Offering Carrier Screening Research Articles

Uptake rate of carrier screening among consanguineous couples.

To quantify the uptake rates of Carrier Screening (CS) in consanguineous couples and compare this rate to that of non-consanguineous couples. We performed a matched case control study of 82 consanguineous couples seen at Rutgers-Robert Wood Johnson Medical school who were offered carrier screening between January 1, 2012 and October 10, 2022. We then matched each consanguineous female patient to a non-consanguineous female control patient who was also offered CS at the time of their genetic counseling appointment. A 2×2 contingency table analysis was used to compare rates of acceptance and declination between the consanguineous and non-consanguineous groups. The overall acceptance rate among consanguineous couples was 82.9%, whereas the overall acceptance rate among non-consanguineous couples was 56.1%. After statistical analysis, consanguineous couples were significantly more likely to accept CS as compared to non-consanguineous couples (OR=3.801, 95% CI; p<0.0001). We also report the carrier couple rates and individual carrier statistics between these two groups. This study supports the idea that consanguineous couples are more likely to pursue CS and have a higher carrier couple yield.

Barriers to completion of expanded carrier screening in an inner city population

PurposeThe American College of Medical Genetics and Genomics emphasizes a “consistent and equitable approach for offering carrier screening.” At our academic center, publicly insured prenatal patients underwent universal expanded carrier screening (ECS) to promote equitable care. The aim of the study was to evaluate rates, time, and barriers to complete ECS. This was defined as post-test counseling and partner testing after a patient was found heterozygous for a pathogenic variant. MethodsIn this descriptive retrospective cohort study from 2018 to 2021, patients were offered ECS, consisting of 283 recessive and X-linked genes. Heterozygotes were contacted by genetic counselors (≤5 attempts) for education and partner testing. Rates of counseling, partner testing, diagnostic procedures, follow-up times, and barriers to completion were assessed. ResultsDuring this time, 643 women underwent ECS. Of these 643 women, 462 were heterozygotes and 326 of 462 had undergone counseling. Two hundred twenty-two of 462 partners obtained testing, with a median of 32 days from patient to partner result. Approximately 21 couples were heterozygous for the same pathogenic variant. One patient pursued diagnostic testing. ConclusionECS offers useful information; however, this study highlights significant barriers to completion. There was suboptimal patient follow-up and low partner screening, perhaps from insufficient time to educate and counsel. Future directions include implementing quality measures to ensure optimal completion.

Expanded carrier screening: What conditions should we screen for?

Carrier screening tests reproductive couples for their risk of having children affected by serious monogenic conditions. Carrier screening has historically been offered for certain conditions in high-risk populations. However, more recent evidence has shown that offering carrier screening to all patients, regardless of their ethnicity, more effectively and equitably identifies at-risk couples. Coupled with technology that enables screening for a nearly unlimited number of conditions, this expanded carrier screening (ECS) approach is now supported by professional society guidelines. Despite recent recommendations by the American College of Medical Genetics and Genomics to screen all patients who are pregnant or considering pregnancy for 113 conditions, questions remain about what conditions should be included on a core ECS panel. Here, we briefly review the history of carrier screening and guidelines on criteria for panel design. We then suggest which of these criteria are most critical, as well as thresholds to identify which conditions meet these criteria. Based on these interpretations, we recommend a core panel of 64 conditions that would identify the vast majority of at-risk couples. Widespread adoption of a core panel such as this would result in a marked improvement in the number of patients currently receiving comprehensive carrier screening.

EP461: Barriers to prenatal genetic testing for male partners at a Los Angeles County public teaching hospital

eP461: Barriers to prenatal genetic testing for male partners at a Los Angeles County public teaching hospital

OP053: Barriers to completion of expanded carrier screening in an inner city population

The American College of Medical Genetics and Genomics emphasizes the need for a “consistent and equitable approach for offering carrier screening to all individuals during pregnancy or preconception” in order to facilitate informed reproductive decisions. At our academic center, publicly insured patients obtaining prenatal care underwent universal Expanded Carrier Screening (ECS) to promote equitable access and care. We evaluated barriers to timely ECS completion, namely, receipt of genetic counseling, partner screening, and ability to act on diagnostic testing results.

Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG)

Carrier screening began 50 years ago with screening for conditions that have a high prevalence in defined racial/ethnic groups (e.g., Tay–Sachs disease in the Ashkenazi Jewish population; sickle cell disease in Black individuals). Cystic fibrosis was the first medical condition for which panethnic screening was recommended, followed by spinal muscular atrophy. Next-generation sequencing allows low cost and high throughput identification of sequence variants across many genes simultaneously. Since the phrase “expanded carrier screening” is nonspecific, there is a need to define carrier screening processes in a way that will allow equitable opportunity for patients to learn their reproductive risks using next-generation sequencing technology. An improved understanding of this risk allows patients to make informed reproductive decisions. Reproductive decision making is the established metric for clinical utility of population-based carrier screening. Furthermore, standardization of the screening approach will facilitate testing consistency. This practice resource reviews the current status of carrier screening, provides answers to some of the emerging questions, and recommends a consistent and equitable approach for offering carrier screening to all individuals during pregnancy or preconception.

Genetic Carrier Screening for Cystic Fibrosis, Fragile X Syndrome, Hemoglobinopathies, and Spinal Muscular Atrophy

&#x0D; People generally describe wanting access to carrier screening because knowing about the risk of passing along a genetic condition is considered important and supportive of their desires to be prepared. In the context of expanded carrier screening programs, this could mean that an increased number of people would want to access these programs.&#x0D; Supporting people who are considering carrier screening can be challenging and is likely to be more involved than simply sharing high-level descriptive information about testing details and potential outcomes. Descriptive information is important to help people understand the screening process and the types of results that could emerge from testing; however, programs might be more supportive of informed decision-making if the providers take a proactive role and are open to facilitating speculative conversations about potential ramifications in people’s actual lives. This is challenging given the expressed desire by health care providers, clinical geneticists in particular, to provide “neutral information” that patients would not experience as prescriptive.&#x0D; Given the challenge of supporting people making decisions about whether or not to pursue carrier screening, and the likely increase in people who would consider carrier screening if targeted programs were expanded to population-level screening, it is important to ensure that health care providers are both aware of jurisdictional carrier screening programs and competent in what carrier screening can offer their patients in terms of clinical actionability. Although this is particularly true for general practitioners who are often the primary point of contact with the health care system for their patients, it is also important for people who work in family planning clinics and women’s health clinics.&#x0D; Having the option to engage with carrier screening at the preconception stage was universally preferred by participants across the included studies. Compared with prenatal carrier screening, preconception carrier screening was seen as providing prospective parents with more reproductive options. Health care providers were concerned that offering carrier screening during pregnancy might lead pregnant people and their partners to confuse it with other prenatal testing which would limit people’s ability to be truly informed before deciding whether or not to pursue screening. However, if offered as a prenatal option, most people consider it important to do so as early as possible because it could be paired with other prenatal tests. Although not referred to specifically by any of the included studies, we note that offering carrier screening prenatally rather than at preconception, could place the responsibility to make the decision on cisgender women and non-binary or transgender people with uteruses.&#x0D; Sequentially designed carrier screening programs were the most common across the included studies; however, people moving through programs with this design found the interim period between receiving their positive carrier results and receiving their partners’ results difficult. This was particularly true for people who were already pregnant because this interim period forced them to reimagine both their relationship with the fetus and the future they had imagined with that child. Of course, this reimagining might be necessary if both partners’ screening results came back positive for the condition in question, but to stagger the return of the results could put undue anxiety on potential parents.&#x0D; Carrier screening will not affect everyone in the same way, and reproductive decision-making will still be complex and difficult. As such, the opportunity to engage with genetic counsellors on reproductive options following positive carrier status result is considered valuable.&#x0D;

Spinal Muscular Atrophy: Inheritance, Screening, and Counseling for the Obstetric Provider.

Spinal muscular atrophy (SMA) confers significant risk of neonatal and infant morbidity and mortality. Screening women during or before pregnancy for carrier status of SMA presents an opportunity to identify pregnancies at risk for this potentially devastating condition. The objective of this review is to describe the different forms of SMA and their inheritance. In addition, this review guides obstetric providers in interpreting results of carrier screening. A MEDLINE search of "prenatal genetic testing," "spinal muscular atrophy," and "inheritance of spinal muscular atrophy" in the review was performed. The evidence cited in this review includes 4 medical society committee opinions and 14 additional peer-reviewed journal articles that were original research or expert opinion summaries. Spinal muscular atrophy is a severe, heterogeneous neurodegenerative disorder. The American College of Obstetricians and Gynecologists recommends that obstetricians offer carrier screening for SMA to all pregnant women. Given the different types and inheritance of SMA, understanding of the disease and interpreting carrier screening results is of paramount importance to the prenatal care provider.

Factors influencing medical practitioner participation in population carrier screening for cystic fibrosis.

Cystic fibrosis (CF) carrier screening should be offered to people planning a pregnancy or in early pregnancy, according to current recommendations. However, research indicates rates of offering CF carrier screening are low. Health professionals (HPs) play an important role in offering population carrier screening. To determine the opinions, knowledge and practice patterns of HPs with regard to the routine offering of population carrier screening for CF. Five key informant interviews informed the development of an online questionnaire which was distributed to a select group of HPs involved in prenatal care in Victoria, Australia. Of the participants who completed the questionnaire (n=87), 35.6% reported offering CF carrier screening to all patients attending for preconception or early pregnancy consultations. High referrers of CF carrier screening were more likely to be female, work in the private sector, in metropolitan areas and specialise as an obstetrician. High referrers demonstrated a greater level of knowledge of CF and carrier screening than low referrers (t=-3.779, P<0.001). Low referrers perceived more barriers to offering carrier screening than high referrers (t=2.125, P=0.037). Low referrers were more likely to perceive lack of community awareness and HP knowledge as a barrier to offering CF carrier screening, compared to high referrers, who were more likely to perceive time constraints as a barrier. To promote routine offering of population CF carrier screening, resources are needed to improve knowledge and provide clinical support thereby reducing perceived barriers.

Which types of conditions should be included in reproductive genetic carrier screening? Views of parents of children with a genetic condition

Reproductive genetic carrier screening identifies couples with an increased chance of having children with autosomal and X-linked recessive conditions. Initially only offered for single conditions to people with a high priori risk, carrier screening is becoming increasingly offered to individuals/couples in the general population for a wider range of genetic conditions. Despite advances in genomic testing technology and greater availability of carrier screening panels, there is no consensus around which types of conditions to include in carrier screening panels. This study sought to identify which types of conditions parents of children with a genetic condition believe should be included in carrier screening. Participants (n = 150) were recruited through Royal Children's Hospital (RCH) Melbourne outpatient clinics, the Genetic Support Network of Victoria (GSNV) and a databank of children with hearing loss (VicCHILD). This study found that the majority of participants support offering carrier screening for: neuromuscular conditions (n = 128/134, 95.5%), early fatal neurodegenerative conditions (n = 130/141, 92.2%), chronic multi-system disorders (n = 124/135, 91.9%), conditions which cause intellectual disability (n = 128/139, 92.1%) and treatable metabolic conditions (n = 120/138, 87.0%). Views towards the inclusion of non-syndromic hearing loss (n = 88/135, 65.2%) and preventable adult-onset conditions (n = 75/135, 55.6%) were more mixed. Most participants indicated that they would use reproductive options to avoid having a child with the more clinically severe conditions, but most would not do so for clinically milder conditions. A recurring association was observed between participants’ views towards carrier screening and their lived experience of having a child with a genetic condition.

Practices in synagogues regarding Jewish genetic disease education.

Approximately one in three Ashkenazi Jews are carriers for an autosomal recessive Jewish genetic disease (JGD). However, studies indicate that most Jews are uneducated on this topic and obstetricians do not routinely offer carrier screening to Jewish patients. Both the Reform and Conservative movements of Judaism call for JGD education to take place within the synagogue; however, little is known about the extent of this education occurring today. An online survey was created for Reform and Conservative rabbis to assess the types of JGD education taking place within the synagogue. Additionally, the survey included questions to assess JGD knowledge and possible factors that could predict counseling activity and knowledge level. Of the 94 participants, 91% had provided education about JGDs to congregants, with 98.8% providing this education during premarital counseling sessions. For most respondents, explaining recessive inheritance pattern and carrier screening was the extent of the discussion. Additionally, the majority of rabbis scored below 50% on the knowledge portion of the survey, with an average score of 1.9/4. There were no statistically significant differences between JGD education in Reform vs. Conservative synagogues, and there were no statistically significant predictors of knowledge score or JGD education frequency. In conclusion, while the number of rabbis discussing this topic is encouraging, discussion topics were found to be limited and their knowledge of JGDs was found to be poor.

Adopted Individuals' Views on the Utility and Value of Expanded Carrier Screening.

Adoptees may not have family medical history and ethnicity information. Carrier screening assesses reproductive risk. Expanded carrier screening (ECS) screens for many genetic conditions regardless of a patient's knowledge of family history and ethnicity. This study aimed to better understand the opinions and attitudes of adopted individuals on the use of ECS in determining a patient's reproductive genetic risks. Specifically, the study assessed how adopted individuals feel that results of ECS may be useful to them and whether adoptees feel that meeting with a genetics professional in the process of undergoing ECS would be useful. Adult adoptees (N = 124) were recruited online. Their opinions on ECS were explored. The majority reported they had never been offered carrier screening (92%). The majority of adoptees wanted ECS (76%). Neither the amount of contact with biological relatives nor having medical knowledge about biological relatives was significantly associated with adoptees' desire to pursue ECS. There was a significant positive correlation between adoptees of higher education levels and the amount they would pay for ECS (p = 0.004). The majority of participants (95%) indicated a genetics professional would be helpful when undergoing ECS. The findings suggest this population may want ECS and support from genetics healthcare professionals. Advocacy for genetic counseling and testing for adoptees appears justifiable.

Reproductive genetic carrier screening for cystic fibrosis, fragile X syndrome, and spinal muscular atrophy in Australia: outcomes of 12,000 tests.

PurposeTo describe our experience of offering simultaneous genetic carrier screening for cystic fibrosis (CF), fragile X syndrome (FXS), and spinal muscular atrophy (SMA).MethodsCarrier screening is offered through general practice, obstetrics, fertility, and genetics settings before or in early pregnancy. Carriers are offered genetic counseling with prenatal/preimplantation genetic diagnosis available to those at increased risk.ResultsScreening of 12,000 individuals revealed 610 carriers (5.08%; 1 in 20): 342 CF, 35 FXS, 241 SMA (8 carriers of 2 conditions), approximately 88% of whom had no family history. At least 94% of CF and SMA carriers' partners were tested. Fifty couples (0.42%; 1 in 240) were at increased risk of having a child with one of the conditions (14 CF, 35 FXS, and 1 SMA) with 32 pregnant at the time of testing. Of these, 26 opted for prenatal diagnosis revealing 7 pregnancies affected (4 CF, 2 FXS, 1 SMA).ConclusionThe combined affected pregnancy rate is comparable to the population risk for Down syndrome, emphasizing the need to routinely offer carrier screening. The availability of appropriate genetic counseling support and a collaborative approach between laboratory teams, genetics services, health professionals offering screening, and support organizations is essential.

"It gives them more options": preferences for preconception genetic carrier screening for fragile X syndrome in primary healthcare.

This study aims to explore stakeholder views about offering population-based genetic carrier screening for fragile X syndrome. A qualitative study using interviews and focus groups with stakeholders was undertaken to allow for an in-depth exploration of views and perceptions about practicalities of, and strategies for, offering carrier screening for fragile X syndrome to the general population in healthcare settings. A total of 188 stakeholders took part including healthcare providers (n = 81), relatives of people with fragile X syndrome (n = 29), and members of the general community (n = 78). The importance of raising community awareness about screening and providing appropriate support for carriers was emphasized. There was a preference for preconception carrier screening and for providing people with the opportunity to make an informed decision about screening. Primary care was highlighted as a setting which would ensure screening is accessible; however, challenges of offering screening in primary care were identified including time to discuss screening, knowledge about the test and possible outcomes, and the health professionals' approach to offering screening. With the increasing availability of genetic carrier tests, it is essential that research now focuses on evaluating approaches for the delivery of carrier screening programs. Primary healthcare is perceived as an appropriate setting through which to access the target population, and raising awareness is essential to making genetic screening more accessible to the general community.

State-offered ethnically targeted reproductive genetic testing.

report on a program that involves state-offered carrier screening for cystic fibrosis, spinal mus-cular atrophy, and fragile X for the entire population of Israel, with screening for a wide array of additional diseases selected based on a combination of ethnicity, religious affiliation, and locality of origin. To their credit, Zlotogora et al.

Validation for Clinical Use of, and Initial Clinical Experience with, a Novel Approach to Population-Based Carrier Screening using High-Throughput, Next-Generation DNA Sequencing

Traditional carrier screening assays are designed to look for only the most common mutations within a gene owing to cost considerations. Although this can yield high detection rates in specific populations for specific genes (such as cystic fibrosis in Caucasians), they are suboptimal for other ethnicities or for patients of mixed or unknown ethnic background. Next-generation DNA sequencing provides an opportunity to provide carrier screening using more comprehensive mutation panels that are limited primarily by information about the clinical impact of detected sequence changes. We describe a next-generation DNA sequencing-based assay capable of reliably screening patient samples in a timely and comprehensive manner. The analytic accuracy in a research setting has been documented. Here, we describe the additional studies performed to ensure the accuracy (analytic validity) and robustness of our assay for use in clinical practice and provide data from our experience offering this testing. Our clinical experience using this approach to screen 11,691 invitro fertilization patients has identified 449 mutant alleles: 447 in carriers and 2 in an affected individual. In total, we found 87 distinct mutations in 14 different genes. Approximately one quarter of the mutations found are not included in traditional, limited, mutation panels, including 16 known mutations unique to our panel, and novel truncating mutations in several genes.

Current Practice and Attitudes of Australian Obstetricians Toward Population-Based Carrier Screening for Inherited Conditions

An anonymous survey of Australian Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists was conducted with the aim of understanding current practice and attitudes toward population-based carrier screening for inherited conditions in the setting of routine pregnancy care. Of 1,121 Fellows invited to complete the online questionnaire by e-mail, 237 (21%) responded, and of these 156 were practicing obstetricians and completed the whole survey. Of the respondents, 83% expressed support for population-based carrier screening for at least some conditions, with 97% supporting carrier screening for β-thalassaemia, and 83% supporting carrier screening for cystic fibrosis (CF). A small proportion of obstetricians reported offering carrier screening as part of routine pregnancy care (20% for β-thalassaemia, 8% for CF, 5% for fragile X syndrome, and 2% for spinal muscular atrophy). The main practical barriers identified for screening were cost, time constraints, and availability of supporting services. Addressing these issues is crucial for the successful implementation of population-based carrier screening programs in Australia and internationally.

Attitudes of health care professionals toward carrier screening for cystic fibrosis. A review of the literature

Recent technological developments in molecular genetics facilitate the large-scale detection of inherited genetic disorders and allow an increasing number of genetic conditions to be screened for (American College of Medical Genetics 2012). This technological evolution creates the background which makes reflection necessary about the desirability to offer community-based (preconception) carrier screening in the healthcare system. A positive attitude of potential providers is vital to the success of a screening program. Therefore, the objective of this article is to elaborate a review of the attitudes of healthcare professionals toward carrier screening. Examination of existing carrier screening programs could provide such information. The literature review will be focused on the attitudes toward carrier screening for cystic fibrosis (CF). The databases Pubmed and Web of Science, as well as the interface Google Scholar, were searched using the keywords for the period 1990-2011. Studies were selected if they were published in a peer-reviewed journal in English and described the attitudes of potential providers toward carrier screening. Eleven studies were retrieved describing the attitudes toward carrier screening for CF. In total, seven studies reported attitudes toward the best time for carrier screening; four studies described opinions toward the best setting to offer CF carrier screening; six studies investigated the willingness to be involved in a carrier screening program, and in total 11 articles reported the concerns about offering carrier screening. Ten papers described a general attitude toward carrier screening. We can conclude that health care providers state willingness to be involved in a carrier screening program, but there is need for appropriate education as well as adequate support given the time constraints already present in consultation. The prospect of an increasing number of genetic disorders for which screening becomes possible, and the potential increasing demand for such screening in the future calls for the need for further debate on the desirability of carrier screening and relevant questions such as the conditions screened, the providers involved, the information provision, and counseling.

“It's something I need to consider”: Decisions about carrier screening for fragile X syndrome in a population of non‐pregnant women

Population carrier screening for fragile X syndrome can provide women with information about their risk of having a child with fragile X syndrome and their risk of fragile X-associated primary ovarian insufficiency and fragile X-associated tremor ataxia syndrome. Few studies have explored women's decisions when offered carrier screening for fragile X syndrome. Interviews were conducted with 31 women who participated in a pilot study offering carrier screening to non-pregnant women. A qualitative approach was used to gain an in-depth understanding of women's experiences and examine their decision-making processes, including women who were tested and those who decided not to be tested. The decision-making process occurred in two phases. In the first phase, the participant's reproductive stage of life and experience with illness and disability were major factors influencing whether she would consider screening. In the second phase of decision-making, participants' perceptions of the value of knowing their carrier status was the most notable factor for influencing whether a woman actually had the carrier test. Some women appreciated having time for deliberation and those who were tested did not express regret about their decision. Our findings support offering carrier screening for fragile X syndrome to non-pregnant women and suggest that women from the general population will have specific informational and counseling needs when offered carrier testing. This study highlights the unique challenges encountered by women from the general population when making a decision about testing for fragile X syndrome carrier status and illustrates the importance of understanding how women make decisions.

ACOG Committee Opinion No. 442: Preconception and Prenatal Carrier Screening for Genetic Diseases in Individuals of Eastern European Jewish Descent

Certain autosomal recessive disease conditions are more prevalent in individuals of Eastern European Jewish (Ashkenazi) descent. Previously, the American College of Obstetricians and Gynecologists recommended that individuals of Eastern European Jewish ancestry be offered carrier screening for Tay-Sachs disease, Canavan disease, and cystic fibrosis as part of routine obstetric care. Based on the criteria used to justify offering carrier screening for Tay-Sachs disease, Canavan disease, and cystic fibrosis, the American College of Obstetricians and Gynecologists' Committee on Genetics recommends that couples of Ashkenazi Jewish ancestry also should be offered carrier screening for familial dysautonomia. Individuals of Ashkenazi Jewish descent may inquire about the availability of carrier screening for other disorders. Carrier screening is available for mucolipidosis IV, Niemann-Pick disease type A, Fanconi anemia group C, Bloom syndrome, and Gaucher disease.