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Study Question: How does a national prenatal screening program for Down syndrome (DS) perform in detecting sex chromosome abnormalities (SCAs)-Turner syndrome (TS), Klinefelter syndrome, 47,XXX and 47,XYY syndromes.Summary Answer: The SCA detection rate resulting from DS screening was below 50% for all four groups of SCAs.What Is Known Already: The detection rates of SCAs are higher in countries with DS screening. TS is associated with greater nuchal translucency (NT) and lower pregnancy-associated plasma protein-A (PAPP-A). However, specific detection rates of SCAs using prenatal DS screening have not been determined. No clear trend in PAPP-A, free beta human chorionic gonadotropin (β-hCG) and NT has been found in the remaining SCAs. Several lines of inquiry suggest that it would be advantageous for individuals with SCA to be detected early in life, leading to prevention or treatment of accompanying conditions. There is limited information about pre- and perinatal status that distinguishes SCA embryogenesis from normal fetal development.Study Design, Size, Duration: A register-based case-control study from the Danish Central Cytogenetic Register (DCCR), cross-linked with the Danish Fetal Medicine Database (DFMD), was performed from 2008 to 2012. Groups of SCAs were compared with DS and then matched with non-SCA controls to assess differences between these groups in prenatal markers and birth outcomes.Participants/materials, Setting, Methods: We included cases with prenatal and post-natal SCA karyotypes (n = 213), DS (n = 802) and 168 056 controls. We screened 275 037 individuals examined prenatally. We retrieved information regarding maternal age, NT, β-hCG and PAPP-A, as well as details regarding maternal and newborn characteristics.Main Results and the Role Of Chance: The DS screening procedure detected 87 per 100 000 TS (42% of expected), 19 per 100 000 Klinefelter syndrome (13% of expected), 16 per 100 000 47,XXX (16% of cases) and 5 per 100 000 47,XYY (5% of expected) SCAs, with an overall detection rate of 27%. Compared with controls, all four SCA groups showed significantly higher NT and lower PAPP-A compared with controls (all P < 0.01) and similar to DS. The legal abortion rate was high for all four syndromes (47,XXX: 24%; 47,XYY: 29%; Klinefelter syndrome: 48%, TS: 84%). For SCA fetuses carried to term, only TS fetuses had consistently lower birthweights and placenta weights than non-SCA controls (both P = 0.0001). A few SCA cases localized in DCCR could not be found in DFMD (n = 16).Limitations, Reason For Caution: Controls were matched on sex of the fetus of cases, meaning that all electively aborted fetuses (before week 12) were excluded, possibly reducing the diversity in the control group. We were not able to localize all diagnosed cases of SCA and DS in DFMD. Although these cases were present in DCCR, we were not able to account for the discrepancy. In addition, we suspect that several SCA children have not been diagnosed yet and future post-natal diagnosis of these cases would reduce the diagnostic yield reported here even further.Wider Implications Of the Findings: The prenatal detection rate is below 50% for all SCAs. The approach used for detecting DS cannot be extended to also include SCAs. In addition, all SCAs have low PAPP-A and increased NT, thus probably reflecting an abnormal embryogenesis. Growth retardation of TS fetuses is if anything more pronounced than previously reported, both when evaluating fetus and placenta.Study Funding/competing Interests: This study received support from Aarhus University and the Novo Nordisk Foundation. The authors have no competing interests that may be relevant to the study. [ABSTRACT FROM AUTHOR]

This article is a review of current and emerging methods used for prenatal detection of chromosomal aneuploidies. Chromosomal anomalies in the developing fetus can occur in any pregnancy and lead to death prior to or shortly after birth or to costly lifelong disabilities. Early detection of fetal chromosomal aneuploidies, an atypical number of certain chromosomes, can help parents evaluate their pregnancy options. Current diagnostic methods include maternal serum sampling or nuchal translucency testing, which are minimally invasive diagnostics, but lack sensitivity and specificity. The gold standard, karyotyping, requires amniocentesis or chorionic villus sampling, which are highly invasive and can cause abortions. In addition, many of these methods have long turnaround times, which can cause anxiety in mothers. Next-generation sequencing of fetal DNA in maternal blood enables minimally invasive, sensitive, and reasonably rapid analysis of fetal chromosomal anomalies and can be of clinical utility to parents. This review covers traditional methods and next-generation sequencing techniques for diagnosing aneuploidies in terms of clinical utility, technological characteristics, and market potential. [ABSTRACT FROM AUTHOR]

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OBJECTIVE: To estimate how many additional chromosomal abnormalities can be detected by diagnostic testing compared with noninvasive prenatal testing in a high-risk prenatal population. METHODS: All karyotype results of invasive prenatal testing in singleton pregnancies performed in response to a positive prenatal screen through the California Prenatal Screening Program from April 2009 through December 2012 were examined. Abnormal karyotypes were categorized as to whether the abnormality is detectable by current noninvasive prenatal testing methods. RESULTS: Of 1,324,607 women who had traditional screening during the study period, 68,990 (5.2%) were screen-positive. Of screen-positive women, 26,059 (37.8%) underwent invasive diagnostic testing and 2,993 had an abnormal result (11.5%). Of these, 2,488 (83.1%) were predicted to be detectable with current noninvasive prenatal testing methods, and 506 (16.9%) were considered not currently detectable. Trisomy 21 accounted for 53.2% of the abnormal results (n = 1,592). Common aneuploidies, detectable by noninvasive prenatal testing, comprised a higher percentage of abnormal results in older women (P<01). CONCLUSION: For pregnant women with a positive aneuploidy screen who pursued diagnostic testing, 16.9% of chromosome abnormalities are not currently detectable by noninvasive prenatal testing. Undetectable aneuploidies range from relatively mild to those associated with significant disability. This is important information to be considered by patients, health care providers, and screening programs in evaluating the use of traditional screening and invasive prenatal diagnosis compared with noninvasive prenatal testing. [ABSTRACT FROM AUTHOR]

Objectives: To analyze trends in screening and invasive prenatal diagnosis over a 13-year period in relation to changes in the national prenatal screening policy. Methods: Fetal karyotypes obtained following 11 045 prenatal invasive procedures between January 1999 and December 2011 were retrospectively reviewed. Referral indications were classified as medical and non-medical (anxiety). The number of tests per relevant chromosomal abnormalities (CA) detected in both groups adjusted for indication was calculated. Results: A total of 414 CA were detected (3.8%), 355 of which were considered clinically significant. The percentage of invasive procedures has declined from 49% to 12%, although cases referred by anxiety have increased from 22% to 55%. A total of 3129 invasive procedures did not have any medical indication (28%) and 13 relevant CA (0.42%) were found in this group. In this low-risk series, the index "number of invasive testing needed to detect 1 relevant CA" adjusted for indication was 241. Conclusions: Changes in our national prenatal policy through this 13-year period show an increasing efficiency of prenatal detection of CA. However, despite the intensifying screening policies, low-risk pregnant women show a growing demand for prenatal invasive testing and a baseline risk for cytogenetic abnormality of 1/241. [ABSTRACT FROM AUTHOR]

Objective To investigate the prevalence of soft markers identified at second trimester ultrasound in a low-risk population and the association of these markers with trisomies and invasive testing. Design Prospective observational study. Setting Swedish University Hospital. Population All women with fetuses examined by ultrasound at 15+0-22+0 weeks gestation between July 2008 and March 2011. Methods Cases with soft markers were compared with non-cases with regard to trisomies and invasive testing. Main outcome measures Prevalence of soft markers, likelihood ratio for trisomies and risk ratio for invasive tests after detection of soft markers. Results Second trimester ultrasound was performed on 10 710 fetuses. Markers were detected in 5.9% of fetuses. 5.1% were isolated, 0.7% were multiple and 0.1% were combined with an anomaly. Presence of markers showed a positive likelihood ratio for Down syndrome, but the association (likelihood ratio = 7.1) was only statistically significant for the combined category of any marker (isolated, multiple or combined with anomaly). The risk ratio for invasive testing after the second trimester ultrasound was 24.0 in pregnancies with isolated soft markers compared with those without markers. Conclusion In a low-risk population, soft markers were found in 5.9% of fetuses at second trimester ultrasound. The likelihood ratio for Down syndrome was significant only for any marker (isolated, multiple or combined with anomaly). The presence of soft markers increased the incidence of invasive procedures substantially. Soft markers should be noted when information on second trimester ultrasound is formulated, and all units performing fetal ultrasound examinations should have established routines concerning information management when soft markers are identified. [ABSTRACT FROM AUTHOR]

Objective:The objective of this study was to investigate whether women who screened positive for both trisomy 18 (T18) and trisomy 21 (T21) yet had euploid karyotypes were at increased risk for adverse pregnancy outcomes.Study Design:This was a retrospective cohort study of women who had first trimester aneuploidy screening. Double-positive subjects had risks greater than screening cutoffs for T21 and T18 and confirmed euploid karyotypes. Singleton subjects were matched 1:2 by maternal age to controls with normal screening. Perinatal outcomes were investigated using t-tests and χ2-tests; statistical significance was set at P<0.05.Result:Of 9733 women who had first trimester screening, 33 euploid pregnancies screened positive for both T21 and T18. Compared with controls, these study subjects were more likely to have abnormalities identified by prenatal ultrasounds, including renal, fetal membrane and fluid, as well as multiple anomalies (P=0.01). In addition, double-positive subjects had a lower mean gestational age at birth (P=0.02) and lower mean birth weight (P=0.03) than controls. Maternal outcomes were not significantly different.Conclusion:Pregnancies with double false-positive first trimester aneuploidy screening were associated with pregnancy/fetal abnormalities. [ABSTRACT FROM AUTHOR]

Aim To establish reference values for the nuchal translucency ( NT) thickness in Japanese fetuses. Material and Methods Ultrasonographic measurements of the crown-rump length ( CRL) and NT were performed from 11 to 13 + 6 weeks of gestation in consecutive Japanese fetuses examined during prenatal visits between February 2011 and January 2012. The median, 5th and 95th percentiles of the NT thickness with 5 mm intervals of the CRL were confirmed. Results A total of 970 cases were enrolled in the study. The median NT thickness for a CRL between 45 and 80 mm ranged from 1.2 mm to 1.9 mm, and the 95th percentile of these values ranged from 2.1 mm to 3.2 mm, respectively. Conclusion The reference values for the NT thickness in Japanese fetuses were determined. These values should be useful for fetal biometry, morphological assessment and first trimester screening for chromosomal abnormalities in Japan. [ABSTRACT FROM AUTHOR]

Objective: To screen for chromosomal defects on the basis of maternal age and fetal nuchal translucency thickness at 10 to 14 weeks of gestation. Method: Fetal nuchal translucency thickness was measured by ultrasound examination at 10-14 weeks of gestation in living singleton pregnancies in women attending routine antenatal care at Prince Ali Bin Hussein. Amman Jordan. The risks for trisomy 21 and other chromosomal defects by ultrasound measurment of fetal nuchal translucency thickness and maternal age were calculated, using the software provided by The Fetal Medicine Foundation. Results: Chromosomal defects were diagnosed in 10 cases, including 4 cases of trisomy 21 and 6 cases with other chromosomal abnormalities (trisomy 18, 13, triploidy, Turner). The estimated risk based on maternal age and fetal NT was 1 in 300 .Conclusion: The combination of maternal age and fetal nuchal translucency thickness was an effective method of screening for chromosomal defects. [ABSTRACT FROM AUTHOR]

Ütine GE, Boduroğlu K. (Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey). Prevention of congenital anomalies. Çocuk Sağlığı ve Hastalıkları Dergisi 2013; 56: 28-37. Major congenital anomalies affect 2-3% of neonates. Anomalies may be detected in another 2-3% during the first five years of life, thereby affecting 4-6% of all children. Congenital anomalies may be genetic or environmental in origin. The underlying etiology is undetermined in 50-60% of all major anomalies, multifactorial in 20-25%, genetic in 7-8%, chromosomal in 6-7%, and teratogenic in 6%. Primary prevention is of major importance, since treatment for most anomalies is either impossible or difficult. Major preventive goals for our population are: (1) decreasing the frequency of consanguineous marriages, which increase the incidence of rare autosomal recessive disorders, (2) decreasing the frequency of births among >35-year-old women, which increase chromosomal disorders, mainly Down syndrome, and (3) improving the socioeconomic and environmental factors that affect the frequency of multifactorial diseases. Antenatal maternal factors, including dietary folate intake, smoking, caffeine and alcohol consumption, rubella infection, and uncontrolled diabetes, may also affect the frequency of major anomalies. [ABSTRACT FROM AUTHOR]

Objective: To analyze trends in screening and invasive prenatal diagnosis of chromosome abnormalities (CA) over a 13-year period and correlate them to changes in the national prenatal screening policy. Methods: We retrospectively reviewed Down syndrome (DS) screening tests and fetal karyotypes obtained by prenatal invasive testing (IT) in our fetal medicine unit between January 1999 and December 2011. Results: A total of 24,226 prenatal screening tests for DS and 11,045 invasive procedures have been analyzed. Over a 13-year period, utilization of non-invasive screening methods has significantly increased from 57% to 89%. The percentage of invasive procedures has declined from 49% to 12%, although the percentage of IT performed for maternal anxiety has increased from 22% to 55%. The percentage of detected CA increased from 2.5% to 5.9%. Overall, 31 invasive procedures are needed to diagnose 1 abnormal case, being 23 procedures in medical indications and 241 procedures in non-medical indications. Conclusions: Our experience on screening and invasive prenatal diagnostic practice shows a decrease of the number of IT, with a parallel decline in medical indications. There is an increasing efficiency of prenatal screening program to detect CA. Despite the increasing screening policies, our population shows a growing request for prenatal IT. The a priori low risk population shows a not negligible residual risk for relevant CA. This observation challenges the current prenatal screening strategy focused on DS; showing that the residual risk is higher than the current cut-off used to indicate an invasive technique. [ABSTRACT FROM AUTHOR]

Abstract: Nuchal translucency (NT) identified at the time of the 11–14week scan has been established as one of the best tools for screening for Down syndrome. It has also proven to be of value in screening for other conditions such as cardiac defects and extra-cardiac structural abnormalities. In this article, we present data from our fetal medicine unit that highlight the importance of using NT measurement as a stratifying tool when referring for early scans. We propose that, whenever possible, in selected cases with increased NT, provision should be made for additional early scans at 14–18weeks of gestation with a view to providing information on fetal structural integrity well ahead of the routine scheduled appointments. Early scans should incorporate detailed assessment of the fetal cardiac as well as extra-cardiac anatomy to diagnose or rule out major structural defects. This strategy will provide reassurance to a large number of prospective parents. [Copyright &y& Elsevier]

In all, 80% of antenatal karyotypes are generated by Down's syndrome screening programmes (DSSP). After a positive screening, women are offered prenatal foetus karyotyping, the gold standard. Reliable molecular methods for rapid aneuploidy diagnosis (RAD: fluorescence in situ hybridization (FISH) and quantitative fluorescence PCR (QF-PCR)) can detect common aneuploidies, and are faster and less expensive than karyotyping.In the UK, RAD is recommended as a standalone approach in DSSP, whereas the US guidelines recommend that RAD be followed up by karyotyping. A cost-effectiveness (CE) analysis of RAD in various DSSP is lacking. There is a debate over the significance of chromosome abnormalities (CA) detected with karyotyping but not using RAD. Our objectives were to compare the CE of RAD versus karyotyping, to evaluate the clinically significant missed CA and to determine the impact of detecting the missed CA. We performed computer simulations to compare six screening options followed by FISH, PCR or karyotyping using a population of 110 948 pregnancies. Among the safer screening strategies, the most cost-effective strategy was contingent screening with QF-PCR (CE ratio of $24 084 per Down's syndrome (DS) detected). Using karyotyping, the CE ratio increased to $27 898. QF-PCR missed only six clinically significant CA of which only one was expected to confer a high risk of an abnormal outcome. The incremental CE ratio (ICER) to find the CA missed by RAD was $66 608 per CA. These costs are much higher than those involved for detecting DS cases. As the DSSP are mainly designed for DS detection, it may be relevant to question the additional costs of karyotyping. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 40-year-old pregnant woman, who was referred to clinic at 32 weeks' gestation because of oligohydramnios and severe intrauterine growth restriction (IUGR). The patient was diagnosed for confined placental mosaicism (CPM) of double trisomies 9 and 21. The article discusses that CPM of trisomy 9 have been reported with features of skeletal abnormalities and neurodevelopmental impairment.

The article presents poster presentations on prenatal diagnosis. The effect of parity in small for gestational age births, perinatal outcome and obstetric mother future was investigated by Amelia Almeida et al. The results of first trimester screening for chromosomal anomalies were presented by Manuela Silva et al. A description of ethnic disparities in participation to prenatal screening for Down syndrome was discussed by Mirjam Fransen et al.

Background: Down syndrome, the most common birth defect, is caused by trisomy 21. The aim of this study was to investigate whether quantitative real-time PCR can be used as a sensitive technique for prenatal diagnosis of Down syndrome. Methods: We used a quantitative real-time PCR technique to measure the gene dosage of the Down syndrome critical region (DSCR3) by calculating the ratio of DSCR3 to GAPDH using standard curves. Sex-determining region Y was simultaneously detected by real-time PCR to identify the sex of the fetus. Results: The DSCR3/GAPDH ratio of the trisomy 21 fetus samples and that of normal controls was 0.72 ± 0.34 and 0.54 ± 0.18, respectively. Conclusion: In this study, there was no significant difference in the DSCR3/GAPDH ratio between the fetal and peripheral blood DNA samples of trisomy 21 fetuses and those of normal controls. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The diagnosis of duodenal atresia is commonly made prenatally, either as an isolated lesion or due to its association with other chromosomal abnormalities (Robertson et al. in Semin Perinatol 18:182-195, 1994; Hemming and Rankin in J Prenat Diagn 27:1205-1211, 2007). The aim of this study was to describe the prevalence of associated anomalies, prenatal diagnostic accuracy and survival of cases of congenital duodenal atresia in our institution.Methods: All cases of duodenal atresia registered with our local congenital anomaly register over a 10-year period, 1995-2004 inclusive, were studied, including those resulting in termination of pregnancies, stillbirths, intrauterine deaths and neonatal deaths. To ensure high-case ascertainment, data were cross checked with prenatal ultrasound, cytogenetic laboratory, pathology department and neonatal surgical data base. Data were analysed for associated anomalies, accuracy of prenatal diagnosis and neonatal outcomes.Results: A total of 65 patients were initially diagnosed as having duodenal atresia, of these 4 were subsequently excluded (1 postnatal normal bowel and 3 high jejunal atresias). In the remaining 61 cases, 35 (57%) had an association with other congenital abnormalities and 26 (43%) were isolated anomalies. Thirty-five were male and 26 female (M:F = 1.4:1). Twenty-one out of 29 (72%) patients prenatally diagnosed, compared with 14 out of 32 (44%) patients diagnosed postnatally had associated anomalies. Duodenal atresia was suspected on routine prenatal ultrasonography at 20-week gestation in 33 cases and confirmed in 29 (48%) cases with 4 false-positive diagnoses (1 normal bowel and 3 high jejunal atresias). No prenatal diagnosis was made in 32 (52%) babies. Of the 61 cases, 53 were live births with 2 early neonatal deaths (1 cardiac and 1 VACTERL), 5 terminations, 2 intrauterine deaths and 1 stillbirth (Fig. 3). Overall neonatal survival was 96% (51 cases). Mortality in the group diagnosed prenatally was 34 % (10 cases).Conclusion: This study shows an overall increased association of duodenal atresia with Down's syndrome. In the group diagnosed prenatally, mortality as well as the association with other congenital anomalies was found to be higher. We have demonstrated a greater prenatal diagnostic accuracy, but confirm postnatal outcomes similar to previous studies. [ABSTRACT FROM AUTHOR]

The article discusses the case of a 37-year-old pregnant woman in relation to the importance of prenatal screening for aneuploidy. The disorder refers to a deviation from the normal number of 46 chromosomes in humans and is related to significant morbidity and mortality during infancy and childhood. It is recommended that screening tests to estimate a woman's age-related risk of having a child with trisomy 21 or 18 be done in the first or second trimester.

In February 2007, the “Fetal Medicine Foundation Germany (FMF-D)” introduced its new calculation software for First Trimester Screening (FTS), called “Prenatal risk calculation (PRC)”. The aim of this study was to retrospectively investigate the test performance of PRC in comparison to the “NT module of the JOY software (JOY)”. A total of 3,516 combined first trimester screenings from 11 + 0 to 13 + 6 weeks of gestation were accomplished according to the FMF-standard. Adjusted risk calculation for aneuploidy was performed with PRC and JOY. A total of 2,202 complete data sets of singleton pregnancies were analyzed, including 10 trisomy 21 cases, 4 trisomy 18 cases, and 1 trisomy 13 case. Risk calculation with PRC and JOY showed highly significant results ( P value < 0.0001). JOY attained, at a cut-off of 1:300 (sensitivity 82.4%, false-positive rate 3.6%, positive predictive value 15.2%) and at a cut-off of 1:230 (82.4, 2.4, 21.2%), a better test performance in comparison to PRC (76.5, 7.1, 7.7% and 76.5, 5.3, 10.2%, respectively). The differences were highly significant ( P value < 0.0001). In this preliminary study, PRC demonstrated highly significant results in detecting aneuploidies in FTS. However, in comparison to JOY, its test performance was significantly inferior. A twice higher false positive rate would have doubled unnecessary invasive testing in a prospective setting. We therefore recommend a methodical revision of PRC. [ABSTRACT FROM AUTHOR]

The article presents a retrospective study which evaluates the effectivity of the second-trimester genetic sonogram to detect Down syndrome and other chromosomal abnormalities in a community-based antenatal testing unit. 660 fetal ultrasound examinations were analyzed to identify the detection rate for fetal Down syndrome and other chromosomal abnormalities. The results reveal that 32 among the study population have chromosomal abnormalities but only 12 were noted as Down Syndrome.

Objectives: Two methods have been proposed for standardizing measures of nuchal translucency thickness (NT) for risk calculation in first-trimester screening for chromosomal defects: differential delta NT (delta-NT) and multiples of the median (MoM) of NT. There is currently some debate as to which of these is more appropriate. The aims of this study were to determine whether delta-NT could be extrapolated successfully from one center-specific NT reference curve to another and thus to empirically calculate the likelihood ratios (LRs) of delta-NT. Methods: This was a retrospective analysis of a database of 4248 singleton pregnancies, including 13 cases of Down syndrome. The delta-NT was extrapolated to the reference curve of the NT values of the original group of patients for whom the LRs were calculated empirically, using a scale factor. The Down syndrome risk was calculated by standardizing the NT, using both extrapolated delta-NT and MoM methods, both for the screening based on maternal age and NT alone, and for the combined screening, in which biochemical markers are also taken into account. We analyzed detection rates and false positives, the precision of the risk prediction obtained by each of the methods and the effectiveness when each of the methods was used with a cut-off point based on a fixed post-test risk. Results: The risk calculation using extrapolated delta-NT presented an effectiveness profile that was similar to that obtained using MoMs, both when NT was used as the sole marker and when it was used in combination with biochemical markers. The precision of the risk prediction was similar with both methods. Conclusions: Delta-NT can be extrapolated for use in risk calculation between two populations with different distributions and medians of NT values. The precision of the risk estimate obtained is similar to that derived using MoMs. [ABSTRACT FROM AUTHOR]

A recent report by Dennis Lo and colleagues has indicated that the analysis of placentally derived cell-free mRNA can be used to detect fetal Down syndrome. The unique aspect of this work is that fetal ploidy for chromosome 21 was determined by a quantitative assessment of gene expression for a chromosome 21-specific gene, namely PLAC4. This technical feat was achieved by quantifying the relative expression of PLAC4 alleles to each other by the mass spectrometric analysis of single nucleotide polymorphism loci. By these means, fetal trisomy 21 could be detected noninvasively with a sensitivity of 90% for a false-positive rate of less than 3.5%. Hence, it is highly probable that this salient development could usher in a new era in noninvasive prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To investigate geodemographic characteristics of women having prenatal diagnosis for Down syndrome and other fetal chromosome abnormalities in Victoria, Australia. Methods: A descriptive analysis of population-based data on all confinements, amniocenteses and chorionic villus sampling for 1998 and 2002 was undertaken. Multivariate logistic regression analysis of 2002 data investigated geographical differences, including selected maternal features and a socioeconomic status measure that may be associated with uptake of diagnostic testing. Results: After adjusting for age, parity of three or more children was associated with a significantly decreased likelihood of testing ( P < 0.001). Women from Africa were 61% less likely to have testing than women born in Australia ( P < 0.01). While overall uptake of testing was lower than average in rural regions, only the Loddon Mallee had a significantly decreased likelihood of testing (OR 0.71 (0.53, 0.95), P = 0.02). A socioeconomic index of place of residence showed no association with uptake. Metropolitan and rural women giving birth in private hospitals were 31 and 60% more likely to have a test than women giving birth in public hospitals ( P < 0.01). Conclusion: Geographical differences influence uptake of prenatal diagnosis, probably related to access to services. However, other maternal demographic factors also play a role in uptake. To ensure equity in access and autonomy in women's reproductive choices, reasons for exceptionally low uptake in certain localities or within certain subgroups of pregnant women should be investigated further, followed by appropriate changes in service provision. [ABSTRACT FROM AUTHOR]

Objective: The primary objective of this study was to determine if isolated pyelectasis is a risk factor for trisomy 21. Study design: Twelve thousand, six hundred and seventy-two unselected singleton fetuses were examined by prenatal ultrasound during the second trimester at a single institution. The sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio of pyelectasis (either isolated or in association with other soft markers/structural anomalies) to detect trisomy 21 were calculated. Results: Pyelectasis (anteroposterior pelvic diameter ⩾4 mm) was detected in 2.9% (366/12,672) of the fetuses. Among these, 83.3% (305/366) were isolated, and 16.7% (61/366) were associated with other markers/structural anomalies. The prevalence of trisomy 21 was 0.087% (11/12,672) and, among these fetuses, 2 (18.1%) had pyelectasis, 1 isolated, and 1 associated with other markers/structural anomalies. The presence of isolated pyelectasis had 9.09% sensitivity, 97.6% specificity, 0.33% positive predictive value, and 99.9% negative predictive value to detect fetuses with trisomy 21. The likelihood ratio of trisomy 21 in this group of fetuses was 3.79 (95% CI 0.582-24.616). Among fetuses with pyelectasis and other associated markers/structural anomalies, the sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio for trisomy 21 were 9.09%, 99.5%, 1.64%, 99.9%, and 19.2 (95% CI 2.91-126.44). Conclusion: In the absence of other findings, isolated pyelectasis is not a justification for the performance of an amniocentesis. [ABSTRACT FROM AUTHOR]

Objective To ascertain, by means of a questionnaire, women's preferences for four different approaches to prenatal screening for Down syndrome. Methods Women attending antenatal clinics at six UK maternity units were asked to put in order of preference four different approaches to screening for Down syndrome all of which had the same false positive rate of 5%. The options were: (1) first-trimester testing, 90% detection of Down syndrome with results available in 1 h at one-stop clinics for the assessment of risk (OSCAR); (2)first-trimester testing, 90% detection and results available within 2–3 days (combined screening); (3) first-trimester testing plus second-trimester testing, 93% detection and results available within 2–3 days of second test (integrated testing); (4)second-trimester testing, 75% detection and results available within 2–3 days. Results Over 1100 women attending antenatal clinics at six maternity units across the UK returned the questionnaire. A total of 75% of women selected a first-trimester test (option 1 or option 2) as their first choice with 68.2% expressing a preference for the OSCAR approach and a further 6.8% for combined screening. Twenty-four percent of women opted for integrated testing as their first choice with only 1% expressing a preference for second-trimester screening. Conclusions A first-trimester test is preferred by the majority of women over a test with marginally higher detection rate that delivers results later in pregnancy. Timing and rapid reporting of results appear to influence women's choice of test. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to investigate the natural course of enlarged nuchal translucency (NT) and to determine if its disappearance before 14 weeks' gestation is a favorable prognostic sign in relation to fetal karyotype and pregnancy outcome. Methods A total of 147 women with increased NT (> 95th centile) at first measurement were included in this study. A second measurement was performed in all cases, at an interval of at least 2 days. Both measurements were taken between 10 + 3 and 14 + 0 weeks. All women underwent chorionic villus sampling or amniocentesis for subsequent karyotyping. In those women with a normal karyotype, a fetal anomaly scan was performed at 20 weeks' gestation. Pregnancy outcome was recorded in all cases. The finding of persistent or disappearing NT enlargement was analyzed in relation to fetal karyotype and pregnancy outcome. Results Of the 147 paired measurements, NT remained enlarged at the second measurement in 121 (82%) cases. An abnormal karyotype was found in 35% of these cases. In 26 (18%) fetuses the NT measurement was found to be below the 95th percentile at the second measurement and in only two of them an abnormal karyotype was found (8%). In the 103 chromosomally normal fetuses an adverse outcome (i.e. fetal loss or structural defects) was recorded in 22 fetuses with persistent enlargement (28%) and in four fetuses with disappearing enlargement (17%). Conclusions Disappearance of an enlarged NT before 14 weeks' gestation is not a rare phenomenon and seems to be a favorable prognostic sign with respect to fetal karyotype. Overall, no significant difference in pregnancy outcome was found between chromosomally normal fetuses with persisting or disappearing NT enlargement. [ABSTRACT FROM AUTHOR]

Objective: A fetus having partial trisomy of the distal part of chromosome 21q due to a de novo translocation is reported here. Method: A 29-year-old woman received amniocentesis at 18 weeks of gestation because of abnormal ultrasound findings including bilateral choroid plexus cysts, atrioventricular septal defects, rocker-bottom feet, and possible hydrocephalus. Results: Cytogenetic analysis revealed 46,XY, add(1)(p36.3), in which an additional material of unknown origin was attached to one of the terminal short arms of chromosome 1. Parental blood studies showed normal karyotypes in both parents. Spectral karyotyping was then performed and the origin of the additional material locating at chromosome 1p was found to be from chromosome 21. Conventional fluorescence in situ hybridization analysis was also used and confirmed the spectral karyotyping findings by use of a chromosome 21 specific painting probe, a locus specific probe localized within bands 21q22.13-q22.2 and a 21q subtelomeric probe. A hidden Down syndrome caused by a de novo translocation in this fetus was therefore diagnosed and the karyotype was designated as 46,XY, der(1)t(1;21)(p36.3;q22.1).ish der(1)(WCP21+, LSI 21+, 1pTEL-, 21q TEL+) de novo. Clinical features of the 1p36 deletion syndrome are also reviewed and may contribute to some features of this fetus. Termination of pregnancy was performed at 20 weeks of gestation. Conclusion: To our knowledge, our case appears to be the first to have partial monosomy 1p and partial trisomy 21q caused by de novo translocation being diagnosed prenatally. [ABSTRACT FROM AUTHOR]

Both intact fetal cells as well as cell-free fetal DNA are present in the maternal circulation and can be recovered for non-invasive prenatal genetic diagnosis. Although methods for enrichment and isolation of rare intact fetal cells have been challenging, diagnosis of fetal chromosomal aneuploidy including trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50–75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. Real-time PCR assays are robust in detecting low-level fetal DNA concentrations, with sensitivity of approximately 95–100% and specificity near 100%. Comparing intact fetal cell versus cell-free fetal DNA methods for non-invasive prenatal screening for fetal chromosomal aneuploidy reveals that the latter is at least four times more sensitive. These preliminary results do not support a relationship between frequency of intact fetal cells and concentration of cell-free fetal DNA. The above results imply that the concentration of fetal DNA in maternal plasma may not be dependent on circulating intact fetal cells but rather be a product of growth and cellular turnover during embryonic or fetal development. [ABSTRACT FROM PUBLISHER]

ABSTRACT Objective To investigate the feasibility and repeatability of nuchal translucency thickness measurement using three-dimensional ultrasound. Methods Forty consecutive women with uncomplicated singleton pregnancies attending for Down syndrome screening at 11–14 weeks’ gestation were included in this prospective crossover trial. Nuchal translucency thickness was measured using both two-dimensional and three-dimensional ultrasound. In each case two three-dimensional volumes were recorded and then examined by using the technique of planar reformatted sections. The initial plane of the first volume always contained a clear image of the nuchal region (‘sagittal volume’), whilst the initial plane of the second volume was selected randomly regardless of fetal position (‘random volume’). The repeatability of nuchal translucency measurement was examined by constructing a scatter diagram of the difference between the measurements plotted against the mean of two readings. Results Nuchal translucency measurements could be repeated in 38/40 (95%) sagittal volumes and 24/40 (60%) random volumes. The mean difference between two-dimensional measurements and those obtained by reslicing of sagittal three-dimensional volumes was -0.097 mm (95% limits of agreement from -0.481 to 0.675) and 0.225 mm (95% limits of agreement from -0.369 to 0.819) when random volumes were examined. Conclusions Reslicing of stored three-dimensional volumes can be used to replicate nuchal translucency measurements only when nuchal skin can also be clearly seen on two-dimensional ultrasound. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Fetal nuchal translucency measurement has been introduced as a screening test for the calculation of risk of chromosomal abnormalities. The purpose of this study was to investigate: (1) the feasibility of obtaining nuchal translucency measurements using three-dimensional ultrasound; (2) whether three-dimensional ultrasound could improve and facilitate the required repeated measurements of nuchal translucency; (3) the correlation between two- and three-dimensional nuchal translucency measurement values. Subjects and methods Between September 1999 and May 2000, in a prospective cohort study, 229 unselected pregnant women with a mean age of 34.6 (range, 20–46) years were examined. The mean fetal crown–rump length was 64.3 (range, 45–84) mm. Nuchal translucency thickness was measured first by two- and then by three-dimensional ultrasound in two planes (three-dimensional mid-sagittal and three-dimensional transverse). An attempt was made to repeat each nuchal translucency measurement three times (totalling nine measurements per patient) and the means of the two- and three-dimensional measurements were compared. The majority (95%) of the measurements were made transabdominally and 5% were made transvaginally. The time limit for each examination was 20 min. Results With the two-dimensional method, nuchal translucency could be measured in 96.8% of cases. Of these, three measurements could be obtained in 51.7%, two in 23.2% and only one in 25.1%. The three-dimensional examination was successful in 98.6% of cases. Of these, three measurements could be obtained in 60%, two in 22.8% and one in 17.2%. Transvaginally, all examinations were successful. The main reason for the failure of two-dimensional ultrasound was the fetal position, which in some cases precluded the distinction between fetal skin and amnion or the uterine wall. Using two-dimensional ultrasound, 6.3% of the cases of measurement failure were due to an inability to differentiate clearly between fetal skin and amnion, whilst the equivalent value for the three-dimensional method was only 3.3%. For the three-dimensional technique, fetal movement was the main reason for failure. The mean time for both methods was similar (9 min and 10 min for two- and three-dimensional ultrasound, respectively) and the correlation between the measurements obtained by the two- and three-dimensional techniques was very high (r = 0.97). Conclusion The number of fetuses in which nuchal translucency could be measured tended to be higher with three-dimensional ultrasound, although the difference was not statistically significant. The possibility of rotating a stored volume and inspecting it in three orthogonal planes makes three-dimensional ultrasound a useful tool for nuchal translucency measurements, especially in doubtful cases. [ABSTRACT FROM AUTHOR]

Twenty-nine patients with congenital duodenal obstruction (DO) detected as a “double bubble” (DB) on antenatal ultrasound (US) or diagnosed postnatally were seen at the Women's and Children's Hospital between 1985 and 1994; 24 (83%) had antenatal scans, with 21 (87%) DBs visualised. The 3 fetuses with normal scans who developed DO postnatally had duodenal “windsocks”. Five of the 24 scanned patients (21%) were found to have a DB before 20 weeks' gestation: 1 simple duodenal atresia, 2 duodenal atresias with chromosomal abnormalities (1 trisomy 21 and 1 triploidy), 1 biliary atresia with a pre-pyloric vein, and 1 malrotation. Sixteen (67%) cases were detected with scans after 20 weeks (range 28–36 weeks); 12 (75%) of these were done for polyhydramnios. In response to a questionnaire to 9 of the 16 parents whose fetuses underwent a late scan, 5 had had normal early scans elsewhere and 4 did not respond (4 of the remaining 7 had died and 3 were lost to follow-up). Eleven of the 29 patients (38%) had abnormal karyotypes, and 4 (22%) of the 18 with a normal karyotype had associated anomalies. Two sets of familial cases were noted. Early antenatal diagnosis of DO is possible in a minority of cases, and this early diagnosis may be associated with an increased risk of other pathology. Furthermore, early demonstration of a DB at routine US prior to 20 weeks allows appropriate counseling and the option of mid-trimester termination, whereas this is more difficult later in the pregnancy. In all cases detected antenatally, planning of delivery and parent counseling should be achieved. [ABSTRACT FROM AUTHOR]

Introduction. Chromosomal abnormalities, one of the leading causes of pregnancy complications, attract attention of both researchers and clinicians. They use two approaches to identify chromosomal abnormalities, namely screening and diagnostic tests. Ultrasonography is a very reliable screening and diagnostic tool, but the only way to determine if there are any chromosomal defects in the fetus, is performing one of invasive diagnostics tests chorionic villus sampling (CVS), cordocentesis or amniocentesis. Unfortunately, these invasive diagnostic procedures carry a potentially high risk of complications. Using amniocentesis means a procedure-related miscarriage risk at a rate of about 0.5-1%. Aim. The aim of this paper was to present our own experience, results in performing amniocentesis and a review of the literature. Material and methods. During a 10-year period 237 mid-trimester, transabdominal amniocenteses were performed. Results. The follow-up revealed one spontaneous abortion within seven days after the procedure. Premature delivery occurred in fourteen cases (two of them with chromosomal abnormalities). No neonatal deaths related to amniocentesis were noticed. Chromosomal abnormalities were detected in 33 patients. Conclusions. In the group with chromosomal abnormalities the main indications to perform amniocentesis were: improper ultrasound scan and the first trimester biochemical, noninvasive screening tests. This is a proof that modern, non-invasive procedures like the first-trimester ultrasound scan and biochemical tests should be made available to every pregnant woman and not only to mothers' aged >35 years or those with a poor obstetrics history. [ABSTRACT FROM AUTHOR]

Women who are 35 years or older are offered invasive prenatal testing because of the increased risk of chromosomal abnormalities, especially Down syndrome. In an attempt to increase the number of Down syndrome fetuses being detected and decrease the number of invasive procedures being performed on pregnancies not affected with a chromosome abnormality, both biochemical and ultrasound screening methods are being studied and are summarized in this article. The ultrasound markers reviewed include increased nuchal thickness, increased nuchal lucency, shortened femur, shortened humerus, pyelectasis, hypoplastic ears, echogenic intracardiac focus, hypoplasia of the fifth middle phalanx, and echogenic bowel. [ABSTRACT FROM AUTHOR]

Objective To examine the discriminative capacity of nuchal translucency measurement in the detection of trisomy 21 and other chromosomal anomalies. Design Prospective cohort study. Subjects A total of 2247 women with viable singleton pregnancies between 10 and 14 weeks' gestation attending a prenatal diagnosis center for fetal karyotyping. Methods The fetal nuchal translucency was measured transabdominally in all women before invasive prenatal testing. Results Chromosomal abnormalities were found in 63 fetuses, including 36 with Down's syndrome. The likelihood of the presence of chromosomal abnormalities increased with larger nuchal translucency thickness. A nuchal translucency of 3 mm or more identified 25 out of 36 fetuses (69%) with trisomy 21 at the expense of a 4.0% false-positive rate. Correction of nuchal translucency measurements for differences due to variation of the measurement with gestational age, either by using the ‘delta-value’ or multiples of the median (MoM), did not improve the detection rate in our patient data set. Conclusions The discriminative capacity of nuchal translucency measurement makes it a useful tool in screening for trisomy 21 and other chromosomal anomalies. [ABSTRACT FROM AUTHOR]

Objective: Currently, prenatal diagnosis of chromosome abnormalities requires invasive techniques such as amniocentesis and chorionic villus sampling that carry small but finite risks of fetal loss. A noninvasive approach is to isolate fetal cells from maternal blood by flow sorting followed by genetic interphase analysis with fluorescence in situ hybridization. Because the ratio of fetal to maternal cells is relatively low after flow sorting and to detect 90% to 95% of fetal aneuploidies associated with serious birth defects, a 5-color fluorescent in situ hybridization strategy is necessary for simultaneous detection of chromosomes X, Y, 13, 18, and 21 in all flow-sorted nuclei recovered from a specimen.Study Design: Fetal nucleated red blood cells were isolated from maternal blood in 40 cases (10.4 to 27.0 weeks' gestation) by flow cytometry on the basis of positive selection of CD71+ (transferrin receptor), CD45-, and LDS751 staining. Each case was evaluated for 5-color fluorescent in situ hybridization efficiency by determining the percentage of flow-sorted nuclei containing 8 hybridization signals for chromosomes X, Y, 13, 18, and 21.Results: A total of 42,312 flow-sorted nuclei from maternal blood samples were analyzed. In 5 of 16 (31%) cases with a male fetus, 0.16% of nuclei scored were identified as fetal by the presence of 1 signal each for chromosomes X and Y. Fetal trisomy 21 nuclei were accurately detected in 2 cases with a female fetus, each of which was subsequently confirmed.Conclusions: Five-color interphase fluorescent in situ hybridization analysis can be used to effectively analyze rare fetal aneuploid nuclei in enriched flow-sorted cells isolated from maternal blood. [ABSTRACT FROM AUTHOR]

Determines the incidence of all types of chromosome abnormalities in women receiving prenatal chromosome analysis after a Down syndrome screen-positive result by maternal serum triple-marker testing. Findings that approximately 5 percent of prenatal diagnoses on patients screen positive for Down Syndrome will show some type of chromosome abnormality.

OC02.02: Performance of a genome-wide PCR-free, paired-end sequencing-based non-invasive prenatal screening test, VeriSeq NIPT Solution v2 Frozen plasma samples from pregnant women with a gestational age of >=10 weeks were tested using VeriSeq™ NIPT Solution v2, which has two reporting options: basic and genome wide analysis. The paired-end sequencing-based VeriSeq NIPT Solution v2, with basic and genome-wide reporting options, showed high sensitivities and high specificities with a low failure rate. [Extracted from the article]

A 32-year-old woman at 17 weeks of gestation had a high possibility (1:82) of having a child with Down syndrome. Fetal chromosome according to amniocentesis revealed 46,XX,del(7)(q11.23q21.2). The fetus' chromosomal defect was not inherent because the chromosome analysis of the parents did not have any abnormal findings. We were regularly monitoring the pregnant woman by routine prenatal schedule and she had a normal spontaneous delivery. The baby showed a typical facial malformation, epicanthal fold, decreased muscle tone, and cardiac abnormalities. This is the first patient prenatally diagnosed with de novo 7q deletion by positive triple marker screening test. We consider the triple test, which is the most popular examination used to clarify the risk of chromosome abnormality in obstetrics, will be used not only for trisomy 21 and 18, but also for any other chromosome abnormalities. [ABSTRACT FROM AUTHOR]

The article focuses on a new concept for non-invasive prenatal diagnosis of aneuploidies by analysis of free fetal DNA circulating in maternal plasma. Free fetal DNA has been successfully used for the determination of fetal sex and rhesus D status on a routine basis by some specialized laboratories. Ravinder Dhallan and colleagues proposed the idea that single-nucleotide polymorphisms (SNPs) could be used to determine the number of fetal chromosomes in maternal blood. Though the approach is not new, the method that Dhallan proposes is. This approach can be used to detect trisomy 21, an aneuploidy that causes Down's syndrome. Details of clinical studies are presented.

Objective: Our objective was to evaluate changes in the timing of prenatal diagnosis and abortion for chromosomal abnormalities over the past 10 years.Study Design: This retrospective review identified singleton pregnancies with fetal chromosomal abnormalities that were diagnosed from 2005-2014 and included Down syndrome, Trisomy 18, and Trisomy 13. The study period was divided into 3 intervals: 2005-2006; 2007-2011; and 2012-2014. Gestational ages at prenatal diagnosis and abortion were compared over these intervals.Results: The 213 cases included 142 cases of Down syndrome (66.7%), 47 cases of Trisomy 18 (22.1%), and 24 cases of Trisomy 13 (11.3%). Two hundred one women (94.4%) chose to undergo abortion. The median gestational ages at prenatal diagnosis and abortion for Trisomy 18 or 13 were 12 weeks (interquartile range, 12-13 weeks) and 13 weeks (interquartile range, 12-15.5 weeks) and did not change over the study period. In contrast, in pregnancies with Down syndrome, the median gestational age at prenatal diagnosis (16, 13, and 12 weeks; P < .001) and abortion (17, 14, and 13 weeks; P < .001) both decreased significantly over the study intervals. In Down syndrome pregnancies, the proportion of women who underwent chorionic villus sampling significantly increased over the 3 study intervals (36%, 63%, and 86%; P < .001).Conclusion: Since 2005, the gestational ages at prenatal diagnosis and abortion for Down syndrome have declined significantly. These changes are likely attributable to improvements in early screening that leads to higher rates of chorionic villus sampling. [ABSTRACT FROM AUTHOR]