By how much does increased nuchal translucency increase the risk of adverse pregnancy outcome in chromosomally normal fetuses? A study of 16,260 fetuses derived from an unselected pregnant population

Abstract

Objective: In this study we aimed to estimate the magnitude of a possible increase in risk of adverse outcome in fetuses with normal karyotype and increased nuchal translucency (NT), and to determine how well NT measurements can distinguish between fetuses with normal and adverse outcome.

Methods: We studied 16,260 consecutive fetuses with normal karyotype derived from an unselected pregnant population. The following cut-offs for increased risk of adverse outcome were chosen a priori: NT > or = 95th percentile, > or = 3 mm, > or = 3.5 mm, and > or = 4.5 mm. The positive and negative likelihood ratios (+LR, - LR) of the risk cut-offs with regard to fetal malformation, miscarriage, perinatal death, termination of pregnancy and total adverse outcome were calculated, and receiver-operating characteristics (ROC) curves were drawn.

Results: The total rate of adverse outcome was 2.7%. + LR and - LR of NT > or = 3.0 mm were: for lethal or severe malformation, + LR 15.0 (95% CI 7.0-28.6), - LR 0.89 (95% CI 0.81-0.95); for malformation of at least intermediate severity, + LR 8.1 (95% CI 4.3-14.0), - LR 0.95 (95% CI 0.92-0.97); for termination of pregnancy, + LR 41.6 (95% CI 17.1-86.6), - LR 0.67 (95% CI 0.41-0.85); for any adverse outcome, + LR 6.4 (95% CI 3.4-11), - LR 0.96 (95% CI 0.94-0.98). The odds for these adverse outcomes increased with increasing NT. NT > or = 3 mm did not significantly increase the risk of miscarriage or perinatal death. Areas under ROC curves for NT were small, with 95% CI below or only slightly above 0.5.

Conclusion: Our likelihood ratios can be used to calculate the individual risk of unfavorable outcome, but NT screening cannot reliably distinguish between normal and adverse outcome in fetuses with normal karyotype.