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Ultrasonography is another potential screening test for Down syndrome. Abnormalities associated with Down syndrome (including intrauterine growth retardation, cardiac anomalies, hydrops, duodenal and esophageal atresia) and differences in long-bone length and nuchal fold thickness between Down syndrome and normal pregnancies observable on midtrimester ultrasound have been reviewed.52 In prospective cohort studies of midtrimester ultrasound screening in high-risk women who were undergoing amniocenteses for chromosome studies, nuchal fold thickening identified 75% of Down syndrome fetuses; shortened humerus or femur length detected 31%; and an index based on thickened nuchal fold, major structural defect, and certain other abnormalities identified 69%.53-55 The likelihood of Down syndrome given a positive result was 7-25% in these high-risk samples, but would be substantially lower in low-risk women. No published cohort studies have evaluated the accuracy of ultrasound screening for detection of chromosome abnormalities in low-risk women, nor have interventional cohort studies evaluated its efficacy as a screening tool in high-risk women. The use of ultrasound as a screening test for Down syndrome is limited by the technical difficulty of producing a reliable sonographic image of critical fetal structures.56,57 Incorrect positioning of the transducer, for example, can produce artifactual images resembling a thickened nuchal skin fold in a normal fetus.58 Sonographic indices are therefore subject to considerable variation. Imaging techniques require further standardization before routine screening by ultrasound for Down syndrome can be considered for the general population.56,59,60 In addition, results obtained by well-trained and well-equipped operators in a research context may not generalize to widespread use. In a multicenter cohort study in high-risk women that involved a large number of ultrasonographers of varying ability, the sensitivity of nuchal fold thickening for Down syndrome was only 38%.59 The false-psitive rate in this study was 8.5%, many times higher than that reported in studies involving expert ultrasonographers.55,61
51. Haddow JE, Palomaki GE, Knight GJ, et al. Reducing the need for amniocentesis in women 35 years of age or older with serum markers for screening. N Engl J Med 1994;330:1114-1118.
52. Lockwood JC, Lynch L, Berkowitz RL. Ultrasonographic screening for Down syndrome fetus. Am J Obstet Gynecol 1991;165:349-352.
53. Benacerraf BR, Nadel A, Bromley B. Identification of second-trimester fetuses with autosomal trisomy by use of a sonographic scoring index. Radiology 1994;193:135-140.
54. Nyberg DA, Resta RG, Luthy DA, et al. Humerus and femur length shortening in the detection of Down's syndrome. Am J Obstet Gynecol 1993;168:534-538.
55. Crane JP, Gray DL. Sonographically measured nuchal skinfold thickness as a screening tool for Down syndrome: results of a prospective clinical trial. Obstet Gynecol 1991;77:533-536.
56. Lockwood C, Benacerraf B, Krinsky A, et al. A sonographic screening method for Down syndrome. Am J Obstet Gynecol 1987;157:803-808.
57. Benacerraf BR, Gelman R, Frigoletto FD. Sonographic identification of second-trimester fetuses with Down's syndrome. N Engl J Med 1987;317:1371-1376.
58. Toi A, Simpson GF, Filly RA. Ultrasonically evident fetal nuchal skin thickening: is it specific for Down syndrome? Am J Obstet Gynecol 1987;156:150-153.
59. Grandjean H, Sarramon M-F, and the AFDPHE Study Group. Sonographic measurement of nuchal skinfold thickness for detection of Down syndrome in the second-trimester fetus: a multicenter prospective study. Obstet Gynecol 1995;85:103-106.
60. Elias S, Annas GJ. Routine prenatal genetic screening. N Engl J Med 1987;317:1407-1409.
61. Benacerraf BR, Barss VA, Laboda LA. A sonographic sign for the detection in the second trimester of the fetus with Down syndrome. Am J Obstet Gynecol 1985;151:1078-1079.
In: American Journal of Obstetrics and Gynecology. 1995 Mar;172(3):837-44
By: Vintzileos AM, Egan JF. Department of Obstetrics and Gynecology, Robert Wood Johnson Medical School/St. Peter's Medical Center, University of Medicine and Dentistry of New Jersey, New Brunswick 08903.
OBJECTIVE: Our purpose was to establish the sensitivity and specificity of various ultrasonographic markers of trisomy 21 in the second trimester of pregnancy on the basis of literature review and to generate tables that would allow adjusting the risk for trisomy 21, and therefore the need for genetic amniocentesis, depending on the presence or absence of these markers.
STUDY DESIGN: A computer search was performed of the English literature, including the years 1983 through 1993, of studies that used second-trimester ultrasonography to detect fetuses with trisomy 21. After statistical analysis of the reported studies was performed, the average sensitivity and specificity of the following ultrasonographic markers were determined: structural malformations, short femur, short humerus, combination of short femur and short humerus, pyelectasis, nuchal fold thickening, echogenic bowel, and short ear length. After the average sensitivity and specificity of these ultrasonographic markers were established, appropriate tables were generated by Bayes' theorem to adjust the risk for trisomy 21 in the second trimester depending on the presence or absence of these markers. Statistical analyses were performed with the statistical package Excel on a personal computer.
RESULTS: The average detection rate (sensitivity) of structural fetal malformations was 28%, short femur 31%, short humerus 33%, short femur and humerus 32%, nuchal fold thickening 32%, echogenic bowel 7%, and short ear length 71%. The nuchal fold thickening had the highest specificity (99.5%). Isolated pyelectasis was not associated with an increased risk for trisomy 21. However the risk was increased when pyelectasis was associated with other markers. In the presence of normal ultrasonographic results, the negative prediction can be combined with maternal age-related or biochemical prediction of trisomy 21 to help in the informed consent process in counseling women about the benefits and harms of genetic amniocentesis. Genetic amniocentesis should be considered in women of any age when second-trimester ultrasonography reveals the presence of one or more of the following: fetal structural malformations, short femur (determined by biparietal diameter-to-femur length ratio), combination of short femur and humerus, abnormal (> or = 6 mm) nuchal fold thickening, echogenic bowel, or short ear length.
CONCLUSION: In experienced hands second-trimester ultrasonography may be used to adjust the priori risk of both high and low-risk women for trisomy 21 and therefore the need for genetic amniocentesis.
In Downs syndrome both the femur and the humerus tend to be shortened.
The expected FL = -9.645 + 0.9338 x BPD
If the ratio is below 0.84 the likelihood of Down's syndrome is high.*
The BPD/FL ratio should be established for each individual population, and it's value varies with gestation. The mean +1.5 SD is usually used as the cutoff level.
GA (weeks) ------- BPD/FL ratio#
15 ---------------------------- 1.93
16 ---------------------------- 1.93
17 ---------------------------- 1.76
18 ---------------------------- 1.74
19 ---------------------------- 1.69
20 ---------------------------- 1.58
21 ---------------------------- 1.54
22 ---------------------------- 1.47
Positive predictive value 1/294 for the general population ( normally 1/1000 ) > and 1/112 for maternal age over 35 (normally 1/270).
The BPD/FL ratio and the nuchal skin fold can be used in conjunction with the maternal age incidence to arrive at a new probability for the occurrence of Down's syndrome in a particular fetus.
In the measurement of the nuchal skin fold thickness, critical landmarks should include the cavum septum pellucidum, the cerebral peduncles and the cerebellar hemispheres. Calipers are placed from the outer skull table to the outer skin surface.
Percentage of Down's syndrome fetuses with nuchal fold > 6 mm after 16 weeks vary from 69% (Benacerraf 1991) to as low as 3.8% (Grandjean 1995) in different reports. A mean value of about 50% can be obtained from different reports.
The Percentage of Down's syndrome with Nuchal folds equal or greater than 3mm before 14 weeks ranges from 1.5% (Rodeck 1995) to 18% (Nicolaides 1994) and 45% (Salvesen 1995) in different reports
Nicolaides basing on his findings in 1015 fetuses at 10-13 weeks with Nuchal fold greater than 3mm arrived at the following risks estimates:
3mm ------ 3 times
4mm ------ 18 times
5mm ------ 28 times
6mm ------ 36 times
the incidence by maternal age.
Corteville, J.E., Gray, D.L., Crane, J.P. Congenital hydronephrosis: Prenatal sonographic findings predictive of postnatal outcome. Am. J. Obstet. Gynecol. 165:384-388 (1991).
Dicke, J.M., Crane, J.P. Sonographic recognition of major malformations and aberrant fetal growth in trisomic fetuses. J. Ultrasound Med. 10:433-438 (1991).
A scoring system has been developed to evaluate fetuses for the presence of Down syndrome. Two points are given to a thickened nuchal fold and to any major structural malformation. The other markers each receive one point- which includes: a short femur, short humerus, pyelectasis, hyperechoic bowel, intracardiac echogenic focus, and widened iliac angle. A score of two indicates the need for karyotyping and will detect 80% of fetuses with Down syndrome, with a false-positive rate of just over 4%. A score of zero in a women aged 35 years decreases the likelihood of the patient having a Down fetus from 5.5 to 0.9 in 1,000.