International perspectives on the implementation of reproductive carrier screening

Reproductive carrier screening started in some countries in the 1970s for hemoglobinopathies and Tay-Sachs disease. Cystic fibrosis carrier screening became possible in the late 1980s and with technical advances, screening of an ever increasing number of genes has become possible. The goal of carrier screening is to inform people about their risk of having children with autosomal recessive and X-linked recessive disorders, to allow for informed decision making about reproductive options. The consequence may be a decrease in the birth prevalence of these conditions, which has occurred in several countries for some conditions. Different programs target different groups (high school, premarital, couples before conception, couples attending fertility clinics, and pregnant women) as does the governance structure (public health initiative and user pays). Ancestry-based offers of screening are being replaced by expanded carrier screening panels with multiple genes that is independent of ancestry. This review describes screening in Australia, Cyprus, Israel, Italy, Malaysia, the Netherlands, Saudi Arabia, the United Kingdom, and the United States. It provides an insight into the enormous variability in how reproductive carrier screening is offered across the globe. This largely relates to geographical variation in carrier frequencies of genetic conditions and local health care, financial, cultural, and religious factors.     

膳食Cd摄入对土壤筛选值确定的影响

收集了2000~2014年发表的关于国内不同膳食中Cd浓度研究文献,统计出不同区域各种主要膳食中Cd含量,结合2002年开展的膳食总调查结果,计算了不同地区居民膳食Cd暴露量,推导了考虑膳食Cd暴露情景下土壤中Cd的健康风险评估筛选值.结果显示,我国居民膳食Cd摄入量低于FAO/WHO(联合国粮农组织/世界卫生组织)于2010年颁布的允许Cd摄入量0.833μg/(kg体重?d).其中,全国范围内居民膳食Cd摄入量的平均值为0.444μg/(kg体重?d),高于北方[0.240μg/(kg体重?d)]、北京[0.160μg/(kg体重?d)]和上海[0.408μg/(kg体重?d)]地区的平均值,低于南方地区的平均值[0.518μg/(kg体重?d)].全国、北方及南方地区对Cd摄入量贡献最大的膳食主要为蔬菜、米及其制品、面及其制品、水产和肉类;北京地区对Cd摄入贡献较大的膳食依次为蔬菜、面及其制品、水果、米及其制品和水产;上海地区对Cd摄入贡献较大的膳食依次为蔬菜、水产、米及其制品、肉类.考虑膳食Cd摄入后推导的工商业用地情形下的筛选值低于不考虑膳食Cd摄入情形下的推导值(829mg/kg),其中,全国范围、北方、南方、北京和上海地区的筛选值分别为461,630,400,697和492mg/kg.基于不同尺度膳食摄入量的统计结果推导的筛选值差异明显,其中,南方地区筛选值是全国筛选值的86.8%,北方、北京和上海地区分别是全国范围推导值1.4倍、1.5倍和1.1倍.在制订国家层面Cd的筛选值时,应充分考虑各区域膳食Cd的暴露特性,以避免因制订统一值导致高估或低估局部区域居民的健康风险.     

Gender impact on first trimester markers in Down syndrome screening

The influence of fetal gender on the level in the first trimester of the serological markers alpha-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (βhCG) and on nuchal translucency is described for 2637 singleton pregnancies with normal outcome. Mean log MoM values for pregnancies with female and male fetuses were calculated using regression of log marker values on gestational age expressed as crown rump length and on maternal weight. A pronounced gender impact was found for free βhCG, being 16% higher for female than for male fetuses. Copyright © 2002 John Wiley & Sons, Ltd.     

Cell-free DNA screening in twin pregnancies: A more accurate and reliable screening tool

Objective

Outcome data from cell-free DNA (cfDNA) screening in twin gestations are limited. This study adds an appreciable number of confirmed outcomes to the literature, and assesses performance of cfDNA screening in twins over a 4.5-year period at one large clinical laboratory.

Method

Prenatal cytogenetic and SNP microarray results were cross-referenced with cfDNA results for twin pregnancies, yielding 422 matched cases. Using diagnostic results as truth, performance of cfDNA screening in this population was assessed.

Results

Of the 422 twin pregnancies with both cfDNA and diagnostic results, 3 specimens failed amniocyte analysis, and 48 samples (11.5%) were nonreportable from the initial cfDNA draw. Analysis of the 371 reportable samples demonstrated a collective sensitivity of 98.7% and specificity of 93.2% for trisomies 21/18/13. Positive predictive values (PPVs) in this study population, which is enriched for aneuploidy, were 78.7%, 84.6%, and 66.7% for trisomy 21, 18, and 13, respectively.

Conclusion

CfDNA screening in a cohort of twin pregnancies with matched diagnostic results showed superior performance compared to traditional serum biochemical screening in twins. This study adds to a growing body of evidence suggesting that cfDNA is an accurate and reliable screening tool for the major trisomies in twin pregnancies.

     

Prenatal screening for Down syndrome in twin pregnancies: Estimates of screening performance based on 61 affected and 7302 unaffected twin pregnancies

The aims of this study were to determine whether assumptions used in prenatal screening for Down syndrome in twin pregnancies are valid and derive estimates of risk and screening performance in twin pregnancies using observed data. Data were collected on nuchal translucency, chorionicity, pregnancy associated plasma protein-A (PAPP-A), and free ß human chorionic gonadotrophin (free ß-hCG) from 61 twin pregnancies with Down syndrome and 7302 unaffected twin pregnancies. Distribution parameters were determined and used to estimate screening performance. The assumption that proportional differences in serum marker levels in affected and unaffected singleton pregnancies apply to twin pregnancies was not confirmed. Median free β-hCG value in monochorionic affected twin pregnancies (2.63 multiples of the median [MoM]; 95% CI, 1.79-3.22 MoM) was lower than that assuming proportionality (3.76 MoM), and the median PAPP-A value in dichorionic affected twin pregnancies (1.88 MoM; 95% CI, 1.60-2.17 MoM) was higher than that based on proportionality (1.33 MoM). The detection rate was 87% for a 3% false-positive rate in monochorionic twin pregnancies and 74% in dichorionic twin pregnancies compared with 86% in singleton pregnancies. Estimates of screening performance in Down syndrome twin pregnancies do not need to rely on assumptions and can take account of chorionicity and gestational age.     

民用清洁煤技术的定量评价与筛选

选用合适的民用清洁煤技术是提高居民生活用煤能源利用效率、减少环境污染的重要途径之一,本文利用笔者提出的清洁煤技术定量评价方法对民用清洁煤技术进行了定量评价与筛选,评价结果表明,在标准状态下各种民用适用清洁煤技术的单位综合成本分别为选煤48元/GJ,民用型煤45.73元/GJ,炼焦制气28.53元/GJ,加压气化联产甲醇54.73元/GJ,加压气化联产油蜡50.71元/GJ,两段炉气化88.66元/GJ,直立炉气化38.84元/GJ,其中炼焦制气是单位综合成本最小的民用清洁煤技术．敏感度分析表明,煤气化将是民用清洁煤技术的主要发展方向     

Prenatal screening for haemoglobin disorders

The technology has been available to detect carriers of haemoglobin disorders since the late 1960s. Prenatal diagnosis has been available since 1978. First trimester diagnosis by chorionic villus sampling and DNA analysis was introduced in 1982, and subsequent simplifications in DNA technology have made screening, counselling and prenatal diagnosis cost-effective at the community level, in countries at all levels of development. Audit of prenatal diagnosis for haemoglobin disorders in countries which have the resources and infrastructure necessary for genetic population screening (such as the UK and other European countries), has shown that the number of prenatal diagnoses actually performed fall far short of expectation. The demonstration that this reflects failures in delivering information, screening and counselling to the populations at risk, rather than rejection of prenatal diagnosis, shows the importance of placing more emphasis on the organisational and social requirements for genetic population screening. In some countries current attitudes towards abortion exclude provision of prenatal diagnosis within the health service, but in many such cases it has been set up in the private sector. It is also being introduced through combined private and charitable efforts in an increasing number of developing countries, including some with extremely limited health resources: such centres are likely to act as nuclei for emergence of genetics services in these communities. A particularly notable recent achievement is the introduction of prenatal diagnosis in Nigeria, where 1–2% of all children born suffer from sickling disorders.     

Ultrasound screening for fetal abnormalities

Ultrasound screening for fetal abnormalities is increasingly becoming part of routine antenatal care in Europe and the UK. However, there has been very little formal evaluation of this practice. In this article reports of routine ultrasound screening are reviewed and the advantages and disadvantages discussed. The majority of routine anomaly scanning is done in the second trimester but there may be a case for screening at other times in pregnancy and alternative anomaly screening policies are discussed.     

Carrier screening for cystic fibrosis

A number of different models of CF carrier screening have now been tested in pilot trials. Apart from opportunistic and cascade testing (which are strictly speaking not true forms of screening), the major programmes have been directed either to young adults in primary care or to pregnant women in antenatal clinics. Only in the latter form of screening has sufficient data been collected to allow conclusions to be reached on the optimum mode of delivery. It seems very probable that when CF carrier screening passes into routine service, it will be the antenatal couple model that is used.     

Women's opinions on the offer and use of maternal serum screening

We studied the opinions and experiences concerning maternal serum screening of two groups of women: (A) women who were not eligible for prenatal diagnosis; and (B) women for whom prenatal diagnosis was available because of advanced maternal age, and who either underwent chorionic villus sampling or amniocentesis. Many of the women were in favour of the availability of serum screening and would apply for this test in a future pregnancy. This applied also to many respondents who had previously undergone prenatal diagnosis. Most of these women, however, did not intend to decline diagnostic amniocentesis if the screening results did not indicate an increased risk. The majority of the group of respondents of 36 years and over did not consider it acceptable if age indication was dropped altogether. A system based on serum screening will have other implications than a policy based on age indication, since specific individual risk assessment is perceived as being of more significance than a risk statistically derived from age alone. Serum screening is often seen as a means of reassurance and many women are not aware of the possible drawbacks. As technology becomes increasingly complicated, counselling has to be adjusted correspondingly. Further research is needed to establish whether and how distress can be minimized and well-considered individual choice can be achieved.