When is prenatal exome sequencing considered?

What does the evidence say about prenatal exome sequencing?

1. Exome sequencing examines protein-coding regions across many genes. It asks a different question from chromosome counting or looking for larger missing or duplicated DNA segments. Because some relevant changes lie outside those regions or evade detection, a negative exome cannot exclude every genetic condition. 1
2. ACOG describes selected situations in which prenatal sequencing may be considered after standard testing has not explained multiple or recurring fetal findings. It also emphasizes specialist counseling. An offer of broader testing should include a clear explanation of why that test fits this pregnancy. 2
3. A systematic review of fetuses with structural abnormalities found that the additional information from exome sequencing varied substantially with case selection and the organs affected. Those results do not apply directly to a pregnancy with normal imaging. Ask for expectations based on the actual referral finding. 3
4. Sequencing may find a variant whose effect is unclear. An uncertain result cannot, by itself, establish that a fetus has the suspected condition or predict its severity. Discuss how the laboratory reports uncertainty and whether parental samples or later reassessment could help interpretation. 4
5. Pretest counseling should address your priorities and the choices you can make about testing. Ask whether the laboratory reports unexpected findings, how results will be returned, and who will discuss implications for family members. Consent should reflect the test being ordered, not a generic promise to find everything. 5

When should you discuss prenatal exome sequencing?

• First trimester. A known familial condition may call for a targeted genetics plan rather than a broad test ordered without a specific question.
• Second trimester. If ultrasound findings remain unexplained, discuss whether specialist sequencing would add useful information.
• Third trimester. Agree on who will receive pending results and connect them with the baby's care team after birth.

Questions to bring to your prenatal team