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. 2012;7(10):e46955.
doi: 10.1371/journal.pone.0046955. Epub 2012 Oct 3.

Antenatal screening for Down syndrome using serum placental growth factor with the combined, quadruple, serum integrated and integrated tests

Nicholas J Wald  1 , Jonathan P Bestwick, Lynne M George, Wayne J Huttly
Affiliations

Antenatal screening for Down syndrome using serum placental growth factor with the combined, quadruple, serum integrated and integrated tests

Nicholas J Wald et al. PLoS One. 2012.

Abstract

Objective: To estimate the value of first or second trimester placental growth factor (PlGF) as an additional antenatal screening marker for Down syndrome.

Design: Nested case-control study.

Setting: Antenatal screening service.

Population or sample: 532 Down syndrome pregnancies and 1,155 matched unaffected pregnancies.

Methods: Stored maternal serum samples (-40°C) were assayed for PlGF. Monte Carlo simulation was used to estimate the screening performance of PlGF with the Combined, Quadruple, serum Integrated and Integrated tests.

Main outcome measures: Median PlGF levels in affected and unaffected pregnancies and screening performance (detection rates [DR] for specified false-positive rates [FPR] and vice versa).

Results: First trimester median PlGF was 15%, 28% and 39% lower in Down syndrome than unaffected pregnancies at 11, 12 and 13 completed weeks' gestation respectively (all p<0.001). Second trimester median PlGF was 31% lower at 14 weeks (p<0.001), and the difference decreased (6% lower at 17 weeks). At a 90% DR with first trimester markers measured at 13 weeks, adding PlGF decreased the FPR from 11.1 to 5.1% using the Combined test, 9.3% to 4.5% using the serum Integrated test, and 3.4% to 1.5% using the Integrated test (or 1.5 to 1.4% with first trimester markers measured at 11 weeks). Adding PlGF to the Quadruple test (measured at 15 weeks) decreased the FPR from 10.0% to 9.6% at a 90% DR.

Conclusions: First trimester PlGF measurements improve the performance of antenatal screening for Down syndrome using the Combined, serum Integrated and Integrated tests. Second trimester PlGF measurements are of limited value.

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Conflict of interest statement

Competing Interests: The authors have the following interests: PerkinElmer provided the PlGF assay kits free of charge. N. Wald has a patent for the Integrated test as follows: Application No.; Country; Filing Date; Patent No.; Issue/Grant Date 09/301,621; US; 29.04.99; 6,573,103; 03.06.03 36213/99; Australia; 29.04.99; 763171; 31.10.06 2330538; Canada; 29.04.99; 2330538; 11.09.07 99918188; Europe; 29.04.99; 1076824; 14.06.06 139302; Israel; 29.04.99; 139302; 26.10.05 With others, he held a patent in connection with the use of uE3 as a second trimester screening marker in prenatal screening for Down syndrome, although this has now expired. He is Director of Logical Medical Systems Ltd, which produces software for the interpretation of Down syndrome screening tests. There are no further patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Figure 1
Figure 1. First trimester (a) and second trimester (b) placental growth factor (PlGF) according to gestational age in Down syndrome pregnancies (circles) and medians in 2-day intervals* (a) and weekly intervals (b) in unaffected pregnancies (squares, with 95% confidence intervals) together with expected (regressed) median in unaffected pregnancies.
Figure 2
Figure 2. First trimester (a) and second trimester (b) placental growth factor (PlGF) maternal weight, smoking and ethnicity adjusted MoM values according to gestational age and medians (squares, with 95% confidence intervals) in 2-day intervals* (a) and weekly intervals (b) in Down syndrome pregnancies together with expected (regressed) median.
See this image and copyright information in PMC

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