Could high levels of cell-free DNA in maternal blood be associated with maternal health and perinatal outcomes?

The aim of this study was to evaluate the maternal and foetal factors affect higher cell-free DNA (cfDNA) levels and to investigate a possible relationship between high cfDNA levels and adverse perinatal outcomes. From a total of 4594 women who underwent non-invasive prenatal testing from January 2016 to March 2018 in our hospital, 112 women had high levels of cfDNA, which was not appropriate for testing. Maternal characteristics and perinatal outcomes were compared between patients with high levels of cfDNA and normal levels of cfDNA. Patients with high levels of cfDNA had greater risks than patients with normal cfDNA levels of pregnancy complications but no statistically significant difference was found. Patients with high cfDNA levels had higher foetal death rates with a statistically significant difference (9.8% versus 1.8%,  = .024). An increase in foetal death could be expected in patients with increased cfDNA levels; therefore, these patients should be carefully followed up during pregnancy.IMPACT STATEMENT Most studies about cfDNA levels are focussed on the foetal fraction. There are new arguments about maternal health and cfDNA. It is known that autoimmune diseases as systemic lupus erythematosus (SLE) and maternal obesity increase cell turnover. There are also clinical studies suggesting a relationship between low molecular weight heparin therapy and the amount of cfDNA. This is the first study evaluating the maternal and foetal biological factors affecting cfDNA concentrations and investigating the possible relationship between high cfDNA levels and adverse perinatal outcomes in patients with high levels of cfDNA compared to patients with normal levels of cfDNA. In the present study, it was found that an increase in foetal death could be expected in patients with higher cfDNA levels. If potential effects and underlying causes of increased cfDNA could be explained, cfDNA might be used as a biomarker for adverse perinatal outcomes.