Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2010 Feb;115(2 Pt 1):297-303.
doi: 10.1097/AOG.0b013e3181cbc652.

Comparison of multiplex ligation-dependent probe amplification and karyotyping in prenatal diagnosis

Elisabeth M Boormans  1 , Erwin Birnie, Dick Oepkes, Robert Jan Galjaard, Gijsbertha H Schuring-Blom, Jan M van Lith; MLP and Karyotyping Evaluation (M.A.K.E.) Study Group
Affiliations
Comparative Study

Comparison of multiplex ligation-dependent probe amplification and karyotyping in prenatal diagnosis

Elisabeth M Boormans et al. Obstet Gynecol. 2010 Feb.

Abstract

Objective: To estimate whether multiplex ligation-dependent probe amplification (MLPA), a molecular technique used for detecting the most common chromosomal aneuploidies, is comparable with karyotyping for the detection of aneuploidies of chromosomes X, Y, 13, 18, and 21 in routine clinical practice and to estimate the costs differences of both techniques.

Methods: In this prospective, nationwide cohort study, we consecutively included 4,585 women who had an amniocentesis because of their age (36 years or older), increased risk after prenatal screening, or maternal anxiety. Amniotic fluid samples were tested independently with both MLPA and karyotyping. The primary outcome was diagnostic accuracy of MLPA to detect aneuploidies of chromosomes X, Y, 13, 18, and 21. Secondary outcome measures were turnaround time for test results and costs. A sample size was calculated using a critical noninferiority margin of 0.002; therefore, at least 4,497 paired test results were needed (one-sided alpha 0.05, power 0.90).

Results: Diagnostic accuracy of MLPA was 1.0 (95% confidence interval [CI] 0.99-1.0), sensitivity was 100% (95% CI 0.96-1.0) and specificity was 100% (95% CI 0.999-1.0). Diagnostic accuracy of MLPA was statistically similar (noninferior) to that of karyotyping (P<.001). In 75 cases, MLPA failed (1.6%); karyotyping failed once (0.02%). Compared with karyotyping, MLPA shortened the waiting time by 14.5 days (P<.001, 95% CI 14.3-14.6) and cost less (-47, P<.001).

Conclusion: In routine clinical practice, diagnostic accuracy of MLPA for detection of trisomies X, Y, 13, 18, and 21 is comparable with that of karyotyping, and it reduces waiting time at lower costs.

Level of evidence: II.

PubMed Disclaimer

References

    1. Ogilvie CM, Lashwood A, Chitty L, Waters JJ, Scriven PN, Flinter F. The future of prenatal diagnosis: rapid testing or full karyotype? An audit of chromosome abnormalities and pregnancy outcomes for women referred for Down's Syndrome testing. BJOG 2005;112:1369–75.
    1. Midtrimester amniocentesis for prenatal diagnosis. Safety and accuracy. JAMA 1976;236:1471–6.
    1. Tabor A, Madsen M, Obel EB, Philip J, Bang J, Norgaard-Pedersen B. Randomised controlled trial of genetic amniocentesis in 4606 low-risk women. Lancet 1986;1:1287–93.
    1. Los FJ, van Den Berg C, Wildschut HI, Brandenburg H, den Hollander NS, Schoonderwaldt EM, et al. The diagnostic performance of cytogenetic investigation in amniotic fluid cells and chorionic villi. Pren Diagn 2001;21:150–8.
    1. Golbus MS, Loughman WD, Epstein CJ, Halbasch G, Stephens JD, Hall BD. Prenatal genetic diagnosis in 3000 amniocentesis. N Engl J Med 1979;300:157–63.

Publication types