Second trimester serum tests for Down's Syndrome screening

Department of Women’s and Children’s Health, The University of Liverpool, Liverpool, UK. .
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 06/2012; 6(6):CD009925. DOI: 10.1002/14651858.CD009925
Source: PubMed


Down's syndrome occurs when a person has three copies of chromosome 21 - or the specific area of chromosome 21 implicated in causing Down's syndrome - rather than two. It is the commonest congenital cause of mental retardation. Noninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing.
To estimate and compare the accuracy of second trimester serum markers for the detection of Down's syndrome.
We carried out a sensitive and comprehensive literature search of MEDLINE (1980 to May 2007), EMBASE (1980 to 18 May 2007), BIOSIS via EDINA (1985 to 18 May 2007), CINAHL via OVID (1982 to 18 May 2007), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 2007, Issue 1), MEDION (May 2007), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (May 2007), The National Research Register (May 2007), Health Services Research Projects in Progress database (May 2007). We studied reference lists and published review articles.
Studies evaluating tests of maternal serum in women at 14-24 weeks of gestation for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection.
Data were extracted as test positive/test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS criteria. We used hierarchical summary ROC meta-analytical methods to analyse test performance and compare test accuracy. Analysis of studies allowing direct comparison between tests was undertaken. We investigated the impact of maternal age on test performance in subgroup analyses.
Fifty-nine studies involving 341,261 pregnancies (including 1,994 with Down's syndrome) were included. Studies were generally high quality, although differential verification was common with invasive testing of only high-risk pregnancies. Seventeen studies made direct comparisons between tests. Fifty-four test combinations were evaluated formed from combinations of 12 different tests and maternal age; alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free beta human chorionic gonadotrophin (βhCG), free alpha human chorionic gonadotrophin (αhCG), Inhibin A, SP2, CA125, troponin, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PGF) and proform of eosinophil major basic protein (ProMBP).Meta-analysis of 12 best performing or frequently evaluated test combinations showed double and triple tests (involving AFP, uE3, total hCG, free βhCG) significantly outperform individual markers, detecting six to seven out of every 10 Down's syndrome pregnancies at a 5% false positive rate. Tests additionally involving inhibin performed best (eight out of every 10 Down's syndrome pregnancies) but were not shown to be significantly better than standard triple tests in direct comparisons. Significantly lower sensitivity occurred in women over the age of 35 years. Women who miscarried in the over 35 group were more likely to have been offered an invasive test to verify a negative screening results, whereas those under 35 were usually not offered invasive testing for a negative screening result. Pregnancy loss in women under 35 therefore leads to under ascertainment of screening results, potentially missing a proportion of affected pregnancies and affecting the accuracy of the sensitivity.
Tests involving two or more markers in combination with maternal age are significantly more sensitive than those involving one marker. The value of combining four or more tests or including inhibin have not been proven to show statistically significant improvement. Further study is required to investigate reduced test performance in women aged over 35 and the impact of differential pregnancy loss on study findings.

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  • 03/2014; 1(1):25-27. DOI:10.1007/s40556-014-0009-8
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    ABSTRACT: BACKGROUND: Down's syndrome is an important congenital chromosomal disorder that can be seen around the world. The antenatal screening for this disorder is an important processing in present obstetrics. OBJECTIVE: Due to the concept of first do no harm, the use of noninvasive test is recommended. The triple marker screening test has been introduced for a few years and acceptable for its efficacy. RESULT: However, an important concern is on its cost-effectiveness. Here, the author analyze and present the cost-effectiveness of the triple markers serum screening for Down's syndrome in Thai setting. CONCLUSION: According to this work, the cost per effectiveness of triple markers serum screening is slightly lower than standard amniocentesis test.
    Indian Journal of Human Genetics 04/2014; 20(2):153-4. DOI:10.4103/0971-6866.142880
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    ABSTRACT: ABSTRACT Objective: Second-trimester maternal serum screening has become a routine part of prenatal care. We aimed to identify if triple test measurements were affected by regional differences and maternal factors. We compared our results with the results of a previous study on Turkish population, and with the values of the manufacturer firm. Material and Methods: The study group consisted of 984 pregnant women between 14–22 weeks of gestation who had undergone a triple test. The original PRISCA software was used for calculating the statistical risk. Results: Comparison of median values for serum AFP, between published Turkish population, manufacturer values and Gaziantep population were: 1% between Gaziantep population and Turkish population, and 3 % between Gaziantep population and manufacturer values in 16. gestational week; 5 % and 4 % in 17. gestational week; 13 % and 14 % in 18. gestational week, respectively. 19. gestational week showed no difference. Same comparison for β-hCG showed; 5 % and 1 % in 16. gestational week; 4 % and 2 % in 17. gestational week; 13 % and 1 % in 18. gestational week; 1 % and 24 % in 19. gestational week, respectively. Comparison for uE3 values showed; 36 % and 95 % in 16. gestational week; 39 % and 89 % in 17. gestational week; 25 % and 67 % in 18. gestational week; 34 % and 72 % in 19. gestational week, respectively. Conclusion: This study showed that, screening tests may vary based on regional differences. Our study presents a potential risk factor that may be an explanation for some problems with the triple test evaluations in some laboratories.
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