Gestational age standardized nuchal thickness values for estimating mid-trimester Down's syndrome risk

Objective: Our aim was to develop gestational age standardized indices of fetal nuchal thickening. In addition, we wanted to develop a method for combining nuchal thickness data with maternal age for calculating individual Down's syndrome risk. Methods: Nuchal thickness was measured prospectively in pregnancies undergoing genetic amniocentesis. A regression equation for expected median nuchal thickness based on the biparietal diameter (BPD) was developed. Nuchal thickness values were expressed as multiples of the median (MoM). Additionally, a new parameter, percentage increase in nuchal thickness (PIN) (measured minus expected nuchal thickness) × 100/expected nuchal thickness, was used. Receiver operator characteristics curves for Down's syndrome detection based on nuchal thickness values expressed as MoM, PIN, and in mm were compared. Log₁₀ transformation of MoM data resulted in a Gaussian distribution, and the Down's syndrome likelihood ratios were calculated based on the heights of the Gaussian curves. Likelihood ratios were also calculated based on PIN values. The screening efficiency of maternal age alone was compared to age plus MoM, and age plus PIN values by multiplying age-related risk by the likelihood ratio corresponding to the given nuchal thickness MoM or PIN values. Results: There were 3,574 chromosomally normal and 50 Down's syndrome fetuses in the study. Both PIN and MoM values for nuchal thickness were closely correlated (R = 1.00, P < 0.001) and each was poorly correlated with gestational age (R = 0.018, P = 0.28). The Down's syndrome screening efficiency of PIN, MoM, and nuchal thickness values in mm were not significantly different. The addition of nuchal thickness data to maternal age-related risk significantly improved the Down's syndrome screening efficiency: Area under the ROC curve for maternal age risk = 0.58, maternal age + PIN area = 0.79 (P < 0.001 compared to maternal age alone) and for maternal age + MoM = 0.77 (P < 0.005 compared to maternal age alone). Conclusions: The development of gestational age standardized nuchal thickness indices makes it possible to combine ultrasound and maternal age-related risk to derive individual Down's syndrome odds.