Nuchal fold and nasal bone: how should we use them in Down syndrome screening?

Langdon Down in 1866 described many of the characteristics of children with the syndrome that now bears his name, but not until 1959 did the French human geneticist Jerome Jean Louis Marie Lejeune discover the diagnostic test that would demonstrate the underlying chromosomal aberration. Hence, for almost 100 years, the diagnosis of Down syndrome could be suspected by a constellation of nondiagnostic physical findings but could not be confirmed. Even today, a pediatrician cannot be certain of the diagnosis of Down syndrome based on phenotype alone. Because many of the characteristic findings of trisomy 21 are also present in unaffected infants, a suspicion of Down syndrome is confirmed only by karyotype in about two-thirds of cases. 1 This situation is analogoustoantenatalscreeninginwhichcertaincharacteristicsof the fetus may suggest an affected pregnancy, but none are diagnostic. Odibo et al 2 in this issue of the American Journal of Obstetricians and Gynecologists give us additional information that can be used to fine tune this evaluation. 2 In their present study, Odibo et al 2 compared the performanceofnuchalfold(NF)thicknessandnasalbonehypoplasia in a single population. 2 As an independent marker, an absent nasal bone proved to be superior to an enlarged NF (6 mm), with a likelihood ratio of 29 compared with 12. Based on these results, the authors rightly suggest that an absent nasal bone is the best single second-trimester ultrasound parameter for suspectingtrisomy21andhasthepotentialtoidentifyaboutonethird of affected pregnancies. Because absent nasal bone and a very large NF are rare in a euploid population and their presence or absence can be identified relatively easily by ultrasound,screeningwiththesedichotomousvariablesmaybereasonable in centers with limited ultrasound experience. In such cases, the presence of either finding should suggest referral for further evaluation and possible invasive testing. However, in experienced centers conversion of these variables to likelihood ratios and incorporation of the results into more sophisticated Down syndrome risk algorithms is preferable. Measurement of the NF in the second trimester was 1 of the earliest ultrasound markers that was used to alter Down syndrome risk and remains 1 of the most specific. Many studies, including that of Odibo et al, have used this measurement as a dichotomous variable with an upper limit threshold of 5o r 6 mm. With the use of the NF alone, the detection rate for Down syndrome is relatively unimpressive, ranging from 4-35%, 3 and was only 12% in the present evaluation. 2 Using NF in this way is suboptimal for 2 reasons. First, the NF thickness in unaffected pregnancies increases with advancing gestation, so a relatively small thickening could be more important at an earlier gestation than could a larger thickening later. For similar reasons, the use of a single cut-off with a fixed likelihood ratio throughout the entire second trimester is equally misleading. Second, the reassuring value of a small NF is diminished because women with moderately increased NFs are nottreateddifferentlythanthosewithNFvaluesnearorbelow the median. Because NF measurements fit a log Gaussian distribution, measurement-specific likelihood ratios can be calculated, for example,withtheparametersofBorrelletal 4 thatarebasedon results in multiples of the median (MoM) for gestation. The differencesinindividualriskassessmentcomparedwitharigid