Congenital anomalies are defects that are not acquired during life but are already existent at an individual’s birth. About half of the defects are of unknown etiology, a quarter is multifactorial, and the others are either due to teratogens, mutations, or chromosomal aberrations (Fig. 5.3) [3]. The most prevalent numeric or structural chromosomal aberration is trisomy 21.

Trisomy 21 is typically associated with physical growth delay, characteristic facial features, and mild to moderate intellectual disability. People with trisomy 21 may have some or all of these physical characteristics: a small chin, slanted eyes, poor muscle tone, a flat nasal bridge, a single crease of the palm, and a protruding tongue. They have an increased risk of a number of other health problems, including congenital heart disease, leukemia, and thyroid disorders.

Other less frequently occurring trisomies are trisomies 13 and 18, also known as Patau and Edwards syndrome, respectively. These trisomies, however, are lethal and result in stillbirth or the demise of a severely handicapped child during delivery or soon afterward. Besides the triplication of one chromosome, there exist also triploidies of the entire chromosome set, which generally lead to an early demise of the fetus. Another relatively frequently occurring numeric chromosomal aberration is aneuploidies of the sex chromosomes resulting in Turner syndrome (X aneuploidy), Klinefelter syndrome (XXY), and other less frequent sex aneuploidies.

The development and implementation of prenatal diagnosis started in the 1960s (Fig. 5.4). At that time amniocentesis (AC) and ultrasound were introduced. In the 1980s chorionic villi sampling (CVS) followed and allowed early detection of structural chromosomal aberrations such as trisomy 21. However, the procedure was at the cost of a risk of 1–2 % of inducing a miscarriage [4, 5]. In order to reduce the number of women exposed to this risk, noninvasive screening tests were developed then. In the 1990s, the relatively imprecise alpha-fetoprotein plus test, which could only be performed in the second trimester, could soon be replaced by the first trimester risk assessment combining the nuchal translucency with the biochemical markers PAPP-A (pregnancy-associated plasma protein A) and free β(beta)-hCG, as well as the age of the pregnant woman [6–8] (Table 5.1). The detection rate for trisomy 21 is about 90 %, and the test is constructed in such a way that about 5 % of the women have a positive test result. To further reduce the persisting risk of CVS-induced miscarriages for the women who screen positive, further research concentrated on noninvasive diagnostic procedures. These are now available with the so-called noninvasive prenatal test (NIPT). The underlying investigational technology is based on the fact that a pregnant mother’s blood contains free fetal DNA fragments [9]. By quantifying them, aneuploidies such as trisomies 21, 18, and 13 can be detected, as well as a triploidy (tripling of all chromosomes) and anomalies of the sex chromosomes. The sensitivity for trisomy 21 of the currently available tests is 99.1 % (CI 97–100); the rate of false-positive results is 0.3 % (CI 0.2–0.7) [10]. The test is validated for women with a positive first trimester risk assessment, is applicable in singleton and recently also in twin pregnancies, and cannot detect mosaic trisomies. It can be performed from the tenth week of gestation onward. To date a positive NIPT should be confirmed by CVS or AC.

Congenital anomalies can be classified as minor or major birth defects. Furthermore, they can be subdivided in (at least partly) treatable malformations and untreatable chromosomal aberrations. This is an important aspect when couples that are confronted with an affected fetus have to be guided and supported in making the decision whether to continue or terminate pregnancy.

The legal framework concerning termination of pregnancy (i.e., abortion) differs from one country to the other. This has an impact on the choices that can be made in the case of fetal anomalies and chromosomal aberrations, such as trisomy 21. In general, the diagnosis of an anomaly is not made until the first 12 weeks of gestations, and the common limits of legal abortion on the woman’s demand have passed. Thus other regulations are in duty then. In many countries abortions are induced no later than the beginning of the stadium of prematurity, i.e., 24 weeks of gestation. After this time point, feticide has to be performed before labor induction, in order to prevent delivering a viable neonate. In some countries this practice is allowed; meanwhile, in others this is not an option, as feticide is not allowed beyond 24 weeks of gestation.

In general, health professionals are educated to save lives, to cure, and to care. In the context of prenatal diagnosis, they are sometimes confronted with the conflicting situation that the diagnostic procedure they perform does not contribute to treatment of a condition but only leads to elimination of the unborn individual (fetus) that suffers from it. When considering the principles of biomedical ethics that are autonomy, beneficence, non-maleficence, and justice, at least the second and the third of these four principles are not considered from the perspective of the fetus [12]. Depending on their personal attitudes and beliefs, physicians may experience ethical and moral conflicts when they are confronted with a request for termination of pregnancy. The conflict might be minor in case of severe anomalies and major when the condition in question is compatible with life, such as trisomy 21.

Being confronted with a positive prenatal screening test or the prenatal diagnosis of a fetal chromosomal aberration is a very challenging situation for the pregnant women/couples concerned. It causes a high level of distress. As a consequence the capacity to make a decision is impaired, even though a decision with an impact on the future life of the couple has to be made within a short time period and thus under considerable pressure. The confrontation with a positive test result can never be anticipated entirely and will always be a psychological shock, but pretest counseling might nevertheless set the framework for the decision-making and reduce excessive stress. Our case demonstrates this exemplarily.