# Invasive Prenatal Diagnostics: A Cornerstone of Perinatal Management
## 1 Introduction to Prenatal Diagnostics
Moreover, the newly introduced ultrasonographic markers--ductus venous flow impedance, tricuspid regurgitation, and the absence of nasal bone--proved to improve the screening performance to 93-96% and decrease the false-positive rate to 2.5% [35; 36; 37]. Since its introduction, the FTS programme has proven to be successful in various validation studies [38; 39; 40]. Therefore, it is used as a gold standard in many countries. Apart from assessing the individual risk for trisomy 21, 18, and 13, FTS provides a broad spectrum of clinical implications. Ultrasound examination conducted at 11-14 weeks of gestation enabled the early detection of 60% of major foetal anomalies [41], such as neural tube and brain anomalies, abdominal wall, and cardiac and skeletal defects [42; 43]. Along with constant development in ultrasound technology, the first-trimester ultrasound has become a tool for screening major morphological abnormalities. Therefore, the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) eventually published practice guidelines for anatomical assessment in the first trimester in 2013 [44], which were appropriately updated 10 years later [45]. Ultimately, an early anomaly scan provides the patient with extensive information regarding the foetus and may contribute to further invasive diagnostics. Another milestone in prenatal diagnostics happened in 1997 when [PERSON] et al. discovered cell-free foetal DNA in the plasma and serum of pregnant women through the extraction and amplification of Y chromosomal DNA from a plasma analyte [46]. DNA fragments were thought to originate from the placenta, where cytotrophoblasts and syncyotrophoblasts go through cycles of fusion and apoptosis, releasing DNA into the bloodstream [47]. Cell-free DNA typically mirrors the genetic makeup of the foetus, as both the foetus and placenta normally originate from the same embryo [48]. The foetal component accounts for around 3-13% of the total cell-free DNA in maternal blood and rises as pregnancy progresses [49]. This finding indicated that maternal plasma or serum DNA may be an invaluable asset for non-invasive prenatal diagnosis. Validation studies conducted in the next decade led to the commercial availability of the first tests in 2012. Non-invasive prenatal testing has rapidly been implemented in aneuploidy screening since then. By late 2017, around 4 million to 6 million pregnant women had undergone cell-free DNA analysis to detect foetal aneuploidy [50]. Despite its high screening success rates, cfDNA is not as accurate as diagnostic testing and may produce false-positive results. Patients should not make pregnancy management decisions, such as termination, purely contingent upon NIPT [51]. False-positive screening test findings can be caused by confined placental mosaicism, vanishing twins, maternal chromosomal abnormalities and copy number variants, maternal malignancy, and maternal transplant recipients. While not prevalent, the aforementioned situations are occasionally observed in clinical practice [52; 53; 54; 55]. In addition, the success rate of cfDNA testing in twin pregnancies decreases with maternal weight and is higher in IVF pregnancies compared with spontaneous conceptions. Screening twins with cfDNA testing is possible, although the failure rate is higher, and the detection rate may be lower compared with singletons [57]. aneuploidy is not the only disease entity that is in dire need of being prenatally detected. Numerous companies providing non-invasive prenatal tests offer the choice to test for microdeletion and microduplication disorders. Screening for microdeletions and microduplications using cfDNA-based technology is a new method that lacks substantial clinical validation and is not endorsed by ACOG or SMFM. The high rate of false-positive and false-negative outcomes in non-invasive prenatal testing for subchromosomal abnormalities makes cfDNA-based screening for these conditions not of clinical benefit presently [58; 59; 60].