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Comparison of serum markers in first-trimester down syndrome screening.

AbstractOBJECTIVE:
To estimate patterns of total hCG and inhibin A levels in the late first trimester of Down syndrome pregnancies, compare them with that of free beta-hCG, and assess screening performance of these markers individually and in combination with pregnancy-associated plasma protein-A (PAPP-A) and nuchal translucency.
METHODS:
Seventy-nine matched case-control sets of maternal serum samples (each Down syndrome case matched to 5 controls) from 11 through 13 completed weeks of gestation were taken from the sample bank of the First and Second Trimester Evaluation of Risk Consortium, a population-based study, and assayed for levels of free beta-hCG, total hCG, and inhibin A. Distribution characteristics and correlations of the multiples of the median values were estimated in cases and controls. Screening performance for each marker, alone and in combination with PAPP-A, nuchal translucency, and maternal age, was calculated.
RESULTS:
Median multiples of the median levels of free beta-hCG, total hCG, and inhibin A in cases were more elevated as gestation increased from 11 to 13 weeks, with univariate detection rates of 31%, 23%, and 29%, respectively, at a 5% false-positive rate. At 12 weeks, the multivariate detection rates at a 5% false-positive rate for nuchal translucency and PAPP-A (with maternal age) with either free beta-hCG, total hCG, or inhibin A were 84%, 83%, and 85%, respectively. The improvement in performance from nuchal translucency and PAPP-A to any of the three-marker tests was significant, while performance of any of the three-marker combinations was not significantly different from each other.
CONCLUSION:
Although levels of free beta-hCG in affected pregnancies were higher earlier than the levels of either total hCG or inhibin A, there was no significant difference in screening performance when either of the three markers was used with nuchal translucency and PAPP-A at 11-13 weeks of pregnancy.
LEVEL OF EVIDENCE:
II-2.
AuthorsJacob A Canick, Geralyn M Lambert-Messerlian, Glenn E Palomaki, Louis M Neveux, Fergal D Malone, Robert H Ball, David A Nyberg, Christine H Comstock, Radek Bukowski, George R Saade, Richard L Berkowitz, Pe'er Dar, Lorraine Dugoff, Sabrina D Craigo, Ilan E Timor-Tritsch, Stephen R Carr, Honor M Wolfe, Mary E D'Alton, First and Second Trimester Evaluation of Risk (FASTER) Trial Research Consortium
JournalObstetrics and gynecology (Obstet Gynecol) Vol. 108 Issue 5 Pg. 1192-9 (Nov 2006) ISSN: 0029-7844 [Print] United States
PMID17077242 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
Chemical References
  • Biomarkers
  • Chorionic Gonadotropin
  • Chorionic Gonadotropin, beta Subunit, Human
  • inhibin A
  • Inhibins
  • Pregnancy-Associated Plasma Protein-A
Topics
  • Adult
  • Biomarkers
  • Case-Control Studies
  • Chorionic Gonadotropin (blood)
  • Chorionic Gonadotropin, beta Subunit, Human (blood)
  • Confidence Intervals
  • Down Syndrome (diagnosis)
  • Female
  • Gestational Age
  • Humans
  • Inhibins (blood)
  • Nuchal Translucency Measurement
  • Pregnancy
  • Pregnancy Trimester, First
  • Pregnancy-Associated Plasma Protein-A (analysis)
  • Prenatal Diagnosis
  • Ultrasonography, Prenatal

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