Timing of diagnosis of fetal structural abnormalities after the introduction of universal cell-free DNA in the absence of first-trimester anatomical screening

Introduction: Since 2021, first-trimester anatomical screening (FTAS) is offered in the Netherlands alongside genome-wide cell-free DNA (cfDNA). Previously, only second-trimester anatomical screening (STAS) was offered. This study identifies structural abnormalities amenable to first-trimester diagnosis detected at/after STAS in the period following cfDNA implementation and preceding FTAS introduction.

Methods: This retrospective cohort includes 547 fetuses referred between 2017 and 2020 because of suspected structural abnormalities before/at/after STAS. Additional prenatal investigations and postnatal follow-up were searched. Abnormalities were classified into "always", "sometimes", and "never" detectable in the first-trimester based on a previously suggested classification.

Results: Of the 547 pregnancies, 13 (2.6%) received FTAS and 534 (97.6%) received a dating ultrasound and STAS. In 492/534 (92.1%) anomalies were confirmed; 66 (13.4%) belonged to the "always detectable" group in the first trimester, 303 (61.6%) to the "sometimes detectable", and 123 (25.0%) to the never detectable. Of the "always detectable" anomalies 29/66 (44%) were diagnosed during dating ultrasounds and 37 (56%) during STAS. The rate of termination of pregnancy for anomalies detected during FTAS and at/after STAS was 84.6% (n = 11/13) and 29.3% (n = 144/492) (p < 0.01).

Conclusion: When FTAS is not part of screening paradigms, most fetal anomalies remain undetected until the second trimester or later in pregnancy, including 56% of anomalies "always detectable" in the first trimester.