy in about 50% of affected pregnancies and would lead to an estimated 10 percentage point increase in the detection rate, with only a very small increase in the false-positive rate.

Modified Multiple Marker Aneuploidy Screening as a Primary Screening Test for Preeclampsia

2021 ◽  
Author(s):  
Tianhua Huang ◽  
H. Melanie Bedford ◽  
Shamim Rashid ◽  
Evasha Rasasakaram ◽  
Megan Priston ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Early Onset ◽  
Biochemical Markers ◽  
Gestational Hypertension ◽  
First Trimester ◽  
Second Trimester ◽  
Aneuploidy Screening ◽  
Maternal Characteristics ◽  
Screening Performance ◽  
Β Hcg

Abstract Background: Maternal biochemical markers used in multiple marker aneuploidy screening have been associated with adverse pregnancy outcomes. This study aims to assess if a combination of maternal characteristics and biochemical markers in the first and second trimesters can be used to screen for preeclampsia (PE), gestational hypertension and preterm birth. Methods: This case-control study used information on maternal characteristics and residual blood samples from pregnant women who have undergone multiple marker aneuploidy screening. The median multiple of the median (MoM) of first and second trimester biochemical markers in cases (women with PE, gestational hypertension and preterm birth) and controls were compared. Biochemical markers included pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), human chorionic gonadotropin (hCG), alpha feto-protein (AFP), unconjugated estriol (uE3) and Inhibin A. Logistic regression analysis was used to estimate screening performance using different marker combinations. Screening performance was defined as detection rate (DR) and false positive rate (FPR). Preterm and early-onset preeclampsia PE were defined as women with PE delivered < 37 and < 34 weeks of gestation.Results: There were 147 pregnancies with PE (81 term, 49 preterm and 17 early-onset), 295 with gestational hypertension, and 166 preterm birth. Compared to controls, PE cases had significantly lower median MoM of PAPP-A (0.77 vs 1.10, p<0.0001), PlGF (0.76 vs 1.01, p<0.0001) and free-β hCG (0.81 vs. 0.98, p<0.001) in the first trimester along with PAPP-A (0.82 vs 0.99, p<0.01) and PlGF (0.75 vs 1.02, p<0.0001) in the second trimester. The lowest first trimester PAPP-A, PlGF and free β-hCG were seen in those with preterm and early-onset PE. At a 20% FPR, 67% of preterm and 76% of early-onset PE cases can be predicted using a combination of maternal characteristics with PAPP-A and PlGF in the first trimester.Conclusions: Maternal characteristics with first trimester PAPP-A and PlGF measured for aneuploidy screening provided reasonable accuracy in identifying women at risk of developing early onset PE, allowing triage of high-risk women for further investigation and risk-reducing therapy.

scholarly journals Clinical and Economic Evaluation after Adopting Contingent Cell-Free DNA Screening for Fetal Trisomies in South Spain

2020 ◽  
Vol 47 (10) ◽  
pp. 749-756
Author(s):  
José A. Sainz ◽  
María R. Torres ◽  
Ignacio Peral ◽  
Reyes Granell ◽  
Manuel Vargas ◽  
...  
Keyword(s):  
False Positive Rate ◽  
Cost Effective ◽  
First Trimester ◽  
Nuchal Translucency ◽  
University Hospitals ◽  
Combined Test ◽  
Positive Rate ◽  
Fetal Malformations ◽  
Cfdna Screening ◽  
Singleton Pregnancies

<b><i>Introduction:</i></b> Contingent cell-free (cf) DNA screening on the basis of the first-trimester combined test (FCT) results has emerged as a cost-effective strategy for screening of trisomy 21 (T21). <b><i>Objectives:</i></b> To assess performance, patients’ uptake, and cost of contingent cfDNA screening and to compare them with those of the established FCT. <b><i>Methods:</i></b> This is a prospective cohort study including all singleton pregnancies attending to their FCT for screening of T21 at 2 university hospitals in South Spain. When the FCT risk was ≥1:50, there were major fetal malformations, or the nuchal translucency was ≥3.5 mm, women were recommended invasive testing (IT); if the risk was between 1:50 and 1:270, women were recommended cfDNA testing; and for risks bellow 1:270, no further testing was recommended. Detection rate (DR), false-positive rate (FPR), patients’ uptake, and associated costs were evaluated. <b><i>Results:</i></b> We analyzed 10,541 women, including 46 T21 cases. DR of our contingent strategy was 89.1% (41/46) at 1.4% (146/10,541) FPR. Uptake of cfDNA testing was 91.2% (340/373), and overall IT rate was 2.0%. The total cost of our strategy was €1,462,895.7, similar to €1,446,525.7 had cfDNA testing not been available. <b><i>Conclusions:</i></b> Contingent cfDNA screening shows high DR, low IT rate, and high uptake at a similar cost than traditional screening.

scholarly journals Maternal Serum Invasive Trophoblast Antigen (Hyperglycosylated hCG) as a Screening Marker for Down Syndrome during the Second Trimester

2004 ◽  
Vol 50 (10) ◽  
pp. 1804-1808 ◽  
Author(s):  
Glenn E Palomaki ◽  
Louis M Neveux ◽  
George J Knight ◽  
James E Haddow ◽  
Raj Pandian
Keyword(s):  
United States ◽  
Down Syndrome ◽  
False Positive Rate ◽  
The United States ◽  
Maternal Serum ◽  
Second Trimester ◽  
Marker Panel ◽  
Screening Performance ◽  
Β Hcg ◽  
Screening Marker

Abstract Background: Approximately two million pregnancies in the United States are screened for Down syndrome annually by use of second-trimester maternal serum markers. At present, a combination of four markers can identify 75% of affected pregnancies when 5% of screened women are classified as candidates for amniocentesis. Although not currently included in screening panels, invasive trophoblast antigen (ITA) is a promising screening marker in serum or urine in both the second and first trimesters. This study aims at better defining the screening performance of serum ITA in the second trimester. Methods: In an earlier study, serum samples from an unbiased sampling of 45 Down syndrome (cases) and 238 unaffected (control) pregnancies between 14 and 20 weeks of gestation were collected from various centers in the United States. Samples were aliquoted and stored at −20 °C for 8 years. We measured ITA in these samples and determined the screening performance both univariately and in combination with other screening markers. Results: The median ITA in Down syndrome pregnancies was &gt;3.00 multiples of the median, higher than that found for human chorionic gonadotropin (hCG) or free β-hCG. At a 5% false-positive rate, ITA univariately detected 38% and 40% of Down syndrome pregnancies, respectively, when assigned by date of last menstrual period or ultrasound date. Modeling yielded rates of 45% and 48%. ITA correlated strongly with hCG and free β-hCG. When substituted for either of these in a multiple marker panel, ITA performed comparably. Conclusions: This study indicates that serum ITA is an effective marker for Down syndrome. It is highly correlated with both hCG and free β-hCG and could replace either of them in a multiple marker panel.

Performance of free β-human chorionic gonadotrophin (free β-hCG) and pregnancy associated plasma protein-A (PAPP-A) analysis between Delfia Xpress and AutoDelfia systems in The Netherlands

2009 ◽  
Vol 47 (2) ◽  
Author(s):  
Ingeborg H. Linskens ◽  
Marieke Levitus ◽  
Anneke Frans ◽  
Peter C.J.I. Schielen ◽  
John M.G. van Vugt ◽  
...  
Keyword(s):  
The Netherlands ◽  
Plasma Protein ◽  
Screening Program ◽  
Medical Center ◽  
Protein A ◽  
First Trimester ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Serum Samples ◽  
Β Hcg

Abstract: The VU University Medical Center (VUmc) was the first hospital in the Netherlands to introduce the Delfia Xpress for the analysis of free β-human chorionic gonadotrophin (β-hCG) and pregnancy associated plasma protein-A (PAPP-A) in the first trimester screening program for Down syndrome. Since then, others have implemented this system. In this study, we tested the equality of measurements for free β-hCG and PAPP-A between Delfia Xpress systems and one AutoDelfia system.: A total of 40 serum samples were aliquoted and stored at –20°C. Samples were analyzed by six Delfia Xpress systems and one AutoDelfia system over a time period of 2 years.: The relationships between free β-hCG and PAPP-A were excellent for the different Delfia Xpress systems (r>0.99, p<0.0001). For PAPP-A, the agreement between the main system at VUmc and five other systems was linear with slopes between 0.99 and 1.06. Similarly, agreement for free β-hCG was linear with slopes between 0.99 and 1.09. Likewise, agreement for PAPP-A and free β-hCG was excellent for the AutoDelfia vs. the main Delfia Xpress at the VUmc (r>0.99, p<0.0001). For both PAPP-A and free β-hCG, the relationships were linear with slopes of 1.08 and 1.07.: We demonstrate an excellent agreement for the analysis of PAPP-A and free β-hCG between Delfia Xpress systems and one AutoDelfia system.Clin Chem Lab Med 2009;47:222–6.

The influence of different sample collection types on the levels of markers used for Down's syndrome screening as measured by the Kryptor Immunosassay system

2003 ◽  
Vol 40 (2) ◽  
pp. 166-168 ◽  
Author(s):  
Kevin Spencer
Keyword(s):  
Processing Time ◽  
Point Of Care ◽  
Protein A ◽  
First Trimester ◽  
Maternal Serum ◽  
Blood Collection ◽  
Chromosomal Anomalies ◽  
Sample Collection ◽  
Edta Plasma ◽  
Β Hcg

Background: In a rapid point-of-care screening programme for chromosomal anomalies, analysis of biochemical markers in maternal blood can now be accomplished in a rapid time frame (less than 20 min). The need to leave whole blood samples some 10 min for coagulation and a further 5 min for centrifugation adds additional processing time. Methods: The possibilities for reducing this processing time were investigated using various anticoagulated blood collection systems and the Kryptor analytical platform. Plasma levels of α-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A) and free human chronic gonadotrophin β-subunit (β-hCG) were compared with those in maternal serum. Results: From the mean results from ten patients it was shown that use of heparin plasma resulted in a statistically significant reduction in levels of PAPP-A and that EDTA plasma reduced the levels of PAPP-A dramatically. For AFP, levels in citrated plasma and EDTA plasma were also significantly reduced, whereas levels of free β-hCG were not affected. Conclusion: Use of alternative sample types for PAPP-A is not possible. The sample of choice for first trimester screening using the Kryptor platform is maternal serum.

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