PRENATAL SCREENING: CURRENT PRACTICE, NEW DEVELOPMENTS, ETHICAL CHALLENGES

Prenatal screening pathways, as nowadays offered in most Western countries consist of similar tests. First, a risk-assessment test for major aneuploides is offered to pregnant women. In case of an increased risk, invasive diagnostic tests, entailing a miscarriage risk, are offered. For decades, only conventional karyotyping was used for final diagnosis. Moreover, several foetal ultrasound scans are offered to detect major congenital anomalies, but the same scans also provide relevant information for optimal support of the pregnancy and the delivery. Recent developments in prenatal screening include the application of microarrays that allow for identifying a much broader range of abnomalities than karyotyping, and non-invasive prenatal testing (NIPT) that enables reducing the number of invasive tests for aneuploidies considerably. In the future, broad NIPT may become possible and affordable. This article will briefly address the ethical issues raised by these technological developments. First, a safe NIPT may lead to routinisation and as such challenge the central issue of informed consent and the aim of prenatal screening: to offer opportunity for autonomous reproductive choice. Widening the scope of prenatal screening also raises the question to what extent reproductive autonomy' is meant to expand. Finally, if the same test is used for two different aims, namely detection of foetal anomalies and pregnancy-related problems, non-directive counselling can no longer be taken as a standard. Our broad outline of the ethical issues is meant as an introduction into the more detailed ethical discussions about prenatal screening in the other articles of this special issu

Bridging the gap: challenging attitudes towards smoking in pregnancy among healthcare professionals

Background Clean Air for Babies is a Global Bridges project to reduce smoking in pregnancy in a healthcare organization, 'Meuhedet', with 1.2M members. One aim is empowering health professionals to provide brief smoking cessation interventions. In this study we assessed the effectiveness of an education program for nurses and ultrasound technicians. Methods The program consists of 8 hours, and includes smoking and ETS effects during pregnancy, practical tools and behavioral interventions. Evaluation includes before and after questionnaires based on Global Bridges tools, and focus groups. We are at the initial stage of analysis. We will conduct another round of questionnaires 3 months post intervention. Results We conducted 6 courses for 120 maternal health nurses and 60 technicians. Qualitative analysis demonstrates ambivalence regarding ability to intervene (“This will damage the therapeutic space”) and identification with smokers (“I have seen how difficult it is to stop, my husband became unbearable.”). A second theme was hesitance in approaching Muslim or Jewish-Orthodox spouses due to gender-based hierarchies in the cultural context (“In our culture it is hard for the women to tell a man what to do…"). A common theme among technicians was insecurity regarding their role in smoking cessation. We completed analysis of 29 nurses´ questionnaires pre and immediately post intervention. Using paired-t-test analysis we found a significant improvement in the level of knowledge (mean knowledge items 3.27 to 4.38 on a scale of 5, p< 0.001). No difference was found in self efficacy or reported behavior. Conclusions Initial results indicate that it is possible to identify specific barriers among caregivers that create resistance to smoking cessation interventions. Addressing them creates an opportunity for real organizational change. The improvement in knowledge is indicative of the appropriateness of the training sessions. We expect that improvement in self efficacy and reported behavior at the 3 month evaluation

Potential Founder Variants in COL4A4 Identified in Bukharian Jews Linked to Autosomal Dominant and Autosomal Recessive Alport Syndrome

Background: Alport syndrome is a hereditary disorder caused by pathogenic variants in the COL4A gene, which can be inherited in an autosomal recessive, dominant, or X-linked pattern. In the Bukharian Jewish population, no founder pathogenic variant has been reported in COL4A4. Methods: The cohort included 38 patients from 22 Bukharian Jewish families with suspected Alport syndrome who were referred the nephrogenetics clinic between 2012 and 2022. The study collected demographic, clinical, and genetic data from electronic medical records, which were used to evaluate the molecular basis of the disease using Sanger sequencing, and next-generation sequencing. Results: Molecular diagnosis was confirmed in 20/38 patients, with each patient having at least one of the three disease-causing COL4A4 variants detected: c.338GA (p.Gly1008Arg), and c.871-6T>C. In addition, two patients were obligate carriers. Overall, there were 17 heterozygotes, 2 compound heterozygotes, and 3 homozygotes. Each variant was detected in more than one unrelated family. All patients had hematuria with/without proteinuria at referral, and the youngest patient with proteinuria (age 5 years) was homozygous for the c.338G>A variant. End-stage renal disease was diagnosed in two patients at the age of 38 years, a compound heterozygote for c.338G>A and c.871-6T>C. Hearing deterioration was detected in three patients, the youngest aged 40 years, all of whom were heterozygous for c.338G>A. Conclusion: This study unveils three novel disease-causing variants, c.3022G>A, c.871-6T>C, and c.338G>A, in the COL4A4 gene that are recurrent among Jews of Bukharian ancestry, and cause Alport syndrome in both dominant and recessive autosomal inheritance patterns

Should We Report 15q11.2 BP1-BP2 Deletions and Duplications in the Prenatal Setting?

Copy number variations of the 15q11.2 region at breakpoints 1-2 (BP1-BP2) have been associated with variable phenotypes and low penetrance. Detection of such variations in the prenatal setting can result in significant parental anxiety. The clinical significance of pre- and postnatally detected 15q11.2 BP1-BP2 deletions and duplications was assessed. Of 11,004 chromosomal microarray tests performed in a single referral lab (7596 prenatal, 3408 postnatal), deletions were detected in 66 cases: 39 in prenatal tests (0.51%) and 27 in postnatal tests (0.79%). Duplications were detected in 94 cases: 62 prenatal tests (0.82%) and 32 postnatal tests (0.94%). The prevalence of deletions and duplications among clinically indicated prenatal tests (0.57% and 0.9%, respectively) did not differ significantly in comparison to unindicated tests (0.49% and 0.78%, respectively). The prevalence of deletions and duplications among postnatal tests performed for clinical indications was similar to the prevalence in healthy individuals (0.73% and 1% vs. 0.98% and 0.74%, respectively). The calculated penetrance of deletions and duplications over the background risk was 2.18% and 1.16%, respectively. We conclude that the pathogenicity of 15q11.2 BP1-BP2 deletions and duplications is low. Opting out the report of these copy number variations to both clinicians and couples should be considered