Comparison of serum markers in first-trimester Down syndrome screening

Jacob 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 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

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: 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 β-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 β-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 β-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 β-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 β-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.

Original languageEnglish (US)
Pages (from-to)1192-1199
Number of pages8
JournalObstetrics and Gynecology
Volume108
Issue number5
DOIs
StatePublished - Nov 2006
Externally publishedYes

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Pregnancy-Associated Plasma Protein-A
Nuchal Translucency Measurement
First Pregnancy Trimester
Down Syndrome
Biomarkers
Pregnancy
Maternal Age
Second Pregnancy Trimester
Mothers
inhibin A
Serum
Population

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Canick, J. A., Lambert-Messerlian, G. M., Palomaki, G. E., Neveux, L. M., Malone, F. D., Ball, R. H., ... D'Alton, M. E. (2006). Comparison of serum markers in first-trimester Down syndrome screening. Obstetrics and Gynecology, 108(5), 1192-1199. https://doi.org/10.1097/01.AOG.0000241095.19638.f2

Comparison of serum markers in first-trimester Down syndrome screening. / Canick, Jacob A.; Lambert-Messerlian, Geralyn M.; Palomaki, Glenn E.; Neveux, Louis M.; Malone, Fergal D.; Ball, Robert H.; Nyberg, David A.; Comstock, Christine H.; Bukowski, Radek; Saade, George; Berkowitz, Richard L.; Dar, Pe'er; Dugoff, Lorraine; Craigo, Sabrina D.; Timor-Tritsch, Ilan E.; Carr, Stephen R.; Wolfe, Honor M.; D'Alton, Mary E.

In: Obstetrics and Gynecology, Vol. 108, No. 5, 11.2006, p. 1192-1199.

Research output: Contribution to journalArticle

Canick, JA, Lambert-Messerlian, GM, Palomaki, GE, Neveux, LM, Malone, FD, Ball, RH, Nyberg, DA, Comstock, CH, Bukowski, R, Saade, G, Berkowitz, RL, Dar, P, Dugoff, L, Craigo, SD, Timor-Tritsch, IE, Carr, SR, Wolfe, HM & D'Alton, ME 2006, 'Comparison of serum markers in first-trimester Down syndrome screening', Obstetrics and Gynecology, vol. 108, no. 5, pp. 1192-1199. https://doi.org/10.1097/01.AOG.0000241095.19638.f2
Canick JA, Lambert-Messerlian GM, Palomaki GE, Neveux LM, Malone FD, Ball RH et al. Comparison of serum markers in first-trimester Down syndrome screening. Obstetrics and Gynecology. 2006 Nov;108(5):1192-1199. https://doi.org/10.1097/01.AOG.0000241095.19638.f2
Canick, Jacob A. ; Lambert-Messerlian, Geralyn M. ; Palomaki, Glenn E. ; Neveux, Louis M. ; Malone, Fergal D. ; Ball, Robert H. ; Nyberg, David A. ; Comstock, Christine H. ; Bukowski, Radek ; Saade, George ; Berkowitz, Richard L. ; Dar, Pe'er ; Dugoff, Lorraine ; Craigo, Sabrina D. ; Timor-Tritsch, Ilan E. ; Carr, Stephen R. ; Wolfe, Honor M. ; D'Alton, Mary E. / Comparison of serum markers in first-trimester Down syndrome screening. In: Obstetrics and Gynecology. 2006 ; Vol. 108, No. 5. pp. 1192-1199.
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T1 - Comparison of serum markers in first-trimester Down syndrome screening

AU - Canick, Jacob A.

AU - Lambert-Messerlian, Geralyn M.

AU - Palomaki, Glenn E.

AU - Neveux, Louis M.

AU - Malone, Fergal D.

AU - Ball, Robert H.

AU - Nyberg, David A.

AU - Comstock, Christine H.

AU - Bukowski, Radek

AU - Saade, George

AU - Berkowitz, Richard L.

AU - Dar, Pe'er

AU - Dugoff, Lorraine

AU - Craigo, Sabrina D.

AU - Timor-Tritsch, Ilan E.

AU - Carr, Stephen R.

AU - Wolfe, Honor M.

AU - D'Alton, Mary E.

PY - 2006/11

Y1 - 2006/11

N2 - OBJECTIVE: 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 β-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 β-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 β-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 β-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 β-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.

AB - OBJECTIVE: 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 β-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 β-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 β-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 β-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 β-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.

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