Counseling for non‐invasive prenatal testing (NIPT): what pregnant women may want to know

Sequencing of cell-free fetal and maternal DNA fragments (cfDNA) in maternal plasma can be used to test for fetal chromosomal abnormalities. In particular, prediction of the presence or absence of fetal trisomy 21, the most common fetal chromosomal abnormality, has been proved to be highly accurate. The first studies, showing > 99% accuracy, were done in selected high-risk groups1,2. More recent studies in average-risk populations of pregnant women confirm, as was expected biologically, that the test works equally well in the general population3–7. Not surprisingly, this safe and accurate test, commonly referred to as non-invasive prenatal testing (NIPT), increasingly is being offered by clinicians and requested by pregnant women who want to be informed about the possibility of trisomy 21 in their unborn child. With the first studies suggesting very high accuracy of trisomy 21 detection, there was hope that after decades of searching for this ‘Holy Grail’, a safe blood test could replace chorionic villus sampling and amniocentesis, eliminating (fear of) procedure-related miscarriages. From larger follow-up studies, we now know that while an NIPT result positive for trisomy 21 often means that the fetus is affected, this is not always the case, and therefore confirmation using an invasive test remains necessary, at least when the woman is considering an irreversible decision. Furthermore, sensitivity for detection of trisomy 21 is > 99% in practically all studies, but some missed cases have been reported. Thus, although highly accurate, NIPT is not perfect. In the not-so-distant past, the use of maternal age alone to select women to undergo invasive testing was replaced by various forms of measuring maternal serum markers with or without nuchal translucency (NT) measurement. In countries in which this was implemented well, unnecessary invasive tests (and related miscarriages) significantly decreased, with concomitant improved detection, thus improving women’s reproductive choices8. Still, the vast majority of invasive tests following screening for trisomy reveal a normal result, while the screening test is falsely reassuring in at least one in 10 pregnancies with a trisomy 21 fetus. The use of NIPT enables us to further improve the quality of prenatal testing for fetal abnormalities. The aim of counseling a pregnant woman before she chooses to undergo any test which can have major consequences is to provide sufficient understanding of the test characteristics, limitations and risks for her to make what we call an ‘informed choice’ regarding whether she wants to undergo this test, another one or no test at all. The introduction of NIPT does not change this general principle. We have been counseling women of advanced maternal age on invasive testing for decades, and we are used to discussing serumand NT-based screening, which, when all aspects of the various tests are to be explained, is quite a complex task. Following the first publications on NIPT for trisomy 21, clinicians for a while were under the impression that pretest counseling would become an easier, if not almost superfluous, task. A simple message (‘If you want to know about trisomy 21, we take a tube of blood and let you know in a week or so whether your baby is affected.’) was thought, at least by some, to be capable of replacing the complex explanation involving serum markers, the meaning of this rim of fluid in the baby’s neck, an algorithm including the age of the mother and not so easy-to-understand reasons behind the cut-off between high and low risk. However, with the increasing use of NIPT in clinical practice, there is a rising awareness among professionals and policy makers that adequate pre-test counseling is still important, even for NIPT, in order to prevent misconceptions, disappointments and, in some cases, inappropriate selection of this test by women or doctors. In this Opinion paper, we describe what pregnant women may want to know about NIPT before consenting to undergo this test, and summarize useful aspects, which could be included in various forms of patient information (websites, guidelines, booklets or by personal contact in the clinic).