Publications Supporting the Utility of Expanded Carrier Screening
Beauchamp et al. Systematic design and comparison of expanded carrier screening panels. Genet Med. 2018; 20, 55-63.
Summary: Design principles for ECS panels might improve clinical detection of at-risk couples and facilitate objective discussions of panel choice.
Beauchamp et al. Clinical impact and cost-effectiveness of a 176-condition expanded carrier screen. Genet Med. 2019.
Summary: Preconception expanded carrier screening is predicted to reduce the burden of Mendelian disease in a cost-effective manner compared with minimal screening.
Ben-Shachar et al. A Data-Driven Evaluation of the Size and Content of Expanded Carrier Screening Panels. Genet Med. 2019; (in press).
*1-in-100 criteria translates to ≥1/10,000 for XL diseases
Summary: This study is the first data-driven evaluation of medical society guidelines by the American College of Obstetricians and Gynecologists for expanded carrier screening (ECS) and shows that current guidelines limit detection of couples at-risk for pregnancies affected with serious conditions.
Ghiossi C, Goldberg J, Haque I, et al. Clinical utility of expanded carrier screening: reproductive behaviors of at-risk couples. J Genet Couns. 2018;3:616–25.
Summary: 76% of at risk carrier couples used their expanded carrier screening results to make changes to their family planning. (n=64)
Grody WW, Thompson BH, Gregg AR, et al. ACMG position statement on prenatal/preconception expanded carrier screening. Genet Med. 2013;15:482–3.
Summary: ACMG suggestions on selection of disorders to include on expanded carrier screening panels.
Guo, M.H., Gregg, A.R. Estimating yields of prenatal carrier screening and implications for design of expanded carrier screening panels. Genet. Med. 2019; (in press)
Summary: It’s desirable to apply a single panel across all ethnicities. Screening a subset of expanded carrier screening panels captures the vast majority of at-risk couples
Haque IS, Lazarin GA, Kang HP, Evans EA, Goldberg JD, Wapner RJ. Modeled fetal risk of genetic diseases identified by expanded carrier screening. JAMA. 2016;316:734.
Summary: Guidelines based screening misses the vast majority of at risk carrier couples even within high risk ethnicity groups. Ex: 55% of affected pregnancies in the Ashkenazi Jewish population would be missed via guidelines based carrier screening.
Johansen Taber et al. Clinical utility of expanded carrier screening: results-guided actionability and outcomes. Genet. Med. 2018.
DOI: https://doi.org/10.1038/s41436-018- 0321-0
Summary: Follow-up study (n=391) that also showed that 77% of at risk carrier couples planned or pursued actions to avoid having affected offspring.
Larazin et al. An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: Results from an ethnically diverse clinical sample of 23,453 individuals. Genet. Med. 2013; 15: 178-186
Summary: Most carriers identified were outside of ACOG/ACMG ethnicity recommendations.
Peyser et al. Comparing ethnicity-based and expanded carrier screening methods at a single fertility center reveals significant differences in carrier rates and couple rates. Genet. Med. 2018
DOI: 10.1038/s41436-018-0331-y.
Summary: Ethnicity based screening & the ACOG panel miss a significant amount of carriers and at risk carrier couples. ECS = 29.4% carrier rate, ethnicity based = 8.5% carrier rate, ACOG panel = 15.6% carrier rate. 47% of at risk carrier couples would have been missed via ethnicity based screening.
Terhaar C, Teed N, Allen R, et al. Clinical experience with multigene carrier panels in the reproductive setting [published online ahead of print, 2018 May 17]. Prenat Diagn. 2018;38(8):572–577.
doi:10.1002/pd.5272
Summary: Supports the statement that genetic diseases are cumulatively common and that expanded carrier testing panels are an effective way to identify carriers of genetic conditions in ethnically diverse populations.
Jeffrey Cannon, Eva Van Steijvoort, Pascal Borry & Davit Chokoshvili (2019) How does carrier status for recessive disorders influence reproductive decisions? A systematic review of the literature, Expert Review of Molecular Diagnostics, 19:12, 1117-1129
DOI: 10.1080/14737159.2020.1690456
Summary: Expanded Carrier Screening is becoming increasingly common, which will result in the routine identification of many autosomal recessive conditions. Reproductive decision-making is a complex and emotionally challenging process, highlighting the critical role of genetic counseling in the care for these potentially vulnerable patients.
Johansen Taber, K, Lim‐Harashima, J, Naemi, H, Goldberg, J. Fragile X syndrome carrier screening accompanied by genetic consultation has clinical utility in populations beyond those recommended by guidelines. Mol Genet Genomic Med. 2019;e1024
https://doi.org/10.1002/mgg3.1024
Summary: Fragile X syndrome guidelines recommend screening only for those with a family history or undergoing fertility evaluation. Wider screening has been resisted due to various reasons, but this study suggests that screening regardless of family history has proven to be beneficial.
Sparks, T.N. Hum Genet (2019).
https://doi.org/10.1007/s00439-019-02080-y
Summary: Discussion of the goal of expanded carrier screening and how it is accomplished. Additionally, benefits and limitations are reviewed as well as recommendations once results are reported.
Joe Leigh Simpson, Svetlana Rechitsky, Anver Kuliev, Before the beginning: the genetic risk of a couple aiming to conceive, Fertility and Sterility, Volume 112, Issue 4, 2019, Pages 622-630, ISSN 0015-0282
https://doi.org/10.1016/j.fertnstert.2019.08.002.
Summary: Identifying couples with increased susceptibility for offspring with anomalies or genetic disorders is increasingly effective as a result of molecular advances. Discussion includes the various methods for pre-implantation or prenatal testing and how they have become more accessible, but limitations that still exist.
Medical Society Guidelines/Statements on ECS
ACOG Committee Opinion #690
- Ethnic-specific, panethnic, and expanded carrier screening are acceptable strategies for prepregnancy and prenatal carrier screening.
- Prenatal carrier screening does not replace newborn screening, nor does newborn screening diminish the potential benefit of prenatal carrier screening.
- Given the multitude of conditions that can be included in expanded carrier screening panels, the disorders selected for inclusion should meet several of the following consensus-determined criteria: have a carrier frequency of 1 in 100 or greater, have a well-defined phenotype, have a detrimental effect on quality of life, cause cognitive or physical impairment, require surgical or medical intervention, or have an onset early in life.
- Each obstetrician-gynecologist or other health care provider or practice should establish a standard approach that is consistently offered to and discussed with each patient, ideally before pregnancy.
ACOG Committee Opinion #691
- Information about carrier screening should be provided to every pregnant woman. Carrier screening and counseling ideally should be performed before pregnancy because this enables couples to learn about their reproductive risk and consider the most complete range of reproductive options.
American College of Medical Genetics and Genomics (ACMG)
American College of Medical Genetics and Genomics (ACMG)
- The proper selection of appropriate disease-causing targets for general population-based carrier screening (i.e., absence of a family history of the disorder) should be developed using clear criteria, rather than simply including as many disorders as possible.
- For a particular disorder to be included in carrier screening, the following criteria should be met:
- Disorders should be of a nature that most at-risk patients and their partners identified in the screening program would consider having a prenatal diagnosis to facilitate making decisions surrounding reproduction.
- When adult-onset disorders (disorders that could affect the offspring of the individual undergoing carrier screening once the offspring reaches adult life) are included in screening panels, patients must provide consent to screening for these conditions, especially when there maybe implications for the health of the individual being screened or other family members.
- For each disorder, the causative gene(s), mutations, and mutation frequencies should be known in the population being tested, so that meaningful residual risk in individuals who test negative can be assessed.
- There must be validated clinical association between the mutation(s) detected and the severity of the disorder.
- Compliance with the American College of Medical Genetics and Genomics Standards and Guidelines for Clinical Genetics Laboratories, including quality control and proficiency testing.
Joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine: Expanded carrier screening in reproductive medicine-points to consider
- Expanded carrier screening can provide information about carrier status beyond population estimates and eliminates the need for ethnicity-based screening. However, this approach introduces complexities that require special consideration. Health care providers are reminded that the focus of carrier screening is to identify the at-risk fetus
- The following considerations should be addressed when health care providers select a preconception or prenatal carrier panel for use in practice and as laboratories consider inclusion and exclusion of conditions:
The condition being screened for should be a health problem that encompasses one or more of the following:
- Cognitive Disability
- Need for surgical or medical intervention
- Effect on quality of life
- Conditions for which a prenatal diagnosis may result in:
- Prenatal intervention to improve perinatal outcome and immediate care of the neonate.
- Delivery management to optimize newborn and infant outcomes such as immediate, specialized neonatal care.
- Prenatal education of parents regarding special needs care after birth; this often may be accomplished most effectively before birth.
Health care providers may choose not to screen for some conditions on expanded carrier screening panels (see Appendix 2). It may be preferable to exclude conditions in which:
- The disorder is associated most often with an adult-onset phenotype and molecular testing cannot distinguish between childhood or adult onset (eg, a 1 antitrypsin deficiency).
- Variants have high allele frequencies and low penetrance of a phenotype (eg, MTHFR).
- The most appropriate approach to screening is something other than molecular testing, often because of low penetrance when molecular variants are identified (eg, hereditary hemochromatosis).
European Society of Human Genetics (ESHG)
European Society of Human Genetics (ESHG)
- Moreover, while some current screening programmes are ancestry based, expanded carrier screening (sometimes referred to as ‘panethnic’ or ‘universal’) allows testing of all individuals regardless of ancestry, which in this respect increases equity and potentially reduces the risk of stigmatisation of ethnic groups.
- Expanded carrier screening: In line with the primary purpose, priority should be given to carrier screening panels that include (a comprehensive set of) severe childhood-onset disorders. Tests should be designed to achieve high clinical validity (clinical sensitivity, negative and positive predictive values) and should have established clinical utility. The main focus should be on reporting sequence variants that clearly affect function (with clear clinical significance).
The Royal Australian and New Zealand College of Obstetricians and Gynaecologists
The Royal Australian and New Zealand College of Obstetricians and Gynaecologists
- Information on carrier screening for other genetic conditions should be offered to all women planning a pregnancy or in the first trimester of pregnancy. Options for carrier screening include screening with a panel for a limited selection of the most frequent conditions (e.g. cystic fibrosis, spinal muscular atrophy and fragile X syndrome) or screening with an expanded panel that contains many disorders (up to hundreds).
Learn how you can help make ECS accessible
Keep up to date and find ways to help