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Effect on Down syndrome screening performance of adjusting for marker levels in a previous pregnancy.

AbstractOBJECTIVES:
In prenatal screening for Down syndrome, serum marker values can be adjusted using values from a previous pregnancy to avoid the problem of women having a high chance of recurrent false-positive results. We investigate the effect of such adjustment on overall screening performance.
METHODS:
Monte Carlo simulation was used to investigate the effect of this adjustment on five widely used screening tests for Down syndrome (Triple, Quadruple, Combined, serum Integrated, Integrated tests).
RESULTS:
Adjustment for screening marker values (expressed in multiples of the median, (MoM)) in a previous pregnancy improved screening performance. The detection rate for a 1% false-positive rate (FPR) increased from 54 to 59% with the Triple test, from 63 to 68% with the Quadruple test, from 70 [corrected] to 75% for the Combined test, from 70 [corrected] to 76% for the serum Integrated test, and from 85 to 88% for the Integrated test. The FPR for an 85% detection rate decreased from 10 to 7.9%, 7.1 to 4.9%, 4.9 to 3.7%, 4.7 to 2.9% and 1.1 to 0.7% respectively for the five tests. Among women who have had a false-positive result in a previous pregnancy, adjustment substantially lowers the false-positive rate, for example, from 18 [corrected] to 7.3% with the Combined test using a 1 in 250 risk cut-off.
CONCLUSION:
MoM adjustment for values in a previous pregnancy improves overall screening performance and substantially reduces the high recurrent false-positive rate. This adjustment can be routinely applied in screening programmes through the screening software used to interpret a woman's screening results.
AuthorsNicholas J Wald, Isobel M Barnes, Ruthie Birger, Wayne Huttly
JournalPrenatal diagnosis (Prenat Diagn) Vol. 26 Issue 6 Pg. 539-44 (Jun 2006) ISSN: 0197-3851 [Print] England
PMID16634123 (Publication Type: Evaluation Study, Journal Article)
CopyrightCopyright 2006 John Wiley & Sons, Ltd.
Chemical References
  • Biomarkers
  • Chorionic Gonadotropin, beta Subunit, Human
  • Pregnancy-Associated Plasma Protein-A
Topics
  • Adolescent
  • Adult
  • Biomarkers (blood)
  • Chorionic Gonadotropin, beta Subunit, Human (blood)
  • Down Syndrome (diagnosis, embryology)
  • False Positive Reactions
  • Female
  • Gestational Age
  • Gravidity
  • Humans
  • Maternal Age
  • Middle Aged
  • Models, Theoretical
  • Nuchal Translucency Measurement (methods, statistics & numerical data)
  • Pregnancy
  • Pregnancy Trimester, First (blood)
  • Pregnancy Trimester, Second (blood)
  • Pregnancy-Associated Plasma Protein-A (analysis)
  • Prenatal Diagnosis (methods)
  • Risk Adjustment (methods)

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