title: Multiplex ligation-dependent probe amplification versus karyotyping in prenatal diagnosis: the M.A.K.E. study.
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
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  The protocol is registered in the clinical trial register number ISRCTN47252164.
authors.affiliation: Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, The Netherlands. e.m.boormans@amc.nl
authors.forename: Elisabeth M A
authors.initials: EM
authors.lastname: Boormans
authors.forename: Erwin
authors.initials: E
authors.lastname: Birnie
authors.forename: Hajo I
authors.initials: HI
authors.lastname: Wildschut
authors.forename: Heleen G
authors.initials: HG
authors.lastname: Schuring-Blom
authors.forename: Dick
authors.initials: D
authors.lastname: Oepkes
authors.forename: Carla A C
authors.initials: CA
authors.lastname: van Oppen
authors.forename: Jan G
authors.initials: JG
authors.lastname: Nijhuis
authors.forename: Merryn V E
authors.initials: MV
authors.lastname: Macville
authors.forename: Angelique J A
authors.initials: AJ
authors.lastname: Kooper
authors.forename: Karin
authors.initials: K
authors.lastname: Huijsdens
authors.forename: Mariëtte V J
authors.initials: MV
authors.lastname: Hoffer
authors.forename: Attie
authors.initials: A
authors.lastname: Go
authors.forename: Johan
authors.initials: J
authors.lastname: Creemers
authors.forename: Shama L
authors.initials: SL
authors.lastname: Bhola
authors.forename: Katia M
authors.initials: KM
authors.lastname: Bilardo
authors.forename: Ron
authors.initials: R
authors.lastname: Suijkerbuijk
authors.forename: Katelijne
authors.initials: K
authors.lastname: Bouman
authors.forename: Robert-Jan H
authors.initials: RJ
authors.lastname: Galjaard
authors.forename: Gouke J
authors.initials: GJ
authors.lastname: Bonsel
authors.forename: Jan Mm
authors.initials: JM
authors.lastname: van Lith
mesh_terms: D000649:Amniocentesis / Q000379:methods*; D004314:Down Syndrome / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000235:genetics*; D017048:Health Care Costs; D006801:Humans; D007621:Karyotyping / Q000379:methods*; D008967:Molecular Biology / Q000379:methods; D021141:Nucleic Acid Amplification Techniques; D010043:Outcome and Process Assessment, Health Care; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods* / Q000592:standards; D011788:Quality of Life; D012107:Research Design; D025064:Sex Chromosome Disorders / Q000175:diagnosis / Q000235:genetics; D011795:Surveys and Questionnaires; D014314:Trisomy / Q000175:diagnosis / Q000235:genetics