Non-intuitive trends of fetal fraction development related to gestational age and fetal gender, and their practical implications for non-invasive prenatal testing

Abstract

ABSTRACTObjectiveDiscovery of fetal cell-free DNA fragments in maternal blood revolutionized prenatal diagnostics. Although non-invasive prenatal testing (NIPT) is already a matured screening test with high specificity and sensitivity, the accurate estimation of the proportion of fetal fragments, called fetal fraction, is crucial to avoid false-negative results.MethodsWe collected 6999 samples from women undergoing NIPT testing with a single male fetus to demonstrate the influence of fetal fraction by the maternal and fetal characteristics.ResultsWe show several fetal fraction discrepancies that contradict the generally presented conventional view. At first, the fetal fraction is not consistently rising with the maturity of the fetus due to a drop in 15 weeks of maturation. Secondly, the male samples have a lower fetal fraction than female fetuses, arguably due to the smaller gonosomal chromosomes. Finally, we discuss not only the possible reasons why this inconsistency exists but we also outline why these differences have not yet been identified and published.ConclusionWe demonstrate two non-intuitive trends to better comprehend the fetal fraction development and more precise selection of patients with sufficient fetal fraction for accurate testing.Bulleted statementsWhat is already known about this topic?Non-invasive prenatal testing has become a well-known mature screening test, and the fetal fraction is studied in detail by research teams worldwide.What does this study add?Here we demonstrate two non-intuitive trends to better comprehend fetal fraction development that can further increase the sensitivity of routine testing by proper selection of blood sampling according to gestational age and fetus gender.