Fetal Fraction of Cell-Free DNA in the Prediction of Adverse Pregnancy Outcomes: A Nationwide Retrospective Cohort Study

To assess the added value of fetal fraction of cell-free DNA in the maternal circulation in the prediction of adverse pregnancy outcomes. Retrospective cohort study. Nationwide implementation study on non-invasive prenatal testing (NIPT; TRIDENT-2 study). Pregnant women in the Netherlands opting for NIPT between June 2018 and June 2019. Two logistic regression prediction models were constructed for each adverse pregnancy outcome. The first model (base model) included prognostic clinical parameters that were selected from existing first-trimester prediction models for adverse pregnancy outcomes. The second model (fetal fraction model) included fetal fraction as a predictor on top of the prognostic clinical parameters included in the base model. The added prognostic value of fetal fraction was assessed by comparing the base and fetal fraction models in terms of goodness of fit and predictive performance. Likelihood ratio test (LRT), area under the curve (AUC) and Integrated Discrimination Improvement (IDI) index. The study cohort consisted of 56 110 pregnancies. The incidence of adverse pregnancy outcomes was 5.7% for hypertensive disorders of pregnancy (HDP; n = 3207), 10.2% for birthweight