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Reproductive genetic screening has introduced the possibility for pregnant women to learn, during the pregnancy or sometimes earlier, about the likelihood of their baby being affected with certain genetic conditions. As medicine progresses, the options afforded by this early information have expanded. This has led to a shifting paradigm in prenatal screening, wherein the early knowledge is seen as useful not solely for its inherent value to the pregnant woman, but also as enabling an expansion of conditions whose identification may allow early intervention and clinical impact. This article discusses this paradigm against the backdrop of prenatal genetic screening that is available today. [ABSTRACT FROM AUTHOR]

The most well-known goal of non-invasive prenatal testing (NIPT) is still to determine whether or not a fetus has trisomy 21. Since women often terminate the pregnancy upon a positive result, there is concern that the use of NIPT contributes to discrimination against persons with disabilities. If this concern is justified, it could have an impact on the wider social acceptability of existing testing practices and their potential further expansion. This paper demonstrates four different versions of the discrimination worry, indicates how international policy papers have reacted to them, and identifies the ethically most relevant feature of the concern. [ABSTRACT FROM AUTHOR]

By implementation of non-invasive prenatal testing (NIPT) for the diagnosis of Down syndrome (DS) in maternity care, an ethical debate is newly inflamed how to deal with this information. Fears of the consequences of an increased use of NIPT are justified with the same arguments when amniocentesis and preimplantation genetic diagnosis (PGD) were introduced decades ago. It can be expected that the prevalence of people with DS would significantly increase in Western societies as a result of the increasing age of pregnant women and the improved medical care for people with DS. The net effect as to whether an increasing uptake of NIPT will result in more abortions of fetuses with trisomy 21 cannot be reliably estimated. This holds true since more and more couples will use results of NIPT for information only, but will not opt for termination of pregnancy. Although parents love their children with DS, in a society where reproductive autonomy is seen as an achievement, access to NIPT cannot be limited. On this background, comprehensive and qualified pretest counseling is vital, also to avoid possible stigmatization of people with DS and as the resulting consequence to avoid feared deterioration in their living conditions, for which, however, there is no evidence to date. The personal view of a mother of a child with DS illustrates the complexity in dealing with NIPT, which does not allow simple answers and must be understood as a challenge for society as a whole. [ABSTRACT FROM AUTHOR]

This study aims to present the termination of pregnancy (TOP) rates and elucidate the decision-making process following a prenatal diagnosis of Trisomy 21 in Turkey. This retrospective single-center study was conducted with 146 pregnant women between January 2016 and December 2019 in a tertiary hospital. Data on maternal characteristics, sonographic findings, indications for chromosome analysis, and educational, religious, and economic factors that can influence the parental decision process were collected. The TOP rate of Down syndrome (DS) in our center was 78.8%. We concluded that maternal age, earlier diagnosis, indication for chromosome analysis, and previous pregnancies had no effect on the TOP decision. On the other hand, not having a minor or a major sonographic sign, employed mothers, middle- and high-income families, and families having a secondary or higher education tended to terminate the pregnancy affected by DS at statistically higher rates. There are many studies worldwide investigating the TOP preferences for DS. However, there is limited data about TOP rates and influential factors affecting the decision-making process in Muslim countries. This study contributes by clarifying the factors in the decision-making process and elucidating perspectives about TOP in a Muslim country with a unique status: Turkey. [ABSTRACT FROM AUTHOR]

Background: The ductus venosus agenesis (DVA) is a rare condition with a variable prognosis that relies partly on the presence of associated conditions. The purpose of our study was to analyze the literature regarding the post-natal outcome of fetuses with DVA associated with fetal malformations, in order to discuss the best management options for couples. Methods: We performed a systematic review of the literature of MEDLINE and SCOPUS electronic databases in a 25-year period from 1992 to September 2017. Methods: We found 340 cases of DVA associated with fetal abnormalities. The most common chromosomal abnormalities were: monosomy X (12/48, 25%), trisomy 21 (11/48, 22.9%) and trisomy 18 (6/48, 12.5%). From the 340 cases with DVA, in 31 cases the umbilical venous shunt type was not reported. Of the fetuses, 60.8% (188/309) had an extrahepatic umbilical venous drainage while 39.2% (121/309) presented an intrahepatic connection. The DVA was associated in 71 cases (23.0%) with cardiac abnormalities, in 82 cases (26.5%) with extracardiac abnormalities and in 85 cases (27.5%) with both cardiac and extracardiac abnormalities. Conclusion: DVA associated with both cardiac and extracardiac malformations may confer a poorer fetal outcome, a clinically relevant fact that should clarify what can be expected from this entity and help prenatal counseling. [ABSTRACT FROM AUTHOR]

The article discusses the study that determined the effect of maternal age (MA) on the screening performance of traditional combined screening (CS) and ultrasound-based screening (US), two first-trimester screening strategies. Topics discussed include higher detection rate (DR) of trisomy 21 (T21) showed by US protocol compared to the CS one, and potential of US protocol as viable alternative to CS for T21 in cases where access to biochemical testing is limited.

Aims: To evaluate the prevalence of congenital heart defects (CHDs) in live-born infants with Down syndrome (DS) and to investigate whether these CHDs might be detected during routine second trimester ultrasound screening performed at the primary level. Methods: A retrospective analysis of 66 cases of DS in live-born infants. The infants with DS underwent a detailed echocardiographic examination to evaluate cardiac morphological characteristics and function. Results: Thirty-six live-born DS infants (54.5%) had associated CHDs. According to the apical four-chamber view at the first postnatal echocardiographic examination, we estimated that 20 (55.6%) of the 36 patients with associated CHDs should have been identified during the routine second-trimester prenatal scan [17 infants with complete atrioventricular septal defect (AVSD), two with partial AVSD, and one with non-restrictive perimembranous ventricular septal defect] if the results had been correctly interpreted. An additional seven patients with associated CHDs should have been identified if the evaluation of both outflow tracts had been included into the screening protocol. Conclusion: Our data suggest that the prenatal DS detection rate can be significantly increased by improving obstetricians' skills of performing adequate foetal cardiac examination as part of the routine 18- to 23-week ultrasound examination at the primary level. [ABSTRACT FROM AUTHOR]

Objective: To assess the sensitivity (Sen) and false positive ratio (FPR) of stepwise sequential screening [1st step: combined test (CT), 2nd step: modified genetic sonography (major malformation and nuchal fold, MGS)] as a screening method for Down's syndrome (DS) in the general population of pregnant women. Methods: Prospective study. During a 5-year study period (July 2005 to June 2010), 17,911 pregnant women were screened for DS using a stepwise sequential screening method (CT+MGS). We evaluated the Sen and FPR (95% CI) of the two chromosomal disorder screening methods for DS: CT and CT+MGS. Results: Seventeen thousand nine hundred and eleven cases were analysed, including 67 with chromosome abnormalities and 45 with DS. The Sen of CT for DS was 80% (95% CI; 68.3-91.7) (36/45) with a FPR of 4.2% (95% CI; 3.9-4.5) (752/17, 866). The Sen of CT+MSG for DS was 93.3 (95% CI; 85.9-99) (42/45) with a FPR of 4.8% (95% CI; 4.5-5.1) (860/17, 866). Conclusions: MGS coupled with CT increases the Sen of DS diagnosis by 13.3% (95% CI; 2.7-25.9), with an increase in FPR of 0.6% (95% CI; 0.5-0.7). [ABSTRACT FROM AUTHOR]

The noninvasive prenatal diagnosis of trisomy 21 (Down syndrome) is an actively researched area of prenatal medicine, as this is the most common aneuploidy compatible with life and a major cause of mental retardation. The isolation of intact fetal cells, and most importantly, the successful detection of fetal-origin nucleic acids (cell-free fetal DNA and RNA), in maternal plasma even from the early stages of pregnancy has inspired scientists to develop discriminative genetic markers for the prenatal detection of aneuploidy. In the near future, the development of epigenetic fetal-specific markers will possibly allow the universal application of a cell-free fetal DNA-based diagnostic test regardless of the gender of the fetus or its polymorphic status. Other promising approaches rely upon the detection of free placentally derived RNA transcribed from genes located on chromosome 21 and the application of highly sensitive techniques, such as digital polymerase chain reaction and high-throughput shotgun sequencing. However, irrespective of which strategy is selected for isolating or distinguishing fetal genetic material in maternal plasma, the small quantity of fetal origin nucleic acids poses severe technical challenges. In this review article, we present an overview of the current knowledge in the field of noninvasive prenatal assessment of fetuses with Down syndrome and the future perspectives regarding new fetal markers and novel molecular techniques that may eventually be applied in the clinical setting as a valid and safe option for women who opt for noninvasive accurate prenatal diagnosis. [ABSTRACT FROM AUTHOR]

In the Netherlands, both the LifeCycle Elipse (LC) and the Astraia software package are used to calculate the risk of having a child with Down syndrome. Therefore, pregnant women can be presented with dissimilar risks. In this study the conformity between these risks before and after harmonization of the screening program and its influence on the performance indicators of the first trimester screening were evaluated. The agreement between combined risks (based on the biochemical parameters PAPP-A and fβ-hCG and a nuchal translucency measurement) was expressed as intraclass correlation coefficient (ICC)=0.99. Conformity between combined risks was better after harmonization (Cohen's κ=0.75) than before harmonization (Cohen's κ=0.63). For both risk calculation software packages the area under the ROC-curve was 0.84. The database contained 42 Down syndrome cases; based on the odds of being affected given a positive result (OAPR), LC performed slightly better than Astraia before harmonization (17.9 vs. 21.5, respectively). It has been acknowledged that using different software packages could lead to dissimilar risk calculations. In this study the screening performance indicators of two software packages were quite similar. The agreement of the screening performance after harmonization remains to be seen, but is expected to be even higher. [ABSTRACT FROM AUTHOR]

The article presents poster presentations on prenatal diagnosis. The effect of parity in small for gestational age births, perinatal outcome and obstetric mother future was investigated by Amelia Almeida et al. The results of first trimester screening for chromosomal anomalies were presented by Manuela Silva et al. A description of ethnic disparities in participation to prenatal screening for Down syndrome was discussed by Mirjam Fransen et al.

Aims: Recent advances in prenatal screening, including first and second trimester genetic screening as well as targeted sonography, have significantly improved the detection of trisomy 21. Therefore, several investigators have questioned the validity of recommending genetic amniocentesis to all women who are 35 years or older at delivery. Thus, we sought to investigate the risks and benefits associated with performing genetic amniocentesis in women whose sole indication for testing was advanced maternal age (AMA). Methods: A retrospective review of a Genzyme Genetics amniocentesis database (January 2006–December 2006) was performed. All specimens obtained from women of AMA as the sole indication were eligible for analysis. The amniocentesis-related potential fetal loss was calculated based on the traditional fetal loss rate of 1/200 as well as the recently published loss rate of 1/1600 procedures. Risk-benefit analysis was performed by comparing the number of trisomy 21 fetuses identified within the AMA group to the potential number of amniocentesis-related fetal losses within this group. Results: A total of 87,241 amniocentesis specimens were processed during the study period. AMA was the sole indication for genetic amniocentesis in 43,303 cases which formed the study group. In 399 (0.92%) of these cases, a trisomy 21 was identified. Assuming an amniocentesis related fetal loss rates of 1/200 or 1/1600; 217 or 27 fetal losses would have been expected, respectively. Conclusions: Our analysis suggests that the benefit of genetic amniocentesis for the sole indication of AMA far outweighs the potential amniocentesis-related fetal loss rate, regardless of the actual rate one considers. [ABSTRACT FROM AUTHOR]