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

Area of Science:

• Genetics
• Prenatal Diagnostics
• Molecular Biology

Background:

• Traditional karyotyping (TKT) has been the standard for prenatal diagnosis of fetal chromosomal aberrations for 30 years.
• TKT is accurate but labor-intensive, with long turnaround times (14-21 days), high costs, and potential for incidental findings.
• Multiplex ligation-dependent probe amplification (MLPA) is an emerging molecular genetic technique for prenatal diagnosis, with preclinical data suggesting comparable performance to TKT.

Purpose of the Study:

• To evaluate whether MLPA can serve as a substitute for TKT in prenatal diagnosis.
• To compare the diagnostic accuracy, maternal quality of life, patient preferences, and costs associated with MLPA versus TKT.
• To provide comprehensive data for deciding on MLPA's potential replacement of TKT in low-risk pregnancies.

Main Methods:

• A multicenter diagnostic substitute study involving pregnant women undergoing amniocentesis.
• Both MLPA and TKT will be performed on amniotic fluid samples from approximately 4500 women.
• Primary outcome is diagnostic accuracy; secondary outcomes include maternal quality of life, women's preferences, and costs. Analysis will follow intention-to-treat and per-protocol principles.

Main Results:

• This section is to be filled once the study is completed and results are available.

Conclusions:

• The study is expected to determine if MLPA can replace TKT for prenatal diagnosis in low-risk pregnancies.
• Results will inform clinical practice regarding diagnostic accuracy, patient-reported outcomes, and economic factors.
• This research represents the first clinical study to assess all relevant aspects of MLPA as a TKT replacement.