() Cohort III-2 14,684 Aim: To estimate the proportion of other Combined screening followed by CVS for Estimates based chromosomal anomalies that could be risk >1:10 and cfDNA testing for risk on cfDNA missed if combined screening was replaced could detect 97% of trisomy 21 and detection rates by cell-free (cf) DNA testing as the method 98% of trisomies 18 and 13. Additionally, 86% of 99.0% for of screening for trisomies 21, 18 and 13. of monosomy X, half of 47,XXY, 47,XYY or trisomy 21, 96.8% 47,XXX, half of other chromosomal for trisomy 18, Setting: United Kingdom anomalies and one third of triploidies that 92.1% for trisomy Population: singleton pregnancies are currently detected by combined 13 and a false undergoing CVS following screening for screening and CVS for risk>1:100, could be positive rate of trisomies 21, 18 and 13 by the combination detected. 0.2% of maternal age, fetal NT and FHR and Screening by cfDNA testing, contingent on maternal serum-free and PAPP-A at β-hCG results of combined testing, improves 11–13 weeks’ gestation detection of trisomies, but misses a few of Methods: The prevalence of trisomies 21, 18 the other chromosomal anomalies detected or 13, sex chromosome aneuploidies, by screening with the combined test. triploidy and other chromosomal anomalies Current combined screening with invasive was examined in pregnancies undergoing testing at risk would detect 87% of ≥1:100 first-trimester combined screening and trsiomy 21, 91.8% of trisomies 13 and 18, chorionic villus sampling (CVS). 86.0% of monosomy X, 8.1% of other sex Outcomes: Detection of trisomies 21, 18 and chromosome aneuploidies, 89.3% of triploidy 13, sex chromosome aneuploidies, triploidy and 13.0% of other high-risk outcome, with and other chromosomal anomalies an invasive test rate of 2.6%. Modelling studies Trisomy 21 only Study ref Design LoE N Aim, setting, population, methods Results Comments
() Cohort III-2 14,684 Aim: To estimate the proportion of other chromosomal anomalies that could be missed if combined screening was replaced by cell-free (cf) DNA testing as the method of screening for trisomies 21, 18 and 13. Setting: United Kingdom Population: singleton pregnancies undergoing CVS following screening for trisomies 21, 18 and 13 by the combination of maternal age, fetal NT and FHR and maternal serum-free β-hCG and PAPP-A at 11–13 weeks’ gestation Methods: The prevalence of trisomies 21, 18 or 13, sex chromosome aneuploidies, triploidy and other chromosomal anomalies was examined in pregnancies undergoing first-trimester combined screening and chorionic villus sampling (CVS). Outcomes: Detection of trisomies 21, 18 and 13, sex chromosome aneuploidies, triploidy and other chromosomal anomalies Combined screening followed by CVS for risk >1:10 and cfDNA testing for risk could detect 97% of trisomy 21 and 98% of trisomies 18 and 13. Additionally, 86% of monosomy X, half of 47,XXY, 47,XYY or 47,XXX, half of other chromosomal anomalies and one third of triploidies that are currently detected by combined screening and CVS for risk>1:100, could be detected. Screening by cfDNA testing, contingent on results of combined testing, improves detection of trisomies, but misses a few of the other chromosomal anomalies detected by screening with the combined test. Current combined screening with invasive testing at risk ≥1:100 would detect 87% of trsiomy 21, 91.8% of trisomies 13 and 18, 86.0% of monosomy X, 8.1% of other sex chromosome aneuploidies, 89.3% of triploidy and 13.0% of other high-risk outcome, with an invasive test rate of 2.6%. Estimates based on cfDNA detection rates of 99.0% for trisomy 21, 96.8% for trisomy 18, 92.1% for trisomy 13 and a false positive rate of 0.2% Modelling studies Trisomy 21 only Study ref Design LoE N Aim, setting, population, methods Results Comments