Ultrasonographic markers for chromosomal abnormalities in women with negative nuchal translucency and second trimester maternal serum biochemistry.

OBJECTIVE: To analyze the value of second trimester ultrasound examination among those women whose fetuses were indicated to be at low risk of chromosomal anomalies on the basis of both first trimester nuchal translucency measurement and second trimester biochemical screening. METHODS: A retrospective study of 5500 pregnancies carried out at the fetal medicine unit, Royal Free Hospital. During a period of over 3 years 5500 pregnancies underwent a first trimester scan and nuchal translucency measurement which enabled the detection of 62% (20 of 32) of all chromosomal anomalies. From the remaining pregnancies that underwent second trimester biochemical screening, 3548 were considered negative (risk < 1:250; using maternal serum free beta human chorionic gonadotrophin and alpha fetoprotein). The ultrasound markers that were examined were: shortened femur length, echogenic bowel, pyelectasis, choroid plexus cysts and echogenic intracardiac foci. The likelihood ratios for chromosomal aneuploides for each of these markers were calculated. RESULTS: Of the 3548 screen negative pregnancies, 3541 (99.8%) had a normal karyotype. Seven (0.2%) fetuses had an abnormal karyotype including four (0.11%) with trisomy 21, one with trisomy 18 and two with 47XXY. Second trimester ultrasound markers were found in two of the five (40%) with severe chromosomal anomalies compared to 184 of 3541 (5.2%) with normal karyotypes. Detection of one or more ultrasound markers in a screen negative pregnancy increased the possibility of chromosomal aneuploidy and a negative ultrasound decreased the risk by a likelihood ratio of 0.6 (95% confidence interval, 0.3-1.3). The risk was considerably increased when two or more markers were detected and we would recommend karyotyping under these circumstances. CONCLUSION: This preliminary data indicates a possible role for abnormal ultrasound markers in assessing the risk of chromosomal abnormalities in patients considered to be at low risk by nuchal translucency and serum screening. However analysis of a much larger study group will have to be conducted to assess the significance of individual markers.

First trimester sonographic detection of chromosomal abnormalities in an unselected population.

OBJECTIVE: To investigate the role of first trimester sonography in detecting chromosomal abnormalities in an unselected obstetric population. METHODS: 2281 women (mean maternal age 30 years [range 16-47]; mean gestational age 12(+3) weeks [range 11-14]) underwent transabdominal scanning to assess fetal structure and, if anatomical survey was considered to be incomplete (31% of cases), transvaginal sonography was also performed. Measurement of nuchal translucency was included and karyotyping performed as considered appropriate. RESULTS: There were 16 chromosomal abnormalities; 13 (81%) were diagnosed at 11-14 weeks either because of a nuchal translucency greater than or equal to the 99th centile for gestational age (7/16; 44% [95% CI 25-63]) or due to the presence of structural abnormalities (6/16; 38% [95% CI 14.2-61.8]). Seventy-five percent of cases of trisomy 21 were also diagnosed either because of having a nuchal translucency greater than or equal to the 99th centile (5/8; 63%) or due to the presence of a structural abnormality (1/8; 13%). CONCLUSIONS: A significant proportion of fetal chromosomal abnormalities can be detected by first trimester sonographic screening to assess fetal structural appearance. The sensitivity of detection can be improved by combining measurement of nuchal translucency with detailed examination of fetal anatomy.

The role of ultrasonographic markers for trisomy 21 in women with positive serum biochemistry.

OBJECTIVE: To assess the value of particular markers detected by second trimester ultrasound examination among those women whose fetuses were shown to be at increased risk of Down's syndrome on the basis of biochemical screening. DESIGN: A retrospective study of 459 pregnancies. SETTING: Fetal Medicine Unit, Royal Free Hospital. PARTICIPANTS: Four hundred and fifty-nine pregnant women, including four twin pregnancies, registered at the Royal Free Hospital, who were considered screen positive (risk > 1:250) based on the results of mid-trimester biochemical markers (maternal serum free beta human chorionic gonadotrophin and alpha-fetoprotein). MAIN OUTCOME MEASURES: The ultrasound markers that were examined included structural defects, shortened femur length, echogenic bowel, dilation of the renal pelvis and choroid plexus cysts. The likelihood ratios for trisomy 21 for each of these markers were calculated. RESULTS: Of the 463 fetuses which were screen positive, 449 (97%) had a normal karyotype detected by amniocentesis (n = 344) or postnatal follow up (n = 105). Fourteen fetuses had an abnormal karyotype including 11 (2.4%) with trisomy 21. Ultrasound markers were found in 9/11 (81.8%) fetuses with trisomy 21, compared with 44/449 (9.8%) with a normal karyotype. Detection of one or more ultrasonographic markers in a screen positive pregnancy increased the risk of trisomy 21 by a likelihood ratio of 8.4, and the absence of such markers decreased the risk by a likelihood ratio of 0.2. The risk was considerably increased when the presence of two or markers were detected (likelihood ratio 41). In trisomy 21 fetuses the two most commonly detected markers, shortened femur and dilation of the renal pelvis, had likelihood ratios of 49.3 and 20.5, respectively. Choroid plexus cysts were detected in 27 of the normal karyotypic fetuses compared with none of those with trisomy 21. CONCLUSION: The presence or absence of abnormal ultrasonographic markers can significantly change the risk of Down's syndrome among pregnant women already found to have abnormal serum biochemistry. This data may be useful in counselling such women.

Prenatal diagnosis of trisomy 21 in monozygotic twins with increased nuchal translucency and abnormal serum biochemistry.

We present a case of a monozygotic twin pregnancy who underwent routine screening for chromosomal abnormalities at 14 weeks of gestation by ultrasonographic measurement of nuchal translucency and biochemical analysis of maternal serum alpha fetoprotein and free beta human chorionic gonadotrophin levels. Both screening methods indicated the pregnancy to be at increased risk of Down syndrome, with the ultrasound findings suggesting both fetuses to be affected. An amniocentesis was performed, and karyotype analysis revealed trisomy 21 in both fetuses; the mother subsequently opted for a termination of pregnancy. This case illustrates that screening for trisomy 21 in twin pregnancies is possible by both nuchal translucency measurement and maternal serum markers.