Maternal serum biochemistry at 11-13(+6) weeks in relation to the presence or absence of the fetal nasal bone on ultrasonography in chromosomally abnormal fetuses: an updated analysis of integrated ultrasound and biochemical screening

BACKGROUND: Screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free beta-hCG and pregnancy associated plasma protein-A (PAPP-A) at 11-13(+6) weeks of gestation is associated with a detection rate of 90%, for a false-positive rate of 5%. Recent evidence suggests that in about 70% of fetuses with trisomy 21 the nasal bone is not visible at the 11-13(+6) week scan and that the frequency of absence of nasal bone differs in different ethnic groups. In addition, there is a relationship between absent nasal bone and nuchal translucency thickness. In a preliminary study we showed that while PAPP-A levels were lower and free beta-hCG levels were higher in trisomy 21 fetuses with an absent nasal bone, this difference was not statistically different. In fetuses with trisomy 13 and trisomy 18, there is also a high (57 and 67%) incidence of an absent nasal bone. The aim of this present study was to extend our examination of whether the level of maternal serum biochemical markers is independent of the presence or absence of the nasal bone in cases with trisomy 21 and to ascertain if any differences exist in cases with trisomies 13 and 18. METHODS: This study data comprised 100 trisomy 21 singleton pregnancies at 11-13(+6) weeks of gestation from our previous study and an additional 42 cases analysed as part of routine OSCAR screening. A total of 34 cases with trisomy 18 and 12 cases with trisomy 13 were also available. Ultrasound examination was carried out for measurement of fetal NT and assessment of the presence or absence of the fetal nasal bone. Maternal serum free beta-hCG and PAPP-A were measured using the Kryptor rapid random access immunoassay analyser (Brahms Diagnostica AG, Berlin). The distribution of maternal serum free beta-hCG and PAPP-A in chromosomally abnormal fetuses with absent and present nasal bone was examined. RESULTS: The nasal bone was absent in 29 and present in 13 of the new trisomy 21 cases and in 98 (69%) and 44 respectively in the combined series. For the trisomy 18 cases, the nasal bone was absent in 19 (55.9%) cases and in 3 (25%) of cases of trisomy 13. There were no significant differences in median maternal age, median gestational age, NT delta, free beta-hCG MoM and PAPP-A MoM in trisomy 21 fetuses with and without a visible nasal bone, and similarly for those with trisomies 13 or 18. For a false-positive rate of 5%, it was estimated that screening with the four markers in combination with maternal age would be associated with a detection rate of 96% of cases with trisomy 21. For a false-positive rate of 0.5%, the detection rate was 88%. CONCLUSIONS: There is no relationship between an absent fetal nasal bone and the levels of maternal serum PAPP-A or free beta-hCG in cases with trisomies 13, 18 or 21. An integrated sonographic and biochemical test at 11-13(+6) weeks can potentially identify about 88% of trisomy 21 fetuses for a false-positive rate of 0.5%.     

Sonographic features of chromosomal defects at 11(+0) to 13(+6) weeks of gestation

Each chromosomal defect has its own syndromal pattern of detectable abnormalities. The authors describe the sonographic features of trisomy 21 and other major chromosomal defects in the first trimesters of pregnancy. At 11(+0) - 13(+6) weeks, all major chromosomal defects are associated with increased NT thickness. In trisomies 21, 18 and 13 the pattern of increase in NT is similar and the average NT in these defects is about 2.5 mm above the normal median for crown-rump length. In Turner syndrome, the median NT is about 8 mm above the normal median. In addition to increased NT there are sonographic features that are often seen in some affected fetuses at 11(+0) - 13(+6) weeks. In trisomy 21 fetuses have absent nasal bone, short maxilla and abnormal Doppler waveforms in the ductus venosus. In trisomy 18, there is early onset fetal growth restriction, a tendency for bradycardia, exomphalos, absent nasal bone and single umbilical artery. In trisomy 13, there is tachycardia, early onset fetal growth restriction, megacystis, holoprosencephaly and exomphalos. In Turner syndrome, there is tachycardia and early onset fetal growth restriction. In triploidy, there is early onset asymmetrical fetal growth restriction, bradycardia, holoprosencephaly, exomphalos, posterior fossa cyst and molar changes in the placenta.     

Integrated ultrasound and biochemical screening for trisomy 21 using fetal nuchal translucency,absent fetal nasal bone,free beta-hCG and PAPP-A at 11 to 14 weeks

BACKGROUND: Screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free beta-hCG and pregnancy-associated plasma protein-A (PAPP-A) at 11 to 14 weeks of gestation is associated with a detection rate of 90% for a false-positive rate of 5%. Recent evidence suggests that in about 70% of fetuses with trisomy 21, the nasal bone is not visible at the 11th- to 14th-week scan (Cicero et al., 2001). The aim of this study was to examine whether fetal NT thickness and the level of maternal serum biochemical markers is independent of the presence or absence of the nasal bone, and to estimate the performance of a screening test that integrates the two sonographic and the two biochemical markers. METHODS: This was a retrospective case-control study comprising 100 trisomy 21 and 400 chromosomally normal singleton pregnancies at 11 to 14 weeks of gestation. Ultrasound examination was carried out for measurement of fetal NT and assessment of the presence or absence of the fetal nasal bone. Maternal serum free beta-hCG and PAPP-A were measured using the Kryptor rapid random-access immunoassay analyser (Brahms Diagnostica GmbH, Berlin). The distribution of fetal NT, maternal serum free beta-hCG and PAPP-A in trisomy 21 fetuses with absent and present nasal bone was examined. RESULTS: The nasal bone was absent in 69 and present in 31 of the trisomy 21 fetuses. There were no significant differences in median maternal age, median gestational age, NT delta, free beta-hCG MoM and PAPP-A MoM in trisomy 21 fetuses with and without a visible nasal bone. For a false-positive rate of 5%, it was estimated that screening with the four markers in combination with maternal age would be associated with a detection rate of 97%. For a false-positive rate of 0.5%, the detection rate was 90.5%. CONCLUSIONS: An integrated sonographic and biochemical test at 11 to 14 weeks can potentially identify about 90% of trisomy 21 fetuses for a false-positive rate of 0.5%.     

First-trimester ultrasonographic screening for trisomy 21 using fetal nuchal translucency and nasal bone

OBJECTIVE: To report our experience with first-trimester screening for trisomy 21 by using the combination of nuchal translucency thickness and nasal bone assessment. METHODS: Pregnant women from a predominantly Latin American population consisting of patients at both low risk and high risk for chromosomal defects underwent first-trimester ultrasonographic screening. Nuchal translucency thickness and nasal bone were assessed by two accredited fetal medicine specialists. Cases of trisomy 21 were identified from the cytogenetics laboratory logbook. RESULTS: Over a 3-year period, 1,287 consecutive singleton pregnancies were screened. The median maternal age was 33 years (range 14-47 years), with 456 (35.4%) women aged 35 years or older at the time of the scan. Overall, 110 fetuses (8.5%) had nuchal translucency thickness greater than the 95th percentile for gestational age and 25 (1.9%) had absent nasal bone. Trisomy 21 was diagnosed in 31 cases. Among them, the nuchal translucency thickness was increased in 28 and the nasal bone was absent in 13 (detection rates of 90.3% and 41.9%, respectively; P<.01). All but one (92.3%) of the trisomy 21 fetuses with absent nasal bone had increased nuchal translucency. Only two of the normal fetuses had an absent nasal bone in the first trimester. CONCLUSION: In our population, increased nuchal translucency thickness is the most important ultrasonographic marker of trisomy 21. In contrast, the nasal bone seems to have a less prominent role in identifying the fetus at risk for trisomy 21 due to its lower detection rate. However, an absent nasal bone should be considered as a highly predictive marker of trisomy 21.     

First-trimester nuchal translucency measurement and echocardiography at 16 to 18 weeks of gestation in prenatal detection for trisomy 18

BACKGROUND: Trisomy 18, the second most common autosomal trisomy, has the highest incidence of congenital heart disease of all chromosomal abnormalities. This study assessed the use of nuchal translucency (NT) measurement and fetal echocardiography at 16 to 18 weeks of gestation in prenatal detection for trisomy 18. METHODS: Screening for chromosomal aneuploidy using fetal NT measurement was performed at 10 to 14 weeks of gestation. Detailed fetal echocardiography was performed at 16 to 18 weeks of gestation immediately before genetic amniocentesis for fetal karyotyping in singleton pregnancies with increased fetal NT thickness. RESULTS: Of the 3151 singleton pregnancies included in our study, 171 cases (5.4%) of increased (> or =3.0 mm) NT were noted. Fetal chromosomal abnormalities were identified in 22 (12.9%) of these pregnancies, including 9 with trisomy 21, 5 with trisomy 18, 4 with 45,X and 4 with unbalanced structural abnormalities. Major defects of the heart and the great arteries were identified in 13 (7.6%) of these pregnancies with increased NT. These included eight pregnancies that also had the diagnosis of chromosomal aneuploidy. Among the 22 fetuses with confirmed aneuploidy, all 5 fetuses with trisomy 18, 1 of the 4 fetuses with 45,X and 2 of the 9 fetuses with trisomy 21 had increased fetal NT thickness associated with abnormal fetal echocardiography findings. CONCLUSIONS: Screening for Down syndrome and cardiac defects using first-trimester fetal NT measurement in combination with fetal echocardiography at 16 to 18 weeks of gestation is a feasible and sensitive procedure for the prenatal detection of trisomy 18.     

Fetal nasal bone and trisomy 21 in the second trimester

OBJECTIVES: To assess the feasibility of measuring nasal bone length in the second trimester of pregnancy and to confirm if fetal nasal bone absence or hypoplasia is a marker for Down syndrome. METHODS: Fetal nasal bone assessment was performed in 439 consecutive singleton pregnancies at high risk of Down syndrome between 15 and 21 weeks. All ultrasound examinations were performed transabdominally by five skilled sonographers. If the nasal bone was present, its length was measured. The biparietal diameter: nasal bone length ratio (BPD/NBL) was also calculated. RESULTS: Nasal bone assessment was successfully achieved in all fetuses. The nasal bone was absent in 2(0.47%) of the 417 unaffected fetuses and in 10(55.5%) of the 18 fetuses with trisomy 21. Of the 8 Down syndrome cases with a nasal bone present, 4 had nasal bone hypoplasia and 4 had a normal nasal bone. BPD/NBL was 9 or greater in 7 of the 8 fetuses affected by trisomy 21 with nasal bone present and in 86 (20.6%) of the 417 normal fetuses; it was 10 or greater in 5 of the 8 (62.5%) fetuses affected by trisomy 21 and in 41 of the 417 (9.8%) euploid fetuses. CONCLUSIONS: Nasal bone absence is a marker for Down syndrome in the second trimester of pregnancy. Inclusion of nasal bone length into the second-trimester screening protocol could potentially obviate the false-negative cases from other screening tests. The measurement of nasal bone length in the second trimester seems to provide additional benefits beyond the assessment of the presence or absence of the nasal bone.     

New ultrasonographic markers of aneuploidies: nasal bones

The ultrasound sign of the absence of nasal bones in aneuploidies is discussed. Among several skeletal abnormalities in trisomy 21 fetuses, the absence or delay in the development of the nasal bones has been described by radiological and histological studies. The finding of absent nasal bones is recognizable by prenatal ultrasound examinations in first- and second-trimester fetuses, and about two-thirds of fetuses with trisomy 21 reveal absent nasal bones. There is evidence that an appropriate technique is required to visualize the fetal nasal bones by ultrasound. As, from preliminary studies, the absence of nasal bones does not appear to be related to fetal nuchal thickness, the two signs could be combined in a single test for prenatal screening of trisomy 21 that seems to be very accurate.

Prenatal ultrasound studies have shown the absence of nasal bone visualization also in first-trimester fetuses affected by trisomy 18, Turner's syndrome and trisomy 9.     

Ultrasound evaluation of fetal nasal bone at 11 to 14 weeks in a consecutive series of 1906 fetuses

OBJECTIVE: The aim of this study is to evaluate the significance of nasal bone ossification as a marker for trisomy 21 at 11 to 14 weeks' gestation in an unselected obstetric population referred to our Centre. METHODS: A total of 1906 consecutive fetuses undergoing nuchal translucency scan at 11 to 14 weeks' gestation were evaluated for the presence of hypoplasia/absence of nasal bone. The data obtained were correlated with fetal karyotype. RESULTS: A successful view of the fetal profile was obtained in 1752 fetuses (91.9%). The nasal bone was hypoplastic/absent in 12 of 19 fetuses with chromosomal abnormalities. There were 10 cases of trisomy 21, in 8 of which hypoplastic/absent nasal bone was observed. Furthermore, absence of nasal bone was recorded in 24 of 1733 chromosomally normal fetuses. CONCLUSIONS: Nasal bone evaluation may improve the detection of trisomy 21 in the first trimester in an unselected obstetric population. Although numerically limited, our experience confirms that delayed nasal bone ossification (hypoplasia/absence of nasal bone) is rarely observed in chromosomally normal fetuses (1.4%). An appropriate training of operators is mandatory in order to achieve an acceptable performance.     

Ultrasonographic evaluation of fetal nasal bone in a low-risk population at 11-13 + 6 gestational weeks

OBJECTIVE: To evaluate the utility of determining the presence/absence of nasal bone in a low-risk fetal population. METHODS: Prospective study of the presence/absence of nasal bone among 1800 consecutive unselected fetuses, with complete follow-up of results. RESULTS: An adequate sonographic evaluation of nasal bone was obtained in 1682 (93.44%) of the fetuses. Nasal bone was considered absent in 19 (1.06%) of 1790 fetuses with a normal karyotype and in 2 (28.57%) of the seven recorded cases of Down syndrome (DS). The overall first-trimester sensitivity for DS to the absence of nasal bone was two of the six cases (33.3%) and the false-positive rate was 1.13%. The positive predictive value for DS of the absence of nasal bone was 2/21 (9.52%). CONCLUSIONS: In a low-risk population, the evaluation of the presence/absence of nasal bone in DS screening during the first trimester has a low sensitivity. First-trimester assessment of the nasal bone in population screening may play a lesser role than in the re-evaluation of high-risk pregnancies.     

First-trimester screening for trisomy 21 in twin pregnancy: does the addition of biochemistry make an improvement?

OBJECTIVE: To evaluate the effectiveness of the addition of first-trimester biochemistry to fetal nuchal translucency (NT) measurement in the Combined Test when screening for trisomy 21 in twin pregnancies. METHODS: Maternal serum free beta-hCG and PAPP-A were determined at 8 to 12 weeks and fetal NT was measured at 11 to 14 weeks. The individual risks were estimated for each of the fetuses using both NT screening alone and the Combined Test. An invasive diagnostic procedure was offered when the risk was 1:250 or over in either one of the fetuses. In the first period, only the results of NT screening were clinically applied. After previous analysis, the Combined Test was introduced into clinical practice. RESULTS: In the two-and-a-half-year study period, a complete follow-up was obtained in 100 twin pregnancies. Three fetuses (two pregnancies) with trisomy 21 were detected by both methods. The false-positive rate achieved by NT screening (14.3% of pregnancies and 8.6% of fetuses) was substantially reduced when first-trimester biochemistry was added in the Combined Test (5.1% of pregnancies and 3.6% of fetuses). CONCLUSION: The Combined Test appears to maintain the detection rate achieved by NT screening for trisomy 21 in twin pregnancies, but false-positive rates and invasive diagnostic procedures are reduced.     

Nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities

There is extensive evidence that effective screening for major chromosomal abnormalities can be provided in the first trimester of pregnancy. Prospective studies in a total of 200,868 pregnancies, including 871 fetuses with trisomy 21, have demonstrated that increased nuchal translucency can identify 76.8% of fetuses with trisomy 21, which represents a false-positive rate of 4.2%. When fetal nuchal translucency was combined with maternal serum free-beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A in prospective studies in a total of 44,613 pregnancies, including 215 fetuses with trisomy 21, the detection rate was 87.0% for a false-positive rate of 5.0%. Studies from specialist centers with 15,822 pregnancies, which included 397 fetuses with trisomy 21, have demonstrated that the absence of the nasal bone can identify 69.0% of trisomy 21 fetuses, which represents a false-positive rate of 1.4%. It has been estimated that first-trimester screening by a combination of sonography and maternal serum testing can identify 97% of trisomy 21 fetuses, which represents a false-positive rate of 5%, or that the detection rate can be 91%, which represents a false-positive rate of 0.5%. In addition to increased nuchal translucency, important sonographic markers for chromosomal abnormalities, include fetal growth restriction, tachycardia, abnormal flow in the ductus venosus, megacystis, exomphalos and single umbilical artery. Most pregnant women prefer screening in the first, rather than in the second, trimester. As with all aspects of good clinical practice, those care givers who perform first-trimester screening should be trained appropriately, and their results should be subjected to external quality assurance.     

First-trimester ductus venosus, nasal bones, and Down syndrome in a high-risk population

OBJECTIVE: Assessing the role of fetal ductus venosus and nasal bones evaluation in first-trimester screening for Down syndrome. METHODS: This was a prospective cohort study in a tertiary referral fetal medicine unit involving 628 consecutive fetuses undergoing chorionic villus sampling. The indication for chorionic villus sampling was an increased risk (more than 1:300) for trisomy 21 based on maternal age and nuchal translucency screening in 313 cases (54.7%), increased maternal age in 195 (34.1%), and other in 64 (11.2%). Immediately before chorionic villus sampling, an ultrasound examination was performed. The pattern of blood flow in the ductus venosus and the presence or absence of the nasal bones was noted. RESULTS: A satisfactory examination of both ductus venosus and nasal bones was possible in 572 fetuses. Of these, 497 (86.9%) had a normal karyotype, and 47 (8.2%) were affected with Down syndrome. The likelihood ratio for trisomy 21 was 7.05 (95% confidence interval 4.27-11.64) in the case of abnormal ductus venosus flow and 6.42 (95% confidence interval 3.86-10.67) in the case of absent nasal bones. CONCLUSION: In addition to increased fetal nuchal translucency, Down syndrome is significantly associated with first-trimester abnormal flow velocity patterns in the ductus venosus and hypoplasia of the nasal bones.     

Fetal nuchal translucency thickness and risk for chromosomal defects

In normal pregnancy fetal nuchal translucency (NT) thickness increases with gestation, in trisomy 21 and other major chromosomal defects fetal NT is increased. The risk for trisomies can be derived by multiplying the a priori maternal age and gestation related risk by a likelihood ratio, which depends on the degree of deviation in fetal NT measurement from the normal median for that crown-rump length. In a pregnant population with a mean maternal age of 28 years, using the risk cut-off of 1 in 300 to define the screen positive group would detect about 80% of trisomy 21 fetuses for a false positive rate of 5%. It was estimated that, for a 5.4% false positive rate, 90% of trisomy 21 fetuses could be detected. Prospective studies have demonstrated that such results are achievable by screening with fetal NT and maternal serum free b-hCG and PAPP-A in the first-trimester. It is therefore essential that, in screening, attention is paid to the provision of high quality sonographic and biochemical services for early diagnosis of chromosomal defects.     

Association between first trimester absence of fetal nasal bone on ultrasound and Down syndrome

OBJECTIVES: To evaluate the association between absence of nasal bone on ultrasound and Down syndrome in fetuses at 11-14 weeks of pregnancy. METHODS: One hundred and ninety-four consecutive fetuses from singleton pregnancies undergoing chorionic villi sampling (CVS) were evaluated by transabdominal ultrasound. A sagittal view of the fetal face was obtained and the absence or presence of nasal bone was recorded and correlated with the fetal karyotype. RESULTS: A successful view of the fetal profile was possible in 183 of 194 (94%) fetuses. The nasal bone was absent in three of five fetuses with Down syndrome, and in one of 175 (0.6%) chromosomally normal fetuses. CONCLUSION: Absence of nasal bone by first trimester ultrasound was significantly associated with Down syndrome. When a proper view of the fetal face was obtained, the nasal bone was visible in more than 99% of karyotypically normal fetuses.     

Fetal obstructive uropathy in trisomy syndromes

Fetal obstructive uropathy has seldom been described in trisomy syndromes, and its relationship to these syndromes remains unclear. Five trisomic male fetuses, four with trisomy 18 and one with trisomy 21, were identified out of 110 fetuses evaluated for fetal obstructive uropathy. We performed detailed examination on the urinary tracts of four of these fetuses, three with trisomy 18 and one with trisomy 21, following termination in the second trimester. All four had a markedly distended urinary bladder (megacystis), abdominal wall distension, and a small, poorly developed urethra thoughout its full length. All four also had poor development of the prostate with virtual absence of glandular development, as compared to age-matched controls. Posterior urethral valves were not identified in any case. Three of the fetuses (two with trisomy 18 and one with trisomy 21) had unilateral or bilateral hydroureters, and resulting renal tubulocystic or glomerulocystic change. Review of this database reveals an unexpectedly high frequency of trisomies, particularly trisomy 18, suggesting that the relationship may not be coincidental. Abnormal prostate development may be causally related to fetal obstructive uropathies and may be an under-recognized trait in trisomy syndromes. Karyotypic analysis of all fetuses with obstructive uropathy is important since in utero surgical intervention may be contraindicated in cases of fetal aneuploidy.     

Jugular lymphatic maldevelopment in Turner syndrome and trisomy 21: different anomalies leading to nuchal edema

Increased nuchal translucency (NT), morphologically known as nuchal edema, is an ultrasound marker for aneuploidy. Turner syndrome presents with massive NT, called cystic hygroma. Conflicting data exist as to whether cystic hygroma and increased NT are different entities. Both are associated with jugular lymphatic distension. The authors investigated jugular lymphatics of trisomy 21, Turner syndrome, and normal karyotype fetuses. Fetuses were investigated using immunohistochemistry for blood vascular, lymphatic, and smooth muscle cell markers. Trisomy 21 fetuses showed nuchal cavities within the mesenchymal edema negative for endothelial markers. These were extremely large in Turner fetuses, showing similar characteristics. The skin showed numerous dilated lymphatics in the case of trisomy 21 and scanty small lymphatics in Turner fetuses. A jugular lymphatic sac was present in control and trisomy 21 fetuses and was enlarged in trisomy 21 cases. In Turner fetuses, no jugular lymphatic sac was observed. Nuchal edema in trisomy 21 and Turner syndrome appears to be a similar entity caused by different lymphatic abnormalities.     

A characteristic cluster of fetal sonographic markers that are predictive of fetal Turner syndrome in early pregnancy

OBJECTIVE: The purpose of this study was to describe a characteristic cluster of sonographic features of fetuses with Turner syndrome in early pregnancy. STUDY DESIGN: A targeted transvaginal ultrasound examination of all fetal organs was performed for 40123 consecutive pregnant women at 14 to 16 weeks of gestation. Both low- and high-risk pregnancies were included. Fetal karyotyping was performed in 9348 cases. The main indications were major fetal anomalies, advanced maternal age, abnormal biochemical markers, maternal anxiety, and request. RESULTS: Turner syndrome was detected in 13 fetuses (0.03%, 1/3086 early pregnancies). Huge septated cystic hygroma, severe subcutaneous edema, and hydrops were observed in all cases. A short femur was detected in 12 of 13 fetuses. A narrow aortic arch was visualized in all 8 fetuses who were scanned after 1995, when scanning of the aortic arch became mandatory in our institution. Four other fetuses had three or four of the five markers, 2 of the fetuses had trisomy 21, 1 fetus was normal, and one case of missed abortion occurred without a karyotype. CONCLUSION: A reliable diagnosis of Turner syndrome by sonographic means is possible in early pregnancy.     

The association between fetal nasal bone hypoplasia and aneuploidy

OBJECTIVE: To determine the association between fetal nasal bone hypoplasia and aneuploidy in women undergoing prenatal diagnosis. METHODS: A prospective cohort study involving women undergoing chorionic villus sampling and amniocentesis for an increased risk of aneuploidy. Fetal biometric and nasal bone measurements were obtained at the time of prenatal diagnosis and compared with karyotypes. Nasal bone hypoplasia was defined as nasal bone less than 2.5th percentile for the gestational age. RESULTS: A total of 632 fetuses were evaluated. Twenty-nine (4.6%) had an aneuploidy (18 trisomy 21, 5 trisomy 18, 1 Turner's syndrome, one Marker chromosome 1, 2 sex chromosome anomalies, and 2 triploidy). Nasal bone measurements were documented in 29 aneuploid fetuses. The nasal bone was either absent or hypoplastic in 12 of 29 (41%) fetuses with aneuploidy and in 8 of 18 (44%) with trisomy 21. By using receiver operating characteristics curves, the optimal threshold of nasal bone hypoplasia associated with fetal aneuploidy was a biparietal diameter/nasal bone ratio of 11 or greater. The sensitivity, specificity, and positive and negative predictive values for the detection of fetal aneuploidy were 50%, 93%, 24%, and 98%, respectively. CONCLUSION: Absent or hypoplastic nasal bone is a marker for fetal aneuploidy in a high-risk population. However, this marker needs to be evaluated by larger prospective studies in low-risk populations before adoption for clinical use.     

Reversed end-diastolic flow in first-trimester umbilical artery: an ominous new sign for fetal outcome

OBJECTIVE: The purpose of this study was to assess the fetal outcome of first-trimester pregnancies with reversed end-diastolic flow in the umbilical artery. STUDY DESIGN: Doppler studies in the umbilical artery were carried out in 2970 consecutive pregnancies scanned at 10 to 14 weeks. RESULTS: We observed 11 (0.4%) cases of reversed end-diastolic flow. Of these, an autosomal trisomy was shown in 7 and a congenital heart defect in 2 additional fetuses. Fetal demise was observed in 5 pregnancies, neonatal death was observed in 1, and termination of pregnancy was carried out in 4. Only 1 fetus survived. CONCLUSIONS: Reversed end-diastolic flow in first-trimester umbilical artery signals an ominous prognosis even with normal karyotype.     

Fetal nuchal translucency and prenatal diagnosis of beta-thalassaemia.

In Sardinia, fetal karyotyping for couples at risk for beta-thalassaemia is offered only to women >/=35 years and for specific risk of chromosomopathies. This policy is not easily accepted by the couples who incessantly request additional karyotyping. In order to select those at highest risk of chromosomal abnormalities among young women, fetal nuchal translucency (NT) thickness measurement was performed in 510 fetuses to assess the chromosomal risk before chorionic villus sampling. A risk >/=1/100 was judged positive and worthy of additional karyotyping. 126 cases interrupted the pregnancy after a result of homozygous beta-thalassaemia, hence 384 pregnancies were included in the study. 22 (5.7 per cent) fetuses were found NT positive. A total of three chromosomal abnormalities were detected. The NT test was positive in all three cases of chromosomopathies detected (100 per cent) and in 19 of 381 (4.98 per cent) normal karyotype fetuses. No features of major chromosomal abnormalities were reported among the newborns whose NT had resulted normal. These preliminary results have confirmed the efficacy of NT testing to assess the risk of trisomy 21 and other chromosomopathies and enhanced its utility in pregnancies already suited to sampling in the first-trimester for Mendelian disorders.