# Invasive Prenatal Diagnostics: A Cornerstone of Perinatal Management
## 1 Introduction to Prenatal Diagnostics
In 1977, he reported [23] the valuable role of combining ultrasound examination with a measurement of alpha-fetoprotein in maternal serum and amniotic fluid in diagnosing spina bifida, anencephaly, encephaloele, and hydrocephalus. This was considered to be the first method of screening for foetal abnormalities in a high-risk group of patients. Alongside the aforementioned discoveries, ultrasonography became widespread in prenatal diagnostics. It was possible only in the late 1970s when the first commercial linear array real-time ultrasonographic scanner was introduced. As the probes were much more compact and moveable, it was possible to adjust the view's angle and follow the foetus's movement. Moreover, the machines were much less expensive, thus making ultrasonography more accessible to specialists and researchers. This allowed for visualising and measuring various anatomical structures that were not observed previously, such as the length of the femur. As a result, in 1985, [PERSON] et al. [24] introduced an equation for estimating foetal weight and assessing foetal growth, which is still used to this day. The 1980s were a time of significant advancements in prenatal screening. Until that time, invasive diagnostics for genetic reasons were offered only to women aged 35 and above, who were considered a high-risk group. However, this policy of screening based on maternal age resulted in an invasive testing rate of 5% and a detection rate of trisomy 21 of 30%. These highly unsatisfactory numbers demanded improvement. As a part of a search for new screening methods, [PERSON] et al. [25] first reported an increased thickness of a nuchal fold in foetuses with trisomy 21 in the second trimester. Later, she described other classic second-trimester sonographic markers, such as pyelectasis and a shortened femur. The ultimate breakthrough was the paper published by [PERSON] et al. in 1992 [26]. They demonstrated a pathological accumulation of fluid in the nuchal region as an early marker of trisomies 21, 18 and 13. Later, the nuchal translucency was proved to be useful in detecting many more foetal abnormalities, such as congenital heart defects [27], diaphragmatic hernias, exophalos, body stalk anomalies, and much more [28]. In 1998, [PERSON] et al. [29] observed a correlation between abnormal ductus venosus flow measured in 11-14-week gestation and chromosomal abnormalities. The blood flow during atrial contractions was absent or reversed in 90,5% of cases of foetuses with chromosomal defects. In 2001, [PERSON] et al. [30] observed a phenomenon of absence or hypoplasia of the nasal bone in cases of trisomy 21. This was observed in 73% of chromosomally abnormal footuses irrespectively of increased nuchal translucency. This finding might have been caused by a delayed ossification of the nasal bone due to alterations within the extracellular matrix. Two years later, [PERSON] et al. [31] concluded that 83% of foetuses with tricuspid valve regurgitation in an 11-14-week scan proved to have karyotype abnormalities. The chromosomal defect most frequently found in those cases was trisomy 21; however, all types of karyotypic anomalies were seen in association. As a result of all these findings, in the early 2000s, an original screening program called _First-Trimester Screening (FTS)_ was _introduced_[32]. The idea was to counsel patients in one-stop clinics for assessment of risk (_OSCAR_) [33; 34]. The proposed screening policy for trisomy 21 and other chromosomal abnormalities was based on maternal age, much translucency, maternal free beta-hCG and PAPP-A. The overall individual risk for trisomy 21 was calculated by combining the primary risk and the likelihood ratio resulting from a measurement of the aforementioned markers. The background risk depended on maternal age and gestation. Patients would be categorised into a high-risk group with a risk cut-off of 1 to 100 with a detection rate of 90% and a false-positive rate of 5%.