Prenatal diagnosis of susceptibility loci for neurodevelopmental disorders - genetic counseling and pregnancy outcome in 57 cases.

BACKGROUND: Whole genome array testing not only provides an increased diagnostic yield of pathogenic causative findings, but it may also reveal so called susceptibility loci (SL) for neurodevelopmental disorders. The goal of this study was to evaluate the pregnancy outcomes in SL cases and to establish a protocol for pregnancy management, follow-up and additional investigations. METHODS: Fifty seven cases were evaluated: 34 with and 23 without ultrasound anomalies at referral. Each pregnant couple received pretest counseling and extensive posttest genetic counseling. RESULTS: After diagnosis of SL, parental testing and an additional ultrasound examination were offered. The severity of the ultrasound anomalies and not the diagnosis of SL was the most important factor contributing to the decision on pregnancy continuation. In the majority of cases with milder or no ultrasound anomalies, the pregnancy was continued and a normal outcome after birth was observed. CONCLUSIONS: The diagnosis of a SL did not seem to be a reason for termination of pregnancy. Most patients were able to cope with the uncertainty and were interested in both prenatal and postnatal actionability of SL. Long-term follow-up is crucial to assess the actual risks for neurodevelopmental disorders, especially in families with unremarkable history. © 2016 John Wiley & Sons, Ltd.

Offering a choice between NIPT and invasive PND in prenatal genetic counseling: the impact of clinician characteristics on patients' test uptake.

Testing options for pregnant women at increased risk of common aneuploidies are non-invasive prenatal testing (NIPT) and invasive prenatal diagnosis (PND). Clinicians are challenged to comprehensively discuss the complex information in a patient-centered and non-directive manner, to allow for patients' informed decision-making. This study explored the information-centeredness, patient-centeredness, and level of non-directivity of different clinicians and examined group differences between their patients. First, semi-structured interviews with four senior obstetricians and one senior nurse were held regarding their information provision, their adaptation of a patient-centered attitude, and their practice of non-directivity. Interviews were transcribed verbatim and rated by four independent researchers. Secondly, 181 pregnant women were included in the study, of whom 82% opted for NIPT and 18% chose PND. Between clinicians, we assessed the distribution of choice ratios, patients' impression of clinicians' test preferences, and patients' knowledge scores. The results indicate that clinicians do not differ in their information-centeredness, but do differ in their patient-centeredness and their level of non-directivity. Significant differences in patients' NIPT/PND ratios were observed between clinicians, with the largest difference being 35 vs. 4% opting for invasive PND. Between 9 and 22% of the patients had an impression of their clinician's preference and chose in accordance with this preference. Patients' overall knowledge scores did not differ across clinicians. In conclusion, the differences in NIPT/PND ratios between clinicians indicate that clinicians' differing counseling approaches affect the choices their patients make. The interviews indicate a possible framing effect which may unintentionally steer the decision-making process.

The Psychological Challenges of Replacing Conventional Karyotyping with Genomic SNP Array Analysis in Prenatal Testing.

Pregnant couples tend to prefer a maximum of information about the health of their fetus. Therefore, we implemented whole genome microarray instead of conventional karyotyping (CK) for all indications for prenatal diagnosis (PND). The array detects more clinically relevant anomalies, including early onset disorders, not related to the indication and more genetic anomalies of yet unquantifiable risk, so-called susceptibility loci (SL) for mainly neurodevelopmental disorders. This manuscript highlights the psychological challenges in prenatal genetic counselling when using the array and provides counselling suggestions. First, we suggest that pre-test decision counselling should emphasize deliberation about what pregnant couples wish to learn about the future health of their fetus more than information about possible outcomes. Second, pregnant couples need support in dealing with SL. Therefore, in order to consider the SL in a proportionate perspective, the presence of phenotypes associated with SL in the family, the incidence of a particular SL in control populations and in postnatally ascertained patients needs highlighting during post-test genetic counselling. Finally, the decision that couples need to make about the course of their pregnancy is more complicated when the expected phenotype is variable and not quantifiable. Therefore, during post-test psychological counseling, couples should concretize the options of continuing and ending their pregnancy; all underlying feelings and thoughts should be made explicit, as well as the couple's resources, in order to attain adequate decision-making. As such, pre- and post-test counselling aids pregnant couples in handling the uncertainties that may accompany offering a broader scope of genetic PND using the array.