Non-invasive prenatal screening (NIPS) genomics analysis of cell free DNA in maternal blood has the potential to perform well as a first-tier screening test for aneuploidies. NIPS use as a first-tier screening test would simplify, streamline, and enhance the safety of prenatal screening for fetal aneuploidies and could potentially detect other important fetal abnormalities. However, critical challenges must be tackled to offer NIPS to 450,000 pregnant women per year in Canada’s heterogeneous public health care system. This project aims to fill in evidence gaps related to 1) moving NIPS from a 2nd-tier screening test to a 1st-tier screening test, and 2) informing whether NIPS should also screen for other actionable chromosomal conditions. This project aims to develop lower cost NIPS technology that would expand the detection of other anomalies and ensure the quality control of clinical-grade NIPS testing in Canada and worldwide.