Clinical Feasibility of Early First-Trimester Non-Invasive Prenatal Testing: Associations Between Gestational Age, Fetal Fraction, and No-Call Rates

Background: Non-invasive prenatal testing (NIPT) based on cell-free fetal DNA (cffDNA) is widely used for screening common fetal aneuploidies. Although fetal fraction (FF) increases with gestational age, the feasibility and performance of NIPT in the early first-trimester, particularly before 10 weeks of gestation, remain incompletely defined. Methods: This retrospective cohort study included 9,708 singleton pregnancies undergoing first-trimester NIPT between 9 weeks 0 days and 13 weeks 6 days of gestation, which was determined by ultrasound using crown–rump length (CRL) measurement. Participants were stratified into two groups based on gestational age at testing (< 10 weeks and ≥ 10 weeks). Multivariable linear regression was used to assess factors associated with fetal fraction, and multivariable logistic regression was applied to evaluate predictors of no-call results (non-reportable NIPT outcome primarily attributed to fetal fraction < 4%), adjusting for maternal age and body mass index (BMI). Results: Fetal fraction increased significantly with advancing gestational age. After adjustment for maternal age and BMI, testing performed at ≥ 10 weeks was associated with a higher fetal fraction compared with testing at < 10 weeks (β = 1.58; 95% CI, 1.31 to 1.85; p < 0.001). However, gestational age was not independently associated with the risk of a no-call result (adjusted OR 0.88; 95% CI, 0.68 to 1.16; p = 0.40), and no significant difference in no-call rates was observed between the two gestational age groups (3.78% vs. 3.76%). Conclusion: Although fetal fraction increases after 10 weeks of gestation, gestational age is not an independent determinant of no-call results once fetal fraction adequacy is achieved. NIPT performed in the early first-trimester (< 10 weeks of gestation) demonstrates acceptable analytical feasibility and reliable performance, supporting its use for early prenatal screening under appropriate clinical conditions.