Search

Background: Despite the increased risk for pulmonary hypertension in children with Down syndrome, the response to treatment with targeted therapies for pulmonary hypertension in these patients is not well characterized. The Sildenafil in Treatment-naive children, Aged 1-17 years, with pulmonary arterial hypertension (STARTS-1) trial was a dose-ranging study of the short-term efficacy and safety of oral sildenafil in children with pulmonary arterial hypertension. We assessed the safety and efficacy of oral sildenafil in children with Down syndrome and pulmonary arterial hypertension.Methods: This was a post-hoc analysis of children with Down syndrome and pulmonary arterial hypertension enrolled in the STARTS-1 trial. Mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance index (PVRI), and cardiac index (CI) were assessed at baseline and following 16 weeks of treatment with sildenafil.Results: Of 234 patients randomized and treated in the STARTS-1 trial, 48 (20.5%) had Down syndrome. Although sildenafil produced dose-related reductions in PVRI and mPAP, compared with placebo, in non-Down syndrome patients and children developmentally able to exercise, this was not satisfactorily marked in patients with Down syndrome. The dose-related reductions in PVRI, compared with placebo, occurred in all subgroups, with the exception of the Down syndrome subgroup. Sildenafil appeared to be well tolerated in the Down syndrome subpopulation and the most frequently reported AEs were similar to those reported for the entire STARTS-1 population.Conclusion: Sildenafil treatment for 16 weeks had no effect on PVRI or mPAP in children with Down syndrome and pulmonary arterial hypertension. The results suggest that children with Down syndrome may be less responsive to sildenafil for pulmonary arterial hypertension, but the incomplete work-up for the etiology of pulmonary arterial hypertension may have introduced a potential bias.Trial Registration: Study received, September 8, 2005 (retrospectively registered); Study start, August 2003; ClinicalTrials.gov identifier, NCT00159913 . [ABSTRACT FROM AUTHOR]

Objective: To assess the feasibility and performance of the first-trimester combined screening test for trisomy 21 in a resource-limited setting in mainland China.Design: Prospective observational cohort study.Setting: First Affiliated Hospital of Kunming Medical University, China.Population: Ten thousand four hundred and forty-two pregnant women requesting first-trimester screening.Methods: The combined screening test was performed from May 2012 to December 2014. Women with a high-risk result (≥1:600) were offered further confirmatory tests after counselling. The threshold for high risk was determined by Monte Carlo simulation to achieve a 5% false-positive rate according to the local age distribution. Pregnancy outcome and screening results were recorded for all women and monthly audits were conducted.Main Outcome Measures: Sensitivity, screen positive rate, cost per case of Down syndrome detected.Results: Six hundred and ten women (5.8% of the total screened) had a high-risk screening test, of whom 274 (44.9%) underwent a diagnostic test and 169 (27.7%) opted for a noninvasive prenatal screening test (NIPT); 160 (26.2%) declined further testing after counselling. The pregnancy outcome was available for 10 174 (97.4%) of the women. The observed incidence of Down syndrome was 0.13% (1/750). All 14 women with a trisomy 21 pregnancy had a high-risk screening test result. The cost per Down syndrome detected was RMB596 686 compared with RMB1.79 million if all had been screened by NIPT.Conclusions: The combined screening test appears to be a more cost-effective strategy in mainland China. Screening performance in China would be improved by adopting Chinese-specific models, external quality control and assurance, and establishing risk thresholds appropriate for the age distribution of the population.Tweetable Abstract: Combined first-trimester Downs screening in China was improved by adopting Chinese-specific models and external QC. [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]

Objective: The objective of the study is to report the performance of noninvasive prenatal testing (NIPT) in twin pregnancies after the treatment of assisted reproductive technology (ART).Method: In two years period, 565 pregnant women with ART twin pregnancies were prospectively tested by NIPT for screening for trisomy 21 (T21), 18 (T18), and 13 (T13) by sequencing cell-free DNA in maternal plasma. Positive NIPT results were confirmed by karyotyping, while negative results were interviewed after delivery. Pregnant decision based on NIPT and confirmation results was discussed during post-test counseling.Results: In total of 565 cases, NIPT had a failure rate of 0.9% (5/565). Four cases of T21 were identified by NIPT and confirmed by karyotyping, resulting in 100% (95%CI 39.8%-100%) positive predictive value. Among 556 cases with NIPT negative results, 506 cases (91.0%) were confirmed by follow-up of postnatal phenotypes, while 33 cases (5.9%) had adverse pregnant outcomes with unconfirmed reasons because of the lack of cytogenetic samples. The remaining 17 cases (3.1%) refused follow-up. No false negative result was reported.Conclusion: With apparently high positive predictive value and low false positive rate, NIPT has the potential to be used as a good alternative approach of conventional prenatal screening at the first trimester in ART twin pregnancy. © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the potential of maternal serum placental growth factor (PlGF) as a marker for Trisomy 21 in Chinese pregnant women.Study Design: Serum samples were collected and stored from 600 women who have a viable singleton pregnancy and underwent first trimester screening for Trisomy 21 between 2011 and 2014. Serum concentration of PlGF was measured using the automated time-solved immunofluorometric assay and expressed as Multiples of the expected median (MoM) from the 600 women available stored serum samples (558 Euploidy and 42 Trisomy 21). The levels of PlGF MoM were compared between Trisomy 21 cases and Euploid pregnancies. Expected median PlGF levels in Chinese were also compared to that published for Caucasians. Multivariate Gaussian modeling was performed to predict detection and false-positive rates.Results: In euploid pregnancies the concentrations of PlGF increased with Crown Rump Length(CRL) and decreased with maternal weight. The overall median MoM of PlGF in Chinese was higher than that of Caucasian. The median PlGF level was 0.63 MoM in the cases and 1.00 MoM in the controls (p<0.0001). The prediction of Trisomy 21 has been slightly improved by the addition of PlGF to the standard screening test in China. The detection rate of screening after adding PlGF data was increased from 93.4% to 94.6% at a false-positive rate of 3% and the false positive rate decreased from 0.23% to 0.17% for a detection rate of 80%.Conclusion: The median PlGF concentrations in Chinese is higher than those of Caucasians. Results suggest adding PlGF may substantially improve the performance of current first trimester screening strategy for Trisomy 21 in Chinese pregnant women. [ABSTRACT FROM AUTHOR]

Background: Knowledge of the factors that influence maternal serum screening (MSS) service utilization can be used to develop health policies to promote equitable access to MSS and further diagnostic tests. The purpose of this study was to find the factors associated with utilization of MSS as well as the current status of service utilization in mainland China.Methods: This was a hospital-based cross-sectional study with respondents interviewed with a questionnaire designed based on Andersen's behavioral model. Descriptive statistics, univariate analysis, and multilevel logistic regression analysis were used to identify the factors associated with MSS utilization, and to explore potential methods to improve screening uptake.Results: A total of 8110 women who had given birth within the previous 7 days in one of 111 participating institutions from six provinces in mainland China were interviewed. Approximately 36% of the participants had used MSS. Women between 20 and 35 years, who resided in urban areas, were educated, were in a stable occupation, who had health knowledge, who attended maternal preparation classes, who had received eight or more prenatal checkups, who were from a region of higher social economic status, and who delivered in a tertiary healthcare institution were significantly more likely to use MSS than their counterparts. As compared with other factors, insufficient education is the single most important demographic factor for service underutilization.Conclusions: Efforts should not only be made to target the population that underuses MSS, but the overall organization of MSS service delivery should be assessed during policy development to make access to MSS equitable to the entire population of mainland China. [ABSTRACT FROM AUTHOR]

Objective To compare the effectiveness of first trimester, second trimester, and integrated screening for Down's syndrome. Setting Two prenatal diagnosis centres in China. Methods A total of 11,966 pregnant women (≥ 18 years) were screened over 21 months. First trimester screening (11-13 weeks) comprised measurement of serum free beta-human chorionic gonadotrophin (β-hCG) and pregnancy-associated protein-A concentrations, and fetal nuchal translucency thickness. Second trimester screening (15-20 weeks) comprised measurement of β-hCG and alpha fetoprotein concentrations. Computer software was used to calculate the risk of carrying a Down's syndrome fetus. Results The overall incidence of Down's syndrome was 0.2% (23/11,966). When the false-positive rate was fixed at 5%, detection rates for first trimester, second trimester, and integrated screening were 73.9%, 69.6%, and 82.6%, respectively. When the false-positive rate was fixed at 3%, detection/ sensitivity rates for first trimester, second trimester, and integrated screening were 65.2%, 56.5%, and 73.9%, respectively. Conclusions These findings suggest that integrated screening was the most effective means of screening for Down's syndrome in a Chinese population. [ABSTRACT FROM AUTHOR]

Objective: To determine the influence of free invasive prenatal testing on the uptake of non-invasive prenatal testing (NIPT).Study Design: Over a 2-year period at a Chinese tertiary prenatal diagnostic unit, women at risk of fetal trisomy were given the option of NIPT or invasive prenatal testing. Invasive prenatal testing was offered free of charge to women with a local Hukou (household registration); however, women without a local Hukou were charged for invasive prenatal testing. Both women with and without a local Hukou were charged for NIPT.Results: During the first year, 2647 women with a positive trisomy 21 screening test were referred (474 women with a local Hukou and 2173 women without a local Hukou). Only 1.6% of the women with a local Hukou underwent NIPT, while this proportion was 20.6% in the women without a local Hukou. During the second year, the price of NIPT was reduced. The total number of women referred was 3047 (502 women with a local Hukou and 2545 women without a local Hukou). The uptake of NIPT in women without a local Hukou doubled, but the uptake of NIPT remained stable in women with a local Hukou.Conclusion: The financial impact on the uptake of NIPT should not be underestimated. [ABSTRACT FROM AUTHOR]

Objective: To determine the best weight-correction model by means of analyzing the relationship between maternal weight and maternal serum markers when screening for Down syndrome in China.Methods: Serum levels of alpha-fetoprotein (AFP) and free beta-human chorionic gonadotropin (hCG) were measured in 35,917 Chinese women during the second semester of a normal singleton pregnancy and converted to multiple of median (MoM) values. Using 2 methods of statistical analysis, the all-point method and the median regression method, 4 weight-correction models were then tried, the simple linear, reciprocal, quadratic, and log-linear regression models.Results: The median regression method performed better than the all-point method, and the quadratic regression model showed the best fit for both AFP and hCG in the median regression method, with adjusted R(2)s of 0.987 and 0.988, respectively.Conclusion: The quadratic regression model was found to be the most suitable for Chinese pregnant women. [ABSTRACT FROM AUTHOR]

Objectives: To compare the performance of double screening (measuring maternal serum levels of alpha-fetoprotein [AFP] and total beta-human chorionic gonadotrophin [hCG] as markers for Down syndrome) with that of triple screening (also measuring levels of unconjugated estriol [uE3]) in the second trimester of pregnancy, and to compare ethnic variance between Chinese and Caucasian populations.Methods: The study investigated 15096 normal singleton pregnancies and 24 pregnancies affected with Down syndrome. Frequency distributions of AFP, hCG, and uE3 levels were analyzed. Likelihood ratios (LRs) were calculated using the multiple of median value (MoM) of AFP, hCG, and uE3 as variables. After multiplying maternal age risk by the LR values for the markers used in double and triple screening, the specific risks obtained with double and triple screening were estimated. The detection rate (DR) and false-positive rate (FPR) were calculated at different cut-off points. The serum markers' levels were also compared with those of Caucasian women.Results: The median MoM value of hCG was higher in women with affected pregnancies (1.40) than those with unaffected pregnancies (1.00). However, the median MoMs of AFP and uE3 (0.79 and 0.68) were lower in affected than in unaffected pregnancies. At a FPR of 5%, the detection rates reached with double and triple screening were 50% and 66.7%, respectively. Ratios of the 3 serum markers' medians to those in a study with Caucasian women were 1.06 (range=1.04-1.09) for AFP, 1.14 (range=1.10-1.17) for hCG, and 1.28 (range=1.23-1.41) for uE3 for the relevant gestational weeks.Conclusion: Triple screening performed better than double screening in the second trimester. Ethnic variance should be taken into account in Down syndrome screening. [ABSTRACT FROM AUTHOR]

Background: Next-generation sequencing is emerging as a viable alternative to chromosome microarray analysis for the diagnosis of chromosome disease syndromes. One next-generation sequencing methodology, copy number variation sequencing, has been shown to deliver high reliability, accuracy, and reproducibility for detection of fetal copy number variations in prenatal samples. However, its clinical utility as a first-tier diagnostic method has yet to be demonstrated in a large cohort of pregnant women referred for fetal chromosome testing.Objective: We sought to evaluate copy number variation sequencing as a first-tier diagnostic method for detection of fetal chromosome anomalies in a general population of pregnant women with high-risk prenatal indications.Study Design: This was a prospective analysis of 3429 pregnant women referred for amniocentesis and fetal chromosome testing for different risk indications, including advanced maternal age, high-risk maternal serum screening, and positivity for an ultrasound soft marker. Amniocentesis was performed by standard procedures. Amniocyte DNA was analyzed by copy number variation sequencing with a chromosome resolution of 0.1 Mb. Fetal chromosome anomalies including whole chromosome aneuploidy and segmental imbalances were independently confirmed by gold standard cytogenetic and molecular methods and their pathogenicity determined following guidelines of the American College of Medical Genetics for sequence variants.Results: Clear interpretable copy number variation sequencing results were obtained for all 3429 amniocentesis samples. Copy number variation sequencing identified 3293 samples (96%) with a normal molecular karyotype and 136 samples (4%) with an altered molecular karyotype. A total of 146 fetal chromosome anomalies were detected, comprising 46 whole chromosome aneuploidies (pathogenic), 29 submicroscopic microdeletions/microduplications with known or suspected associations with chromosome disease syndromes (pathogenic), 22 other microdeletions/microduplications (likely pathogenic), and 49 variants of uncertain significance. Overall, the cumulative frequency of pathogenic/likely pathogenic and variants of uncertain significance chromosome anomalies in the patient cohort was 2.83% and 1.43%, respectively. In the 3 high-risk advanced maternal age, high-risk maternal serum screening, and ultrasound soft marker groups, the most common whole chromosome aneuploidy detected was trisomy 21, followed by sex chromosome aneuploidies, trisomy 18, and trisomy 13. Across all clinical indications, there was a similar incidence of submicroscopic copy number variations, with approximately equal proportions of pathogenic/likely pathogenic and variants of uncertain significance copy number variations. If karyotyping had been used as an alternate cytogenetics detection method, copy number variation sequencing would have returned a 1% higher yield of pathogenic or likely pathogenic copy number variations.Conclusion: In a large prospective clinical study, copy number variation sequencing delivered high reliability and accuracy for identifying clinically significant fetal anomalies in prenatal samples. Based on key performance criteria, copy number variation sequencing appears to be a well-suited methodology for first-tier diagnosis of pregnant women in the general population at risk of having a suspected fetal chromosome abnormality. [ABSTRACT FROM AUTHOR]

Reports on the claims by a team of medical researchers in Hong Kong that they have developed a non-invasive diagnostic technique by which fetal DNA can be tested for Down's syndrome as early as the first trimester. Use of fluorescence in situ hybridisation (FISH) technology; Belief of the researchers that plasma is not entirely acellular, as was previously thought; Skepticism of the medical community.