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Cochrane Database of Systematic Reviews

First and second trimester serum tests with and without first trimester ultrasound tests for Down's syndrome screening

Overview of attention for article published in Cochrane database of systematic reviews, March 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (77th percentile)
  • Average Attention Score compared to outputs of the same age and source

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First and second trimester serum tests with and without first trimester ultrasound tests for Down's syndrome screening
Published in
Cochrane database of systematic reviews, March 2017
DOI 10.1002/14651858.cd012599
Pubmed ID

S Kate Alldred, Yemisi Takwoingi, Boliang Guo, Mary Pennant, Jonathan J Deeks, James P Neilson, Zarko Alfirevic


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 disability. Non-invasive 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.  Before agreeing to screening tests, parents need to be fully informed about the risks, benefits and possible consequences of such a test. This includes subsequent choices for further tests they may face, and the implications of both false positive (i.e. invasive diagnostic testing, and the possibility that a miscarried fetus may be chromosomally normal) and false negative screening tests (i.e. a fetus with Down's syndrome will be missed). The decisions that may be faced by expectant parents inevitably engender a high level of anxiety at all stages of the screening process, and the outcomes of screening can be associated with considerable physical and psychological morbidity. No screening test can predict the severity of problems a person with Down's syndrome will have. To estimate and compare the accuracy of first and second trimester serum markers with and without first trimester ultrasound markers for the detection of Down's syndrome in the antenatal period, as combinations of markers. We conducted a sensitive and comprehensive literature search of MEDLINE (1980 to 25 August 2011), Embase (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), the Database of Abstracts of Reviews of Effectiveness (the Cochrane Library 25 August 2011), MEDION (25 August 2011), the Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (25 August 2011), the National Research Register (Archived 2007), and Health Services Research Projects in Progress database (25 August 2011). We did not apply a diagnostic test search filter. We did forward citation searching in ISI citation indices, Google Scholar and PubMed 'related articles'. We also searched reference lists of retrieved articles SELECTION CRITERIA: Studies evaluating tests of combining first and second trimester maternal serum markers in women up to 24 weeks of gestation for Down's syndrome, with or without first trimester ultrasound markers, 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. Twenty-two studies (reported in 25 publications) involving 228,615 pregnancies (including 1067 with Down's syndrome) were included. Studies were generally high quality, although differential verification was common with invasive testing of only high risk pregnancies. Ten studies made direct comparisons between tests. Thirty-two different test combinations were evaluated formed from combinations of eight different tests and maternal age; first trimester nuchal translucency (NT) and the serum markers AFP, uE3, total hCG, free βhCG, Inhibin A, PAPP-A and ADAM 12. We looked at tests combining first and second trimester markers with or without ultrasound as complete tests, and we also examined stepwise and contingent strategies.Meta-analysis of the six most frequently evaluated test combinations showed that a test strategy involving maternal age and a combination of first trimester NT and PAPP-A, and second trimester total hCG, uE3, AFP and Inhibin A significantly outperformed other test combinations that involved only one serum marker or NT in the first trimester, detecting about nine out of every 10 Down's syndrome pregnancies at a 5% false positive rate. However, the evidence was limited in terms of the number of studies evaluating this strategy, and we therefore cannot recommend one single screening strategy. Tests involving first trimester ultrasound with first and second trimester serum markers in combination with maternal age are significantly better than those without ultrasound, or those evaluating first trimester ultrasound in combination with second trimester serum markers, without first trimester serum markers. We cannot make recommendations about a specific strategy on the basis of the small number of studies available.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 195 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 195 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 34 17%
Student > Bachelor 29 15%
Researcher 28 14%
Student > Ph. D. Student 16 8%
Other 14 7%
Other 30 15%
Unknown 44 23%
Readers by discipline Count As %
Medicine and Dentistry 61 31%
Psychology 20 10%
Nursing and Health Professions 17 9%
Social Sciences 14 7%
Biochemistry, Genetics and Molecular Biology 6 3%
Other 21 11%
Unknown 56 29%

Attention Score in Context

This research output has an Altmetric Attention Score of 8. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 April 2018.
All research outputs
of 12,858,386 outputs
Outputs from Cochrane database of systematic reviews
of 10,449 outputs
Outputs of similar age
of 252,650 outputs
Outputs of similar age from Cochrane database of systematic reviews
of 265 outputs
Altmetric has tracked 12,858,386 research outputs across all sources so far. Compared to these this one has done well and is in the 84th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 10,449 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 20.3. This one has gotten more attention than average, scoring higher than 55% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 252,650 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 77% of its contemporaries.
We're also able to compare this research output to 265 others from the same source and published within six weeks on either side of this one. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.