Down's syndrome screening: population statistic dependency of screening performance

Objectives To determine the second trimester Down's syndrome screening performance of maternal serum dimeric inhibin A, both alone and in combination with existing serum markers. Setting A case-control set of serum samples from patients with Down's syndrome (52) and subjects with matched unaffected pregnancies obtained in a previous cohort study before second trimester amniocentesis and karyotyping. The amniocenteses were performed for reasons other than a positive serum screening test result. Methods For each serum from a Down's syndrome pregnancy, five serum samples from pregnancies with a normal karyotype were matched for recruitment centre, gestational age, maternal age, and date of amniocentesis. A specific form of inhibin (dimeric inhibin A) was measured using monoclonal antibodies. Measurements of α fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin and its free β subunit were already available. Screening performance was modelled using distribution variables of the analytes coupled with the 1993 age distribution of pregnant women in the United States. Results The median dimeric inhibin A level was 2.10 times higher in Down's syndrome pregnancies. When dimeric inhibin A was combined with maternal age and three other serum markers (α fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin) the Down's syndrome detection rate increased to 75% (from 66%) at a 5% false positive rate. If dimeric inhibin A could be added for less than &dollar;31 (ranging from &dollar;16 to &dollar;39 depending on the detection rate, markers chosen, and method of dating), the cost of detecting each Down's syndrome pregnancy and the number of procedure related fetal losses would both be reduced. Conclusions The addition of dimeric inhibin A to prenatal screening programmes for Down's syndrome should be considered, or possibly it could be substituted for an existing serum marker. One barrier to implementation in the United States, however, is the unavailability of kits with Food and Drug Administration approval.

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Evaluation of Down's syndrome screening population data sets by simulation: analyser-specific parameters may be superior to meta-analysis-derived parameters

International Journal of Clinical Practice ◽

10.1111/j.1742-1241.2007.01287.x ◽

2007 ◽

Vol 62 (5) ◽

pp. 735-743 ◽

Cited By ~ 2

Author(s):

T. M. Reynolds ◽

G. Vranken ◽

J. Van Nueten ◽

J. Aldis

Keyword(s):

Meta Analysis ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Population Data ◽

Data Sets ◽

Screening Population

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Empirical Validation of Risk Screening for Down's Syndrome

Journal of Medical Screening ◽

10.1177/096914139600300405 ◽

1996 ◽

Vol 3 (4) ◽

pp. 185-187 ◽

Cited By ~ 30

Author(s):

N J Wald ◽

A K Hackshaw ◽

W Huttly ◽

A Kennard

Keyword(s):

Maternal Age ◽

Risk Group ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Maternal Serum ◽

Individual Risk ◽

Triple Test ◽

Risk Estimates ◽

Screening Performance ◽

Predicted Risk

Objective— To validate individual risk estimates in antenatal serum screening for Down's syndrome. Methods— Women screened for Down's syndrome using maternal serum a fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotrophs (hCG) with maternal age (the triple test) or AFP, uE3, free β subunit and free a 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. Subjects— About 100 000 pregnant women screened for Down's syndrome from 1989 to 1995. Results— 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. Conclusion— 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.

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Combined First-Trimester Screening in Northern Finland: Experiences of the First Ten Years

Clinical Medicine Insights Reproductive Health ◽

10.4137/cmrh.s14958 ◽

2014 ◽

Vol 8 ◽

pp. CMRH.S14958

Author(s):

Merilainen Anna ◽

Peuhkurinen Sini ◽

Honkasalo Timppa ◽

Laitinen Paivi ◽

Kokkonen Hannaleena ◽

...

Keyword(s):

Detection Rate ◽

False Positive Rate ◽

Down's Syndrome ◽

Down’S Syndrome ◽

First Trimester ◽

First Trimester Screening ◽

Invasive Procedures ◽

Screening Performance ◽

Positive Rate ◽

Trimester Screening

Objective To evaluate the efficacy of first trimester combined screening for Down's syndrome in Northern Finland during the first 10 years of practice. Methods During 1 January 2002 to 31 December 2011, 47,896 women participated voluntarily in combined screening during first trimester. The risk cutoff was 1:250. The study period was divided into two time periods; 2002-2006 and 2007-2011. Results During the first half of the study period, the detection rate (DR) was 77.3% with a 4.9% false-positive rate (FPR). During the latter half, the DR was 77.1% with a 2.8% FPR. Conclusions An important issue is the number of invasive procedures needed to detect one case of Down's syndrome. The screening performance improved markedly in the latter five years period since the FPR lowered from 4.9% to 2.8% and the number of invasive procedures needed to detect one case of Down's syndrome lowered from 15 to 11.

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Can Reliable Down's Syndrome Detection Rates Be Determined from Prenatal Screening Intervention Trials?

Journal of Medical Screening ◽

10.1177/096914139600300105 ◽

1996 ◽

Vol 3 (1) ◽

pp. 12-17 ◽

Cited By ~ 28

Author(s):

Glenn E Palomaki ◽

Louis M Neveux ◽

James E Haddow

Keyword(s):

Prenatal Screening ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Intervention Trial ◽

Detection Rates ◽

Live Births ◽

Screening Performance ◽

Overall Performance ◽

Collective Performance ◽

Intervention Trials

Objectives— To develop a standardised approach for analysing Down's syndrome screening performance in clinical practice and to apply it to published intervention trials in order to estimate detection and false positive rates more accurately. Methods— Peer reviewed intervention trials, grouped by specific combination of analytes, were reanalysed. Revised detection rates were calculated for each study, taking into account both the high spontaneous loss during the last half of pregnancy and the possible under ascertainment of Down's syndrome live births not detected by screening. Collective screening performance was estimated, when possible, using a published methodology based on fitting receiver—operator characteristic curves. Results— Sixteen trials were analysed; 11 using three, and five using two, analytes. Collective screening performance for the triple analyte trials was Down's syndrome detection rates of 57, 64, and 69% at amniocentesis referral rates of 3, 5, and 7% respectively. Four of the five studies involving two analytes performed less well, individually, when compared with the overall performance of the three analyte studies. It was not possible to estimate collective performance for the two analyte studies because there were too few. Conclusions— Accurate Down's syndrome detection rates are difficult to obtain in intervention trials owing to two potential biases, both of which tend to produce overestimates of the true rates. These sources of bias need to be taken into account when analysing and reporting Down's syndrome intervention trials. The methodology presented here offers the opportunity to achieve a more reliable, standardised estimate of both individual and collective intervention trial screening performance.

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