Carrier screening—choose something
ACOG Committee on Genetics. Committee opinion No. 690: Carrier screening in the age of genomic medicine. Obstet Gynecol. 2017;129(3):e35-e40.
ACOG Committee on Genetics. Committee opinion No. 691: Carrier screening for genetic conditions. Obstet Gynecol. 2017;129(3):e41-e55.
Ideally, carrier screening should be offered prior to pregnancy to fully inform couples of their reproductive risks and options for pregnancy. If not performed in the preconception period, carrier screening should be offered to all pregnant women. If a patient chooses screening and screens positive for a particular disorder, her reproductive partner should then be offered screening so that the risk of having an affected child can be determined.
New ACOG guidance on prepregnancy and prenatal screening
Carrier screening recommendations have evolved as the technology available has expanded. All 3 of the following strategies now are considered "acceptable" according to 2 recently published ACOG committee opinions.
Traditional ethnic-specific carrier screening, previously ACOG's sole recommendation, involves offering specific genetic screening to patients from populations with a high prevalence for certain conditions. One such example is Tay-Sachs disease screening in Ashkenazi Jewish patients.
Panethnic screening, which takes into account mixed or uncertain backgrounds, involves screening for a certain panel of disorders and is available to all patients regardless of their background (for example, cystic fibrosis screening offered to all pregnant patients).
Expanded carrier screening is when a large number of disorders can be screened for simultaneously for a lower cost than previous testing strategies. Expanded carrier screening panels vary in number and which conditions are tested by the laboratory. An ideal expanded carrier screening panel has been debated in the literature but not agreed on.7
ObGyns and practices therefore are encouraged to develop a standard counseling and screening protocol to offer to all their patients while being flexible to make available any patient-requested screening that is outside their protocol. Pretest and posttest counseling, including a thorough family history, is essential (as with any genetic testing) and should include residual risk after testing, potential need for specific familial mutation testing instead of general carrier screening, and issues with consanguinity.
Three essential screens
Regardless of the screening strategy chosen from the above options, 3 screening tests should be offered to all pregnant women or couples considering pregnancy (either individually or in the context of an expanded screening panel):
- Cystic fibrosis. At the least, a panel of the 23 most common mutations should be used. More expanded panels, which include hundreds of mutations, increase detection in non-Caucasian populations and for milder forms of the disease or infertility-related mutations.
- Hemoglobinopathies (sickle cell, α- and β-thalassemia). Complete blood count and red blood indices are recommended for all, with hemoglobin electrophoresis recommended for patients of African, Middle Eastern, Mediterranean, or West Indian descent or if mean corpuscular volume is low.
- Spinal muscular atrophy (SMA). The most recent addition to ACOG's recommendations for general carrier screening due to the relatively high carrier frequency (1-in-40 to 1-in-60) and the severity of the disease, SMA causes degeneration of the spinal cord neurons, skeletal muscular atrophy, and overall weakness. Screening is via polymerase chain reaction for SMN1 copy number: 2 copies are normal, and 1 copy indicates a carrier of the SMN1 deletion. About 3% to 4% of patients will screen negative but still will be "carriers" due to having 2 copies of the SMN1 gene on 1 chromosome and no copies on the other chromosome.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
All pregnant patients or patients considering pregnancy should be offered carrier screening as standard reproductive care, including screening for cystic fibrosis, hemoglobinopathies, and spinal muscular atrophy. Ethnic, panethnic, or expanded carrier screening (and patient-requested specific screening) all are acceptable options, and a standard screening and counseling protocol should be determined by the ObGyn or practice.
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