Role of second-trimester genetic sonography after down syndrome screening

Kjersti M. Aagaard-Tillery, Fergal D. Malone, David A. Nyberg, T. Flint Porter, Howard S. Cuckle, Karin Fuchs, Lisa Sullivan, Christine H. Comstock, George Saade, Keith Eddleman, Susan Gross, Lorraine Dugoff, Sabrina D. Craigo, Ilan E. Timor-Tritsch, Stephen R. Carr, Honor M. Wolfe, Diana W. Bianchi, Mary E. D'Alton

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: To estimate the effectiveness of second-trimester genetic sonography in modifying Down syndrome screening test results. METHODS: The First and Second Trimester Evaluation of Risk (FASTER) aneuploidy screening trial participants were studied from 13 centers where a 15-to 23-week genetic sonogram was performed in the same center. Midtrimester Down syndrome risks were estimated for five screening test policies: first-trimester combined, second-trimester quadruple, and testing sequentially by integrated, stepwise, or contingent protocols. The maternal age-specific risk and the screening test risk were modified using likelihood ratios derived from the ultrasound findings. Separate likelihood ratios were obtained for the presence or absence of at least one major fetal structural malformation and for each "soft" sonographic marker statistically significant at the P<.005 level. Detection and false-positive rate were calculated for the genetic sonogram alone and for each test before and after risk modification. RESULTS: A total of 7,842 pregnancies were studied, including 59 with Down syndrome. Major malformations and 8 of the 18 soft markers evaluated were highly significant. The detection rate for a 5% false-positive rate for the genetic sonogram alone was 69%; the detection rate increased from 81% to 90% with the combined test, from 81% to 90% with the quadruple test, from 93% to 98% with the integrated test, from 97% to 98% with the stepwise test, and from 95% to 97% with the contingent test. The stepwise and contingent use of the genetic sonogram after first-trimester screening both yielded a 90% detection rate. CONCLUSION: Genetic sonography can increase detection rates substantially for combined and quadruple tests and more modestly for sequential protocols. Substituting sonography for quadruple markers in sequential screening was not useful.

Original languageEnglish (US)
Pages (from-to)1189-1196
Number of pages8
JournalObstetrics and Gynecology
Volume114
Issue number6
DOIs
StatePublished - Dec 2009
Externally publishedYes

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Second Pregnancy Trimester
Down Syndrome
Ultrasonography
First Pregnancy Trimester
Maternal Age
Aneuploidy
Pregnancy

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Aagaard-Tillery, K. M., Malone, F. D., Nyberg, D. A., Porter, T. F., Cuckle, H. S., Fuchs, K., ... D'Alton, M. E. (2009). Role of second-trimester genetic sonography after down syndrome screening. Obstetrics and Gynecology, 114(6), 1189-1196. https://doi.org/10.1097/AOG.0b013e3181c15064

Role of second-trimester genetic sonography after down syndrome screening. / Aagaard-Tillery, Kjersti M.; Malone, Fergal D.; Nyberg, David A.; Porter, T. Flint; Cuckle, Howard S.; Fuchs, Karin; Sullivan, Lisa; Comstock, Christine H.; Saade, George; Eddleman, Keith; Gross, Susan; Dugoff, Lorraine; Craigo, Sabrina D.; Timor-Tritsch, Ilan E.; Carr, Stephen R.; Wolfe, Honor M.; Bianchi, Diana W.; D'Alton, Mary E.

In: Obstetrics and Gynecology, Vol. 114, No. 6, 12.2009, p. 1189-1196.

Research output: Contribution to journalArticle

Aagaard-Tillery, KM, Malone, FD, Nyberg, DA, Porter, TF, Cuckle, HS, Fuchs, K, Sullivan, L, Comstock, CH, Saade, G, Eddleman, K, Gross, S, Dugoff, L, Craigo, SD, Timor-Tritsch, IE, Carr, SR, Wolfe, HM, Bianchi, DW & D'Alton, ME 2009, 'Role of second-trimester genetic sonography after down syndrome screening', Obstetrics and Gynecology, vol. 114, no. 6, pp. 1189-1196. https://doi.org/10.1097/AOG.0b013e3181c15064
Aagaard-Tillery KM, Malone FD, Nyberg DA, Porter TF, Cuckle HS, Fuchs K et al. Role of second-trimester genetic sonography after down syndrome screening. Obstetrics and Gynecology. 2009 Dec;114(6):1189-1196. https://doi.org/10.1097/AOG.0b013e3181c15064
Aagaard-Tillery, Kjersti M. ; Malone, Fergal D. ; Nyberg, David A. ; Porter, T. Flint ; Cuckle, Howard S. ; Fuchs, Karin ; Sullivan, Lisa ; Comstock, Christine H. ; Saade, George ; Eddleman, Keith ; Gross, Susan ; Dugoff, Lorraine ; Craigo, Sabrina D. ; Timor-Tritsch, Ilan E. ; Carr, Stephen R. ; Wolfe, Honor M. ; Bianchi, Diana W. ; D'Alton, Mary E. / Role of second-trimester genetic sonography after down syndrome screening. In: Obstetrics and Gynecology. 2009 ; Vol. 114, No. 6. pp. 1189-1196.
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T1 - Role of second-trimester genetic sonography after down syndrome screening

AU - Aagaard-Tillery, Kjersti M.

AU - Malone, Fergal D.

AU - Nyberg, David A.

AU - Porter, T. Flint

AU - Cuckle, Howard S.

AU - Fuchs, Karin

AU - Sullivan, Lisa

AU - Comstock, Christine H.

AU - Saade, George

AU - Eddleman, Keith

AU - Gross, Susan

AU - Dugoff, Lorraine

AU - Craigo, Sabrina D.

AU - Timor-Tritsch, Ilan E.

AU - Carr, Stephen R.

AU - Wolfe, Honor M.

AU - Bianchi, Diana W.

AU - D'Alton, Mary E.

PY - 2009/12

Y1 - 2009/12

N2 - OBJECTIVE: To estimate the effectiveness of second-trimester genetic sonography in modifying Down syndrome screening test results. METHODS: The First and Second Trimester Evaluation of Risk (FASTER) aneuploidy screening trial participants were studied from 13 centers where a 15-to 23-week genetic sonogram was performed in the same center. Midtrimester Down syndrome risks were estimated for five screening test policies: first-trimester combined, second-trimester quadruple, and testing sequentially by integrated, stepwise, or contingent protocols. The maternal age-specific risk and the screening test risk were modified using likelihood ratios derived from the ultrasound findings. Separate likelihood ratios were obtained for the presence or absence of at least one major fetal structural malformation and for each "soft" sonographic marker statistically significant at the P<.005 level. Detection and false-positive rate were calculated for the genetic sonogram alone and for each test before and after risk modification. RESULTS: A total of 7,842 pregnancies were studied, including 59 with Down syndrome. Major malformations and 8 of the 18 soft markers evaluated were highly significant. The detection rate for a 5% false-positive rate for the genetic sonogram alone was 69%; the detection rate increased from 81% to 90% with the combined test, from 81% to 90% with the quadruple test, from 93% to 98% with the integrated test, from 97% to 98% with the stepwise test, and from 95% to 97% with the contingent test. The stepwise and contingent use of the genetic sonogram after first-trimester screening both yielded a 90% detection rate. CONCLUSION: Genetic sonography can increase detection rates substantially for combined and quadruple tests and more modestly for sequential protocols. Substituting sonography for quadruple markers in sequential screening was not useful.

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