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In 1959, 63 years after the death of John Langdon Down, Jérôme Lejeune discovered trisomy 21 as the genetic reason for Down syndrome. Screening for Down syndrome has been applied since the 1960s by using maternal age as the risk parameter. Since then, several advances have been made. First trimester screening, combining maternal age, maternal serum parameters and ultrasound findings, emerged in the 1990s with a detection rate (DR) of around 90-95% and a false positive rate (FPR) of around 5%, also looking for trisomy 13 and 18. With the development of high-resolution ultrasound, around 50% of fetal anomalies are now detected in the first trimester. Non-invasive prenatal testing (NIPT) for trisomy 21, 13 and 18 is a highly efficient screening method and has been applied as a first-line or a contingent screening approach all over the world since 2012, in some countries without a systematic screening program. Concomitant with the rise in technology, the possibility of screening for other genetic conditions by analysis of cfDNA, such as sex chromosome anomalies (SCAs), rare autosomal anomalies (RATs) and microdeletions and duplications, is offered by different providers to an often not preselected population of pregnant women. Most of the research in the field is done by commercial providers, and some of the tests are on the market without validated data on test performance. This raises difficulties in the counseling process and makes it nearly impossible to obtain informed consent. In parallel with the advent of new screening technologies, an expansion of diagnostic methods has begun to be applied after invasive procedures. The karyotype has been the gold standard for decades. Chromosomal microarrays (CMAs) able to detect deletions and duplications on a submicroscopic level have replaced the conventional karyotyping in many countries. Sequencing methods such as whole exome sequencing (WES) and whole genome sequencing (WGS) tremendously amplify the diagnostic yield in fetuses with ultrasound anomalies.

Advances in the prognosis of relevant syndromes and severe congenital malformations in infants during the last few decades have enabled the treatment and survival of an ever-increasing number of infants, whose prospects were previously judged futile by professional health care teams. This required detailed counselling for families, which frequently started before birth when a diagnosis was made using genetic testing or ultrasound. Predictions of the estimated prognosis, and frequently the more-or-less broad range of prospects, needed to include the chances of survival and data on acute and long-term morbidities. However, in the interest of a having an informed basis for parental decision-making with a professional interdisciplinary team, this process needs to acknowledge the rights of the parents for a comprehensive presentation of the expected quality of life of their child, the potential consequences for family life, and the couple's own relationship. Besides expert advice, professional psychological and familial support is needed as a basis for a well-founded decision regarding the best treatment options for the child. It needs to be acknowledged by the professional team that the parental estimate of a "good outcome" or quality of life does not necessarily reflect the attitudes and recommendations of the professional team. Building a mutually trusting relationship is essential to avoid decision conflicts. [ABSTRACT FROM AUTHOR]