(1178) Low-Fetal Fraction on NIPT: The role of the 11-14 week ultrasound

Objective: Low fetal fraction (LFF) on non-invasive prenatal testing (NIPT) is associated with a higher risk of chromosomal abnormalities. Our goal was to determine the negative predictive value (NPV) of a normal 11-14 week ultrasound (US) in the setting of LFF on NIPT.

Study Design: This was a retrospective review of patients with LFF on first-trimester NIPT who had an 11-14 week US from 2021-2024. Patients with multiple gestations were excluded. Body mass index (BMI), age and estimated gestational age (EGA) at time of NIPT were assessed. Normal genetic outcomes were defined as normal repeat NIPT, normal invasive testing or normal postnatal evaluation. The primary outcome was the negative predictive value of the 11-14 week US in those with LFF. Fisher’s exact test was used for statistical comparison.

Results: 179 patients with LFF were included. Five (2.8%) had chromosomal abnormalities including Trisomy 18 (n=3), Trisomy 21 (n=1) and Monosomy X (n=1). Eight patients (4.5%) had an abnormal US: all eight had abnormal nuchal translucency, and two had additional structural abnormalities. 167 patients (93.3%) had a normal repeat NIPT or underwent invasive testing. Of those who underwent repeat NIPT, LFF was found again in 18.3%. Of these patients, one patient had an abnormal genetic result of Monosomy X. There was a strong correlation between abnormal US and chromosomal abnormalities (50% vs. 0.6%; p< 0.001), with four of five affected pregnancies having an abnormal US. The NPV of normal US after LFF result was 99.4% and the sensitivity of the 11-14 week US was 80%. There was no significant difference in BMI or gestational age at NIPT between those with normal and abnormal outcomes, and rates of obesity were similar in those with normal vs abnormal outcomes (36.1% vs 40%; p=1.0).

Conclusion: In patients with LFF choosing between repeat NIPT vs invasive testing, the 11-14 week US has high sensitivity and NPV in screening for chromosomal abnormalities. As with all screening tests, patients must be counseled about the potential for false-negative results.