Clinical Implementation of Expanded Carrier Screening in Pregnant Women at Early Gestational Weeks: A Chinese Cohort Study.
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SUBMITTER: Shi M
PROVIDER: S-EPMC8066122 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveRecessive genetic diseases impose physical and psychological impacts to both newborns and parents who may not be aware of being carriers. Expanded carrier screening (ECS) allows screening for multiple genetic conditions at the same time. Whether or not such non-targeted panethnic approach of genetic carrier screening should replace the conventional targeted approach remains controversial. There is limited data on view and acceptance of ECS in general population, as well as the optimal timing of offering ECS to women. This study assesses views and acceptance of ECS in both pregnant women and non-pregnant women seeking fertility counseling or checkup and their reasons for accepting or declining ECS.Materials and methodsThis is a questionnaire survey with ECS information in the form of pamphlets distributed from December 2016 to end of 2018. Women were recruited from the antenatal clinics and the assisted reproductive unit at the Department of Obstetrics and Gynaecology, Queen Mary Hospital and the prepregnancy counseling clinic at the Family Planning Association of Hong Kong.ResultsA total of 923 women were recruited: 623 pregnant women and 300 non-pregnant women. There were significantly more non-pregnant women accepting ECS compared to pregnant women (70.7% vs. 61.2%). Eight hundred and sixty-eight (94%) women perceived ECS as at least as effective as or superior to traditional targeted screening. Significantly more pregnant women have heard about ECS compared with non-pregnant women (42.4% vs. 32.3%, P = 0.0197). Majority of women showed lack of understanding about ECS despite reading pamphlets that were given to them prior to filling in the questionnaires. Cost of ECS was a major reason for declining ECS, 28% (n = 256). Significantly more pregnant women worried about anxiety caused by ECS compared with the non-pregnant group (21.1% vs. 7.4%, P = 0.0006).ConclusionOur study demonstrates that expanded carrier screening was perceived as a better screening by most women. Prepregnancy ECS maybe a better approach than ECS during pregnancy, as it allows more reproductive options and may cause less anxiety. Nevertheless, implementation of universal panethnic ECS will need more patient education, ways to reduce anxiety, and consensus on optimal timing in offering ECS.
| S-EPMC7701308 | biostudies-literature
Project description:Fragile X syndrome (FXS) is the most frequent genetic cause of intellectual disability (ID). It was previously believed that the FXS prevalence was low in Chinese population, and the cost-efficiency of FXS carrier screening was questioned. This retrospective observational study was conducted between September 2014 and May 2017 to determine the prevalence of FXS carriers in a large Chinese cohort of pregnant women. The FMR1 CGG repeat status was determined in 20,188 pregnant Taiwanese women and we identified 26 women with premutation (PM). The PM allele was transmitted to the fetus in 17 pregnancies (56.6%), and six of 17 expanded to full mutation (FM). One asymptomatic woman had a FM allele with 280 CGG repeats. Prenatal genetic diagnosis of her first fetus revealed a male carrying a FMR1 gene deletion of 5' UTR and exon 1. Her second fetus was a female carrying a FM allele as well. This is so far the largest study of the FXS carrier screening in Chinese women. The prevalence of premutation allele for FXS in normal asymptomatic Taiwanese women was found to be as high as 0.13% (1 in 777) in this study. The empirical evidence suggests that reproductive FXS carrier screening in Taiwan might be cost-effective.
| S-EPMC6820721 | biostudies-literature
Project description:BackgroundExpanded carrier screening can provide risk information for numerous conditions. Understanding how individuals undergoing preconception expanded carrier screening value this information is important. The NextGen study evaluated the use of genome sequencing for expanded carrier screening and reporting secondary findings, and we measured participants' willingness to pay for this approach to understand how it is valued by women and couples planning a pregnancy.MethodsWe assessed 277 participants' willingness to pay for genome sequencing reporting carrier results for 728 gene/condition pairs and results for 121 secondary findings. We explored the association between attitudes and demographic factors and willingness to pay for expanded carrier screening using genome sequencing and conducted interviews with 58 of these participants to probe the reasoning behind their preferences.ResultsMost participants were willing to pay for expanded carrier screening using genome sequencing. Willingness to pay was associated with income level and religiosity, but not risk status for a condition in the carrier panel. Participants willing to pay nothing or a small amount cited issues around financial resources, whereas those willing to pay higher amounts were motivated by "peace of mind" from carrier results.ConclusionWomen and couples planning a pregnancy value genome sequencing. The potentially high out-of-pocket cost of this service could result in healthcare disparities, since maximum amounts that participants were willing to pay were higher than a typical copay and related to income.
| S-EPMC6051630 | biostudies-literature
Project description:Gestational diabetes mellitus (GDM) is closely related to adverse pregnancy outcomes and other diseases. Early intervention in pregnant women who are at high risk of developing GDM could help prevent adverse health consequences. The study aims to develop a simple model using the stacking ensemble method to predict GDM for women in the first trimester based on easily available factors. We used the data from the Chinese Pregnant Women Cohort Study from July 2017 to November 2018. A total of 6,848 pregnant women in the first trimester were included in the analysis. Logistic regression (LR), random forest (RF), and extreme gradient boosting (XGBoost) were considered as base learners. Optimal feature subsets for each learner were chosen by using recursive feature elimination cross-validation. Then, we built a pipeline to process imbalance data, tune hyperparameters, and evaluate model performance. The learners with the best hyperparameters were employed in the first layer of the proposed stacking method. Their predictions were obtained using optimal feature subsets and served as meta-learner's inputs. Another LR was used as a meta-learner to obtain the final prediction results. Accuracy, specificity, error rate, and other metrics were calculated to evaluate the performance of the models. A paired samples t-test was performed to compare the model performance. In total, 967 (14.12%) women developed GDM. For base learners, the RF model had the highest accuracy (0.638 (95% confidence interval (CI) 0.628-0.648)) and specificity (0.683 (0.669-0.698)) and lowest error rate (0.362 (0.352-0.372)). The stacking method effectively improved the accuracy (0.666 (95% CI 0.663-0.670)) and specificity (0.725 (0.721-0.729)) and decreased the error rate (0.333 (0.330-0.337)). The differences in the performance between the stacking method and RF were statistically significant. Our proposed stacking method based on easily available factors has better performance than other learners such as RF.
| S-EPMC9489389 | biostudies-literature
Project description:BackgroundCarrier screening for autosomal recessive disorders aims to facilitate reproductive decision-making by identifying couples with a 1-in-4 risk in every pregnancy of having an affected child. Except for a few countries or regions, carrier screening is not widely offered and is mostly ancestry-based. Technological advances enable carrier screening for multiple diseases simultaneously allowing universal screening regardless of ancestry (population-based expanded carrier screening). It is important to study how this can be successfully implemented. This study therefore aims to identify critical factors involved in successful implementation, from a user perspective, by learning from already implemented initiatives.MethodsFactors associated with successful implementation were identified by: (i) a literature review and (ii) two case studies; studying experiences with carrier screening in two high-risk communities (a Dutch founder population and the Ashkenazi Jewish population), including a survey among community members.ResultsFactors identified were familiarity with (specific) genetic diseases and its availability, high perceived benefits of screening (e.g. screening avoids much suffering), acceptance of reproductive options, perceived risk of being a carrier and low perceived social barriers (e.g. stigmatization). In contrast to the Jewish community, the initial demand for screening in the Dutch founder population did not entirely come from the community itself. However, the large social cohesion of the community facilitated the implementation process.ConclusionTo ensure successful implementation of population-based expanded carrier screening, efforts should be made to increase knowledge about genetic diseases, create awareness and address personal benefits of screening in a non-directive way.
| S-EPMC5421354 | biostudies-literature
Project description:BackgroundExpanded carrier screening (ECS) has emerged as an effective approach to identify at-risk couples (ARCs)-before they initiate attempts at reproduction-who possess a high probability of having a child affected by severe recessive diseases. The objective of this study was to evaluate the clinical utility of ECS in Chinese patients seeking the help of assisted reproductive technology (ART).MethodsAn ECS test, which covers 201 genes implicated in 135 recessive (autosomal or X-linked) diseases, was routinely offered to all ART patients in a single genetics and in vitro fertilization clinic. Additional options for preimplantation or prenatal genetic diagnosis were discussed and offered to all ARCs. All ECS results were aggregated and the clinical decisions of the ARCs were surveyed.ResultsA total of 2,923 ART patients, representing 1,462 couples, were screened. Overall, 46.73% of the individuals were found to be the carriers for at least 1 of the 135 diseases. Of the tested couples, 2.26% (n = 33) were identified as ARCs. As of the completion of this study, 21 (63.6%) ARCs have decided to avert an affected pregnancy with the help of preimplantation genetic testing for monogenetic conditions. The cumulative carrier rate of the 187 autosomal recessive genes in the ECS panel for the 2,836 Han Chinese individuals without a family history was estimated to be 45.91%. The estimated at-risk couple rate indicates that the screening for only the top 31 genes with gene carrier rates >0.5% would identify more than 94% of the ARCs identified by screening all 187 genes.ConclusionOur study demonstrates that ESC yields a significant clinical value for ART patients in China. In addition, by estimating the yields of the ECS panel, we identify genes that are appropriate for screening the Han population.
| S-EPMC7507411 | biostudies-literature
Project description:IntroductionFragile X syndrome (FXS) is the leading cause of inherited intellectual and developmental disability. Policy development relating to carrier screening programmes for FXS requires input from large studies examining not only test uptake but also psychosocial aspects. This study will compare carrier screening in pregnant and non-pregnant populations, examining informed decision-making, psychosocial issues and health economics.Methods and analysisPregnant and non-pregnant women are being recruited from general practices and obstetric services. Women receive study information either in person or through clinic mail outs. Women are provided pretest counselling by a genetic counsellor and make a decision about testing in their own time. Data are being collected from two questionnaires: one completed at the time of making the decision about testing and the second 1 month later. Additional data are gathered through qualitative interviews conducted at several time points with a subset of participating women, including all women with a positive test result, and with staff from recruiting clinics. A minimum sample size of 500 women/group has been calculated to give us 88% power to detect a 10% difference in test uptake and 87% power to detect a 10% difference in informed choice between the pregnant and non-pregnant groups. Questionnaire data will be analysed using descriptive statistics and multivariate logistic regression models. Interview data will be thematically analysed. Willingness-to-pay and cost effectiveness analyses will also be performed. Recruitment started in July 2009 and data collection will be completed by December 2013.Ethics and disseminationEthics approval has been granted by the Universities of Melbourne and Western Australia and by recruiting clinics, where required. Results will be reported in peer-reviewed publications, conference presentations and through a website http://www.fragilexscreening.net.au. The results of this study will make a significant contribution to discussions about the wider introduction of population carrier screening for FXS.
| S-EPMC3773647 | biostudies-literature
Project description:BackgroundGrowing evidence suggests that dietary acid load plays an important role in the development of type 2 diabetes. However, prospective studies on the relationship between dietary acid load and gestational diabetes mellitus (GDM) are limited in the pregnant population. This study aimed to investigate the effect of dietary acid load during early pregnancy on the risk of GDM in Chinese pregnant women.MethodsA total of 1,327 pregnant women were enrolled from an ongoing prospective study of the Tongji Birth cohort (TJBC) in Wuhan, China. Dietary intake was assessed before 20 weeks using a 74-item semiquantitative food frequency questionnaire (FFQ). The dietary acid load was estimated using potential renal acid load (PRAL), net endogenous acid production (NEAP), and animal protein to potassium ratio (A:P ratio). A 75g 2-h oral glucose tolerance test (OGTT) was performed at 24-28 gestational weeks to diagnose GDM.ResultsThe mean (standard deviation) values for PRAL score, NEAP score, and A:P ratio were 0.8 ± 11.3 mEq/day, 45.3 ± 16.5 mEq/day, and 9.8 ± 6.0, respectively. There was a significant positive correlation of dietary acid load with the intake of red meat, poultry, fish, and eggs, and a negative correlation with the intake of vegetables, fruits, nuts, and legumes (all P < 0.05). Compared to the lowest tertile, the highest tertile of dietary acid load, including PRAL score (odds ratio [OR]: 2.26, 95% confidence interval [CI] = 1.38-3.71, P-trend = 0.002), NEAP score (OR: 2.02, 95% CI = 1.25-3.27, P-trend = 0.009), and A:P ratio (2.08, 95% CI = 1.30-3.31, P-trend = 0.005), significantly increased the risk of GDM. In addition, the dietary acid load was also significantly associated with an increase in 1-h and 2-h post-load blood glucose concentrations (all P-trend < 0.05).ConclusionWe found a significant positive association between dietary acid load during early pregnancy and the risk of GDM in a Chinese population, suggesting that the reduction of food sources of dietary acid load may be an effective strategy for preventing the risk of GDM.
| S-EPMC9184257 | biostudies-literature
Project description:Next generation sequencing (NGS) can detect carrier status for rare recessive disorders, informing couples about their reproductive risk. The recent ACMG recommendations support offering NGS-based carrier screening (NGS-CS) in an ethnic and population-neutral manner for all genes that have a carrier frequency >1/200 (based on GnomAD). To evaluate current challenges for NGS-CS, we focused on the ciliopathies, a well-studied group of rare recessive disorders. We analyzed 118 ciliopathy genes by whole exome sequencing in ~400 healthy local individuals and ~1000 individuals from the UK1958-birth cohort. We found 20% of healthy individuals (1% of couples) to be carriers of reportable variants in a ciliopathy gene, while 50% (4% of couples) carry variants of uncertain significance (VUS). This large proportion of VUS is partly explained by the limited utility of the ACMG/AMP variant-interpretation criteria in healthy individuals, where phenotypic match or segregation criteria cannot be used. Most missense variants are thus classified as VUS and not reported, which reduces the negative predictive value of the screening test. We show how gene-specific variation patterns and structural protein information can help prioritize variants most likely to be disease-causing, for (future) functional assays. Even when considering only strictly pathogenic variants, the observed carrier frequency is substantially higher than expected based on estimated disease prevalence, challenging the 1/200 carrier frequency cut-off proposed for choice of genes to screen. Given the challenges linked to variant interpretation in healthy individuals and the uncertainties about true carrier frequencies, genetic counseling must clearly disclose these limitations of NGS-CS.
| S-EPMC10400553 | biostudies-literature
Project description:ObjectiveThis study aims to explore barriers to controlling gestational weight gain in pregnant Chinese women.DesignData were collected through semistructured interviews with pregnant women experiencing excessive gestational weight gain who struggled with weight management, and the data were examined using an interpretive content analysis.Settings and participantsFifty participants (≥18 years, with excessive gestational weight gain) were recruited when they visited the hospital for antenatal health checkups in Wuhan city (n=36) and Jinan city (n=14) between September and October 2018.ResultsInterpretive content analysis identified 75 barriers after examining diet, physical activity levels and general issues stemming from knowledge and beliefs, and physical, social, logistical, emotional and structural characteristics. Compared with reported deductive codes, this study inductively extracted 15 new codes. The most frequent codes showed that expectant grandparents greatly influenced pregnant women's lifestyles, through overprotection, traditional and conservative ideas and practices, and a lack of reliable knowledge or acceptable guidance on gestational weight control.ConclusionsThis study provides a better understanding of the most important obstacles faced during decision making about gestational weight control in Chinese settings, especially the influence of traditional ideas/practices and expectant grandparents. Identifying the specific barriers to weight control should facilitate potential tailored supportive interventions. More efforts on health education for the whole family and a better use of maternal handbooks would be particularly beneficial.
| S-EPMC7733166 | biostudies-literature