Performance of a universally offered prenatal screening program incorporating cfDNA in Ontario, Canada: a descriptive population-based cohort study of 280,000 pregnancies.

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSObjectivesC_ST_ABSTo measure the population-based performance and impact of Ontario, Canadas modified-contingent prenatal screening system for the detection of trisomies 21 (T21) and 18 (T18). DesignA retrospective, descriptive cohort study examining routinely collected data from BORN Ontario, which captures linkable population data for prenatal and neonatal health encounters across a variety of settings (e.g., laboratories, birthing hospitals and midwifery practice groups). SettingA province-wide and publicly funded prenatal screening program in Ontario, Canada offering cfDNA screening for those at increased risk of having a pregnancy with T21 or T18. Participants373,682 singleton pregnancies with an estimated due date between September 1 2016 and March 31, 2019 who were offered publicly funded prenatal screening. Main outcome measuresPrenatal detection of T21 or T18, ascertained by cytogenetic results. Performance was assessed by calculating sensitivity, specificity, positive predictive value and negative predictive value against confirmatory diagnostic cytogenetic results and birth outcomes. The secondary objective was to determine the impact of contingent cfDNA screening by measuring uptake and the proportion of T21 screen-positive pregnancies undergoing subsequent cfDNA screening and invasive prenatal diagnostic testing (PND). Results69% of pregnancies in Ontario underwent prenatal screening for T21/T18. The modified-contingent screen sensitivity was 89.9% for T21 and 80.5% for T18. The modified-contingent screen-positive rate was 1.6% for T21 and 0.2% for T18. The cfDNA screening test failure rate was 2.2% (final result including multiple attempts). The PND rate among pregnancies screened was 2.4%. ConclusionsThis study is the largest evaluation of population-based performance of a publicly funded cfDNA prenatal screening system. We demonstrated a robust screening system with high sensitivity and low PND consistent with smaller validation studies