Down Syndrome Screening Markers Research Articles

First-trimester screening for Down syndrome using quadruple maternal biochemical markers.

Placental growth factor (PlGF) is used for first-trimester preeclampsia screening and could be combined with other biochemical markers for Down syndrome screening. We aim to estimate the predictive value of the combination of pregnancy-associated plasma protein (PAPP-A), free β-human chorionic gonadotropin (free β-hCG), placental growth factor (PlGF) and α-fetoprotein (AFP) with and without nuchal translucency. Singleton pregnancies recruited at 11-14weeks and followed until delivery. The four maternal markers were measured using Kryptor (ThermoFisher-BRAHMS) and adjusted for gestational age and maternal characteristics. The risk of Down syndrome was calculated using the Fetal Medicine Foundation algorithm and multivariate linear regression analyses in all cases and in 2,200 controls. Receiver-operator characteristic (ROC) curves were used to calculate the detection and false-positive rates. Twenty-six (0.2%) cases of Down syndrome were diagnosed among 13,386 participants. The combination of the four biomarkers could have detected 88% (95% CI: 72-97%) of the cases at a false-positive rate of 13% (95% CI: 12-15%). The addition of nuchal translucency would have increased the detection rate to 96% (95% CI: 82-99%) at a false-positive rate of 4% (95% CI: 4-5%) using a 1:300 cut-off and to 100% (95% CI: 89-100%) at a false-positive rate of 6% (95% CI: 5-8%) using a 1:500 cut-off. First-trimester screening using biochemical markers allows the identification of approximately 88% of Down syndrome cases for a false-positive rate of 13%. The addition of nuchal translucency raises the detection rate above 95% with a false-positive rate below 5%.

Indigenization of the median of markers for Down syndrome screening based on statistical analysis of medical big data

ObjectiveTo indigenize the median of Down syndrome (DS) screening markers for first and second trimester, and compare the impact of the indigenized and built-in median data on the efficiency of DS screening. Materials and MethodsData derived from first and Second-trimester screening (FTS and STS) for DS, composed of selected pregnancies deemed to be normal, were examined in a retrospective study. Indigenization regression analysis was calculated by using five models to fit statistical the raw data. Multiple of median (MoM) values estimated by using indigenized medians were compared with those calculated by using built-in. ResultsThis study established a regression equation which is more suitable for the median of each screening marker in the local pregnant women. The changes of median MoM of screening markers were statistically significant after indigenization. For FTS, the detection rate was 100% when the false positive rate was 5%, and the cut-off value was 1/262. On the other hand, for STS, the detection rate of the model with indigenized parameters was 77.42%, which is 16.13% higher than that of built-in parameters. ConclusionFor the individual specific risk of pregnancy, when the indigenized parameters was used to calculate, is more accurately and screening effectiveness has been improved. This is a great reference significance for the current prenatal screening whether indigenized data should be used.

Down's syndrome screening at 11-14weeks' gestation using prenasal thickness and nasal bone length.

To perform a multicenter prospective study of ultrasound prenasal thickness (PT), and nasal bone length (NBL) measurement at 11-14weeks' gestation. Ultrasound PT and NBL determination was performed in 504 normal fetuses and 17 fetuses with Down's syndrome (DS). Measurements were made from mid-sagittal 2D images acquired using a standardized technique during nuchal translucency (NT) examination. PT and NBL values were expressed in multiples of the gestation-specific normal median (MoM) and as the PT/NBL ratio. Information on PT and NBL MoMs was also combined using logistic regression. Results were classified as positive according to whether they were greater than the normal 95th centile for PT, PT/NBL and the DS risk from logistic regression equation or below the 5th centile for NBL. The median value in DS cases and unaffected controls were: PT 1.26 and 0.996 MoM; and NBL 0.596 and 0.993 MoM. The proportion of DS fetuses with positive results was 41% for PT, 65% for NBL, and 82% for both the PT/NBL ratio and DS risk from the logistic regression equation. PT/NBL levels did not vary according to gestational age. The PT/NBL ratio is a valuable first trimester DS screening marker that can be easily determined concomitant with the NT measurement.

Prenatal Screening Markers for Down Syndrome: Sensitivity, Specificity, Positive and Negative Expected Value Method.

SummaryBackgroundGenetic screening for chromosomopathy is performed in the first trimester of pregnancy by determining fetal nuchal translucency (NT), and the pregnancy associated plasma protein-A (PAPP-A) and free human chorionic gonadotropin (free-beta HCG) biomarkers in maternal serum.MethodsWe tested the sensitivity, specificity, positive and negative expected values of each marker with the aim of setting a model for prenatal screening readings. Statistical data treatment has been performed on a sample of 340 pregnant women with positive results of prenatal screening.ResultsSensitivity of PAPP-A was 0.6250 (probability 62.50%), free beta HCG 0.5893 (58.93%), NT 0.1785 (17.85%). Specificity of PAPP-A was 0.5106 (probability 51.06%), free beta HCG 0.5246 (52.46%), NT 0.9718 (97.18%). Positive expected value of PAPP-A was 0.2011 (probability 20.11%), free beta HCG 0.1964 (19.64%), NT 0.556 (55.56%). Negative expected value of PAPP-A was 0.8735 (probability 87.35%), free beta HCG 0.8662 (86.62%), NT 0.8571 (85.71%). The NT marker has a significantly higher specificity, which means that its normal value will significantly reduce the final risk of trisomy 21. The sensitivity of NT is much lower than that of biochemical markers, which means that a pathological value of NT does not have a significant influence on the final risk, i.e. the significantly higher sensitivity of biochemical markers will reduce the final risk of trisomy 21.ConclusionsThe analyses stress the importance of using a software which has the possibility to separate the level of a biochemical risk by correlating PAPP-A and free beta HCG and, by adding the NT marker, calculate the level of a final risk of Down syndrome.

Significance of Fetal Aberrant Right Subclavian Artery and Comparison with Other Second Trimester Markers for Down Syndrome Screening

AbstractThe chief objectives of our study were to assess the incidence and significance of fetal aberrant right subclavian artery (ARSA) in a nonreferral cohort of south Indian antenatal woman, and to compare it with other second trimester markers of Down syndrome. This was a prospective study conducted at Edappal hospital, India. After satisfying inclusion and exclusion criteria, 2000 consecutive antenatal women, seeking prenatal care and planning delivery at the same center, were recruited in a consecutive fashion. ARSA was identified as a retrotracheal arterial vessel in the axial three vessel trachea view, coursing towards right axilla. During February 2015 to January 2016, nine cases of ARSA were identified amongst 2000 antenatal women, yielding an incidence of 0.45 % (95 % CI 0.2–0.9 %). Of these, eight cases (8/9, 89 %) were isolated with normal karyotype, and negative for 22q11 microdeletion. Down syndrome was prenatally diagnosed in four cases (4/2000, 0.2 %), with ARSA detected in one case [sensitivity—25 %, specificity—99.6 %, positive likelihood ratio (+LR)—62.5 %, negative likelihood ratio (-LR)—0.75 %; Odds ratio 82.8 %, 95 % CI 7.8–883]. Of the significant second trimester minor markers, an absent nasal bone was the most common (13/2000, 0.65 %), followed by ARSA. All the isolated cases had normal neonatal outcomes. ARSA is relatively common second trimester aneuploidy marker, associated with high global +LR but nil isolated +LR. Indication for fetal karyotype in isolated cases seems to be weak.

Diagnostic value of ultrasonographic combining biochemical markers for Down syndrome screening in first trimester: a meta-analysis.

The meta-analysis was to determine the diagnostic value of the combining tests for Down syndrome and to evaluate their utilities in the Down syndrome screening. Through comprehensive literature search, 24 studies met the inclusion criteria and were included in the databases (PubMed, Wed of knowledge, Chinese National Knowledge Infrastructure (CNKI)). Summary estimates for sensitivity and specificity were calculated by using the bivariate random effect model. The summary receiver operating characteristic curve was also undertaken. The overall sensitivity and specificity of the combination of NT and free β-hCG and PAPP-A for Down syndrome were 0.86(95%CI 0.75-0.92) and 0.96(95%CI 0.95-0.97), respectively. The summary positive likelihood ratio and negative likelihood ratio were 23.3 (95%CI 16.7-32.5) and 0.15(95%CI 0.08-0.26), respectively. The pooled diagnostic odds ratio was 156 (95%CI 75-326). The meta-analysis shows the accumulative evidence for the clinician that the performance of the combined test of MA and NB and NT and PAPP-A and free β-hCG is the most effective test in the four different combined tests, while, the combination of NT and PAPP-A and free β-hCG is a cost-effective screening tool for Down syndrome.

PT/NBL ratio assessment at mid-trimester in prenatal screening for Down syndrome in a Chinese population

Objective: To investigate the ratio of prenasal thickness (PT) to nasal bone length (NBL) in normal and trisomy 21 fetuses in the second and third trimester in Chinese population.Methods: The NBL and PT were measured blindly by using 3D volumes in 143 normal fetuses and 31 trisomy 21 fetuses.Results: The mean PT (r = 0.83, p = 0.004) and NBL (r = 0.87, p = 0.0062) both increased with the gestation age, while the PT/NBL ratio (r = 0.12, p > 0.10) remained stable. There was significant difference between normal and trisomy 21 fetuses (p < 0.001). If we took the 95th of the normal fetuses as the cut-off value, the detection rate was only 46%. By using ROC curve to evaluate the screening value of PT/NBL ratio, the area under receiver operating characteristic (ROC) curve was 0.88 (95% confidence interval 0.81 to 0.94, p < 0.0001).Conclusions: In Chinese population, the PT/NBL ratio is not a very strong ultrasound marker to predict trisomy 21 fetuses. However, it can be used as an ultrasound marker for Down syndrome screening during the second and third trimester of pregnancy.

Down syndrome screening: Suitability of a WHO 5 standardized total hCG assay

ObjectiveTo determine how the adoption of the new WHO 5th International Standard (IS 07/364) will affect the suitability of total βhCG as a marker for second trimester Down syndrome screening, compared to the current WHO 3rd IS (75/537). Design and methodsAssays employing both standards were evaluated on the Beckman Coulter DxI platform. Matched βhCG results from 232 fresh second trimester maternal serum samples were compared. In addition, stored samples from 51 Down syndrome and 251 matched control sera were also tested with both assays and results converted to weight-adjusted multiples of the median (MoMs). These results were combined with maternal age and the existing alpha-fetoprotein, unconjugated estriol and inhibin-A MoM levels to compute patient-specific Down syndrome risk. ResultsCorrelation between the two sets of results on fresh samples was high (r=0.993), but showed a proportional increase of 33% (95% CI 31% to 35%) in results using the new versus old assay across the range of measurements. βhCG results in the case/control dataset were also highly correlated (0.994) and showed a similar proportional increase (34%). After computing assay-specific MoMs, the resulting ‘triple’ and ‘quadruple’ Down syndrome risks were highly correlated, and resulted in no difference in either of the two detection rates (78% and 88%, respectively) or false positive rates (6.4%, 6.8%). ConclusionsLaboratories using the DxI platform with the new total βhCG 5th IS assay will need to compute new reference (medians), but can expect no impact on the clinical validity of the associated Down syndrome screening programs.

Validation of Correction Factors for Serum Markers for First-Trimester Down Syndrome Screening in Singleton Pregnancies Conceived with Assisted Reproduction

Objective: To validate previously computed correction factors for free β-human chorionic gonadotrophin (fβ-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) pregnancies with hormone treatment and to determine the effect on false-positive rate (FPR). Methods: Retrospective study on 249 IVF and 250 ICSI cases and 20,190 controls. Correction factors 1.42 (PAPP-A), 1.17 (fβ-hCG) in IVF; 1.56 (PAPP-A) in ICSI were applied on the absolute serum concentrations. Analysis was done on log₁₀-transformed multiples of medians (MoMs). Results: In the controls, mean PAPP-A and fβ-hCG MoM were 1.004 and 1.062. Before correction, mean PAPP-A MoM was significantly lower in IVF (0.757; p < 0.001) and in ICSI (0.671; p < 0.001) and after correction comparable (1.071; p = 0.053 in IVF; 1.048; p = 0.178 in ICSI). Before correction, mean fβ-hCG MoM was comparable (1.054; p = 0.59 in IVF and 1.051; p = 0.56 in ICSI) and after correction significantly higher in IVF (1.241; p < 0.001). After correction the likelihood for receiving a false-positive result was 1.03 in IVF pregnancies (95% CI 0.98-1.09; p = 0.248) and 1.02 in ICSI pregnancies (95% CI 0.97-1.07; p = 0.448). Conclusions: After correction the FPR in IVF and ICSI pregnancies with hormone treatment reduces to the observed FPR in the controls.

The assessment of nuchal translucency and serum markers for down syndrome screening with ductus venosus Doppler measurements in the first trimester

The aim of the study was to improve nuchal translucency (NT) and serum marker Down syndrome (Tri21) screening methods by including fetal ductus venosus (DV) Doppler measurements. A total of 213 pregnant women were screened consecutively by combining maternal age, fetal NT and maternal serum pregnancy associated plasma protein A (PAPP-A) and free β-human chorionic gonadotropin (f β-HCG) values at 11-14 weeks of gestation. Also, a DV Doppler analysis was performed for the contribution to the screening for Tri21 and other fetal anomalies or adverse pregnancy outcomes. Twelve fetuses had DV PI measurements above the 95th percentile and two (17%) developed intrauterine growth retardation. DV PI values negatively correlated with birth weight (p=0.013, r=0.171). Two patients had T 21 among the study group (0.9%) with abnormal biochemical screening results. In these with Tri21, the combined test risk was above the suggested limit (>1/250). PAPP-A was <0.4 MoM in 23, and f β-HCG was >1.91 MoM in 49 patients. The rates of false positivity were 10% for PAPP-A and 22% for f β-HCG. The sensitivity, specificity, positive and negative predictive values of the combined test was 100%, 95%, 20% and 100%, respectively. The combined test has high sensitivity and specificity for Tri21 detection. The addition of DV Doppler ultrasound in the first trimester might have the advantage of predicting some adverse pregnancy outcomes. However, in the Turkish population, further studies with larger numbers of patients will be needed to establish the usefulness of DV for the detection of Tri21 or the prediction of some major cardiac anomalies.

Proteomics and Down syndrome screening: a validation study

In a previous discovery study, we identified seven potential screening markers for Down syndrome (DS). Here, we report on an extended study to validate the discriminative potential of these markers. Concentrations of the seven analytes were measured using bead-based multiplexed immunoassays in maternal serum from 27 DS pregnancies and 27 matched controls. Control samples were matched to the cases by gestational age (exact day), maternal weight ( ± 5 kg), and maternal age ( ± 1 year) and by closest sample date. Prediction values were obtained for current screening markers [pregnancy-associated plasma protein A (PAPP-A), free beta human chorionic gonadotrophin (fβ-hCG) and nuchal translucency (NT)] and seven markers identified before based on concentration fold ratios between DS and controls. Models were fitted based on data of the discovery study or this study and also tested on both datasets. A significantly higher fold ratio was only found for epidermal growth factor (EGF) (-1.96; p = 0.006). In the prediction model for the current dataset, EGF improved the detection rate (DR) of DS by 5.7% [at a fixed 5% false-positive rate (FPR)] when added to the currently used screening markers. Validation of previously identified biomarkers only confirmed EGF for further consideration as a DS screening marker. This underlines the importance of validating biomarkers; in this study, limiting the range of plausible biomarkers to only one suitable biomarker.

Fetal facial sonographic markers for second trimester Down syndrome screening in a Thai population

Objective To assess the efficacy of using facial sonographic markers for screening fetuses in the second trimester for Down syndrome (DS) in a high-risk Thai population. Method Frontomaxillary facial angle (FMF) and nasal bone length (NBL) were measured prospectively in pregnant women at high-risk for DS who were undergoing genetic amniocentesis from November 2008 to October 2009. The receiver operator characteristic (ROC) curves were constructed to assess the screening efficacy of FMF angle and NBL. Result A total of 460 pregnant women were recruited, and a mid-sagittal facial profile was obtained for 403 fetuses. There were 386 fetuses with normal chromosomes, 10 fetuses with DS, 1 fetus with trisomy 13, and 1 fetus with trisomy 18. The remaining 5 fetuses had balanced translocation (n = 2), deletion (n = 1), and mosaic Turner (n = 2). Two different combinations of FMF angle and biparietal diameter to nasal bone length (BPD:NBL) ratio for DS screening in the second trimester achieved 50% and 90% detection rates and 4.4% and 14.0% false positive rates, respectively. Conclusion The combination of FMF angle and BPD:NBL ratio has a high sensitivity and specificity for screening for DS in the second trimester in a high-risk Thai population.

Quantitative Proteomics Analysis of Maternal Plasma in Down Syndrome Pregnancies Using Isobaric Tagging Reagent (iTRAQ)

Currently no specific biomarkers exist for the screening of pregnancies at risk for down syndrome (DS). Since a quantitative proteomic approach with isobaric labelling (iTRAQ) has recently been suggested to be highly suitable for the discovery of novel plasma biomarkers, we have now used this method to examine for potential quantitative changes in the plasma proteome of the pregnancies bearing DS fetuses in comparison to normal healthy babies. In our study, we used plasma from six women with DS pregnancies and six with uncomplicated pregnancies care were taken to match cases and controls for gestational and maternal age, as these could be a confounder. In our quantitative proteomics analysis we were able to detect 178 proteins using iTRAQ labelling in conjunction with 4800 MALDI TOF/TOF. Amongst these we observed changes in βHCG, a known screening marker for DS, indicating that our assay was functional. We found a number of elevated proteins Ig lambda chain C region, serum amyloid P-component, amyloid beta A4, and under expressed proteins like gamma-actin and titin in DS pregnancies. These proteins are also found in the sera of patients with Alzheimer disease, which share similar pathologies of DS. Our study therefore indicates that the iTRAQ labelling approach may be indeed useful for the detection of novel biomarkers.

Placental growth hormone and growth hormone binding protein are first trimester maternal serum markers of Down syndrome

Placental growth hormone (PGH) is synthesised by the placenta, and its function is modulated by growth hormone binding protein (GHBP). The potential of PGH and GHBP as maternal serum screening markers for Down syndrome (DS) was examined. Maternal serum concentrations of PGH and GHBP were determined by ELISA in 74 DS and 261 control pregnancies in gestational week 8(+0) to 13(+4). Log(10) MoM distributions of the markers were established. The performance of DS screening was estimated by Monte Carlo simulation. PGH log(10) MoM (SD) was decreased (p < 0.001) to -0.201 (0.373) and GHBP log(10) MoM to -0.116 (0.265) (p = 0.04), in DS pregnancies (n = 34) in week 8(+0) to 10(+0). In week 10(+1) to 13(+4), neither PGH (p = 0.16) nor GHBP (p = 0.13) was reduced in DS pregnancies. The detection rate (DR) for PGH in screening for DS in week 8(+0) to 10(+0) was 39% for a false positive rate (FPR) of 5%; increasing to 72% in combination with PAPP-A + hCGbeta. PGH + GHBP in combination with PAPP-A + hCGbeta + nuchal translucency (NT) (CUB test) had a DR of 91% compared with 80% for the CUB test. PGH and GHBP are early first trimester maternal serum markers for DS [Correction made here after initial online publication].

Measurement of nuchal volume in the first trimester Down screening using three‐dimensional ultrasound

Screening of fetuses at 11 to 14 weeks of gestation for Down syndrome using stored volumes acquired by a three-dimensional (3D) scanner. Thirty-four healthy singleton fetuses were recruited consecutively and prospectively during routine first trimester scans in our unit. Two-dimensional (2D) images of nuchal translucency (NT), crown-rump length (CRL), and biparietal diameter (BPD) were obtained by following a standard protocol. The volume of the nuchal area (NV) was obtained by a 3D scanning machine. The mean time to perform a 2D first trimester scan was 15.3 min, while the mean time to obtain and examine the stored volumes was 11.1 min (p<0.001) in a 3D scan. There were no significant differences in NT, CRL, and BPD between the two groups. Two cases with an NT thickness>2.5 mm also revealed increased volume data in the nuchal area. The Pearson's correlations between NT and CRL, BPD and CRL, NT and NV, and NV and CRL were moderate-to-high positive. The nuchal volume data and the standard curve in the first trimester may be possible markers for Down syndrome screening. 3D scans can also minimize the scanning time, providing views not easily following strict NT guidelines.

Combining first and second trimester markers for Down syndrome screening: Think twice

This study compares different screening strategies for the detection of Down syndrome and considers practical implications of using multiple screening protocols. The performance characteristics of each screening strategy were assessed based on datasets of Down syndrome (n=11) and unaffected pregnancies (n=1006) tested in both first and second trimester, as well as data from first trimester (n=18,901) and second trimester (n=40,748) pregnancies. For a detection rate of 91%, the false positive rates for integrated and serum integrated screening were 2.5% and 6.3%, respectively, compared with combined first trimester (4.6%) and second trimester (12.6%) screening. Contingent and sequential screening protocols achieved detection rates of 82 to 91% with false positive rates between 2.6 and 2.9%. Contingent protocols require retesting of 15 to 20% of cases in the second trimester. Sequential and integrated protocols require retesting of 98 to 100% of cases in the second trimester. The various screening strategies did not always detect the same Down syndrome pregnancies. Combining first and second trimester markers for Down syndrome screening better defines the at-risk population. However, integrated protocols complicate management of screening programs and may not be suitable as primary screening strategies. It may be a better use of resources to refine current first and second trimester programs through improved access and new markers. We therefore suggest thinking twice before embracing integrated population screening programs.

Is screening for fetal anomalies reliable in HIV-infected pregnant women? A multicentre study

To assess the impact of HIV infection on the reliability of the first-trimester screening for Down syndrome, using free beta-human chorionic gonadotrophin, pregnancy-associated plasma protein-A and fetal nuchal translucency, and of the second-trimester screening for neural tube defects, using alpha-fetoprotein. Multicentre study comparing the multiples of the median of markers for Down syndrome and neural tube defect screening among 214 HIV-infected pregnant women and 856 HIV-negative controls undergoing a first-trimester Down syndrome screening test, and 209 HIV-positive women and 836 HIV-negative controls with a risk evaluation for neural tube defect. The influence of treatment, chronic hepatitis and HIV disease characteristics were also evaluated. Multiples of the median medians for pregnancy-associated plasma protein-A and beta-human chorionic gonadotrophin were lower in HIV-positive women than controls (0.88 vs. 1.05 and 0.84 vs. 1.09, respectively; P < 0.005), but these differences had no impact on risk estimation; no differences were observed for the other markers. No association was found between HIV disease characteristics, antiretroviral treatment use at the time of screening or chronic hepatitis and marker levels. Screening for Down syndrome during the first trimester and for neural tube defect during the second trimester is accurate for HIV-infected women and should be offered, similar to HIV-negative women.

First trimester screening for Down syndrome in rhesus negative women

To explore the effect of maternal rhesus status on first-trimester screening markers for Down syndrome. We accessed a database of singleton pregnancies undergoing first-trimester genetic screen with maternal Rh status documented and pregnancy outcome information available. Excluded were cases of fetal chromosomal or structural abnormalities, or maternal systemic disease. Results of maternal serum pregnancy-associated plasma protein A (PAPP-A) and beta-human chorionic gonadotrophin (beta-hCG) adjusted for gestational age were compared between Rh-negative and Rh-positive women with p < 0.05 considered significant. Two thousand two hundred and two pregnancies fulfilled the study criteria, and 160 of them (7%) were Rh negative. Only free beta-hCG corrected multiples of the median (MoM) values were statistically increased in Rh-negative women (p < 0.009). Using a cut-off of 1:300, screen-positive rates of maternal serum biochemistry were not significantly different between Rh-negative and Rh-positive women (12.5 vs 10.4%, p = 0.41). The present study focused on measurements of beta-hCG and PAPP-A in the sera of women with Rh-negative blood group. Women with Rh-negative blood type have similar first-trimester serum PAPP-A MoM values as Rh-positive women, but significantly higher beta-hCG MoM values. However, there was no significant difference in the screen-positive rate for Down syndrome between the two groups.

Fetal aberrant right subclavian artery in normal and Down syndrome fetuses

To evaluate the prevalence of fetal aberrant right subclavian artery (ARSA) in a low-risk population and compare it with that among Down syndrome fetuses, in order to estimate its potential as a marker in Down syndrome screening. Women undergoing routine fetal sonographic examination between 13 and 26 weeks of gestation were evaluated once for the presence of ARSA using either a transvaginal multifrequency 5-9-MHz probe or a transabdominal 4-8-MHz probe as appropriate. Early pregnancy outcome was obtained in all cases. Nine hundred and twenty-four fetuses were recruited. An ARSA was detected in 13 fetuses (1.4%) with normal karyotype. During the study period, eight fetuses with Down syndrome referred either with known karyotype or with signs suspicious for Down syndrome were evaluated by the same protocol. Three of eight fetuses (37.5%) were found to have an ARSA. In none of these cases was ARSA an isolated finding. The odds ratio for ARSA in Down syndrome compared with normal fetuses was 42.04 (95% CI, 9.08-194.6). An ARSA was found in 1.4% of the normal population. In the small group of Down syndrome fetuses we observed a trend towards a higher rate of ARSA than in normal fetuses. In none of the Down syndrome fetuses was ARSA an isolated finding. Larger prospective studies are needed to examine the significance of ARSA as an isolated finding and the potential of ARSA as a marker in Down syndrome screening.

OC101: Fetal aberrant right subclavian artery in normal fetuses and in Down syndrome

To evaluate the prevalence of fetal aberrant right subclavian artery (ARSA) in a low-risk population and compare with the rate of its appearance among Down syndrome (DS) fetuses, and to estimate its potential as a marker in DS screening. This was a cross-sectional sonographic study. Women attending routine fetal sonographic examination between 13 and 26 weeks of gestation were evaluated for the presence of an ARSA using either a transvaginal multifrequency 5–9-MHz probe or transabdominal 4–8-MHz probe as appropriate. Early pregnancy outcome was obtained in all cases. Nine hundred and twenty-four fetuses were recruited. ARSA was detected in 13 fetuses (1.41%) with normal karyotype. During the study period, eight fetuses referred either with known karyotype or with signs suspicious of DS were evaluated by the same protocol. Three of eight fetuses (37.5%) were found to have ARSA. In none of these cases was ARSA an isolated finding. The odds ratio for ARSA in DS vs. normal fetuses was 41.9 (95% CI, 8.9–195). ARSA was found in 1.41% of the normal population. In this study we observed a trend toward a higher rate of ARSA among DS fetuses. In none of these was ARSA an isolated finding. Larger prospective studies are needed to test the strength of this marker as an adjunct tool in DS screening and risk assessment.