Open Access Study protocol

Multiplex ligation-dependent probe amplification versus karyotyping in prenatal diagnosis: the M.A.K.E. study

Elisabeth MA Boormans12*, Erwin Birnie3, Hajo I Wildschut4, Heleen G Schuring-Blom5, Dick Oepkes6, Carla AC van Oppen7, Jan G Nijhuis8, Merryn VE Macville9, Angelique JA Kooper10, Karin Huijsdens11, Mariëtte VJ Hoffer12, Attie Go13, Johan Creemers14, Shama L Bhola15, Katia M Bilardo1, Ron Suijkerbuijk16, Katelijne Bouman16, Robert-Jan H Galjaard17, Gouke J Bonsel3 and Jan MM van Lith26

Author Affiliations

1 Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, The Netherlands

2 Department of Obstetrics and Gynecology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands

3 Institute of Health Policy and Management, Erasmus Medical Center, Rotterdam, The Netherlands

4 Department of Obstetrics and Gynecology, Erasmus Medical Center, Rotterdam, The Netherlands

5 Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands

6 Department of Obstetrics and Gynecology, Leiden University Medical Center, Leiden, The Netherlands

7 Department of Obstetrics and Gynecology, University Medical Center Utrecht, Utrecht, The Netherlands

8 Department of Obstetrics and Gynecology, Academic Medical Center Maastricht, Maastricht, The Netherlands

9 Department of Clinical Genetics, Academic Medical Center Maastricht, Maastricht, The Netherlands

10 Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

11 Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands

12 Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands

13 Department of Obstetrics and Gynecology, VU Medical Center, Amsterdam, The Netherlands

14 Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

15 Department of Clinical Genetics, VU Medical Center, Amsterdam, The Netherlands

16 Department of Clinical Genetics, University Medical Center Groningen, Groningen, The Netherlands

17 Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands

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BMC Pregnancy and Childbirth 2008, 8:18  doi:10.1186/1471-2393-8-18

Published: 20 May 2008

Abstract

Background

In the past 30 years karyotyping was the gold standard for prenatal diagnosis of chromosomal aberrations in the fetus. Traditional karyotyping (TKT) has a high accuracy and reliability. However, it is labor intensive, the results take 14–21 days, the costs are high and unwanted findings such as abnormalities with unknown clinical relevance are not uncommon. These disadvantages challenged the practice of karyotyping. Multiplex ligation-dependent probe amplification (MLPA) is a new molecular genetic technique in prenatal diagnosis. Previous preclinical evidence suggests equivalence of MLPA and traditional karyotyping (TKT) regarding test performance.

Methods/Design

The proposed study is a multicentre diagnostic substitute study among pregnant women, who choose to have amniocentesis for the indication advanced maternal age and/or increased risk following prenatal screening test. In all subjects, both MLPA and karyotyping will be performed on the amniotic fluid sample. The primary outcome is diagnostic accuracy. Secondary outcomes will be maternal quality of life, women's preferences and costs. Analysis will be intention to treat and per protocol analysis. Quality of life analysis will be carried out within the study population. The study aims to include 4500 women.

Discussion

The study results are expected to help decide whether MLPA can replace traditional karyotyping for 'low-risk' pregnancies in terms of diagnostic accuracy, quality of life and women's preferences. This will be the first clinical study to report on all relevant aspects of the potential replacement.

Trial Registration

The protocol is registered in the clinical trial register number ISRCTN47252164