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Many commercial reproductive genetic carrier screening (RGCS) panels include genes associated with non‐syndromic hearing loss (NSHL), however little is known about the general acceptability of their inclusion. Although some couples wish to avoid having a deaf child, there are effective interventions and supports available for deafness, and no consensus on whether it is appropriate to reproductively screen NSHL genes. This study explored views of people with personal experience of deafness regarding carrier screening for genes associated with NSHL. We interviewed 27 participants; 14 who identified as deaf and 13 hearing parents of a deaf child. Thematic analysis was undertaken on transcripts of interviews. The findings reveal the complexity of attitudes within these groups. Some vacillated between the wish to support prospective parents' reproductive autonomy and concerns about potential harms, especially the expression of negative messages about deafness and the potential loss of acceptance in society. While some participants felt carrier screening could help prospective parents to prepare for a deaf child, there was little support for reproductive screening and termination of pregnancy. Participants emphasized the need for accurate information about the lived experience of deafness. The majority felt deafness is not as severe as other conditions included in RGCS, and most do not consider deafness as a disability. People with personal experience of deafness have diverse attitudes towards RGCS for deafness informed by their own identify and experience, and many have concerns about how it should be discussed and implemented in a population wide RGCS program. [ABSTRACT FROM AUTHOR]

Background: Current carrier screening methods do not identify a proportion of carriers that may have children affected by spinal muscular atrophy (SMA). Additional genetic data is essential to inform accurate risk assessment and genetic counselling of SMA carriers. This study aims to quantify the various genotypes among parents of children with SMA. Method: A retrospective cohort study was undertaken at Sydney Children's Hospital Network, the major SMA referral centre for New South Wales, Australia. Participants included children with genetically confirmed SMA born between 2005 and 2021. Data was collected on parent genotype inclusive of copy number of SMN1 exons 7 and 8. The number of SMN2 exon 7 copies were recorded for the affected children. Descriptive statistics were used to determine the proportion of carriers of 2+0 genotype classified as silent carriers. Chi-square test was used to correlate the association between parents with a heterozygous SMN1 exon 7 deletion and two copies of exon 8 and ≥3 SMN2 copy number in the proband. Results: SMA carrier testing was performed in 118/154 (76.6%) parents, incorporating 59 probands with homozygous SMN1 deletions and one proband with compound heterozygote pathogenic variants. Among parents with a child with SMA, 7.6% had two copies of SMN1 exon 7. When only probands with a homozygous SMN1 exon 7 deletion were included, 6.9% of parents had two copies of SMN1 exon 7. An association was observed between heterozygous deletion of SMN1 exon 7 with two copies of exon 8 in a parent and ≥3 SMN2 copy number in the affected proband (p = 0.07). Conclusions: This study confirmed a small but substantial proportion of silent carriers not identified by conventional screening within an Australian context. Accordingly, the effectiveness of carrier screening for SMA is linked with genetic counselling to enable health literacy regarding high and low risk results and is complemented by new-born screening and maintaining clinical awareness for SMA. Gene conversion events may underpin the associations between parent carrier status and proband SMN2 copy number. [ABSTRACT FROM AUTHOR]

Many scientific societies have emphasized the importance of evaluating the clinical utility of reproductive carrier screening (RCS). This systematic review aims to assess the clinical utility of RCS and synthesize the outcomes in a meta-analysis. A total of eleven studies were included. The number of conditions screened in the studies varied from three to 176 and led to the identification of one to 24 high-risk couples (HRCs) per 1,000 screened individuals. Pooled estimations were as follows: the prenatal diagnosis (PND) rate among pregnant HRCs 0.644 (95% CI = 0.364, 0.923), the termination rate among affected pregnancies 0.714 (95% CI = 0.524, 0.904), and the rate of in-vitro fertilization (IVF) with preimplantation genetic testing (PGT) 0.631 (95% CI = 0.538, 0.725). There is a statistically significant decrease in the rates of undertaking PND and termination as the number of screened conditions increases. Carriers of conditions classified as having a more severe impact were found to be more likely to choose termination or IVF with PGT. Our review suggests that the number and the severity of screened conditions can significantly impact HRCs' reproductive decisions. Future work needs to investigate the definition of clinical utility and the design of screening panels. [ABSTRACT FROM AUTHOR]

Background: The Royal Australian and New Zealand College of Obstetricians and Gynaecologists and The Royal Australian College of General Practice recommend that information on carrier screening for at least the most common inherited genetic conditions in our population, that is, thalassaemia, cystic fibrosis (CF), spinal muscular atrophy (SMA), and fragile X syndrome (FXS), should be offered to all women planning pregnancy or in early pregnancy regardless of family history or ethnicity. The aim of this study was to investigate patterns of participation by healthcare providers (HCP) and the community in screening. Methods: Participation in a Victorian program screening for CF, SMA and FXS between September 2013 and October 2018 was analysed. Requesting HCP and patient data were extracted from screening request forms. Data were analysed with respect to profession of requesting HCP, and characteristics of women screened (age, pregnancy status, socioeconomic status, geographic location, and family history of CF, SMA or FXS). In total, 21 172 women and 1288 HCPs participated in the program over this period. Results: There was a steep socioeconomic gradient in screening uptake, with nearly half the women screened (10 349) being in the highest socioeconomic quintile. The screening rate was much higher in metropolitan areas than in regional areas. Obstetricians made most of the requests for screening, whereas 20% of requests were by GPs. Most participating GPs only made a single screening request (78%) and very few GPs made >100 screening requests compared with obstetricians (0.2% vs 17%). GPs were more likely to screen women before pregnancy compared with obstetricians (47% vs 11%). Approximately 1.5% of Victorian women of child-bearing age and 3% of pregnant Victorian women were screened by this program over the period of this study. Conclusion: This study highlights the translation gap between recommendations and practice, with marked inequity of access to reproductive genetic carrier screening in relation to socioeconomic status and geography. Increased participation by GPs could improve community access to reproductive genetic carrier screening, particularly access to preconception screening. Addressing the causes of inequity of access will allow more women and couples the opportunity to make informed choices about participation in screening. Offering reproductive genetic carrier screening to all women contemplating pregnancy or in early pregnancy is recommended by professional medical organisations. This study has found marked inequity of access to screening in relation to socioeconomic status and geographical location, and wide variations in healthcare provider participation. Causes of this translation gap between recommendations and practice need to be addressed in order for all women and couples to have the opportunity to make informed choices about screening. [ABSTRACT FROM AUTHOR]

Autosomal recessive (AR) and x-linked (XL) conditions are rare but collectively common which impact millions of people globally on morbidity, mortality and costs. Advanced medical technologies allow prospective parents to make informed reproductive decisions to avoid having affected children. Economic evaluations targeting on reproductive carrier screening (RCS) for AR and/or XL conditions have been conducted, but there has not been a systematic review in this area. A systematic search of economic evaluations for RCS was undertaken using the following databases – EMBASE, MEDLINE and SCOPUS. The search strategy was designed to capture full economic evaluations related to RCS since 1990. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) strategy. The included 23 studies adopted various types of methodologies to conduct economic evaluations. The majority of studies examined a single condition. The various clinical strategies and screened conditions caused the different cost-effectiveness conclusions in the published studies. Establishing a validated and practical clinical strategy of RCS and investigating the cost-effectiveness of multiple conditions in one economic evaluation are critical for implementing RCS in the future. Further economic evaluations are essential to provide evidence-based practice for decision-makers. [ABSTRACT FROM AUTHOR]

Reproductive carrier screening enables the early identification of genetic conditions that may impact the long‐term health of a child, including cystic fibrosis, fragile X syndrome, and spinal muscular atrophy. We used unique data from the major providers of pathology services in Australia to profile women who intend on becoming, or who are, pregnant and access basic to advanced testing for genetic conditions. We found a strong socioeconomic gradient in the uptake of reproductive carrier screening, with women living in the most advantaged postcodes across Australia significantly being more likely to have reproductive carrier screening than those living in the most disadvantaged areas. These results highlight the need to minimise social and financial barriers that are currently limiting access. [ABSTRACT FROM AUTHOR]

The study aimed to explore with consanguineous couples in Australia the acceptability and perceived utility of whole exome reproductive carrier screening for autosomal recessive and X‐linked recessive conditions. Semi‐structured interviews with 21 consanguineous couples were conducted prior to the offer of screening. Interviews were coded, and thematic analysis was informed by an inductive approach. Three major themes were identified: experiences and attitudes of Australian consanguineous couples, childhood genetic conditions and beliefs, and the perceived utility of genomic screening. All but one couple had previously sought genetic advice, and a large majority of couples were aware of childhood conditions within their family or community. Thirteen couples perceived consanguinity as increasing the risk of having affected children. Nine spoke of premarital screening programs routinely conducted in their countries of origin. All supported the concept and availability of genomic reproductive carrier screening. Hypothetically, if found to be carriers of a severe childhood disorder, 13 couples reported they would test a pregnancy, and 12 of whom would consider termination of pregnancy or pre‐implantation genetic diagnosis. Four couples would not test a pregnancy and two were unsure. A majority of couples would communicate potential at‐risk status to family members, although there were some caveats. Fourteen couples chose to have exome screening and reported that they would utilize the results with the goal of preventing childhood conditions. Of these couples, nine (64%) had an affected child but were aware that testing may reveal they were at risk for a child with a different condition and five (71%) without an affected child. While from diverse ethnic and backgrounds, all couples practiced a religion and all but one couple were recruited from the same clinical genetics unit, with a likely higher genetic literacy and bias towards accepting genetic testing. However, the choice made by all couples was reportedly made with consideration of their personal values, their current family situation, and exome testing issues, including fear of incidental findings and concerns about test reliability. [ABSTRACT FROM AUTHOR]

The study aimed to explore with consanguineous couples in Australia the acceptability and perceived utility of whole exome reproductive carrier screening for autosomal recessive and X-linked recessive conditions. Semi-structured interviews with 21 consanguineous couples were conducted prior to the offer of screening. Interviews were coded, and thematic analysis was informed by an inductive approach. Three major themes were identified: experiences and attitudes of Australian consanguineous couples, childhood genetic conditions and beliefs, and the perceived utility of genomic screening. All but one couple had previously sought genetic advice, and a large majority of couples were aware of childhood conditions within their family or community. Thirteen couples perceived consanguinity as increasing the risk of having affected children. Nine spoke of premarital screening programs routinely conducted in their countries of origin. All supported the concept and availability of genomic reproductive carrier screening. Hypothetically, if found to be carriers of a severe childhood disorder, 13 couples reported they would test a pregnancy, and 12 of whom would consider termination of pregnancy or pre-implantation genetic diagnosis. Four couples would not test a pregnancy and two were unsure. A majority of couples would communicate potential at-risk status to family members, although there were some caveats. Fourteen couples chose to have exome screening and reported that they would utilize the results with the goal of preventing childhood conditions. Of these couples, nine (64%) had an affected child but were aware that testing may reveal they were at risk for a child with a different condition and five (71%) without an affected child. While from diverse ethnic and backgrounds, all couples practiced a religion and all but one couple were recruited from the same clinical genetics unit, with a likely higher genetic literacy and bias towards accepting genetic testing. However, the choice made by all couples was reportedly made with consideration of their personal values, their current family situation, and exome testing issues, including fear of incidental findings and concerns about test reliability., (© 2018 National Society of Genetic Counselors.)