Nuchal index: a gestational age independent ultrasound marker for the detection of Down syndrome

Objectives: To determine if the ultrasound marker Nuchal Index (NIx) is gestational age independent, and to determine its specificity and sensitivity for Down syndrome (DS) identification.

Methods: Prospective cohort. A prospective database of fetal biometry and soft markers of aneuploidy was searched for fetuses with the following criteria: confirmed gestational age, at least two measurements of nuchal thickness and biparietal diameter, no major detectable fetal anomalies, and either normal karyotype or normal postnatal exam. Nuchal Index (NIx) was defined as 100x (mean nuchal thickness [mm])/(mean Biparietal Diameter [mm]). This cohort was divided into two groups according to the last digit of their hospital unit number. Initial analysis was carried out in the first group (analysis group), with the second group (normal) used to test the results. A prospective cohort of pre- and postnatally diagnosed DS fetuses with at least two measurements of nuchal thickness and biparietal diameter constituted the abnormal study group (abnormal) and was used to determine the sensitivity of the index. P value <0.05 was considered significant.

Results: Eight hundred and seventy-five fetuses constituted the control group with 455 in the analysis group and 420 in the normal group. In the analysis group, Pearson coefficient and ANOVA confirm that NIx was independent of gestational age between 14 + 0 and 22 + 6 weeks of gestation. For the analysis group, mean NIx was 7.72, (SD = 2.05) and a threshold value of 11.0 yielded a specificity of 94%. Fifty-two DS fetuses made up the abnormal group. Mean NIx in this group was 17.9 (SD = 13.9), which was highly significant (P < 0.00001) compared to the analysis group. Using an NIx threshold of 11.0, sensitivity for any DS was 61.5% (32/52) and specificity (normal group) was 96% (402/420) (False positive rate = 4%). If DS fetuses with effusions, hydrops, cystic hygromas or central nervous system (CNS) defects are excluded, the sensitivity for an NIx of 11.0 was 50.0% (20/40).

Conclusions: Nuchal Index (NIx) can be assumed to be constant between 14 + 0 and 22 + 6. Using a threshold of 11.0, the sensitivity for any Down syndrome (DS) fetus was 62% (32/52) with a specificity of 96% (False positive rate = 4%). Even when obvious fetal conditions that can cause an increase in NIx are excluded, the sensitivity remains acceptable at 50%. NIx appears to be a useful, gestational age independent ultrasound marker for Down syndrome.