Combining fetal nuchal fold thickness with second‐trimester biochemistry to screen for trisomy 21

Open Access
Publisher Website
Google Scholar
Abstract
Objective To assess second‐trimester screening for trisomy 21 by combining ultrasound nuchal fold (NF) measurement with maternal serum biochemistry. Methods NF, maternal serum α‐fetoprotein (AFP) and free β‐human chorionic gonadotropin (β‐hCG) were determined concurrently at 14–19 weeks' gestation in a study population comprising 1813 women with singleton pregnancies, including 1257 unselected women undergoing serum screening for trisomy 21 (1999–2002), and 556 high‐risk pregnancies prior to amniocentesis (2003–2005), 402 of whom had positive serum screening tests. The results were expressed in multiples of the gestation‐specific normal median (MoMs). Results There were 1799 unaffected singleton pregnancies, and their NF values approximately fitted a log Gaussian distribution over a wide range. There was a weak but statistically significant correlation between log NF and log AFP (r = − 0.069, P < 0.005) and the correlation coefficient between log NF and log free β‐hCG was even smaller and not statistically significant (r = 0.038, P = 0.11). Among the seven trisomy 21 pregnancies, the median NF level was 1.53 MoM (geometric mean 1.75 MoM), a highly statistically significant increase compared with unaffected pregnancies (P < 0.0001, one‐tail Wilcoxon Rank Sum Test). In pregnancies referred because of positive serum screening tests (391 unaffected, seven cases of trisomy 21, one of monosomy X and three other chromosomal anomalies) the use of NF to modify the serum screening risk would have reduced the invasive procedures in unaffected pregnancies by 46% without affecting the detection rate of trisomy 21 or other anomalies. Statistical modeling predicted that adding NF to AFP and free β‐hCG would increase detection more than would adding unconjugated estriol as well as inhibin‐A, an analyte that is difficult to measure with precision. Conclusions The addition of NF measurement to second‐trimester biochemical markers improves screening performance, and could overcome drawbacks in the implementation of inhibin‐A assay in clinical practice. Copyright © 2007 ISUOG. Published by John Wiley & Sons, Ltd.