Background: Discovery of cell-free fetal DNA (cffDNA) in maternal blood in 1997 by Lo et al. has opened the possibility of a noninvasive 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: Noninvasive 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.