Extremes of Fetal Fraction on Noninvasive Prenatal Screening and Placental Histopathology: Is There an Association?

Document Type

Article

Publication Date

11-18-2025

Publication Title

J Clin Med

Keywords

fetal fraction; noninvasive prenatal genetic screening; placental/perinatal pathology

Abstract

Objective: To evaluate the association between low and high fetal fraction (FF) of cell-free fetal DNA on non-invasive prenatal screening (NIPS) and placental pathology.

Methods: We undertook a prospective cohort study of patients undergoing NIPS between July 2022 and July 2023 through Natera Inc. Based on the FF percentile, the study cohort was divided into three groups: high FF (≥95th%), low FF (≤5th%), and a control group (FF 6th-94th%). Our primary study outcome was a composite of high-risk placental lesions. We compared the occurrence of the primary study outcome across the study groups using the chi(2) test. Multivariable regression analyses were performed to predict the likelihood of the primary outcome based on the FF percentile. Selected obstetric and neonatal outcomes were assessed as secondary outcomes.

Results: The primary outcome was present in 11 (50.0%), 19 (48.7%), and 11 (35.5%) of participants in the low FF, high FF, and control cohorts, respectively (p = 0.46). In an adjusted model, the FF percentile was not associated with the primary outcome (aOR 2.41 (0.72-8.42) for low FF, aOR 1.55 (0.51-4.82) for high FF). Chorangiosis (p = 0.02) and fetal inflammatory response (p = 0.002) were seen more commonly in the low and high FF groups. Spontaneous preterm birth was more common in the low FF group (p = 0.04).

Conclusions: Our study did not identify a correlation between high-risk histopathological patterns and extremely low or high FF when compared to a control cohort. Chorangiosis and fetal inflammatory response were found more commonly in the low and high FF groups.

PubMed ID

41303220

Volume

14

Issue

22

Find It @ Sladen

Share

COinS