Screening For Fetal Chromosomal Abnormalities Research Articles

Uterine fibroids and non-informative cell-free DNA screening results.

Uterine fibroids are monoclonal tumors, which are often genetically abnormal and associated with false-positive genome-wide cell-free DNA (cfDNA) screening results, particularly when large. It is plausible that fibroids may also increase the risk of cfDNA failure by affecting fetal fraction or due to their genetic anomalies confounding cfDNA algorithms. We aimed to investigate a possible association between fibroids and cfDNA non-informative results. This was a retrospective cohort study of women undergoing cfDNA screening for fetal chromosomal abnormalities between 2013 and 2020, comparing pregnancies with vs without uterine fibroids recorded on any obstetric ultrasound before 24 weeks' gestation. Univariable and multivariable logistic regression models were used to investigate the association between fibroids and cfDNA failure, adjusting for gestational age, maternal age, weight and height at blood sampling, mode of conception, multiple gestation and test platform (chromosome-selective or genome-wide). Analyses were stratified according to the number of fibroids and total fibroid volume. The impact of fibroids on fetal fraction was assessed using linear regression, adjusting for the same covariates. Among 19 818 pregnancies undergoing cfDNA screening, fibroids were reported in 2038 (10.28%) and cfDNA failure at the first screening attempt occurred in 228 (1.15%) pregnancies. Non-informative results occurred in 1.96% of pregnancies with fibroids and 1.06% of pregnancies without fibroids (adjusted odds ratio (aOR), 2.40 (95% CI, 1.65-3.48)). The risk of failure in the first screening attempt increased progressively with the number of fibroids (aOR, 5.05 (95% CI, 2.29-11.13) in women with four or more fibroids) and total fibroid volume, with greater than a 5-fold and 14-fold increase in risk among women with fibroid volumes of 100.1-400 mL (aOR, 5.52 (95% CI, 2.30-13.25)) and > 400 mL (aOR, 14.80 (95% CI, 4.50-48.69)), respectively. Although test failure was more common with chromosome-selective than genome-wide screening, fibroids similarly increased the risk of failure of both screening platforms. Compared to pregnancies without fibroids, those with fibroids had a fetal fraction on average 0.61% lower (adjusted mean difference, -0.61% (95% CI, -0.77% to -0.45%)). Uterine fibroids are associated with lower fetal fraction and an increased risk of cfDNA screening failure. The strength of this association increases with increasing fibroid number and volume. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Performance of expanded non-invasive prenatal testing for fetal aneuploidies and copy number variations: A prospective study from a single center in Jiangxi province, China.

To evaluate the performance of expanded non-invasive prenatal testing (expanded noninvasive prenatal testing, NIPT-Plus) in screening for fetal chromosomal abnormalities includes aneuploidies and copy number variations, a total of 23,116 pregnant women with a singleton pregnancy were recruited for NIPT-Plus. Screening positive results were verified by karyotype analysis and chromosomal microarray analysis after amniocentesis. A total of 264 pregnancies (1.14%) were positive results as predicted by NIPT-Plus, including 233 aneuploidies and 31 copy number variations. Following genetic counseling, 233 (88.26%) pregnant women underwent invasive prenatal diagnosis and 136 were verified as true positives, comprising 72 common trisomies (T21, T18, T13), 47 sex chromosomal abnormalities two rare autosomal aneuploidies (RATs) and 15 copy number variations The positive predictive value for common trisomies, SCAs, RATs and CNVs were 68.57%, 68.12%, 6.67% and 51.72%, respectively. Pregnant women with screen-positive results for common trisomies have higher rates of invasive prenatal diagnosis and pregnancy termination than those with positive results for SCAs, RATs, and CNVs. NIPT-Plus showed a good performance in detecting common trisomies, SCAs and also contributed to detecting pathogenic CNVs, but higher accuracy was required in the detection of RATs. In summary, this study provides a reference for the clinical application of NIPT-Plus for screening fetal chromosomal abnormalities in this region. Therefore, we suggest that NIPT-Plus could be widely used in clinical screening for fetal chromosomal abnormalities in combination with prenatal diagnosis and genetic counseling.

Cell-free DNA versus sequential screening for fetal chromosomal abnormalities varied by age: a cost-effectiveness analysis

Cell-free DNA (cfDNA) and sequential screening (SS) are frequently used for prenatal genetic screening. Though cfDNA has higher detection rates for common aneuploidies, SS may better identify risk for other nontargeted aneuploidies. We compared the cost-effectiveness of cfDNA versus SS for detection of fetal chromosome abnormalities across varied age cohorts. A decision-analytic model compared cfDNA versus SS for diagnosis of chromosomal abnormalities across different maternal age cohorts stratified by 5-year increments of < 20, 20-24, 25-29, 30-34, 35-39, 40-44, and >45 years. Chromosomal abnormalities included trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), 45X syndrome, sex chromosome abnormalities (SCA), and other nontargeted chromosomal abnormalities . Probabilities, costs, and utilities were derived from literature and varied in sensitivity analysis. The primary outcome was incremental cost per quality-adjusted life year (QALY). We also considered affected neonates, missed prenatal diagnoses, procedure-related loss (PRL), pregnancy termination (TOP), stillbirth, and neonatal death (NND). The cost-effectiveness threshold was $100,000/QALY. SS was cost-effective for detection of all fetal chromosome abnormalities until age 39. Cell-free DNA was only cost-effective starting at age 40, with an Incremental Cost Effectiveness Ratio (ICER) of $51,919/QALY (40-44 years) and ICER $16,830/QALY ( >44 years). In all maternal age cohorts, cfDNA led to more frequent identification of T21, T18, T13, 45X and SCA but fewer other nontargeted chromosomal abnormalities. cfDNA was associated with more terminations and fewer stillbirths, NND, and PRL. The model was sensitive to the prevalence of T21. When varying the prevalence of T21 in the age 35-39 cohort cfDNA was cost effective when the prevalence of T21 was greater than 0.017 which corresponds with the prevalence of T21 at a maternal age of 39. Compared to cfDNA, SS is a cost-effective screening method for fetal chromosome abnormalities for pregnant persons under the age of 40 at a population-based level.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin Summary, Number 226.

Prenatal testing for chromosomal abnormalities is designed to provide an accurate assessment of a patient's risk of carrying a fetus with a chromosomal disorder. A wide variety of prenatal screening and diagnostic tests are available; each offers varying levels of information and performance, and each has relative advantages and limitations. When considering screening test characteristics, no one test is superior in all circumstances, which results in the need for nuanced, patient-centered counseling from the obstetric care professional and complex decision making by the patient. Each patient should be counseled in each pregnancy about options for testing for fetal chromosomal abnormalities. It is important that obstetric care professionals be prepared to discuss not only the risk of fetal chromosomal abnormalities but also the relative benefits and limitations of the available screening and diagnostic tests. Testing for chromosomal abnormalities should be an informed patient choice based on provision of adequate and accurate information, the patient's clinical context, accessible health care resources, values, interests, and goals. All patients should be offered both screening and diagnostic tests, and all patients have the right to accept or decline testing after counseling.The purpose of this Practice Bulletin is to provide current information regarding the available screening test options available for fetal chromosomal abnormalities and to review their benefits, performance characteristics, and limitations. For information regarding prenatal diagnostic testing for genetic disorders, refer to Practice Bulletin No. 162, Prenatal Diagnostic Testing for Genetic Disorders. For additional information regarding counseling about genetic testing and communicating test results, refer to Committee Opinion No. 693, Counseling About Genetic Testing and Communication of Genetic Test Results. For information regarding carrier screening for genetic conditions, refer to Committee Opinion No. 690, Carrier Screening in the Age of Genomic Medicine, and Committee Opinion No. 691, Carrier Screening for Genetic Conditions. This Practice Bulletin has been revised to further clarify methods of screening for fetal chromosomal abnormalities, including expanded information regarding the use of cell-free DNA in all patients regardless of maternal age or baseline risk, and to add guidance related to patient counseling.

Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin, Number 226.

Prenatal testing for chromosomal abnormalities is designed to provide an accurate assessment of a patient's risk of carrying a fetus with a chromosomal disorder. A wide variety of prenatal screening and diagnostic tests are available; each offers varying levels of information and performance, and each has relative advantages and limitations. When considering screening test characteristics, no one test is superior in all circumstances, which results in the need for nuanced, patient-centered counseling from the obstetric care professional and complex decision making by the patient. Each patient should be counseled in each pregnancy about options for testing for fetal chromosomal abnormalities. It is important that obstetric care professionals be prepared to discuss not only the risk of fetal chromosomal abnormalities but also the relative benefits and limitations of the available screening and diagnostic tests. Testing for chromosomal abnormalities should be an informed patient choice based on provision of adequate and accurate information, the patient's clinical context, accessible health care resources, values, interests, and goals. All patients should be offered both screening and diagnostic tests, and all patients have the right to accept or decline testing after counseling.The purpose of this Practice Bulletin is to provide current information regarding the available screening test options available for fetal chromosomal abnormalities and to review their benefits, performance characteristics, and limitations. For information regarding prenatal diagnostic testing for genetic disorders, refer to Practice Bulletin No. 162, Prenatal Diagnostic Testing for Genetic Disorders. For additional information regarding counseling about genetic testing and communicating test results, refer to Committee Opinion No. 693, Counseling About Genetic Testing and Communication of Genetic Test Results. For information regarding carrier screening for genetic conditions, refer to Committee Opinion No. 690, Carrier Screening in the Age of Genomic Medicine and Committee Opinion No. 691, Carrier Screening for Genetic Conditions. This Practice Bulletin has been revised to further clarify methods of screening for fetal chromosomal abnormalities, including expanded information regarding the use of cell-free DNA in all patients regardless of maternal age or baseline risk, and to add guidance related to patient counseling.

Positive Impact of Online Education on Physicians’ Knowledge and Confidence in Prenatal Screening Methodologies [21G

INTRODUCTION: Screening for fetal chromosomal abnormalities has become the standard of care for all pregnancies. This study assessed the ability of online continuing medical education (CME) to improve obstetricians/gynecologists (Ob/Gyns) knowledge regarding key considerations and interpretation of analyte and cell-free DNA (cfDNA) prenatal screening tests. METHODS: A 30-minute, CME-certified activity featuring a video-based discussion between two faculty and an associated video commentary in French (in partnership with the Collège National des Gynécologues Et Obstétriciens Français) was developed and launched online on 12/24/2018. Educational effectiveness was assessed with a repeated-pairs pre-/post-assessment study design; each individual served as his/her own control. A chi-square test assessed changes pre- to post-assessment. P values&lt;0.05 are statistically significant. Effect sizes were evaluated using Cramer's V (&lt;0.05 modest; 0.06-0.15 noticeable effect; 0.16-0.26 considerable effect; &gt;0.26 extensive effect). RESULTS: 7,603 HCPs, including 6,788 physicians have participated in the activity. This analysis comprises data from the subset of Ob/Gyns (n=831) who answered all pre-/post-assessment questions through 08/14/19. Following participation, significant improvements were observed overall (P≤.0001, V=.140) and in the following areas: Identifying possible causes for a no-call result (61% pre vs 75% post; 23% relative improvement; P&lt;.0001; V=.144). Recognizing the rationale for screening all pregnancies vs just high-risk pregnancies (61% pre vs 75% post; 21% relative improvement; P&lt;.0001; V=.135). 41% Ob/Gyns reported measurable increases in their ability to interpret cfDNA test results. CONCLUSION: This educational activity significantly improved Ob/Gyn’s knowledge of clinical considerations when performing prenatal screening as well as key differentiating characteristics of analyte and cfDNA screening tests.

Non-invasive prenatal screening: A 20-year experience in Italy.

Over the past two decades, there has been a rapid evolution in prenatal screening for fetal chromosome abnormalities. Initially, testing was focused on the identification of affected pregnancies in either the first, or, the second trimester (e.g. the Combined test or the triple test). This was replaced by sequential modalities (e.g. contingent screening) that have enhanced detection while reducing the need for invasive testing. More recently, the introduction of technologies based on cell-free DNA (cfDNA) in maternal plasma and enrichment of fetal cells in maternal circulation have further refined the concept of sequential screening. In this review, we document our experience with serum and ultrasound-based contingent screening where we were able to achieve a detection rate of 96.8%, a false-positive rate of 2.8% and an odds of being affected given a positive result of 1:11. We also describe our initial experience with a novel sequential protocol that includes the analysis of fetal cells in maternal blood.Methods for enrichment for fetal cells cfDNA and cfDNA technologies offer the possibility of greater sensitivity and specificity as well as expansion in the scope of genetic disorders detectable. As costs decline, these technologies will become increasingly used as primary screening tools. In the meantime, sequential use offers a practical approach to maximizing the benefits of prenatal testing.

Quality assessment of uterine artery Doppler measurement in first-trimester combined screening for pre-eclampsia.

To assess the quality of mean uterine artery (UtA) pulsatility index (PI) measurement in a first-trimester pre-eclampsia screening program. Consecutive women with a singleton pregnancy attending first-trimester screening for fetal chromosomal abnormalities also had combined screening for pre-eclampsia based on the Fetal Medicine Foundation (FMF) algorithm, at a large practice in Sydney, Australia, from May 2014 to February 2017. Distributions of mean UtA-PI multiples of the median (MoM) on a logarithmic scale were plotted in relation to the normal median with 95% CI for each operator and for each month. Central tendency and dispersion and cumulative sum charts were produced. Mean UtA-PI MoM values between 0.95 and 1.05 were considered ideal and those between 0.90 and 1.10 were considered acceptable. The screen-positive rates for preterm pre-eclampsia in different groups of sonographers according to their mean log10 UtA-PI MoM were calculated and compared using the chi-square test. A total of 21 010 women attended for first-trimester ultrasound and had screening for pre-eclampsia. The overall median UtA-PI MoM was 1.042 (interquartile range (IQR), 0.85-1.26). Of 46 sonographers, 42 (91.3%) performed more than 50 examinations and, of those, 41 (97.6%) measured UtA-PI within the acceptable range. Sonographers measuring UtA-PI MoM on average below 0.95 and those measuring it above 1.05 had, respectively, lower and higher screen-positive rates when compared with those with measurements within the 0.95-1.05 UtA-PI MoM interval (7.2% and 13.2% vs 11.2%, respectively, P< 0.001). UtA Doppler is measured well among trained operators when following an established protocol. While slight variations are expected, systematic error in this measurement impacts on the screen-positive rate. Therefore, a quality control process should be in place and retraining of staff may be required. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Middle pregnancy ultrasound screening for fetal chromosomal diseases.

Prenatal examinations, including serological screening and ultrasound screening, are the methods determining a risk of fetal chromosomal disease. The current study is aimed to assess whether ultrasound screening can effectively assist the screening for fetal chromosomal disease among pregnant women with a single abnormal serum marker. Following serologic screening, pregnant women at 18‑32weeks underwent systematic fetal ultrasound analysis. In this study, 99pregnant women with an abnormal serum marker and fetal ultrasound abnormalities underwent prenatal diagnosis of amniotic fluid or umbilical cord blood, with confirmation by pathological examination performed following birth or induced labor. A total of 95cases with an abnormal serum marker but no fetal ultrasound abnormalities were used as the control group, and underwent prenatal karyotype analysis. The rate of fetal chromosomal abnormalities of women with ultrasound abnormalities was significantly higher than in the control group. The fetal chromosomal abnormalities rate in pregnant women with a history of abnormal gestation/birth was higher than in pregnant women with a normal history. The present results suggest that ultrasound examination can facilitate screening for fetal chromosome abnormalities in pregnant women with a single abnormal serum marker.

Ethical and practical challenges in providing noninvasive prenatal testing for chromosome abnormalities: an update.

Noninvasive prenatal testing (NIPT) through the analysis of cell-free DNA in maternal plasma has rapidly changed screening for fetal chromosome abnormalities. We review practical and ethical challenges associated with the transition, progress in their resolution, and identify new emerging difficulties. NIPT is an advanced screening test for trisomies 21, 18, and 13 that was initially limited to women at high risk for an affected pregnancy. It is now recognized as suitable for all women. The testing has been expanded to include sex chromosome abnormalities and some microdeletion syndromes. Some ethicists are concerned about inclusion of disorders that have less severe phenotypes. Clinical providers have experienced difficulty in maintaining an up-to-date knowledge about the scope of NIPT, differences between tests, who should be offered the testing, performance of tests, reasons for false-positive results, and optimal patient management following positive results. Some of the practical difficulties associated with the introduction can be attributed to this knowledge gap. There remain some important ethical issues associated with NIPT. We believe that the same ethical and legal principles that were considered in the justification of conventional prenatal screening can be used to assess the appropriateness of additional NIPT applications.

Socioeconomic Disparities in Diagnostic Testing After Positive Aneuploidy Screening

Approximately 20% to 50% of pregnant women who test positive in screening for fetal chromosomal abnormalities forego diagnostic testing procedures, including chorionic villus sampling and amniocentesis. Many factors influence the decision for screening and diagnostic testing. Previous studies examining the relationship between sociodemographic characteristics and willingness to undergo diagnostic testing after positive screening found mixed results. This study investigated the possible existence of a socioeconomic disparity, specifically, the relationship between insurance type (Medicaid or private) and the refusal of diagnostic testing after positive screening for aneuploidy. The retrospective cohort study took place from 2008 to 2011 and included women pregnant with a singleton who tested positive for increased risk of aneuploidy and gave birth at Northwestern Memorial Hospital. Screening methods included first-trimester screening, sequential screening, or quadruple marker screening. Clinical and demographic data on the patients were collected, as well as whether the patient had received an ultrasound before making a decision about diagnostic testing. Diagnostic testing after positive aneuploidy screening is covered by Medicaid, so testing was equally accessible to all patients. There were 499 women included in the study, 75 of whom were insured through Medicaid. From the remaining 424, 75 women who had private insurance were randomly selected for the control group. The Medicaid group was younger (33.8 ± 6.9 years at delivery vs 36.9 ± 3.7 years, P < 0.001), more likely to be nonwhite (88% vs 27%, P < 0.01), more likely to have a first language other than English (12% vs 0%, P < 0.01), and more likely to be unmarried (65% vs 19%, P < 0.01). The timing of screening was similar between the 2 groups (28% vs 31% for first-trimester screening, 72% vs 69% for second-trimester screening). In the Medicaid group, 35% of women underwent diagnostic testing, whereas in the private insurance group, 57% did so. Insurance by Medicaid was associated with a lower likelihood of electing for diagnostic testing, even after adjusting for variables that differed between the 2 groups (odds ratio, 0.26; 95% confidence interval, 0.09–0.80). The authors of the study believe that factors such as lower household income, lower educational attainment, and health literacy were responsible for the differences between the 2 groups in the use of diagnostic testing and that the women in the Medicaid group may not fully understand the implications and purpose of the screening test. These results likely speak to a difference in patient-physician communication in regard to the choice to undergo diagnostic testing. Further investigation on the topic and interventional strategies are needed.

Resultados obstétricos en cribado combinado de las aneuploidías en el primer trimestre superior al corte con resultado de amniocentesis con cariotipo fetal normal

IntroductionTo evaluate whether there are adverse pregnancy outcomes in pregnant women with a risk index above the cut-off point in first-trimester screening for fetal chromosomal abnormalities and an amniocentesis result of normal fetal karyotype in a sample of pregnant women attending our clinic at the beginning of pregnancy. Subjects and methodsWe performed a case-control study. A series of patients who underwent first-trimester combined screening as part of antenatal care between January 2009 and January 2010 were selected. ResultsOf the maternal complications registered during the pregnancy, gestational diabetes was more frequent among cases. ConclusionsThe incidence of the remaining complications analyzed (intrauterine restricted growth, preeclampsia, oligoamnios) was similar in the two groups. In most of the pregnant women, delivery occurred after 37 weeks through the vaginal route.

Ten years of fetal karyotyping from a single centre

Screening for fetal abnormalities and subsequent karyotyping is a significant component of modern antenatal care. However in 1 year a maternity unit will typically only see a few karyotypic abnormalities....

Prenatal genetic screening and diagnosis for pediatricians

Prenatal genetic screening and diagnostic testing can identify many disorders that will require specialized newborn care and follow-up. Pediatricians should be aware of recent advances in testing that may have implications for their patients and families. Over the last half decade, there have been important changes in the breadth and depth of prenatal screening and diagnostic procedures. Carrier screening for selected genetic disorders is now offered routinely to pregnant women or those contemplating pregnancy. Newly developed strategies for first-trimester screening for fetal chromosome abnormalities have improved the detection rate for these disorders, while maintaining a low screen-positive rate. The American College of Obstetricians and Gynecologists and the American College of Medical Genetics now recommend that invasive prenatal diagnostic testing be made available to all pregnant women, regardless of age or prenatal screening results. And prenatal ultrasound findings of unknown clinical significance require that pediatricians provide appropriate follow-up in the newborn period and beyond. Prenatal genetic screening and diagnostic tests are changing rapidly, and results of these tests may impact the postnatal evaluation and treatment strategies for pediatric care.

Performance of First-Trimester Screening between Gestational Weeks 7 and 13

Screening for fetal chromosome abnormalities in the first trimester includes analysis of the serological markers pregnancy-associated plasma protein A (PAPP-A) and free beta human choriogonadotropin (free beta hCG). The blood sample is traditionally taken around week 12 of gestation, but the performance of earlier blood sampling is not well documented. We studied 44,537 singleton pregnancies. Complete first-trimester screening took place between November 2003 and March 2009, and blood samples were taken between 7 weeks + 5 days and 13 weeks + 6 days. Of 120 cases of trisomy 21, 108 were diagnosed in the first-trimester screening (detection rate 90%). When the blood sample was taken before gestational week 10, the detection rate of trisomy 21 was 97% (70 of 72), whereas 80% were detected (38 of 48) after week 10 (chi(2) = 0.0035). For trisomy 18, trisomy 13, and triploidy, 65% (13 of 20) were detected before gestational week 10, and 73% (11 of 15) after (not significant). All 6 cases of triploidy before and after gestational week 10 were detected. The screen positive rate and the maternal age were similar before and after week 10 of gestation. Screening for fetal aneuploidy can be performed with good results with the blood sample taken as early as week 7 of gestation. Blood samples taken before gestational week 10 showed a high detection rate of fetal trisomy 21, with no difference in the detection of fetal trisomy 18, trisomy 13, or triploidy.

P44.01: Usefulness of ultrasonographic markers in the screening for fetal chromosomal abnormalities

P44.01: Usefulness of ultrasonographic markers in the screening for fetal chromosomal abnormalities

Robust border enhancement and detection for measurement of fetal nuchal translucency in ultrasound images

Ultrasonic measurement of nuchal translucency (NT) thickness in the first trimester of pregnancy has recently been proposed as the most useful marker in early screening for fetal chromosomal abnormalities. However, manual tracing of the two echogenic lines in the image, using on-screen calipers, is hampered by weak edges, together with noise and other artifacts, leading to variable results and inefficiency. Our semi-automatic method of fetal NT thickness measurement uses a coherence-enhancing diffusion filter to enhance the border and reduce noise, followed by detection of the NT by minimization of a cost function, that combines intensity, edge strength and continuity, using dynamic programming. This method has been validated by determining the correlation between manual and semi-automatic measurements.

New Screening Guidelines for Fetal Chromosomal Abnormalities

The development of several markers and strategies for prenatal detection of Down syndrome has prompted the American College of Obstetricians and Gynecologists to update its practice guidelines for screening for fetal chromosomal abnormalities. Counseling all pregnant women, regardless of age, about the availability of screening tests for fetal aneuploidy is now recommended. Several screening schema have been evaluated; many include the combination of biochemical markers (e.g., …

Screening for Fetal Chromosomal Abnormalities with Nuchal Translucency Measurement in the First Trimester

Objective: To describe the detection rate of first-trimester chromosomal abnormality screening with nuchal translucency (NT) measurement and maternal age in our population. Methods: We have screened the fetuses between 11 to 14 weeks’ gestation according to the Fetal Medicine Foundation’s (London) instructions and used the FMF’s software to assess the risk based on maternal age, crown-rump length (CRL) and NT. Fetal karyotyping was offered when screening for Down syndrome identified a risk greater than 1 in 300. Sensitivity and false-positive rates were calculated for different cut-offs. Results: Pregnancy outcome was obtained from 4,598 babies of 4,365 mothers. The median maternal age of the 4,365 women was 28.2 ± 5.3 (range 15–47) years, and the median fetal CRL was 65.4 ± 9.4 (range 45–81) mm. There was risk estimate of ≧1 in 300 in 214 fetuses (4.7%). Chromosomal abnormalities were identified in 32 fetuses, including 19 cases of trisomy 21, and 13 cases of other abnormalities. The sensitivity using NT and maternal age in detecting trisomy 21 with a cut-off 1 in 300 was 73.6% (14/19) with a false-positive rate of 4.7%. At a false-positive rate of 3%, with a cut-off level 1 in 210, the detection rate was 73.6%. The detection rate for all chromosomal abnormalities with a cut-off level 1 in 300 was 68.8% (22/32) at a false-positive rate of 4.7%. Conclusion: The first-trimester screening for chromosomal anomalies with NT measurement, when carried out according to the accepted standards of quality, is useful.

Ductus venosus blood flow assessment at 11 to 14 weeks of gestation and fetal outcome.

To evaluate the association between abnormal ductus venosus (DV) at 11-14 weeks' gestation and chromosomal abnormalities, structural defects and fetal outcome. DV flow-velocity waveform (DV-FVW) and nuchal translucency thickness (NT) were prospectively evaluated in 1217 singleton pregnancies. The DV-FVW was abnormal in 84 fetuses, NT was above the 95th centile in 160 fetuses and both markers were observed in 41 fetuses. Chromosomal defects were diagnosed in 22 fetuses. The sensitivity, specificity and positive and negative predictive values for an abnormal karyotype were 86.4%, 86.9%, 11.9% and 99.7%, respectively, for an increased NT. These values were 68.2%, 96.9%, 31.3% and 99.3%, respectively, for DV-FVW abnormalities and 68.2%, 97.6%, 36.6% and 99.3%, respectively, when both markers were found simultaneously. Regarding structural defects, these values were 43.8%, 92.9%, 8.3% and 99.1% for an abnormal NT, 25.0%, 92.6%, 4.8% and 98.8% for DV-FVW abnormalities and 25.0%, 97.9%, 15.4% and 98.9% for both together. Considering those cases of unexplained fetal demise, the values were 44.4%, 85.9%, 5.0% and 98.9% for NT abnormalities, 22.2%, 92.6%, 4.8% and 98.6% for an abnormal DV-FVW and 22.2%, 98%, 15.4% and 98.7% for both. In cases with increased NT, the percentage of live births with normal karyotype and no major fetal structural defects decreased from 93.8% in normal DV-FVW fetuses to 77.3% in abnormal ones. DV assessment at 11-14 weeks' gestation is useful in screening for fetal chromosomal abnormalities and may help to reduce the false-positive rate when combined with NT measurement. Abnormal DV-FVW is also associated with an increase in adverse perinatal outcome in fetuses with enlarged NT. However, the value of DV-FVW assessment in cases with normal NT is unclear.