The evolution of carrier screening: Understanding current recommendations

Patients are becoming increasingly aware of genetic carrier screening and often have questions. Are you prepared to confidently guide them through the options and interpret the recommendations from organizations like ACOG and ACMG? As genetic testing evolves and the availability of testing rapidly expands, it's understandable that healthcare providers may find it difficult to determine best practices. Below we highlight current recommendations from ACOG and ACMG and point out key differences between them.

Carrier screening began over 50 years ago, initially focusing on testing couples for genetic conditions with a high carrier frequency in their ethnic group. For example, screening for Tay-Sachs disease was only offered to individuals of Ashkenazi Jewish descent. Over time as our understanding of genetics and testing technologies improved, the cost of testing became more accessible, and screening expanded to include more conditions impacting broader populations. Insurance coverage for carrier screening has also evolved. While coverage policies vary among insurers, many now offer some level of coverage for carrier screening, especially for certain high-risk groups or conditions.

ACOG recommendations as of 2023 ^{1, 2}

• Supports 3 screening strategies
  • Ethnic-specific screening: Targeted screening based on an individual's ethnic background (eg, screening for Tay-Sachs disease in individuals of Ashkenazi Jewish descent)
  • Pan-ethnic screening: Screening for conditions common across multiple ethnic groups
  • Expanded carrier screening: Screening for a large panel of genetic conditions, regardless of ethnicity
• Recommends offering carrier screening for cystic fibrosis, spinal muscular atrophy, and hemoglobinopathies to all women considering pregnancy or currently pregnant. It's important to note that this is the minimum panel ACOG recommends, and additional screening may be considered based on family history or specific ethnicity; for example:
  • African descent: Hemoglobinopathies
  • Southeast Asian, Chinese, and African descent: Alpha-thalassemia
  • Mediterranean, Middle Eastern, Southeast Asian, and Indian descent: Beta-thalassemia
  • Ashkenazi Jewish descent: Tay-Sachs disease, Canavan disease, familial dysautonomia, cystic fibrosis, and others
  • Northern European descent: Cystic fibrosis
• Emphasizes that screening is optional, and patients can decline after counseling
• Suggests that testing for the same condition not be repeated, but if there are significant changes in technology, discussion with a genetics provider about retesting and consideration of retesting can be offered

ACMG recommendations as of 2021 ³

• Recommends a tiered approach to carrier screening:
  • Tier 1: CF + SMA + Risk-Based Screening (screening based on family history or ethnicity)
  • Tier 2: Conditions with carrier frequency ≥1/100 (includes Tier 1)
  • Tier 3: Conditions with carrier frequency ≥1/200 (includes Tier 2) and X-linked conditions
  • Tier 4: Conditions with carrier frequency <1/200 (includes Tier 3)
• Recommends offering Tier 3 carrier screening to all pregnant patients and those planning pregnancy
• Suggests considering Tier 4 screening for consanguineous couples or when family/personal medical history warrants further assessment
• Emphasizes an ethnic- and population-neutral approach to promote equity and inclusion
• Discusses that the phrase "expanded carrier screening" should not be used due to providers interpreting this phrase differently

The main difference lies in the number of conditions that are recommended by each organization. ACMG advocates for a more comprehensive, tiered approach, with their Tier 3 screening recommending testing for approximately 112 conditions (corresponding to 113 genes) as a general population screening. However, ACOG recommends a smaller minimum panel (cystic fibrosis, spinal muscular atrophy, and hemoglobinopathies) but suggests a more expanded approach depending on ethnicity, family history, and patient preference.

Given the above recommendations and similarities between them, what should healthcare providers consider for their patients? Here are some practical tips to consider:

• Offer carrier screening to all patients who are pregnant or planning on becoming pregnant. Ideally, carrier screening is done prior to conception
• Provide pre-test counseling on the reasons, benefits, and limitations of carrier screening
• Allow the patient to decide on either targeted screening of selected conditions or expanded carrier screening
• If an individual is identified as a carrier of an autosomal recessive condition, offer screening to their partner. If a female individual is identified as a carrier of an X-linked condition, offer testing and genetic counseling to her and her family members. If timing is a concern, consider offering testing to the patient and their partner at the same time
• Offer post-test counseling, especially when both partners are carriers of the same autosomal recessive condition or when a female is a carrier of an X-linked condition
• Keep in mind that these recommendations for screening may continue to be updated with additional advances in genetic testing. It's important to remember that there is no "one-size-fits-all" approach to carrier screening. Which strategy to use is based on personal and family history, ethnic background, and patient preference

While some specific differences are outlined between ACOG and ACMG guidelines, both support offering carrier screening to all patients with proper counseling. As healthcare providers, our role is to facilitate patients having access to appropriate screening options and ensuring they have the information needed to make informed decisions. By staying up-to-date with current recommendations and offering comprehensive counseling, we can help patients navigate carrier screening and support them in their family planning journey. Remember, this is a rapidly evolving field; recommendations are likely to change. Clinical decisions regarding carrier screening should always be based on the most up-to-date guidelines from professional organizations.

1. ACOG. Committee Opinion No. 690: Carrier screening in the age of genomic medicine. Obstet Gynecol. 2017;129(3):e35-e40. doi:10.1097/AOG.0000000000001951
2. ACOG. Committee Opinion No. 691: Carrier screening for genetic conditions. Obstet Gynecol. 2017;129(3):e41-e55. doi:10.1097/AOG.0000000000001952
3. Gregg AR, Aarabi M, Klugman S, et al. 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). Genetics in Medicine. 2021;23(10):1793–1806. doi:https://doi.org/10.1038/s41436-021-01203-z
4. Guha S, Reddi HV, Aarabi M, DiStefano M, Wakeling E, Dungan JS, & Gregg AR. Laboratory testing for preconception/prenatal carrier screening: A technical standard of the American College of Medical Genetics and Genomics (ACMG). Genetics in Medicine, 26(7), 101137. doi:https://doi.org/10.1016/j.gim.2024.101137