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M.A.K.E.

 

Prenatal Diagnosis: MLPA and Karyotyping, an Evaluation

 

Background

For the past 30 years karyotyping is the gold standard in prenatal diagnosis for the detection of chromosomal aberrations in the fetus, in particular trisomy 21 (Down syndrome).

The main indications for traditional karyotyping (TKT) in the Netherlands are advanced maternal age and increased risk based on prenatal screening tests (PNS)1.

The annual numbers of maternal age-based invasive procedures for TKT are decreasing, in contrast to the numbers of PNS. This is due to a shift of the maternal age distribution, with a relative increase of elderly pregnant women making use of PNS, an increased demand of pregnant women, augmented by a change in government policy allowing PNS (combined test, triple test) for risk estimation of Down syndrome (DS).

MLPA (multiplex ligation-dependent probe amplification) is a new molecular genetic technique in prenatal diagnosis using amniotic fluid. It is a potential alternative test for detecting aneuploidies.

Compared to TKT, MLPA has four potential advantages:

(1) The result is known in 2-4 days instead of 3 weeks

(2) The procedure is considerably less labour intensive

(3) The test requires less amniotic fluid (2-4 ml instead of 20 ml)

(4) MLPA is suitable for high throughput testing.

Previous preclinical evidence suggests equivalence of MLPA and TKT regarding test performance (accuracy in detection of common occurring chromosome aberrations)2 3 4 5.

 

Entry criteria

            (1) Amniocentesis is performed;

            (2) The referral indication is advanced maternal age and/or increased risk after PNS

            (3) No language barriers

            (4) Informed consent is given.

 

Intervention

On each sample of amniotic fluid MLPA and TKT are carried out.

 

Setting

Seven of the total of eight prenatal diagnostic centres will join this study.

 

Outcomes

Diagnostic accuracy, technical performance (inconclusive or missing results), technical capacity, patientís anxiety and distress, cost-effectiveness, unexpected findings and patient preference

 

Project members

Prof. Dr. J.M.M. van Lith, OLVG Amsterdam

Drs. E.M.A. Boormans, AMC Amsterdam

 

01-09-2011: Outcomes of the M.A.K.E. study

 

The aim of prenatal diagnosis is to provide information on chromosomal abnormalities, in order to allow parents an informed choice on the course of pregnancy. Karyotyping is the diagnostic test used to detect chromosomal abnormalities. It is highly accurate, but labour-intense, costly and slow. Karyotyping detects chromosomal abnormalities with no, mild, or unclear clinical consequences. Rapid aneuploidy detection (RAD) techniques can detect the most common chromosomal abnormalities (trisomies 13, 18, 21, X and Y). Multiplex Ligation-dependent Probe Amplification (MLPA) is a RAD test. Its diagnostic accuracy, tested on 4585 amniotic fluid samples in routine clinical practice, is comparable to that of karyotyping (P<0.001) and it reduces waiting time with 14.5 days at lower costs (-Ä240 per sample). Patient quality of life does not differ significantly. While caregivers prefer RAD, experts prefer a test detecting all severe chromosomal abnormalities. Patients' preferences are equally divided; they value the detection of severe chromosomal abnormalities most. Since RAD and karyotyping both detect the most common chromosomal abnormalities with severe consequences, both tests are appropriate for prenatal diagnosis. Based on decision analytic considerations and our study results, women should be offered a choice, since they will bear the responsibility of raising the child.

 

References:

Boormans et al. Obstetrics & Gynecology 2010; 115: 297-303

Boormans  et al. Prenatal Diagnosis 2010; 30: 425-33

Boormans et al. Prenatal Diagnosis 2010; 10: 928-36

Boormans et al. Arch Gynecol Obstet 2011; epub ahead of print

Boormans  et al.  BJOG 2009; 116:1396-9

Boormans et al. Prenatal Diagnosis 2010; 30: 928-36