Analysis of Factors Affecting Fetal Fraction in Cell-Free DNA Test

Abstract

Background: Noninvasive prenatal testing (NIPT) serves as a screening method to assess the risk of chromosomal abnormalities in the fetus, including trisomy 18, 21, and 13. The reliability and success of this test are influenced by the proportion of circulating cell-free DNA obtained from the feto-placental unit, known as the fetal fraction (FF). Objectives: Our study aims to investigate the fetal and maternal factors affecting FF. Methods: Our research involved 1 150 patients referred for NIPT due to various reasons such as maternal age over 35, high-risk screening tests in the first or second trimester, history of trisomy in previous pregnancies, or patient request. Patients completed a questionnaire providing variables including maternal and fetal age, Body Mass Index (BMI), smoking status, multiple pregnancies, and medication use such as Heparin or enoxaparin. Noninvasive prenatal testing was conducted on blood samples using Ion proton technology by Premaitha of the UK. The results, including fetal sex, trisomy risk, fetal fraction, and abnormal sex chromosomes, were analyzed using IBM SPSS 27 to assess the relationship between FF percentage and other variables. Results: The study included 1150 NIPT cases, with maternal ages ranging from 13 to 48 years, BMI from 15 to 70, and gestational age from 10 to 27 weeks. Among these, 96.4% were singleton pregnancies and 3.6% were twin pregnancies. Spontaneous pregnancies accounted for 88.9%, while 9.2% were IVF and 1.2% were IUI. Fetal sex distribution was 45.9% female and 54.1% male. FF ranged from 4% to 20.7%, with a mean FF of 11.07. No significant correlation was found between maternal age, fetal age, maternal BMI, trisomies, and FF. Conclusions: We can see that maternal age has no significant correlation with the fetal fraction. Although fetal age increases, the fetal fraction does too, but this increase was not significant. Body mass index, the route of pregnancy, and the sex of the fetus had no effect on FF. Despite NIPS being safer and yielding better results, other factors can still influence the outcomes of NIPS. Therefore, this test remains a screening tool, and clinical counseling should be conducted both before and after the test.