Noninvasive prenatal testing of aneuploidies: where are we now?

Prenatal diagnosis of chromosomal aneuploidies is the most frequent prenatal test offered to pregnant women. In most cases, they are recommended in the following circumstances: maternal age of 35 years or above; positive firstor second-trimester screening test results, and increased risk of fetal aneuploidies due to family history. During the first trimester, screening tests include: nuchal translucency (NT) combined with maternal age; levels of maternal serum pregnancy associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (β-hCG) combined with maternal age; combination of NT measurement, the first trimester maternal serum analytes (PAPP-A, and free β-hCG or total hCG) and maternal age, referred to as combined first trimester screening. The NT measurement is valid when crown-rump length (CRL) is 45–84 mm, corresponding to 11–13+6 week of gestation, while PAPP-A and free β-hCG may be measured between 9–13+6 week of gestation. More recently, another option, which is the detection of an increased amount of chromosomal material in maternal blood, became available to screen for chromosome aneuploidy. This is called Non-invasive Prenatal Testing (NIPT). Recently, different tests are available, depending on the employed methodologies and algorithms for data analysis. These may involve massively parallel sequencing (MPS), targeted sequencing of specific chromosomal segments, or directed sequence analysis of single nucleotide polymorphisms (SNPs). While all these testing methods have limitations, healthcare providers need to be aware of them in order to give their patients reliable information and genetic counseling. In this paper, we focused on NIPT because it is the most promising screening option. Among the above-mentioned tests, combined first trimester screening has been demonstrated to have higher detection rates for Down Syndrome (78–91%) and trisomy 18 (91–96%) compared to NT only or serum analytes methods. Since pregnancies affected with trisomy 13 have PAPP-A, free β-hCG, and NT patterns similar to trisomy 18, this screening is also used to screen for trisomy 13.