Prenatal diagnostic testing and atypical chromosome abnormalities following combined first-trimester screening: implications for contingent models of non-invasive prenatal testing.

OBJECTIVES: To investigate by means of a population-based analysis of a cohort of women who underwent combined first-trimester screening (CFTS), changes in uptake of invasive prenatal diagnosis according to risk of trisomy 21 (T21) on CFTS, and prevalence and methods for ascertainment of atypical chromosome abnormalities.

METHODS: This was a retrospective cohort study using state-wide prenatal datasets from Victoria, Australia. A three-step approach was taken to analyze the data: (1) linkage of records between serum screening and diagnostic results; (2) comparison of rates of diagnostic testing according to CFTS T21 risk result category in a 2014-2015 cohort with those of a historical 2002-2004 cohort; (3) detailed analysis of atypical abnormalities in the 2014-2015 group according to CFTS T21 risk result, individual serum analyte level and other indications for invasive diagnostic testing.

RESULTS: In 2014-2015, there were 100 418 CFTS results issued for 146 776 births (68.4%). The overall prevalence of atypical chromosome abnormalities in the entire CFTS cohort was 0.10% and was highest in those with CFTS T21 risk > 1 in 10 (4.6%), or serum analyte levels < 0.2 multiples of the median (MoM) (6.9% for pregnancy-associated plasma protein-A (PAPP-A) and 5.2% for beta-human chorionic gonadotropin (β-hCG)). Almost half (49.2%) of women with PAPP-A < 0.2 MoM had a risk for T21 on CFTS of less than 1 in 100. The majority (55%) of atypical abnormalities occurred in women with CFTS T21 risk below 1 in 300, and were most commonly detected on ultrasound examination (47.1%).

CONCLUSION: Concerns regarding missed diagnoses of atypical chromosome abnormalities when non-invasive prenatal testing is offered after a result of high risk on CFTS can be mitigated if invasive diagnostic testing is offered to those women with CFTS T21 risk of > 1 in 100, serum PAPP-A or β-hCG < 0.2 MoM, or ultrasound-detected abnormality. This has implications for contingent models of screening. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.