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Background: Although the traditional contingent screening strategy is effective, there are still undetected low-risk trisomy 21. This study aims to define appropriate cut-off values of serum biochemical markers at low-risk and develop a strategy for sequential prenatal testing associated with first-trimester screening to increase the detection rate of trisomy 21. Methods: This was a 9-year retrospective analysis of singleton pregnant women who underwent serum biochemical screening or combined first-trimester screening (CFTS) in the first trimester. For the low-risk group, the cut-off values of the serum biochemical markers were adjusted to determine the appropriate detection efficiency. Gravidas with abnormal serum biochemical markers at low-risk were advised to undergo further non-invasive prenatal screening (NIPS), whereas others continued with routine prenatal care. Results: When cut-off values of free beta subunit of human chorionic gonadotropin (free β-hCG) multiples of the median (MoM) or pregnancy-associated plasma protein A (PAPP-A) MoM were defined with ≥ 2.75 or ≤ 0.5, 7.72% (2,194/28,405) in the serum biochemical screening group and 12.36% (4,005/32,403) in CFTS group could be detected as abnormal results for further NIPS. Finally, 55.56% (5/9) and 85.71% (6/7) of trisomy 21 cases with false-negative results were detected, and the overall detection rate for trisomy 21 was improved by 10.64% (5/47) and 12.77% (6/47), respectively. Conclusions: The new contingent screening strategy can increase the detection rate of trisomy 21 compared with the traditional contingent screening strategy. [ABSTRACT FROM AUTHOR]

Objective The aim of this work was to compare different local cutoff values (LCV) and inline cutoff values (ICV) in pregnant women in the second trimester at high risk for carrying fetuses with trisomy 21. Methods This retrospective cohort study analyzed prenatal screening outcomes in pregnant women (n = 311,561). The receiver operating characteristic curve was used to evaluate the diagnostic significance of the trisomy 21 risk value, alpha-fetoprotein, and free beta human chorionic gonadotropin multiple of the median for predicting trisomy 21 risk. The cutoff value corresponding to the maximal Youden index was taken as the LCV. The screening efficiency of both cutoff values was compared. Results The LCV cutoff value was lower than the ICV cutoff value (1/643 vs 1/270). The sensitivity increased by 19.80%, the positive predictive value decreased by 0.20%, and the false-positive rate increased by 6.50%. Conclusion The LCV should be used to determine trisomy 21 risk, which can increase the detection rate of trisomy 21 in the second trimester. [ABSTRACT FROM AUTHOR]

Abstract Background Down syndrome myeloid hyperplasia includes transient abnormal myelopoiesis (TAM) and the myeloid leukemia associated with Down syndrome (ML-DS). The mutation of GATA1 gene is essential in the development of Down syndrome combined with TAM or ML-DS. Some patients with TAM are asymptomatic and may also present with severe manifestations such as hepatosplenomegaly and hydrops. Case presentation We report two cases of prenatally diagnosed TAM. One case was a rare placental low percentage 21 trisomy mosiacism, resulting in the occurrence of a false negative NIPT. The final diagnosis was made at 36 weeks of gestation when ultrasound revealed significant enlargement of the foetal liver and spleen and an enlarged heart; the foetus eventually died in utero. We detected a placenta with a low percentage (5–8%) of trisomy 21 mosiacism by Copy Number Variation Sequencing (CNV-seq) and Fluorescence in situ hybridization (FISH). In another case, foetal oedema was detected by ultrasound at 31 weeks of gestation. Two foetuses were diagnosed with Down syndrome by chromosomal microarray analysis via umbilical vein puncture and had significantly elevated cord blood leucocyte counts with large numbers of blasts. The GATA1 Sanger sequencing results suggested the presence of a [NM_002049.4(GATA1):c.220G > A (p. Val74Ile)] hemizygous variant and a [NM_002049.4(GATA1):c.49dupC(p. Gln17ProfsTer23)] hemizygous variant of the GATA1 gene in two cases. Conclusion It seems highly likely that these two identified mutations are the genetic cause of prenatal TAM in foetuses with Down syndrome.

Background: Down syndrome myeloid hyperplasia includes transient abnormal myelopoiesis (TAM) and the myeloid leukemia associated with Down syndrome (ML-DS). The mutation of GATA1 gene is essential in the development of Down syndrome combined with TAM or ML-DS. Some patients with TAM are asymptomatic and may also present with severe manifestations such as hepatosplenomegaly and hydrops. Case presentation: We report two cases of prenatally diagnosed TAM. One case was a rare placental low percentage 21 trisomy mosiacism, resulting in the occurrence of a false negative NIPT. The final diagnosis was made at 36 weeks of gestation when ultrasound revealed significant enlargement of the foetal liver and spleen and an enlarged heart; the foetus eventually died in utero. We detected a placenta with a low percentage (5–8%) of trisomy 21 mosiacism by Copy Number Variation Sequencing (CNV-seq) and Fluorescence in situ hybridization (FISH). In another case, foetal oedema was detected by ultrasound at 31 weeks of gestation. Two foetuses were diagnosed with Down syndrome by chromosomal microarray analysis via umbilical vein puncture and had significantly elevated cord blood leucocyte counts with large numbers of blasts. The GATA1 Sanger sequencing results suggested the presence of a [NM_002049.4(GATA1):c.220G > A (p. Val74Ile)] hemizygous variant and a [NM_002049.4(GATA1):c.49dupC(p. Gln17ProfsTer23)] hemizygous variant of the GATA1 gene in two cases. Conclusion: It seems highly likely that these two identified mutations are the genetic cause of prenatal TAM in foetuses with Down syndrome. [ABSTRACT FROM AUTHOR]

Children with Down syndrome (DS) require multiple sleep studies throughout childhood to diagnose and monitor sleep disordered breathing (SDB). Previous research suggests sensors applied during polysomnography (PSG) are poorly tolerated by children with DS. The Sonomat is a contactless device previously validated in typically developing children, and adult populations. Our study aimed to compare simultaneous Sonomat and PSG recordings in children with DS to determine the suitability of the Sonomat for use in this population. Fifty children with DS undergoing diagnostic PSG were recruited from the Queensland Children's Hospital sleep laboratory. Agreement for sleep and respiratory parameters were assessed using concordance correlation coefficients (CCC), while detection and classification of SDB were assessed using indicators such as sensitivity, specificity, likelihood ratios, and receiver operator characteristic curves. Comparison of parameters including the apnea-hypopnea index (CCC=89%; 95%CI 76, 93), and obstructive events index (CCC=74%; 95%CI 44, 88) showed reasonable agreement between Sonomat and PSG. The Sonomat showed outstanding ability to differentiate between the presence and absence of SDB (area under the curve [AUC]=0.97; 95%CI 0.93, 1.00), though we are uncertain of its ability to classify SDB profile and severity due to sample size limitations resulting in wide confidence intervals. The easy-to-use, non-invasive nature of the Sonomat make it ideal for use in the screening of SDB in children with DS. Further data are needed to determine its suitability for classifying SDB profile and severity, including within the home, and for its use in other neurodevelopmental groups. • Excellent AHI (CCC=89%; 95%CI 76, 93) agreement between Sonomat and PSG. • Reasonable OAHI (CCC=74%; 95%CI 44, 88) agreement between Sonomat and PSG. • Sonomat showed outstanding ability to identify SDB (AUC=0.97; 95%CI 0.93, 1.00). • Ability of Sonomat to classify SDB profile and severity uncertain; more data are required. • Sonomat is a non-invasive tool that appears well suited to SDB screening in children with DS. [ABSTRACT FROM AUTHOR]

Objective: The first trimester combined risk of trisomy 21 is obtained by multiplying the risk related to maternal age by the likelihood ratios of nuchal translucency, free beta‐human chorionic gonadotrophin (β‐hCG) and placenta associated plasma protein‐A. Beyond five multiples of the median (MoM) of β‐hCG, the risk of trisomy 21 is truncated. The objective of the present study was to evaluate the evolution of the first trimester combined risk of trisomy 21 in individuals with first‐trimester free‐β‐hCG levels between 5 and 10 MoM. Methods: We conducted a non‐interventional cohort study from a 6‐year database of combined first‐trimester trisomy 21 screening of all individuals who underwent the screening in a French specialized medical analysis center. We included all pregnant individuals who had a serum‐free β‐hCG between 5 and 10 MoM. Patients for whom the status of the fetus, with or without trisomy 21, was not identified by the outcome of the pregnancy or by a karyotype result were excluded from the study. The discriminatory capacity of free‐β‐hCG above 5 MoM was studied by a receiver operating characteristic curve. We used an orthogonal polynomial regression to represent the evolution of likelihood ratios according to free‐β‐hCG in MoM. Results: Among 413 216 combined first‐trimester screens of trisomy 21, 2239 (0.5%) screens met the inclusion criteria. In the selected population, 801 (35.8%) were excluded from the study because of missing fetal or neonatal status, and 46 (3.2%) fetuses out of 1438 included were diagnosed with trisomy 21. For free β‐hCG values between 5 and 10 MoM, the area under the curve is 0.56 (0.46–0.65). The scatterplot of the likelihood ratio of β‐hCG showed an increasing parabolic pattern: the likelihood of trisomy 21 increases with the free‐β‐hCG threshold. Conclusion: To override the truncated risk of trisomy 21 in case of free β‐hCG values between 5 and 10 MoM, the study has allowed us to estimate the adjusted risk of trisomy 21, enabling health professionals to offer appropriate prenatal counseling. Synopsis: Estimation of the adjusted risk of trisomy 21 in pregnant individuals with a free ß‐hCG level between 5 and 10 multiples of the median in the first trimester. [ABSTRACT FROM AUTHOR]

Trisomy 21 (Down syndrome) is the most common autosomal aneuploidy among newborns. About 90% result from meiotic nondisjunction during oogenesis, which occurs around conception, when also the most profound epigenetic modifications take place. Thus, maternal meiosis is an error prone process with an extreme sensitivity to endogenous factors, as exemplified by maternal age. This contrasts with the missing acceptance of causal exogenous factors. The proof of an environmental agent is a great challenge, both with respect to ascertainment bias, determination of time and dosage of exposure, as well as registration of the relevant individual health data affecting the birth prevalence. Based on a few exemplary epidemiological studies the feasibility of trisomy 21 monitoring is illustrated. In the nearer future the methodical premises will be clearly improved, both due to the establishment of electronic health registers and to the introduction of non-invasive prenatal tests. Down syndrome is a sentinel phenotype, presumably also with regard to other congenital anomalies. Thus, monitoring of trisomy 21 offers new chances for risk avoidance and preventive measures, but also for basic research concerning identification of relevant genomic variants involved in chromosomal nondisjunction. [ABSTRACT FROM AUTHOR]

We analyzed patients with isolated, balanced complete atrioventricular septal defects. We identified 71 patients born in Nevada, between January 2008 and December 2020. We also analyzed prenatal detection rates. Of the 71, 61 (85%) had trisomy 21, 1 (1%) had CHARGE syndrome and 22q.11 deletion, and 10 (14%) had no chromosomal abnormalities. Of the 71, 67 had prenatal care, and 43/67 (64%) were prenatally diagnosed. Prenatal detection rate for 2008-2012 was 9/20 (45%) and 18/21 (86%) for 2018-2020, P =.03. Of the 71, 67 underwent surgical repair with 1 current postpulmonary artery banding and 0 surgical deaths. Of the 67, 3 (4%) had heart block. Only 1 (1.5%) patient had reoperation for a mitral valve replacement. Of the 71, 67 (94%) are alive during a 6-year average (range = 0-12 years) follow-up. In conclusion, surgical and long-term outcomes were excellent. Also, high state-wide, general population prenatal detection rates were achieved. [ABSTRACT FROM AUTHOR]

Non-invasive prenatal testing (NIPT) has been widely adopted as an approach for foetal aneuploidy screening. This study was to evaluate the performance of NIPT for foetal T21 detection in subgroups of pregnancies and the correlation between Z-score and discordant positive predictive values (PPVs). We retrospectively reviewed the NIPT results among 22361 pregnancies undergoing combined second-trimester screening (cSTS) previously. Sixty-four cases with positive NIPT results for foetal T21 were validated by invasive prenatal diagnosis. In pregnancies with cSTS-T21 low-, intermediate-, and high-risk, the PPVs at NIPT were 14.3%, 64.3%, and 86.4%, respectively. Mean Z-scores of positive NIPT cases with cSTS-T21 high- and intermediate-risk were comparable, while were higher than that of cases with pre-test low-risk. Furthermore, PPVs for positive NIPT cases at 3 < Z < 5, 5 ≤ Z < 9, and Z ≥ 9 were 16.7%, 63.2%, and 100.0%, respectively. This study suggested that Z-score value of positive cases might be associated with discordant PPVs for T21 screening in subgroups of pregnancies. Non-invasive prenatal testing has been offered as a primary screening option to high-risk or general pregnancy. However, the accuracy of non-invasive prenatal testing in patients with various pre-test risks remained unveiled. The current study revealed that the true positive probability for foetal trisomy 21 screening in pregnancies with prior high-risk was higher than that in pregnancies of intermediate-risk, and both of them were much higher than that of those with pre-test low-risk. The average of Z-score for chromosome 21 of positive non-invasive prenatal testing case in high-risk group was comparable with that of intermediate-risk group, while was higher than that of low-risk group. There was also an upward trend for the true positive probability of foetal trisomy 21 screening with the increase of Z-score. Our study revealed that pre-test risk and Z-score for chromosome 21 were helpful for accurately interpreting the reliability of positive results for foetal trisomy 21. [ABSTRACT FROM AUTHOR]

Introduction: The right subclavian artery normally arises as the first vessel from the brachiocephalic trunk. An aberrant right subclavian artery (ARSA) arises directly from the aortic arch and crosses behind the trachea towards the right arm. This variant occurs in approximately 1–2% of the population; however, the frequency increases in individuals with chromosomal abnormalities such as trisomy 21 and 22q11.2 microdeletion. Prenatal identification of ARSA therefore has a role in screening for such conditions. Methods: Databases were searched for studies reporting the prenatal ultrasound evaluation of ARSA and its frequency in normal fetuses and in those with chromosomal abnormalities. Results: A total of 23 studies were evaluated. Feasibility for the ultrasound evaluation of ARSA was 85–95%. The sonographic detection of ARSA is best in the three-vessel trachea view; however, sagittal and coronal imaging of the aortic arch may be useful. ARSA in isolation was not found to be associated with chromosomal abnormalities. The prevalence of ARSA in chromosomally abnormal fetuses was up to 24-fold higher than in normal fetuses, but the majority of chromosomally abnormal fetuses with ARSA had additional abnormal ultrasound findings, particularly cardiac abnormalities. Conclusions: The prenatal detection of ARSA is a clinically useful prenatal marker for chromosomal abnormalities. In isolation, it is unlikely to be associated with pathogenic genetic variants. The ultrasound diagnosis of ARSA should prompt meticulous assessment of associated abnormalities. Invasive diagnostic testing should be offered to patients with non-isolated ARSA or in the presence of non-reassuring screening results or other risk factors. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to establish suitable threshold values for biochemical indicators in low-risk pregnant women who underwent second trimester screening and design strategies for consecutive prenatal testing to increase trisomy 21 detection.This study examined singleton pregnant women who underwent double, triple, or quadruple screening in the second trimester over six years. To obtain adequate detection efficiency for low-risk pregnancies, threshold values for serum biochemical indicators were established, and a cost-effectiveness assessment of the improved contingent screening strategy was conducted.Participants were included in serum double- (n = 88,550), triple- (n = 29,991), and quadruple-screening (n = 15,004) groups. Threshold values were defined as having a free beta subunit of human chorionic gonadotropin (free β-hCG) multiple of the median (MoM) ≥ 2.50, alpha-fetoprotein (AFP) MoM ≤ 0.50, or unconjugated estriol (uE3) MoM ≤ 0.70 for low risk. Low-risk pregnancies, comprising 1.35% (988/73,183), 4.45% (1,171/26,286), and 11.91% (1,559/13,085) of the double-, triple-, and quadruple-screening groups, respectively, underwent further non-invasive prenatal screening. In the double-, triple-, and quadruple-screening groups, we detected 11.76% (2/17), 40.00% (2/5), and 66.67% (2/3) of trisomy 21 cases with false negative results, respectively, with the overall detection rates of 85.00% (85/100), 90.63% (29/32), and 95.24% (20/21), respectively, and decreased ratio of overall costs of 5.26%, 16.63%, and 24.36%, respectively.Utilizing threshold values of AFP, free β-hCG, and uE3 to trigger further non-invasive prenatal screening may increase trisomy 21 detection in pregnancies deemed low risk in the second trimester while reducing the overall costs of screening strategies.Methods: This study aimed to establish suitable threshold values for biochemical indicators in low-risk pregnant women who underwent second trimester screening and design strategies for consecutive prenatal testing to increase trisomy 21 detection.This study examined singleton pregnant women who underwent double, triple, or quadruple screening in the second trimester over six years. To obtain adequate detection efficiency for low-risk pregnancies, threshold values for serum biochemical indicators were established, and a cost-effectiveness assessment of the improved contingent screening strategy was conducted.Participants were included in serum double- (n = 88,550), triple- (n = 29,991), and quadruple-screening (n = 15,004) groups. Threshold values were defined as having a free beta subunit of human chorionic gonadotropin (free β-hCG) multiple of the median (MoM) ≥ 2.50, alpha-fetoprotein (AFP) MoM ≤ 0.50, or unconjugated estriol (uE3) MoM ≤ 0.70 for low risk. Low-risk pregnancies, comprising 1.35% (988/73,183), 4.45% (1,171/26,286), and 11.91% (1,559/13,085) of the double-, triple-, and quadruple-screening groups, respectively, underwent further non-invasive prenatal screening. In the double-, triple-, and quadruple-screening groups, we detected 11.76% (2/17), 40.00% (2/5), and 66.67% (2/3) of trisomy 21 cases with false negative results, respectively, with the overall detection rates of 85.00% (85/100), 90.63% (29/32), and 95.24% (20/21), respectively, and decreased ratio of overall costs of 5.26%, 16.63%, and 24.36%, respectively.Utilizing threshold values of AFP, free β-hCG, and uE3 to trigger further non-invasive prenatal screening may increase trisomy 21 detection in pregnancies deemed low risk in the second trimester while reducing the overall costs of screening strategies.Results: This study aimed to establish suitable threshold values for biochemical indicators in low-risk pregnant women who underwent second trimester screening and design strategies for consecutive prenatal testing to increase trisomy 21 detection.This study examined singleton pregnant women who underwent double, triple, or quadruple screening in the second trimester over six years. To obtain adequate detection efficiency for low-risk pregnancies, threshold values for serum biochemical indicators were established, and a cost-effectiveness assessment of the improved contingent screening strategy was conducted.Participants were included in serum double- (n = 88,550), triple- (n = 29,991), and quadruple-screening (n = 15,004) groups. Threshold values were defined as having a free beta subunit of human chorionic gonadotropin (free β-hCG) multiple of the median (MoM) ≥ 2.50, alpha-fetoprotein (AFP) MoM ≤ 0.50, or unconjugated estriol (uE3) MoM ≤ 0.70 for low risk. Low-risk pregnancies, comprising 1.35% (988/73,183), 4.45% (1,171/26,286), and 11.91% (1,559/13,085) of the double-, triple-, and quadruple-screening groups, respectively, underwent further non-invasive prenatal screening. In the double-, triple-, and quadruple-screening groups, we detected 11.76% (2/17), 40.00% (2/5), and 66.67% (2/3) of trisomy 21 cases with false negative results, respectively, with the overall detection rates of 85.00% (85/100), 90.63% (29/32), and 95.24% (20/21), respectively, and decreased ratio of overall costs of 5.26%, 16.63%, and 24.36%, respectively.Utilizing threshold values of AFP, free β-hCG, and uE3 to trigger further non-invasive prenatal screening may increase trisomy 21 detection in pregnancies deemed low risk in the second trimester while reducing the overall costs of screening strategies.Conclusion: This study aimed to establish suitable threshold values for biochemical indicators in low-risk pregnant women who underwent second trimester screening and design strategies for consecutive prenatal testing to increase trisomy 21 detection.This study examined singleton pregnant women who underwent double, triple, or quadruple screening in the second trimester over six years. To obtain adequate detection efficiency for low-risk pregnancies, threshold values for serum biochemical indicators were established, and a cost-effectiveness assessment of the improved contingent screening strategy was conducted.Participants were included in serum double- (n = 88,550), triple- (n = 29,991), and quadruple-screening (n = 15,004) groups. Threshold values were defined as having a free beta subunit of human chorionic gonadotropin (free β-hCG) multiple of the median (MoM) ≥ 2.50, alpha-fetoprotein (AFP) MoM ≤ 0.50, or unconjugated estriol (uE3) MoM ≤ 0.70 for low risk. Low-risk pregnancies, comprising 1.35% (988/73,183), 4.45% (1,171/26,286), and 11.91% (1,559/13,085) of the double-, triple-, and quadruple-screening groups, respectively, underwent further non-invasive prenatal screening. In the double-, triple-, and quadruple-screening groups, we detected 11.76% (2/17), 40.00% (2/5), and 66.67% (2/3) of trisomy 21 cases with false negative results, respectively, with the overall detection rates of 85.00% (85/100), 90.63% (29/32), and 95.24% (20/21), respectively, and decreased ratio of overall costs of 5.26%, 16.63%, and 24.36%, respectively.Utilizing threshold values of AFP, free β-hCG, and uE3 to trigger further non-invasive prenatal screening may increase trisomy 21 detection in pregnancies deemed low risk in the second trimester while reducing the overall costs of screening strategies. [ABSTRACT FROM AUTHOR]

The sequencing of cell-free fetal DNA in the maternal plasma through noninvasive prenatal testing (NIPT) is an accurate genetic screening test to detect the most common fetal aneuploidies during pregnancy. The extensive use of NIPT, as a screening method, has highlighted the limits of the technique, including false positive and negative results. Feto-placental mosaicism is a challenging biological issue and is the most frequent cause of false positive and negative results in NIPT screening, and of discrepancy between NIPT and invasive test results. We are reporting on two cases of feto-placental mosaicism of trisomy 21, both with a low-risk NIPT result, identified by ultrasound signs and a subsequent amniocentesis consistent with a trisomy 21. In both cases, after the pregnancy termination, cytogenetic and/or cytogenomic analyses were performed on the placenta and fetal tissues, showing in the first case a mosaicism of trisomy 21 in both the placenta and the fetus, but a mosaicism in the placenta and a complete trisomy 21 in the fetus in the second case. These cases emphasize the need for accurate and complete pre-test NIPT counselling, as well as to identify situations at risk for a possible false negative NIPT result, which may underestimate a potential pathological condition, such as feto-placental mosaicism or fetal trisomy. Post-mortem molecular autopsy may discriminate between placental, fetal and fetoplacental mosaicism, and between complete or mosaic fetal chromosomal anomalies. A multidisciplinary approach in counselling, as well as in the interpretation of biological events, is essential for the clarification of complex cases, such as feto-placental mosaicisms. [ABSTRACT FROM AUTHOR]

Background: A fast adoption of a non-invasive prenatal testing (NIPT) in clinical practice is a global tendency last years. Firstly, in Russia according a new regulation it was possible to perform a widescale testing of pregnant women in chromosomal abnormality risk. The aim of the study-to assess efficiency of using NIPT as a second-line first trimester screening test in Moscow.Methods: Based on the first trimester combined prenatal screening results 12,700 pregnant women were classified as a high-risk (cut-off ≥ 1:100) and an intermediate-risk (cut-off 1:101 - 1:2500) groups followed by whole genome NIPT. Women from high-risk group and those who had positive NIPT results from intermediate-risk group were considered for invasive prenatal diagnostic.Results: 258 (2.0%) samples with positive NIPT results were detected including 126 cases of trisomy 21 (T21), 40 cases of T18, 12 cases of T13, 41 cases of sex chromosome aneuploidies (SCAs) and 39 cases of rare autosomal aneuploidies (RAAs) and significant copy number variations (CNVs). Statistically significant associations (p < 0.05) were revealed for fetal fraction (FF) and both for some patient's (body mass index and weight) and fetus's (sex and high risk of aneuploidies) characteristics. NIPT showed as a high sensitivity as specificity for common trisomies and SCAs with an overall false positive rate 0.3%.Conclusions: NIPT demonstrated high sensitivity and specificity. As a second-line screening test it has shown a high efficiency in detecting fetus chromosomal anomalies as well as it could potentially lower the number of invasive procedures in pregnant women. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of implementing cell-free DNA (cfDNA) testing on gestational age (GA) at termination of pregnancy in a French perinatal network.Methods: We conducted a retrospective study. All women having undergone a termination of pregnancy between 1 January 2012 and 31 December 2017 were included. We compared the periods before and after the introduction of second-line cfDNA testing, which started on 1 January 2015. Throughout the study period, the invasive procedures were foetal karyotyping and chromosomal microarray analysis. The primary study outcome was GA at termination. The secondary outcomes were GA at termination for trisomy 21 and the frequency and GA at the time of invasive procedures.Results: During the 6-year study period, 840 women underwent termination. The median GA at termination before and after the implementation of cfDNA testing was 19.4 and 19.0 weeks, respectively (p = 0.38). Although the frequency of termination for trisomy 21 increased significantly from 23% to 32% (p < 0.01), the median GA at termination did not change significantly (p = 0.80). The implementation of cfDNA testing was associated with a decrease in the frequency of invasive procedures in general and chorionic villus sampling in particular (p = 0.04).Conclusion: The introduction of cfDNA testing does not increase the GA at termination for trisomy21. [ABSTRACT FROM AUTHOR]

The most well-known goal of non-invasive prenatal testing (NIPT) is still to determine whether or not a fetus has trisomy 21. Since women often terminate the pregnancy upon a positive result, there is concern that the use of NIPT contributes to discrimination against persons with disabilities. If this concern is justified, it could have an impact on the wider social acceptability of existing testing practices and their potential further expansion. This paper demonstrates four different versions of the discrimination worry, indicates how international policy papers have reacted to them, and identifies the ethically most relevant feature of the concern. [ABSTRACT FROM AUTHOR]

Objectives: A classification termed umbilical‐portal‐systemic venous shunt (UPSVS) for an abnormal umbilical vein (UV), portal vein (PV), and ductus venosus (DV) was proposed recently. According to this classification, there are 3 types of UPSVSs: types I, II, and III. Trisomy 21 associated with UV‐PV‐DV anomalies has been described, but the incidence of trisomy 21 in UPSVS cases, the relationship between UPSVS types and trisomy 21, and the pregnancy outcome are poorly documented. This study aimed to address these issues. Methods: All UPSVS cases diagnosed at our department from 2016 to 2019 were retrospectively studied. The English literature describing UV‐PV‐DV anomalies and trisomy 21 from 2000 to 2019 was searched, and the retrieved cases were analyzed. Results: Four of 20 UPSVS cases identified by us also had trisomy 21, with 2 type I and 2 type II UPSVSs. Ultrasound markers of Down syndrome were observed in all 4 cases that underwent termination of pregnancy (TOP). The literature search retrieved 12 reports including 279 patients, with 29 also having trisomy 21, giving a pooled trisomy 21 incidence rate of 10.4%. Of the 29 cases, 16 had type I, and 9 had type II, whereas UPSVS types in 4 were undeterminable, and 22 cases underwent TOP. Conclusions: There is a high incidence of trisomy 21 in UPSVS cases. Trisomy 21 is associated with a type I or II UPSVS. Most cases with the combined defect underwent TOP. These findings may be used to direct prenatal counseling and management of the combined condition. Access the CME test here and search by article title. [ABSTRACT FROM AUTHOR]

Abstract Background Tetrasomy 21 is a very rare aneuploidy which could clinically resemble a Down syndrome. It was most often described in its partial form than complete. We report the prenatal, pathological and genetic characteristics of a fetus with mosaic complete tetrasomy 21. This is the second well‐documented description of a complete tetrasomy 21 in the literature. Methods Prenatal and fetal pathological examinations, cytogenetic and molecular analyses were performed to characterize fetal features with tetrasomy 21. Results Prenatal ultrasound examination revealed an isolated complete atrioventricular septal defect with normal karyotype on amniotic fluid. After termination of pregnancy, clinical examination of the fetus evoked trisomy 21 or Down syndrome. Chromosomal microarray analysis and FISH on lung tissue showed a mosaicism with four copies of chromosome 21 (tetrasomy 21). Conclusion Our observation and the review of the literature reported the possibility of very weak mosaicism and disease‐causing confined tissue‐specific mosaicism in fetus or alive patients with chromosome 21 aneuploidy, mainly Down syndrome. In case of clinical diagnosis suggestive of Down syndrome, attention must be paid to the risk of false‐negative test due to chromosomal mosaicism (very weak percentage, different tissue distribution). To overcome this risk, it is necessary to privilege the diagnostic techniques without culture step and to increase the number of cells and tissues analyzed, if possible. This study highlights the limits of microarray as the unique diagnostic approach in case of weak mosaic and French cytogenetics guidelines recommend to check anomalies seen in microarray by another technique on the same tissue.

Background: Our aim was to evaluate the clinical utility of non-invasive prenatal testing for pregnant women with different diagnostic indications. Methods: In eight counties and districts of Yancheng, we studied 13,149 pregnant women with different indications who were offered NIPT for fetal screening, including for sex chromosomal aneuploidies (SCAs), rare autosomal trisomies (RATs), and subchromosomal copy number variations (CNVs). The purpose was to compare the detection of positive predictive values (PPVs) of different indications with the use of NIPT. The results were validated by karyotyping, chromosomal microarray analysis (CMA), or follow-up of pregnancy outcomes. Results: 13,149 maternal plasma samples were sequenced, among which 28 samples (0.2%) failed the sequencing quality control. The remaining 13,121 samples were analyzed, and birth follow-up missed 2,192 samples (16.7%). The PPVs of NIPT results for trisomy 21 (T21) and trisomy 18 (T18) and SCAs were 96.67, 63.64, and 31.34%, respectively. Among the advanced maternal age (AMA), serum screening high risk (SSHR), serum screening intermediate risk (SSIR), and voluntary screening (VS) groups, the PPVs for the common trisomies were 81.25, 85.71, 100, and 70%, respectively; the PPVs for total chromosomal abnormalities were 55.82, 65.22, 23.08, and 36.59%, respectively. Conclusion: NIPT for T21 and T18 and SCAs screening were ideal, and the PPVs for trisomy 13 (T13), RATs, and CNVs were low. For the AMA and VS groups, NIPT could be used as a first-line screening program; for SSHR and SSIR groups, NIPT could be used as a second-line supplementary screening program. [ABSTRACT FROM AUTHOR]

Prenatal diagnosis of Down syndrome (DS) is based on calculated risk involving maternal age, biochemical and ultrasonographic markers, and, more recently, cell-free DNA (cfDNA). The present study was designed to identify Down Syndrome biomarkers in maternal serum. We quantified the changes in maternal serum protein levels between 10 non-pregnant women, 10 pregnant women with healthy fetuses, and 10 pregnant women with DS fetuses using isobaric tags for relative and absolute quantification (iTRAQ). We subsequently conducted a Gene Ontology (GO) analysis. A total of 470 proteins were identified, 11 of which had significantly different serum levels between the DS fetus group and Healthy fetuses group. Our data shows the identified proteins may be relevant to DS and constitute potential DS biomarkers. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to report on the clinical performance of non-invasive prenatal testing (NIPT) for trisomies 21, 18 and 13 in twin pregnancies and to define the performance of NIPT by combining our cohort study results with published studies in a systematic meta-analysis.Material and Methods: A cohort study was carried out in the First Affiliated Hospital of Sun Yat-sen University and Kanghua Hospital. Meanwhile, searches of PubMed, EMBASE, The Cochrane Library and Web of Science for all relevant peer-reviewed articles were performed with a restriction to English language publication before 15 June 2019. Quality assessments were conducted with the Quality Assessment Tool for Diagnostic Accuracy Studies-2 checklist. Data analysis, heterogeneity, subgroup analysis and publication bias were carried out using META-DISC 1.4 and STATA 12.0.Results: In all, 141 twin pregnancies included in our cohort study; confirmation revealed one true-positive case for trisomy 21 and 140 true-negative cases. The sensitivity and specificity for trisomy 21 by NIPT were both 100%. Twenty-two eligible studies were enrolled in this meta-analysis together with our study. There were 199 cases of trisomy 21, 58 cases of trisomy 18, 14 cases of trisomy 13 and 6347 cases of euploids in total. For trisomy 21, NIPT showed the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 0.99, 1.00, 145.81, 0.06 and 1714.09, respectively. For trisomy 18, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 0.88, 1.00, 200.98, 0.19 and 483.68, respectively.Conclusions: The performance of NIPT for trisomy 21 in twin pregnancy was excellent and it was similar to that reported in singleton pregnancy. However, due to publication bias (trisomy 18) and small number of cases (trisomy 13), accurate assessment of the predictive performance of NIPT for trisomies 18 and 13 could not be achieved. [ABSTRACT FROM AUTHOR]

The introduction of noninvasive prenatal screening (NIPS) using cell-free DNA (cfDNA) is the newest option for aneuploidy screening during pregnancy. Compared with other aneuploidy screening options, NIPS offers a higher detection rate for trisomy 21 with a low false-positive rate. However, pretest and post-test patient counseling is essential and should include a discussion of the benefits and limitations, the screening rather than diagnostic nature of the test, and the association of a test failure with an increased risk of aneuploidy. Refer patients for genetic counseling when appropriate, particularly if test failure occurs due to a low fetal fraction or if maternal mosaicism or malignancy is suspected. [ABSTRACT FROM AUTHOR]

Objectives: To examine multiples of the median (MoM) values of serum free beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in a large series of pregnancies with a vanishing twin, determine the association of these values with the interval between embryonic death and blood sampling, and develop a model that would allow incorporation of these metabolites in first-trimester combined screening for trisomy.Methods: This was a retrospective study comparing maternal serum free β-hCG and PAPP-A levels at 11-13 weeks' gestation in 528 dichorionic pregnancies with a vanishing twin, including 194 (36.7%) with an empty gestational sac and 334 (63.3%) with a dead embryo, with those in 5280 normal singleton pregnancies matched for method of conception and date of examination. In vanishing-twin pregnancies with a dead embryo, marker levels were examined in relation to the estimated time between embryonic death and maternal blood sampling.Results: First, in pregnancies with a vanishing twin, median free β-hCG MoM was not significantly different from that in normal singleton pregnancies (1.000; 95% CI, 0.985-1.016 vs 0.995; 95% CI, 0.948-1.044; P = 0.849). Second, PAPP-A MoM was higher in vanishing-twin pregnancies than in normal singleton pregnancies (1.000; 95% CI, 0.985-1.015), both in the group with an empty gestational sac (1.165; 95% CI, 1.080-1.256; P = 0.0001) and in that with a dead embryo (1.175; 95% CI, 1.105-1.249; P < 0.0001). Third, in vanishing-twin pregnancies with a dead embryo, PAPP-A MoM was related inversely to the interval between estimated gestational age at embryonic demise and blood sampling (P < 0.0001). Fourth, in first-trimester screening for trisomy 21 in singleton pregnancies, the estimated detection rate, at a 5% false-positive rate, was 82% in screening by a combination of maternal age and fetal nuchal translucency thickness, and this increased to 86% with the addition of serum free β-hCG and to 91% with the addition of serum PAPP-A. Fifth, similar performance of screening can be achieved in pregnancies with a vanishing twin, provided the appropriate adjustments are made to the level of PAPP-A for the interval between estimated gestational age at embryonic demise and blood sampling.Conclusions: First-trimester screening for trisomy in pregnancies with a vanishing twin should rely on a combination of maternal age, fetal nuchal translucency thickness and serum free β-hCG, as in singleton pregnancy, without the use of serum PAPP-A. Alternatively, PAPP-A can be included but only after appropriate adjustment for the interval between estimated gestational age at fetal demise and blood sampling. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

In 2011, Skotko, Levine, and Goldstein asked parents who had children with Down Syndrome (DS) in the United States how they felt about having a child with DS. The purpose of the present study was to ask the same questions to parents living in France so that this information could be shared with new and expectant parents. The results were also compared to the findings of Skotko, Levine, and Goldstein (2011a) to see whether some parental feelings might be universally shared and to discuss the differences observed. This web‐based survey was shared with a number of DS organizations and online DS communities. Of the 369 respondents living in France, 99% indicated that they loved their son or daughter with DS; 98% were proud of their child with DS; 78% felt that their outlook on life was more positive because of their son or daughter with DS; 12% felt embarrassed by their child with DS; and 7% expressed regret for having a child with DS. A significant number of respondents admitted that raising a child with DS was not without challenges. Nevertheless, most respondents indicated that their son or daughter with DS had had a positive impact on their life and that of their family and that they were happy to have their child. [ABSTRACT FROM AUTHOR]

Objective: To report on the routine clinical implementation of cell-free DNA (cfDNA) analysis of maternal blood for trisomies 21, 18 and 13, contingent on the results of the first-trimester combined test in twin pregnancy.Methods: Screening for trisomies 21, 18 and 13 was carried out in 959 twin pregnancies by assessment of a combination of maternal age, fetal nuchal translucency thickness, and serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein-A at 11-13 weeks' gestation in two UK NHS hospitals. Women in the high-risk group (risk ≥ 1 in 100) were offered the option of invasive testing, cfDNA testing or no further testing, and those in the intermediate-risk group (risk 1 in 101 to 1 in 2500 in the first phase of the study and 1 in 101 to 1 in 500 in the second phase) were offered cfDNA or no further testing. The trisomic status of the pregnancies was determined by prenatal or postnatal karyotyping or examination of the neonates.Results: In 42 (4.4%) of the 959 pregnancies, there was termination, miscarriage or stillbirth with no known karyotype or there was loss to follow-up. The 917 pregnancies with known trisomic status of both twins included six that were discordant for trisomy 21, four that were discordant for trisomy 18 and 907 with no trisomy 21, 18 or 13. Following combined screening, 47 (5.1%), 203 (22.1%) and 667 (72.7%) of the pregnancies were classified as high risk, intermediate risk and low risk, respectively. The high-risk group included five (83.3%) cases of trisomy 21 and three (75.0%) of trisomy 18. The cfDNA test was carried out in 224 pregnancies and results were provided in 214 (95.5%); this group included six pregnancies with trisomy 21, three with trisomy 18 and 206 with no trisomy 21, 18 or 13. The cfDNA test classified correctly as screen positive all six cases of trisomy 21 and two of the three with trisomy 18, and as screen negative for each of the trisomies all 206 unaffected pregnancies. Contingent screening led to prenatal detection of all cases of trisomy 21 and three of four with trisomy 18.Conclusion: This study has demonstrated the feasibility of introducing cfDNA testing, contingent on the results of the first-trimester combined test for major trisomies, in a routine population of twin pregnancies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: Noninvasive prenatal diagnosing for fetal trisomy 21 could help to avoid unnecessary amniocentesis. It is feasible to target the cell-free placental-specific mRNA in maternal plasma, thus eliminating the interference from the maternal genetic background.Study Design: In this study, placental-specific genes on chromosome 21 were identified by searching the TiGER database and reviewing the published literature. These cell-free placental-specific mRNA fragments in maternal plasma were amplified and sequenced. Then, the allelic ratio of heterozygous single-nucleotide polymorphisms(SNPs) was analyzed.Results: Four placental-specific genes (DNMT3L, KRTAP26-1, PLAC4, DSCR4) were identified. This study included 42 cases of normal pregnancies and 19 cases of trisomy 21 pregnancies. The probability density function showed that the allelic ratio of heterozygous SNPs in normal pregnancy reached a peak at 1.0, and that in the trisomy 21 pregnancy was a double-peaked curve in both 0.5 and 2.0. However, the allelic ratio of heterozygous SNPs demonstrated no statistical difference between the normal and trisomy 21 pregnancies.Conclusion: Fetal trisomy 21 could not be diagnosed by examining the heterozygous SNPs of cell-free placental-specific mRNA on chromosome 21. This might be because the low quantity and quality of cell-free placental-specific mRNA fragments in maternal plasma, and the limited available heterozygous SNPs on the placental-specific genes. [ABSTRACT FROM AUTHOR]

Objective: Rapid genome-wide aneuploidy diagnosis using uncultured amniocytes and array comparative genomic hybridization (aCGH) is useful in pregnancy with abnormal ultrasound findings. The purpose of this report is to report a case of right congenital diaphragmatic hernia (CDH) associated with trisomy 21 diagnosed prenatally by aCGH and to review the literature of chromosomal abnormalities associated with CDH. Case report: A 29-year-old woman was referred for genetic counseling at 25 weeks of gestation because of fetal CDH. The pregnancy was uneventful until 25 weeks of gestation when level II ultrasound detected isolated right CDH. Ultrasound showed that the liver and gallbladder were located in the right hemithorax, and there was levocardia. Fetal magnetic resonance imaging confirmed the diagnosis of right CDH with the gallbladder and part of the liver appearing in the right hemithorax and the heart shifting to the left hemithorax. Amniocentesis was immediately performed. About 10 mL of amniotic fluid was sent for aCGH analysis by use of the DNA extracted from uncultured amniocytes, and 20 mL of amniotic fluid was sent for conventional cytogenetic analysis. aCGH analysis revealed the result of arr 21p11.2q22.3 (9,962,872–48,129,895) × 3, consistent with the diagnosis of trisomy 21. Conventional cytogenetics revealed a karyotype of 47,XY,+21. Postnatally, polymorphic DNA marker analysis using DNAs extracted from the placenta and parental bloods showed a heterozygous extra chromosome 21 of maternal origin consistent with the result of maternal meiosis I nondisjunction. Conclusion: Prenatal diagnosis of right CDH should raise a suspicion of chromosomal abnormalities especially trisomy 21 and the association of Morgagni hernia.

Cell‐free DNA screening has quickly become established in Australia as an accurate – albeit costly – prenatal screening test for trisomy 21, 18 and 13. It is also commonly used for the detection of sex chromosome abnormalities. The increasing number of prenatal screening pathways available to women has increased the complexity of pretest counselling. Concurrent advances in diagnostic testing with the widespread use of chromosomal microarrays create further challenges for the continuing education of clinicians and health consumers. This article aims to answer common clinical questions in this rapidly evolving field and complements the recently updated Royal Australian and New Zealand College of Obstetricians and Gynaecologists Statement on Prenatal Screening for Fetal Chromosome and Genetic Conditions. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Detection of cell‐free fetal DNA in maternal blood is a type of noninvasive prenatal diagnosis test (NIPT), which has already been known for some time but has not yet been introduced in most of public hospitals in Spain. How the implementation of cell‐free fetal DNA (cffDNA) in a contingent protocol has influenced the aneuploidy screening in our hospital is described. Methods: Two cohorts of patients with positive combined screening were compared: the first one (years 2012–2013, 5747 patients) from a period of time in which the protocol valid until March 2016 – that included the use of invasive procedures – was applied; and the second one in which the current protocol – that included NIPT versus invasive procedures – was applied (first 7 months after protocol implementation, 898 patients). Results: Comparison of both periods resulted in a 60.5% reduction of invasive procedures (P < 0,001) preserving the same chromosomopathy detection rate. The ratio of positive invasive procedures–indicated invasive procedures was improved by 15% in the first period to 50% in the second period (P = 0.01). Conclusion: NIPT introduction has caused a significant reduction of 60.5% of IP in high chromosomopathy risk patients after combined screening without modifying detection rate. [ABSTRACT FROM AUTHOR]

Introduction: Prenatal diagnosis of Down syndrome (DS) is based on the calculated risk of maternal age, biochemical and ultrasonographic markers and recently by cfDNA. Differences in proteomic profiles may give an opportunity to find new biomarkers.Objective: Characterize proteome of serum of mothers carrying DS fetus.Material and Methods: Blood serum samples of three groups of women were obtained, (a) 10 non-pregnant, (b) 10 pregnant with healthy fetus by ultrasound evaluation, (c) nine pregnant with DS fetus. Sample preparation was as follows: Albumin/IgG depletion, desalting, and trypsin digestion; the process was performed in nanoUPLC MS/MS. Data analysis was made with Mass Lynx 4.1 and ProteinLynx Global Server 3.0, peptide and protein recognition by MASCOT algorithm and UNIPROT-Swissprot database.Results: Each group showed different protein profiles. Some proteins were shared between groups. Only sera from pregnant women showed proteins related to immune and clot pathways. Mothers with DS fetus had 42 specific proteins.Conclusions: We found a different serum protein profile in mothers carrying DS fetuses that do not reflect expression of genes in the extra chromosome. Further studies will be necessary to establish the role of these proteins in aneuploid fetus and analyze their possible use as potential biomarkers. [ABSTRACT FROM AUTHOR]

/Background : The high rate of obstructive sleep apnea (OSA) in Down Syndrome (DS) is well described in the literature. The impact of the 2011 screening guidelines has not been fully evaluated. The objective of this study is to evaluate the impact of the 2011 screening guidelines on the diagnosis and treatment of obstructive sleep apnea (OSA) in a community cohort of children with Down Syndrome. This is a retrospective, observational study conducted on 85 individuals with DS born between 1995 and 2011 in a nine-county region of southeast Minnesota. The Rochester Epidemiological Project (REP) Database was used to identify these individuals. /Conclusions : Sixty-four percent of the patients with DS had OSA. Post guideline publication, the median age at OSA diagnosis was higher (5.9 years; p = 0.003) and polysomnography (PSG) was used more often to establish the diagnosis. Most children underwent first line therapy with adenotonsillectomy. There was a high degree of residual OSA after surgery (65%). There were trends post guideline publication towards increased PSG use and for consideration of additional therapy beyond adenotonsillectomy. The use of PSG before and after first line treatment for OSA in children with DS is needed due to the high rate of residual OSA. Unexpectedly, in our study, the age at OSA diagnosis was higher after guideline publication. Continued assessment of clinical impact and refinement of these guidelines will be of benefit to individuals with DS given the prevalence and longitudinal nature of OSA in this population. [ABSTRACT FROM AUTHOR]

Down syndrome (DS), the most prevalent autosomal disorder with a global incidence of 1 in 700 live births, was characterized in 1866 clinically and understood in 1959 genetically. However, till date DS patients are marginalized at the social cost and institutionalized for care and rehabilitation. The meiotic non-disjunction results in origin of extra 21 (Hsa21) in 95 %, whereas hereditary t(21;21) or de novo variant Robertsonian translocation contributes to the remaining. Howsoever is the origin, DS patients suffer from systemic disorders to mental retardation with a distinct phenotype, and many die in infancy or early adulthood and many at uterine age. Although the trisomy Hsa21 is the same in most of the DS-individuals, the penetrance of the resulting pathologies varies as most of them have memory and learning difficulties, craniofacial alterations and muscle hypotonia, with differential expression of congenital heart defects, leukemia or gut abnormalities. Furthermore, the severity of the defects varies greatly with varying cognitive impairment. Such variability in clinical expression could be contributed by the site of meiotic recombination of bivalents, chromosomal polymorphisms, epigenetic factors and gene dosage. Therefore, exploration has already been initiated for inactivating excess genes contributed by extra Hsa21 with a view to targeting therapy of DS. Interestingly, a remarkable result has been achieved in induced pluripotent stem cells of DS through insertion of XIST gene, which may promise a cure of future DS. [ABSTRACT FROM AUTHOR]

Objective: To examine the diagnostic accuracy of a previously developed model for the first-trimester combined test in screening for trisomies 21, 18 and 13.Methods: This was a prospective validation study of screening for trisomies 21, 18 and 13 by assessment of a combination of maternal age, fetal nuchal translucency, fetal heart rate and serum free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks' gestation in 108 982 singleton pregnancies undergoing routine care in three maternity hospitals. A previously published algorithm was used to calculate patient-specific risks for trisomy 21, 18 and 13 in each patient. The detection rate (DR) and false-positive rate (FPR) at estimated risk cut-offs from 1 in 2 to 1 in 1000 were determined. The proportions of trisomies detected were compared to their expected values in different risk groups.Results: In the study population, there were 108 112 (99.2%) cases with normal fetal karyotype or birth of a phenotypically normal neonate and 870 (0.8%) cases with abnormal karyotype, including trisomy 21 (n = 432), trisomy 18 (n = 166), trisomy 13 (n = 56), monosomy X (n = 63), triploidy (n = 35) or other aneuploidy (n = 118). The screen-positive rates, standardized according to the maternal age distribution in England and Wales in 2011, of fetuses with abnormal or normal karyotype were compatible with those predicted from the previous model; at a risk cut-off of 1 in 100, the FPR was about 4% and the DRs for trisomies 21, 18 and 13 were 90%, 97% and 92%, respectively. There was evidence that the algorithm overestimated risk. This could, to some degree, reflect under-ascertainment in pregnancies ending in miscarriage or stillbirth.Conclusion: In a prospective validation study, the first-trimester combined test detected 90%, 97% and 92% of trisomies 21, 18 and 13, respectively, as well as > 95% of cases of monosomy X and triploidies and > 50% of other chromosomal abnormalities, at a FPR of 4%. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Introduction: The aim was to investigate the parental decisions about prenatal screening and diagnosis among infants with trisomy 21 (T21) in a national cohort with high uptake of combined first-trimester screening (cFTS).Material and Methods: This was a nationwide population-based study including infants born in 2009-2012. Information from the cFTS, fetal karyotype results and pregnancy outcome was obtained from the Danish Fetal Medicine Database on all women with a cFTS risk assessment. Cut-off for referral for invasive testing was ≥1:300. Karyotype results from pregnancies with no cFTS were obtained from the Danish Cytogenetic Central Registry.Results: The uptake rate of cFTS was 91.6%, and 82.8% (8,032/9,704) of the screen-positive women opted for invasive testing. Overall, 82.2% (454/552) chose to terminate an affected pregnancy. In the 4-year period, 102 of 232,962 singletons were born alive with T21. The cFTS risk was true-positive, false-negative or not obtained in 21.6, 48.0 and 30.4%, respectively, of these pregnancies.Discussion: In this large national cohort, 4.4 per 10,000 live-born infants had T21. Of 102 infants with T21 from 2009 to 2012, 52.0% were born after the women had not opted for cFTS or were true-positive but declined invasive testing or termination, and 48.0% were born after a false-negative risk assessment. [ABSTRACT FROM AUTHOR]

Background Screening for Down syndrome ( DS) is a key component of antenatal care, recommended to be universally offered to women irrespective of age or background. Despite this, the diagnosis of DS is often not made until the neonatal period. Aims To retrospectively describe and compare the differences in populations with an antenatal diagnosis ( AD) and neonatal diagnosis ( ND) of DS and to explore why an antenatal diagnosis was not made. Materials and methods The cohorts were women cared for at Westmead Hospital whose pregnancy received a diagnosis of DS between 2006 and 2015. The demographic variables of the AD and ND cohorts were examined and reasons why an antenatal diagnosis was not made in the ND cohort were analysed. Results There were 127 diagnoses of DS in the 10-year period, of which 41% were in the ND cohort ( n = 52) and 59% in the AD ( n = 75). Declaring a religious affiliation rather than Nil Religion was significantly more common in the ND cohort (88.5%) and especially the ND sub-cohort who declined DS screening/testing (95.8%) than the AD cohort (72%, P < 0.05). Women who were not offered screening were significantly younger ( P < 0.001) than those who were, with 69% and 20% being ≤30 years, respectively. Conclusions The proportion of DS pregnancies diagnosed in the antenatal period in western Sydney could be increased by ensuring younger women are not falsely reassured that DS screening is unnecessary for them. While religious affiliation may be a factor when women decline screening, ensuring appropriate counselling remains important. [ABSTRACT FROM AUTHOR]

Objective: To evaluate first-trimester screening protocols for detecting trisomy 21 in an Indian population.Methods: The present prospective study collected data from women with singleton pregnancies and a crown-to-rump length of 45-84 mm who presented at the fetal medicine unit of a tertiary care center in North India between June 1, 2006, and December 31, 2015, for combined first-trimester screening. Maternal age, nuchal translucency, nasal bone, and maternal serum levels of free beta human chorionic gonadotropin and pregnancy-associated plasma protein A were assessed for calculating the risk of trisomy 21. Tricuspid regurgitation and qualitative analysis of ductus venosus data were available from June 2010, and were included where available. Trisomy-21 detection rates were calculated for various screening protocols and were compared.Results: There were 4523 women screened and 24 records of trisomy 21. Combined screening with maternal age, nuchal translucency, nasal bone, tricuspid regurgitation, and ductus venosus demonstrated optimal detection and false-positive rates of 93.8% and 1.9%, respectively. Screening using only maternal age yielded a detection rate of 37.5%; using fixed nuchal translucency cut-off values of 2.5 and 3 mm resulted in detection rates of 66.7% and 37.5%, respectively.Conclusion: Combined first-trimester screening performed well in an Indian population; combining maternal age, nuchal translucency, nasal bone, ductus venosus, and tricuspid regurgitation yielded the most accurate screening. [ABSTRACT FROM AUTHOR]

Background: Patient decision aids (PtDAs) help people make difficult, values-sensitive decisions. Prenatal screening for assessing the risk of genetic conditions in the fetus is one such decision and patient decision aids are rarely used in this clinical context. We sought to identify factors influencing pregnant women's use of a patient decision aid for deciding about prenatal screening for Down syndrome (DS).Methods: This qualitative study was embedded in a sequential mixed-methods research program whose main aim is to implement shared decision-making (SDM) in the context of prenatal screening for DS in the province of Quebec, Canada. We planned to recruit a purposive sample of 45 pregnant women with low-risk pregnancy consulting for prenatal care at three clinical sites. Participating women watched a video depicting a prenatal care follow-up during which a pregnant woman, her partner and a health professional used a PtDA to decide about prenatal screening for DS. The women were then interviewed about factors that would influence the use of this PtDA using questions based on the Theoretical Domains Framework (TDF). We performed content analysis of transcribed verbatim interviews.Results: Out of 216 eligible women, 100 agreed to participate (46% response rate) and 46 were interviewed. Regarding the type of health professional responsible for their prenatal care, 19 participants (41%) reported having made a decision about prenatal screening for DS with an obstetrician-gynecologist, 13 (28%) with a midwife, 12 (26%) with a family physician, and two (4%) decided on their own. We identified 54 factors that were mapped onto nine of the 12 TDF domains. The three most frequently-mentioned were: opinion of the pregnant woman's partner (n = 33, 72%), presentation of the PtDA by health professional and a discussion (n = 27, 72%), and not having encountered a PtDA (n = 26, 57%).Conclusion: This study allowed us to identify factors influencing pregnant women's use of a PtDA for prenatal screening for DS. Use of a PtDA by health professionals and patients is one step in providing the needed decision support and our study results will allow us to design an effective implementation strategy for PtDAs for prenatal screening for DS. [ABSTRACT FROM AUTHOR]

Objective: To assess predictors for survival and complications among a relatively large cohort of fetuses with hydrothorax treated by thoracoamniotic shunting. Methods: All cases with hydrothorax treated by thoracoamniotic shunting in a 10-year period (2002-2011) in two centers were retrospectively reviewed. Results: A total of 78 fetuses with hydrothorax treated with thoracoamniotic shunting were included in the study. Mean gestational age at diagnosis was 25.6 weeks (12-34 weeks). Initial thoracoamniotic shunting was performed at a mean gestational age of 26.5 weeks (16-33 weeks). A mean of 2.53 shunts (1-7) were inserted per fetus. Of the 78 fetuses, 9 (11.5%) died in utero, 69 (88.5%) were born alive and 46 (59%) survived. Prognostic markers significantly associated with nonsurvival were polyhydramnios, hydrops placentae and mediastinal shift at initial scan, onset of hydrops after first shunt placement, rupture of membranes, a shunt-birth interval <4 weeks and low gestational age at birth. In our cohort, fetuses with trisomy 21 had a significantly better survival than euploid fetuses. Conclusions: Although associated with a significant rate of repeated interventions, thoracoamniotic shunting in fetuses with severe hydrothorax results in an overall survival rate of 59%. Fetuses with hydrothorax and trisomy 21 have a better survival when compared to euploid fetuses. [ABSTRACT FROM AUTHOR]

The article discusses the study that determined the effect of maternal age (MA) on the screening performance of traditional combined screening (CS) and ultrasound-based screening (US), two first-trimester screening strategies. Topics discussed include higher detection rate (DR) of trisomy 21 (T21) showed by US protocol compared to the CS one, and potential of US protocol as viable alternative to CS for T21 in cases where access to biochemical testing is limited.

Background: To evaluate the impact of the introduction of prenatal screening on time of detection and pregnancy outcome for trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13).Methods: We performed a retrospective, population-based cohort study in the Northern Netherlands including 503 trisomy cases born between 2005 and 2012. Screening tests and invasive procedures, timing of diagnosis and pregnancy outcome were compared between the period before (2005-2006) and after introduction (2007-2012) using X 2 tests.Results: There was an increase in proportion of women who had a prenatal screening and/or invasive test, from 62% in 2005-2006 to 84% in 2010-2012 (p < 0.01), while the proportion of prenatally diagnosed cases did not change (60% overall). In women < =35 years 47% of the cases were diagnosed prenatally vs 73% in women >35 years (p < 0.01). More T13/T18 cases were diagnosed <24 weeks after introduction (62% vs 84%; p < 0.01). In T13/T18 intra-uterine death decreased (26% vs 15%), while terminations increased: 55% vs 72%.Conclusion: The introduction of prenatal screening had limited impact on the time of detection and outcome of the most common trisomies. The introduction of the 20-week anomaly scan has resulted in more trisomy cases diagnosed <24 weeks and a shift from fetal death to terminations. [ABSTRACT FROM AUTHOR]

Objective: Atrioventricular septal defect is associated with a high risk of a chromosomal abnormality, particularly trisomy 21. The aim of this study is to assess the rate of trisomy 21 in fetuses diagnosed with an atrioventricular septal defect and to examine the influence of prior screening on the rate of trisomy 21.Methods: Electronic ultrasound database was searched to identify fetuses diagnoses with an atrioventricular septal defect from 2002 to 2014. Rate of trisomy 21 and other aneuploidies was calculated among fetuses with normal situs. The prevalence of trisomy 21 and other aneuploidies was assessed in women with low and high first trimester risk for trisomy 21, using a cut-off value of 1:150 and 1:250.Results: A total 110 fetuses with a diagnosis of atrioventricular septal defect were identified. Among the 98 fetuses with normal situs, the prevalence of trisomy 21 was 46% (95% CI: 36-56%). Using a 1:150 threshold, the rate of trisomy 21 within the low-risk group was 41% (95% CI: 27-57%) while in the high-risk group it was 70% (95% CI: 52-83%), significantly higher than in the low risk group (p=0.028). Similar results were obtained when the 1:250 threshold was applied (66% versus 41%, p=0.055).Conclusions: The rate of trisomy 21 among fetuses identified with an atrioventricular septal defect in the second trimester is high even in those that undergo first trimester combined screening. Some fetuses with a high-risk screening result show a normal karyotype. Therefore, an offer of an invasive procedure to check fetal karyotyping is indicated. Knowledge of these rates may be helpful for parents in the decision making process. [ABSTRACT FROM AUTHOR]

Objective: This study examines trends in total and live birth prevalence of trisomy 21 (T21) with regard to increasing maternal age and the introduction of prenatal diagnosis in Bosnia and Herzegovina.Method: The prenatal detection was introduced in January 2008 in 3 hospitals and assessed until December 31, 2015. In this study, 99 fetuses and 330 babies were diagnosed with T21 in the studied period.Results: On average, each year 33 T21 individuals were born and 13 T21 fetuses were diagnosed prenatally. The calculated incidence for the live born T21 individuals in Bosnia is 1:999. The live-birth prevalence of T21 was 9.6 per 10,000 births and the total prevalence of T21 was 19.1. The total T21 prevalence increases exponentially with the advanced maternal age. Prenatal T21 prevalence is 1.29 per 10,000 births for mothers <35, but increases exponentially with increasing age (32 for >40 years). The most common indications for invasive prenatal testing were ultrasound screening combined with biochemical serum analysis followed by the advanced maternal age.Conclusion: The prevalence of liveborn Down syndrome children remained constant. Despite the fact that increasing maternal age in the last decade contributed to the rise in the total T21 prevalence, the effect of the introduction of prenatal diagnosis on the live-birth T21 prevalence of T21 was minimal, leading to the conclusion that the prenatal screening has to be improved in developing countries. [ABSTRACT FROM AUTHOR]

Background: Controversies about the performance of conventional prenatal screening using maternal serum and ultrasound markers (PSMSUM) in detecting Down syndrome (DS) have been raised as a result of a recently available noninvasive prenatal test based on cell-free fetal DNA sequencing.Objectives: To evaluate the screening performance of PSMSUM in detecting DS in Chinese women.Search Strategy: An exhaustive literature search of MEDLINE, Embase, the Cochrane Library, ISI Web of Science and China BioMedical Disc.Selection Criteria: Primary studies, published from January 2004 to November 2014, which examined the screening accuracy of PSMSUM in pregnant Chinese women, compared with a reference standard, either chromosomal verification or inspection of the newborn.Data Collection and Analysis: Data were extracted as screening positive/negative results for Down and non-Down syndrome pregnancies, allowing estimation of sensitivities and specificities. Risks of bias within and across studies were assessed. Screening accuracy measures were pooled using a bivariate random effects regression model.Main Results: Seventy-eight studies, involving six categories of PSMSUM, were included. Second-trimester double serum [pooled sensitivity (SEN) = 0.80, pooled specificity (SPE) = 0.95] and triple-serum (pooled SEN = 0.79, pooled SPE = 0.96) screening were the predominant PSMSUM methods. The screening performances of these methods achieved the national standard but varied enormously across studies. First-trimester combined screening (pooled SEN = 0.92, pooled SPE = 0.93) and second-trimester quadruple serum screening (median SEN = 0.86, median SPE = 0.96) performed better, but were rarely used.Author's Conclusions: Second-trimester maternal serum screening has the potential to achieve satisfactory screening performance in middle- and low-income countries. The reported enormous range in screening performance of second-trimester PSMSUM calls for urgent implementation of methods for performance optimization.Tweetable Abstract: Meta-analysis results show good accuracy of maternal serum and ultrasound screening for trisomy 21 in Chinese women. [ABSTRACT FROM AUTHOR]

Purpose: To determine correlations between macrophage colony-stimulating factor (MCSF) levels in maternal blood during first trimester screening with respect to normal and pathological pregnancies.Methods: This was a prospective single centre study. First trimester screening was performed according to FMF London certificates. Nuchal translucency, PAPP-A and free β-HCG were obtained as well as M-CSF serum levels in maternal blood. Fetal karyotyping was achieved by chorionic villi sampling.Results: 125 patients were enrolled in this study. 21 pregnancies had confirmed aberrant karyotypes. Trisomy 21 cases showed significantly elevated M-CSF levels of 270 ± 91 pg/ml (p = 0.032), whereas cases of trisomy 13 (183 ± 68 pg/ml) and trisomy 18 (143 ± 40 pg/ml) had low M-CSF levels. Furthermore M-CSF levels tended to be low in preterm deliveries, placental insufficiency and nicotine consumption. In cases with gestational diabetes M-CSF tended to be elevated. Furthermore we found a positive correlation between high free β-human chorionic gonadotropin (hcg) and MCSF values. There was no correlation between pregnancy associated plasma protein (PAPP-A) and M-CSF.Conclusions: M-CSF is a cytokine promoting placental growth and differentiation. M-CSF is known to be involved in the process of implantation in pregnancy. The role of M-CSF with respect to disturbed pregnancy outcomes such as placental insufficiency in normal or aberrant karyotypes, for example, is yet subject to further research. [ABSTRACT FROM AUTHOR]

Objectives: First, to examine in twin pregnancies the performance of first-trimester screening for fetal trisomies 21, 18 and 13 by cell-free (cf) DNA testing of maternal blood and, second, to compare twin and singleton pregnancies regarding the distribution of fetal fraction of cfDNA and rate of failure to obtain a result.Methods: This was a prospective study in 438 twin and 10 698 singleton pregnancies undergoing screening for fetal trisomies by cfDNA testing at 10 + 0 to 13 + 6 weeks' gestation. Chromosome-selective sequencing of cfDNA was used and, in twin pregnancies, an algorithm was applied that relies on the lower fetal fraction contributed by the two fetuses. Multivariate regression analysis was used to determine significant predictors of fetal fraction and a failed result.Results: In twin pregnancies, the median fetal fraction was lower (8.0% (interquartile range (IQR), 6.0-10.4%) vs 11.0% (IQR, 8.3-14.4%); P < 0.0001) and failure rate after first sampling was higher (9.4% vs 2.9%; P < 0.0001) compared to in singletons. Multivariate logistic regression analysis demonstrated that the risk of test failure increased with increasing maternal age and body mass index and decreased with fetal crown-rump length. The risk was increased in women of South Asian racial origin and in pregnancies conceived by in-vitro fertilization (IVF). The main contributor to the higher rate of failure in twins was conception by IVF which was observed in 9.5% of singletons and 56.2% of twins. In the 417 twin pregnancies with a cfDNA result after first or second sampling, the detection rate was 100% (8/8) for trisomy 21 and 60% (3/5) for trisomies 18 or 13, at a false-positive rate (FPR) of 0.25% (1/404). In the 10 530 singleton pregnancies with a cfDNA result after first or second sampling, the detection rate was 98.7% (156/158) for trisomy 21 and 80.3% (49/61) for trisomies 18 or 13, at a FPR of 0.22% (23/10 311).Conclusions: In twin pregnancies undergoing first-trimester screening for trisomies by cfDNA testing, the fetal fraction is lower and failure rate higher compared to in singletons. The number of trisomic twin pregnancies examined was too small for an accurate assessment of performance of screening, but it may be similar to that in singleton pregnancies. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: First, to report the distribution of the fetal fraction of cell-free (cf) DNA and the rate of a failed cfDNA test result in trisomies 21, 18 and 13, by comparison with pregnancies unaffected by these trisomies, second, to examine the possible effects of maternal and fetal characteristics on the fetal fraction, and third, to consider the options for further management of pregnancies with a failed result.Methods: This was a cohort study of 10 698 singleton pregnancies undergoing screening for fetal trisomies 21, 18 and 13 by cfDNA testing at 10-14 weeks' gestation. There were 160 cases of trisomy 21, 50 of trisomy 18, 16 of trisomy 13 and 10 472 were unaffected by these trisomies. Multivariate regression analysis was used to determine significant predictors of fetal fraction and a failed cfDNA test result amongst maternal and fetal characteristics.Results: Fetal fraction decreased with increasing body mass index and maternal age, was lower in women of South Asian racial origin than in Caucasians and in assisted compared to natural conceptions. It increased with fetal crown-rump length and higher levels of serum pregnancy-associated plasma protein-A and free β-human chorionic gonadotropin. The median fetal fraction was 11.0% (interquartile range (IQR), 8.3-14.4%) in the unaffected group, 10.7% (IQR, 7.8-14.3%) in trisomy 21, 8.6% (IQR, 5.0-10.2%) in trisomy 18 and 7.0% (IQR, 6.0-9.4%) in trisomy 13. There was a failed result from cfDNA testing after first sampling in 2.9% of the unaffected group, 1.9% of trisomy 21, 8.0% of trisomy 18 and 6.3% of trisomy 13. In the cases with a failed result, 7% of women had invasive testing, mainly because of high risk from the combined test and/or presence of sonographic features suggestive of trisomies 18 and 13. All cases of trisomies were detected prenatally.Conclusions: In cases of a failed cfDNA test, the rate of trisomies 18 and 13, but not trisomy 21, is higher than in those with a successful test. In the management of such cases, the decision in favor of invasive testing should depend on the risk of prior screening and the results of detailed ultrasound examination. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background: Uptake rates for Down syndrome screening in the Netherlands are low compared to other European countries. To investigate the low uptake, we explored women's reasons for participation and possible influences of national healthcare system characteristics. Dutch prenatal care is characterised by an approach aimed at a low degree of medicalisation, with pregnant women initially considered to be at low risk. Prenatal screening for Down syndrome is offered to all women, with a 'right not to know' for women who do not want to be informed on this screening. At the time this study was performed, the test was not reimbursed for women aged 35 and younger.Methods: We conducted a qualitative study to explore reasons for participation and possible influences of healthcare system characteristics. Data were collected via ten semi-structured focus groups with women declining or accepting the offer of Down syndrome screening (n = 46). All focus groups were audio- and videotaped, transcribed verbatim, coded and content analysed.Results: Women declining Down syndrome screening did not consider Down syndrome a condition severe enough to justify termination of pregnancy. Young women declining felt supported in their decision by perceived confirmation of their obstetric caregiver and reassured by system characteristics (costs and age restriction). Women accepting Down syndrome screening mainly wanted to be reassured or be prepared to care for a child with Down syndrome. By weighing up the pros and cons of testing, obstetric caregivers supported young women who accepted in the decision-making process. This was helpful, although some felt the need to defend their decision to accept the test offer due to their young age. For some young women accepting testing, costs were considered a disincentive to participate.Conclusions: Presentation of prenatal screening affects how the offer is attended to, perceived and utilised. By offering screening with age restriction and additional costs, declining is considered the preferred choice, which might account for low Dutch uptake rates. Autonomous and informed decision-making in Down syndrome screening should be based on the personal interest in knowing the individual risk of having a child with Down syndrome and system characteristics should not influence participation. [ABSTRACT FROM AUTHOR]

Non-invasive prenatal screening (NIPS) has the potential to dramatically increase the prenatal detection rate of Down syndrome because of improvements in safety and accuracy over existing tests. There is concern that NIPS could lead to more negative attitudes towards Down syndrome and less support for individuals with Down syndrome. To assess the impact of NIPS on support for prenatal testing, decision-making about testing, and beliefs or attitudes about Down syndrome, we performed an Internet-based experiment using adults (N = 1,789) recruited through Amazon Mechanical Turk. Participants were randomly assigned to read a mock news article about NIPS, a mock news article about amniocentesis, or no article. The content in the two articles varied only in their descriptions of the test characteristics. Participants then answered questions about their support for testing, hypothetical testing decision, and beliefs and attitudes about Down syndrome. Reading the mock NIPS news article predicted increased hypothetical test uptake. In addition, the NIPS article group also agreed more strongly that pregnant women, in general, should utilize prenatal testing. We also found that the more strongly participants supported prenatal testing for pregnant women, the less favorable their attitudes towards individuals with Down syndrome; providing some evidence that NIPS may indirectly result in more negative perceptions of individuals with this diagnosis. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Down syndrome (DS) is the most common congenital anomaly widely studied for at least 150 years. However, the type and the frequency of congenital anomalies associated with DS are still controversial. Despite prenatal diagnosis and elective termination of pregnancy for fetal anomalies, in Europe, from 2008 to 2012 the live birth prevalence of DS per 10,000 was 10. 2. The objectives of this study were to examine the major congenital anomalies occurring in infants and fetuses with Down syndrome. The material for this study came from 402,532 consecutive pregnancies of known outcome registered by our registry of congenital anomalies between 1979 and 2008. Four hundred sixty seven (64%) out of the 728 cases with DS registered had at least one major associated congenital anomaly. The most common associated anomalies were cardiac anomalies, 323 cases (44%), followed by digestive system anomalies, 42 cases (6%), musculoskeletal system anomalies, 35 cases (5%), urinary system anomalies, 28 cases (4%), respiratory system anomalies, 13 cases (2%), and other system anomalies, 26 cases (3.6%). Among the cases with DS with congenital heart defects, the most common cardiac anomaly was atrioventricular septal defect (30%) followed by atrial septum defect (25%), ventricular septal defect (22%), patent ductus arteriosus (5%), coarctation of aorta (5%), and tetralogy of Fallot (3%). Among the cases with DS with a digestive system anomaly recorded, duodenal atresia (67%), Hirschsprung disease (14%), and tracheo-esophageal atresia (10%) were the most common. Fourteen (2%) of the cases with DS had an obstructive anomaly of the renal pelvis, including hydronephrosis. The other most common anomalies associated with cases with DS were syndactyly, club foot, polydactyly, limb reduction, cataract, hydrocephaly, cleft palate, hypospadias and diaphragmatic hernia. Many studies to assess the anomalies associated with DS have reported various results. There is no agreement in the literature as to which associated anomalies are most common in cases with DS with associated anomalies. In this study we observed a higher percentage of associated anomalies than in the other reported series as well as an increase in the incidence of duodenal atresia, urinary system anomalies, musculoskeletal system anomalies, and respiratory system anomalies, and a decrease in the incidence of anal atresia, annular pancreas, and limb reduction defects. In conclusion, we observed a high prevalence of total congenital anomalies and specific patterns of malformations associated with Down syndrome which emphasizes the need to evaluate carefully all cases with Down syndrome for possible associated major congenital anomalies. [ABSTRACT FROM AUTHOR]

Background: Down syndrome (DS) is one of the most common chromosomal abnormalities among newborns. In recent years advances in perinatal and neonatal care have improved chance of survival for the children with DS. The objective of this Registry-Based study was to get more accurate data of DS prevalence with evaluation of antenatal screening, neonatal and maternal features among total births in Croatia from 2009 to 2012. Methods: We used retrospectively collected data for DS newborns from the medical birth database and perinatal mortality database for the period of 2009-2012. Differences between DS and the referent population for each year in quantitative measures were assessed with the independent t-test. Other differences in nominal and categorical values were analyzed with the chi-square test. Results: The total prevalence for DS in the period of 2009-2012 was 7.01 per 10,000 births, while the live-birth prevalence was 6.49 per 10,000 births. The significant differences (p < 0.05) between the DS and reference populations for each year were noticed for birth weight and length, gestational age, mother age, Apgar score of ≥6 after 5 min and breastfeeding. Among newborns with DS, there were 64 (53.33 %) males and 56 (46.67 %) females versus 88,587 (51.76 %) males and 82,553 (48.23 %) females in the reference population. In the DS group compared to the reference population the mean birth weight was 2845 grams versus 3467 grams in males and 2834 grams versus 3329 grams in females, respectively, with a mean birth length of 47 cm versus 50 cm for both genders. The mean gestational age of the DS births was 37 weeks and the mean age of the mothers was 32.6 years, versus 39 weeks and 29.1 years, respectively, in the reference population. Only 68.3 % of children with DS were breastfed from birth, compared with 94.72 % of children in the reference population. Conclusions: The significant differences for neonatal and maternal features between DS and the referent population were found similar to other studies. The total prevalence of DS in Croatia in the period of 2009-2012 was lower than the previously estimated prevalence based on EUROCAT data. The establishment of a new national registry of congenital malformations covering 99 % of all births in Croatia is necessary to improve the health and prosperity of children, adolescents and adults with DS in Croatia. [ABSTRACT FROM AUTHOR]

Background: Prenatal screening tests for Down syndrome (DS) are routine in many developed countries and new tests are rapidly becoming available. Decisions about prenatal screening are increasingly complex with each successive test, and pregnant women need information about risks and benefits as well as clarity about their values. Decision aids (DAs) can help healthcare providers support women in this decision. Using an environmental scan, we aimed to identify publicly available DAs focusing on prenatal screening/diagnosis for Down syndrome that provide effective support for decision making.Methods: Data sources searched were the Decision Aids Library Inventory (DALI) of the Ottawa Patient Decision Aids Research Group at the Ottawa Health Research Institute; Google searches on the internet; professional organizations, academic institutions and other experts in the field; and references in existing systematic reviews on DAs. Eligible DAs targeted pregnant women, focused on prenatal screening and/or diagnosis, applied to tests for fetal abnormalities or aneuploidies, and were in French, English, Spanish or Portuguese. Pairs of reviewers independently identified eligible DAs and extracted characteristics including the presence of practical decision support tools and features to aid comprehension. They then performed quality assessment using the 16 minimum standards established by the International Patient Decision Aids Standards (IPDASi v4.0).Results: Of 543 potentially eligible DAs (512 in DALI, 27 from experts, and four on the internet), 23 were eligible and 20 were available for data extraction. DAs were developed from 1996 to 2013 in six countries (UK, USA, Canada, Australia, Sweden, and France). Five DAs were for prenatal screening, three for prenatal diagnosis and 12 for both). Eight contained values clarification methods (personal worksheets). The 20 DAs scored a median of 10/16 (range 6-15) on the 16 IPDAS minimum standards.Discussion: None of the 20 included DAs met all 16 IPDAS minimum standards, and few included practical decision support tools or aids to comprehension.Conclusions: Our results indicate there is a need for DAs that effectively support decision making regarding prenatal testing for Down syndrome, especially in light of the recently available non-invasive prenatal screening tests. [ABSTRACT FROM AUTHOR]