Diagnosed After Birth-But Detectable Before? A Cohort Study of Prenatal Testing Potential

To evaluate the yield of prenatal genetic testing in infants with a confirmed genetic diagnosis.

We retrospectively reviewed records of infants with a genetic diagnosis who were evaluated using a standardized genetic consult and testing approach. The predicted yield of various prenatal genetic sceening and diagnostic tools in this cohort was determined and compared.

Genome sequencing had the highest predicted diagnostic yield (96.9%), followed by CMA with reflex to exome sequencing (95.5%), exome sequencing alone (93.8%) and CMA alone (43.6%). ACOG-recommended NIPT and carrier screening could have detected 25.4% of diagnoses, while 55.3% were detectable through genome-wide NIPT and a large carrier screening panel. Genome-wide NIPT improved chromosomal abnormality detection by ∼30% compared with ACOG-recommended NIPT. A large commercial carrier screening panel detected 26.1% of single-gene conditions, versus 6.1% with the ACOG-recommended panel. Overall, 62% of single-gene conditions were undetectable with current screening tools.

Prenatal ES or GS offers high diagnostic yields and a streamlined approach, suggesting that CMA may not be the most appropriate first-line test unless there is strong suspicion of a chromosomal diagnosis. Although prenatal genetic screening is valuable, its ability to identify rare genetic conditions remains limited. Our findings support revising the ACOG/ACMG guidelines to align with postnatal testing recommendations, particularly in high-risk pregnancies.