The impact of crown-rump length measurement error on combined Down syndrome screening: a simulation study

To evaluate the impact of a 5-mm error in the measurement of crown-rump length (CRL) in a woman undergoing ultrasound and biochemistry sequential combined screening for Down syndrome.

Based on existing risk calculation algorithms, we simulated the case of a 35-year-old-woman undergoing combined screening based on nuchal translucency (NT) measurement and early second-trimester maternal serum markers (human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) expressed as multiples of the median (MoM)). Two measurement errors were considered (+ or - 5 mm), for four different CRLs (50, 60, 70 and 80 mm), with five different NT measurements (1, 1.5, 2, 2.5 and 3 mm) in a patient undergoing biochemistry testing at 14 + 4, 15, 16, 17 or 18 weeks' gestation. Four different values for each maternal serum marker were tested (1, 1.5, 2 and 2.5 MoM for hCG, and 0.5, 0.8, 1 and 1.5 MoM for AFP), leading to a total of 3200 simulations of the impact of measurement error. In all cases the ratio between the risk as assessed with or without the measurement error was calculated (measurement error-related risk ratio (MERR)).

Over 3200 simulated cases, MERR ranged from 0.53 to 2.14. In 586 simulations (18.3%), it was < 0.66 or > 1.33. Based on a risk cut-off of 1/300, women would have been misclassified in 112 simulations (3.5%). This would go up to 33 (27.5%) out of the 120 simulations in women with 'borderline' risk, with 1.5 MoM for hCG and 0.5 MoM for AFP, and NT measurement of 1 or 2mm.

Down syndrome screening may be highly sensitive to measurement errors in CRL. Quality control of CRL measurement should be performed together with quality control of NT measurement in order to provide the highest standard of care.