{'fraction_non_alphanumeric': 0.044402897873334894, 'fraction_numerical': 0.03879411077354522, 'mean_word_length': 4.676392572944297, 'pattern_counts': {'":': 0, '<': 3, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Prenasal thickness in first‐trimester screening for Down syndrome

Prenatal screening for Down syndrome (DS) during the first trimester is usually carried out using a combination of ultrasound nuchal translucency (NT) and two maternal serum markers, free β-human chorionic gonadotrophin (hCG) and pregnancy-associated plasma protein-A. Additional first trimester ultrasound markers have also been proposed to improve screening performance, such as assessment of nasal bone (NB), ductus venosus (DV) and tricuspid regurgitation (TR) or frontomaxillary facial (FMF) angle. In the second trimester, prenasal thickness (PT) is increased on average in DS pregnancies, and ultrasound measurement of this marker has been shown to substantially improve screening performance. However, the potential role of PT in firsttrimester screening has not been addressed. This prompted us to construct a reference range in low-risk pregnancies and use this to determine the extent of elevation in fetuses with DS or Edwards syndrome (ES). A single experienced and Fetal Medicine Foundation certified sonographer (PM) performed all first-trimester twodimensional transabdominal scans by using a Toshiba Aplio XG ultrasound machine. Fetal PT was measured as previously described. Magnification of the image was such that the fetal head and upper thorax occupied the whole screen. A midsagittal section of the fetus, similar to NB and NT measurements, was obtained. PT was measured from the anterior lower edge of the frontal bone to the nearest point on the facial skin anteriorly. Prenasal thickness was prospectively measured in a low-risk group (controls) comprising 182 singleton pregnancies with no evidence of fetal abnormality and crown–rump length (CRL) between 45 and 84mm. Maternal age ranged from 19 to 41 years with a mean of 29.9 and standard deviation 4.2; the mean gestational age was 12weeks and 5days; the mean CRL was 63.4mm and standard deviation 7.8mm. Figure 1 shows that in the controls, PT increased steadily with CRL. A log-linear regression fitted the data well with the equation log10PT= 0.24475 + 0.00572*CRL (P< 0.0001), and quadratic regression of PT or log PT did not significantly improve the fit. Expressing PT values as multiples of the expected value for CRL using the equation (MoM), the median was 1.006 MoM and the standard deviation of log10MoM, estimated from the 10th to the 90th centile range divided by 2.563, was 0.0472. There was no deviation from log Gaussian fit (P = 0.84, Shapiro–Wilks Test). The normal range was 0.76–1.29 MoM, the 95th centile was 1.18 MoM, and the 99th centile was 1.28 MoM. The extent of correlation between log PT MoM and other first-trimester screening variables, in log MoMs, was examined after excluding outliers exceeding three standard deviations from the median. There was no statistically significant correlation with NT (r= 0.014, P= 0.86), free β-hCG (r= 0.003, P= 0.97), or PAPP-A (r = 0.007, P = 0.93). NT MoMs were calculated from a published regression curve. Nor was there a correlation with maternal age (r= 0.11, P = 0.14) or maternal body mass index (r= 0.082, P= 0.27). There was no material difference in the median MoM between 12 smokers (0.97 MoM) and 170 nonsmokers (1.01 MoM); there were only three non-White mothers, too few for comparison. Prenasal thickness was also measured in high-risk pregnancies when either NT was elevated or NB, DV, TR, or FMF angle was abnormal. This series included nine cases of DS and two ES subsequently diagnosed by chorionic villus sampling or amniocentesis. Figure 1 shows that in all cases, the PT in millimeters was greater than the expected value for CRL, and Table 1 shows the individual MoMs. In DS cases, the median was 1.377 MoM and the standard deviation of log10MoM was 0.0489. The 95% confidence interval on the median was 1.26–1.51 MoM. There was a highly statistically significant difference in PT between the DS and control distributions (P< 0.0001, Wilcoxon Rank Sum Test). All the DS values were above the normal 95th centile, and eight (88%) were above the normal 99th centile. Taking all 11 cases together, there was a highly statistically significant difference with the controls (P< 0.0001, Kruskal–Wallis Test), but too few cases to compare DS and ES.