What helps define outcomes in persistent uninterpretable non‐invasive prenatal testing: Maternal factors, fetal fraction or quality scores?

To assess maternal characteristics and comorbidities in patients with persistent uninterpretable non-invasive prenatal testing (NIPT) and to evaluate the association with adverse pregnancy outcome in a general risk population.A retrospective cohort study (July 2017-December 2020) was conducted of patients with persistent uninterpretable NIPT samples. Maternal characteristics and pregnancy outcomes were compared with the general Belgian obstetric population.Of the 148 patients with persistent uninterpretable NIPT, 37 cases were due to a low fetal fraction (LFF) and 111 due to a low quality score (LQS). Both groups (LFF, LQS) showed more obesity (60.6%, 42.4%), multiple pregnancies (18.9%, 4.5%) and more obstetrical complications. In the LQS group, a high rate of maternal auto-immune disorders (30.6%) was seen and hypertensive complications (17.6%), preterm birth (17.6%) and neonatal intensive care unit (NICU) admission (22%) were significantly increased. In the LFF group hypertensive complications (21.6%), gestational diabetes (20.6%), preterm birth (27%), SGA (25.6%), major congenital malformations (11.4%), c-section rate (51.4%) and NICU admission (34.9%) were significantly increased. Chromosomal abnormalities were not increased in both groups.Patients with persistent uninterpretable NIPT have significantly more maternal obesity, comorbidities and adverse pregnancy outcome than the general population and should receive high-risk pregnancy care. Distinguishing between LFF and LQS optimizes counseling because maternal characteristics and pregnancy outcome differ between these groups.