Invasive or non-invasive prenatal genetic diagnosis?

Abstract

About 40 years ago, invasive prenatal diagnosis techniques were introduced in obstetrics. Initially, amniocentesis was performed followed by placentacentesis, fetoscopy, fetal blood sampling (FBS), and chorionic villus sampling (CVS). These procedures, while invading the uterine environment, have made it possible to proceed with the retrieval of biological tissue of fetal origin for analysis and definitive diagnosis [6,20,21,27]. The development of such techniques was facilitated by improvements in instrumentation and technology, and was further propelled by the advancement of cytogenetics and molecular genetic techniques [3,13,14,22].However, invasive prenatal diagnosis carries the inherent risk of fetal loss, which is low, but not negligible (amniocentesis and CVS approximately 0.3%-0.5% and FBS 1%-2%). In addition, there is a significant economic burden from the costs associated with laboratory techniques. Public health programs of nations interested in the utilization of invasive procedures have generally limited their use to high-risk cases, where the risk of procedure related loss is comparable to the risk of an affected fetus for a given condition [25,26]. As a result, in the 1980s amniocentesis was offered to women at higher risk of trisomy 21 based on maternal age alone, if there was an increased risk due to prior complications or pre-existing conditions (i.e., chromosomal alterations in the parents or in prior offspring), or because of prenatal detection of fetal malformations or other abnormal ultrasound findings. The initial policies led to an offering of invasive prenatal diagnosis to 5% of all pregnant women (positive screen rate), with a 40% detection rate for trisomy 21.With the advent of biochemical screening tests using maternal serum in the second trimester, the "triple" and "quadruple screen", the detection rate of trisomy 21 increased to 60% [28]. Meanwhile, with advancements in ultrasound, numerous reports were published that identified sonographic "markers" for trisomy 21, leading to additional screening with a "genetic ultrasound" in the second trimester [1]. However, second trimester ultrasound for the purposes of screening an unselected population never gained universal acceptance, and was primarily used in higher-risk populations (i.e., a woman with advanced maternal age that wished to avoid invasive testing). At this time, second trimester amniocentesis was the primary invasive diagnostic test practiced, while fetal blood sampling by cordocentesis was utilized when a diagnostic test was desired later in the second trimester, often in the setting of identification of a fetal anomaly in the second trimester ultrasound. As mean maternal age at childbirth continued to increase, especially in Western countries, alongside increasing scientific advancements, the number of indications for prenatal diagnosis rose. This trend led to an increased rate of invasive prenatal diagnosis, based on maternal age alone up to 15-20% in some nations, and spurred a search for new solutions.In the mid-1990s,...

Prenatal screening diagnosis and management in the era of coronavirus: the Sardinian experience

“…The recent introduction and rapid diffusion of noninvasive prenatal screening (NIPS) [45] into obstetrical care, using fetal cell-free DNA (cfDNA) detected from maternal blood, have coincided in centers where invasive procedures are not widely available [46,47] with the decline of invasive prenatal procedures [48,49]. However, in our experience, the introduction of first trimester combined testing remains the cornerstone of prenatal screening which reversed the traditional prenatal care pyramid [50].…”

“…In fact, the ultrasound screening and the combined test remain extremely significant and are far more widely applied in our prenatal center, compared to NIPS. This is due to various reasons: the high-level sonography expertise of the operators in our center which is equipped with the most technologically sophisticated ultrasound tools, including 3D-4D imaging [51,52], the considerable detection rate of fetal malformations as early as the first trimester [53,54], the substantial costs of NIPS (400-700 euros), or because Sardinian women are already familiar with invasive prenatal diagnosis and have grown accustomed to it due to its frequent application for thalassemia and other high-risk genetic pathologies [27,50].…”

“…The number of NIPS performed at the Microcitemico Hospital remained unchanged while in the rest of Sardinia there was a notable decline in its demand because women generally prefer Chorionic Villous Sampling (CVS) to NIPS [50]. There could be various reasons for it: the necessity of couples to be more comprehensively reassured regarding their pregnancy in the recent turbulent period and, surely, the considerable financial cost in these times of particular economic instability.…”

Invasive Diagnostic Testing

“…The introduction of first-trimester combined screening and cell-free DNA NIPS caused an important decrease of the invasive procedures because women are reassured in case of negative or low-risk screening. 18 All prenatal centers are witnessing a reduction of 30 to 70% of prenatal invasive procedures in the last 3 to 5 years and this concerns mainly amniocentesis. In our center, the decrease is about 40% and it is regarding mostly amniocentesis; in the meanwhile, TA-CVS is increasing (Graph 1).…”

Metabolomics Analysis of Amniotic Fluid in Euploid Foetuses with Thickened Nuchal Translucency by Gas Chromatography-Mass Spectrometry

“…Among contemporary developments is the rapid diffusion of non-invasive prenatal screening (NIPS), using foetal cell-free DNA (cfDNA) obtained from maternal blood, as a diagnostic technique for aneuploidies [ 2 ]. However, the scientific community must carefully consider the impact that NIPS may have on more well-established methods of prenatal screening and diagnosis [ 4 , 5 ].…”