2015, Number 05
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Ginecol Obstet Mex 2015; 83 (05)
Non invasive prenatal test (NIPT) in maternal blood by parallel massive sequencing. Initial experience in Mexican women and literature review
Hernández-Gómez M, Ramírez-Arroyo E, Meléndez-Hernández R, Garduño-Zarazúa LM, Mayén-Molina DG
Language: Spanish
References: 21
Page: 277-288
PDF size: 401.78 Kb.
ABSTRACT
Background: Discovery of cell-free fetal DNA (cffDNA) in maternal
blood in 1997 by Lo et al. has opened the possibility of a non-invasive
prenatal test (NIPT). Currently, it is employed in the analysis of aneuploidies
and fetal sex determination. Massive parallel sequencing
(MPS) detects the origin of each amplified sequence, and analyses
over-representation of sequences or any decrease in the fetal chromosomes
in maternal plasma. This technique has been validated
and allows assessment of trisomies 13, 18 and 21, obtaining the
result in about a week from 10-weeks of gestational age. By using
NIPT, we expect a reduction in the number of invasive studies and
the risk of fetal loss.
Objective: To communicate the experience obtained at Genetics Clinic
of the Hospital Angeles Lomas, in the use of NIPT by MPS as a method
of prenatal screening for aneuploidies and fetal sex determination.
Material and methods: A prospective, observational and descriptive
study was carried out in order to develop a database of patients who
underwent NIPT (Harmony test®) from August 2013 to date. Maternal
blood samples were analyzed at Ariosa Diagnostics Inc. at San Jose
California, USA.
Results: Non-invasive prenatal test was applied to 42 patients, with
average maternal age of 37.1 years. The percentage of gestational age
was 13.3 weeks and of fetal fraction was 12.7%. Two cases of high
risk of trisomy 18 and two cases with high risk for X monosomy were
obtained. In only one case the test was used for fetal determination,
because of a story of Wiskott-Aldrich (W-A) disease. In all cases of low
risk, the result was confirmed at birth and fetal sex was consistent with
reports of literature.
Conclusions: NIPT is currently the screening test with the highest
detection rate (greater than 98%, with a false negative rate lesser than
0.5% and a sensitivity and specificity close to 100%), although it can
vary from one chromosome to another. It is indicated for women with
a result of high risk for trisomy 13, 18 and 21. This test has not been
validated for low risk women or multiple pregnancies. In our series, the
most frequent indication was advanced maternal age. The weight of the
patients is important because it is a factor related to the percentage of
fetal DNA. In cases with high risk for X monosomy in which the cytogenetic
result was 46,XX, it is important to consider as much causes as
possible, such as uniparental disomy (UPD), mosaicism and maternal
contamination. Only in a case with W-A story the test was conducted
specifically for fetal sex determination and confirmed by amniocentesis.
In the cases of high-risk results, confirmation by an invasive method,
before an obstetric decision, is indispensable. Further studies are still
needed to continue the validation of this test by different molecular
techniques and in other groups of patients.
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