Quadruple Test Research Articles

The implementation of a combined nuchal translucency screening service

IntroductionCombined nuchal translucency (cNT) screening was established within a 3000 delivery unit at a cost of £18000. The uptake, changes in sensitivity and specificity and effect on the rate of...

First trimester versus second trimester down's syndrome screening in the west of Scotland

During 2010, we compared performance of first versus second trimester Down's syndrome screening in 2 hospitals 4 miles apart, serving the same population in West of Scotland. As the same...

The quadruple test for Down syndrome screening in pregnant women of advanced maternal age

The purpose of the current study was to determine whether or not the quadruple test for screening Down syndrome is an effective method to replace direct amniocentesis in pregnant women ≥ 35 years of age. This study analyzed the screening performance of the quadruple test according to maternal age at delivery among subjects who had a quadruple screening test at 1 of 4 hospitals during a 5-year period and for whom data on fetal chromosomal abnormalities were available. The study population of 9,435 pregnant women was divided into 3 groups according to maternal age: 6,922 women were < 35 years of age; 2,284 were 35-39 years of age; and 229 women ≥ 40 years of age. The detection and false-positive rates of the quadruple screening test for Down or Edward syndrome in the 3 groups of women were 80 and 6.6%, 200 and 15.8%, and 100 and 35.3%, respectively. Under conditions in which first trimester screening test is not available, the quadruple screening test is a better choice than direct amniocentesis for pregnancies complicated by advanced maternal age. When providing genetic counseling, we need to explain the accurate detection and false-positive rates of the screening test according to maternal age.

A practical solution to combining dating and screening for Down's syndrome

The offer of combined Down's syndrome screening to all pregnant women in England requires accurate estimation of gestational age. The guidance issued by the British Medical Ultrasound Society (BMUS) in 2009 recommends dating by crown rump length (CRL) up to 13 weeks 0 days and by head circumference (HC) after this gestation. The guidance issued by the Fetal Anomaly Screening Programme (FASP) in 2010 states that combined screening for Down's syndrome is the recommended strategy. Combined screening requires the measurement of nuchal translucency, which should be performed when the CRL is between 45.0 and 84.0 mm. Uncertainty exists as to how best to combine the BMUS dating guidance and the FASP Down's syndrome screening guidance in routine practice. The solution proposed by the authors is to date the pregnancy by CRL up to and including 84.0 mm and to date using HC when the CRL is greater than 84.0 mm, irrespective of whether or not Down's syndrome screening is requested. Screening for Down's syndrome should be by combined screening when the CRL is between 45.0 and 84.0 mm. Where the CRL is greater than 84.0 mm, screening for Down's syndrome should be by maternal serum quadruple testing, performed after 14 weeks and two days.

Aneuploidy screening: a position statement from a committee on behalf of the Board of the International Society for Prenatal Diagnosis, January 2011

Aneuploidy screening: a position statement from a committee on behalf of the Board of the International Society for Prenatal Diagnosis, January 2011

Impact of smoking on maternal serum markers and prenatal screening in the first and second trimesters

To examine the effects of smoking on first and second trimester screening markers and to determine the overall impact of these effects on Down syndrome and trisomy 18 risks in first trimester combined, second trimester quadruple and integrated tests. Examination of screening records at Women and Infants Hospital during 2006-2008. First trimester pregnancy-associated plasma protein-A (PAPP-A), beta-human chorionic gonadotrophin (hCG) and nuchal translucency and second trimester alpha-fetoprotein (AFP), unconjugated estriol (uE3), hCG and inhibin A (inhA) multiple of the median (MoM) values were extracted from the database along with risk results, smoking status and relevant demographic information. Smoking led to significantly reduced median levels of first trimester PAPP-A (0.89 MoM) and hCG (0.80 MoM), reduced second trimester uE3 (0.96 MoM) and hCG (0.84 MoM), and increased AFP (1.03 MoM) and inhA (1.39 MoM). After accounting for the differences in age between groups, smokers had higher Down syndrome screen positive rates for the second trimester quadruple test, but not for first trimester combined or integrated tests. Screen positive rates for trisomy 18 were markedly increased in smokers relative to age-matched non-smokers when using first trimester combined or integrated tests. Smoking leads to increased screen positive rates, especially for trisomy 18 using combined or integrated tests.

Antenatal Screening Strategies for Down Syndrome: Analysis of Existing Protocols and Implications in the Kingdom of Saudi Arabia

Background: Syndrome (DS) is the most frequent chromosomal abnormality in live births with an incidence of 1 to 1.7 per 1,000 births and a variable physical expression. syndrome screening has been an integral part of routine prenatal care in recent decades. Currently, there is no established DS screening program in the Kingdom of Saudi Arabia. Objective: The total number of DS pregnancies is increasing, probably due mainly to the increasing proportion of older mothers. Live birth with DS increased also so, there is an expected increase in long term survivors. There is a need for a well structured system for prenatal diagnosis and follow up program and an extra health care resource. Design: A systematic literature search for various prenatal screening tests for DS were explored regarding the time of screening during pregnancy, detection rate, false positive rate, advantages and disadvantages. Various search engines like Pub med, Medline, Index Medicus were used to review the published literature using the key words Down syndrome, antenatal screening, and “Chromosomal Results: Different screening strategies for DS are applied worldwide. In the United Kingdom, the combined test, the integrated test or the serum integrated test is offered for women who present in the first trimester, and the quadruple test for those who present in the second trimester. In the United States, Canada, and Australia the combined test is recommended for the first trimester and the quadruple test for the second trimester. Conclusion: The Quadruple test should be offered to all pregnant women in the second trimester, in addition all women should be offered a second –trimester ultrasound scan to identify major and minor fetal abnormalities. Extensive research is needed to establish accurate incidence of DS in the Kingdom of Saudi Arabia and its relation to maternal age and parity. Review Article

Korean-Specific Parameter Models for Calculating the Risk of Down Syndrome in the Second Trimester of Pregnancy

The purpose of the current study was to propose a Korean-specific parameter set for calculating the risk of Down syndrome in the second trimester of pregnancy and to determine the screening performances of triple and quadruple tests in Korean women. Using the data on triple or quadruple screening from three hospitals in Korea during 7 yr, we re-converted the concentrations of four serum markers to multiple of median values according to gestational age and maternal weight. After re-calculating the risk of Down syndrome in each pregnancy by multiplying maternal age-specific risk by the likelihood ratio values for the serum markers, screening performances and optimal cut-off values of triple and quadruple tests were analyzed. Among 16,077 pregnancies, 23 cases had Down syndrome (1.4/1,000 deliveries). Compared to the previous program, the tests with new parameters had improved screening performance. The triple and quadruple tests had detection rates of 65.2% and 72.7%, respectively, at a false-positive rate of 5%. The optimal cut-off value for the quadruple and triple tests was 1:250. We have presented a Korean-specific parameter set for Down syndrome screening. The proposed screening test using this parameter set may improve the performance of Down syndrome screening for Korean women.

A case of terminal deletion of chromosome 10p

Chromosome 10p deletion (partial monosomy 10p) is rare chromosomal disorder. It was first reported in 1970. Since then, as far as we know, about 45 patients have been described. The main feature of this syndrome are craniofacial dysmorphism, congenital heart disease, vesicoureteral abnormalities, and developmental delay. We have experienced a prenatal case of Chromosome 10p terminal deletion by doing cytogenetic study due to high Down syndrome risk on quadruple test and cleft lip on prenatal ultrasonography. Conventional cytogenetic result from cord blood was 46,XY,del(10)(p13), molecular cytogenetic techniques using bacterial artifi cial chromosome array comparative genomic hybridization and fl uorescence in situ hybridization analysis result was 46,XY,del(10)(p14)(NEBL-). To our knowledge, this karyotype may be the first report in Korea. We present this case with brief review of literature.

Understanding Biochemical Markers for Antenatal Screening

ABSTRACT Screening tests to identify fetuses at risk for aneuploidies should be offered to all pregnant women. It should be remembered that screening tests can not diagnose a birth defect; they can only indicate an increased risk. An abnormal screening test result simply mean that additional testing is recommended. Maternal serum biochemical markers in first trimester are free beta-hCG and PAPP-A. In second trimester the markers are AFP, UE3, hCG (Triple test) and inhibin added to these three markers forming the quadruple test. Level of cell free fetal DNA and fetal cells in maternal circulation are some of the molecular techniques for prenatal diagnosis of aneuploidies.

Stability of inhibin A and unconjugated oestriol in the second trimester of pregnancy

The introduction of a second trimester quadruple test for fetal Down's syndrome adds the measurement of serum inhibin A (InhA) and unconjugated oestriol (UE3) to the existing repertoire of alphafetoprotein and intact human chorionic gonadotrophin. The aim of this study was to assess the stability of InhA and UE3 in whole blood and serum. To determine whole blood stability, five extra blood specimens were obtained from each of 10 women attending an antenatal clinic. Samples were stored at room temperature for either two hours, one, three, five or seven days and centrifuged prior to analysis. Serum stability was studied by the analysis of surplus serum from 14 routine second trimester screening samples: seven stored at room temperature and seven stored at 4°C. An aliquot from each specimen was analysed two hours, one, three, five or seven days post centrifugation. Specimens were analysed for InhA and UE3 using the Beckman Access 2(®) Immunoassay analyser. No significant difference (P > 0.05) was shown in InhA or UE3 concentrations between the initial time point on the day of venepuncture and each of the subsequent analyses at one, three, five and seven days following collection for either whole blood or serum. InhA and UE3 are stable in whole blood and serum for seven days.

Automated Automotive Tire Inflation System – Effect of Tire Pressure on Vehicle Handling

The under-inflation of pneumatic tires, a typical problem in sedans and light duty vehicles, affects the vehicle's handling characteristics. An automated tire monitoring and inflation system can ensure adequate tire pressure to better accommodate handling requirements. In this paper, the variance of longitudinal and lateral forces, plus aligning torque, have been numerically investigated for different tire inflation pressures using the STI tire model. The tire/road interface results were integrated into a comprehensive simulation to evaluate vehicle handling behavior. A quadruple lane change test revealed that the required steering wheel angle increased by up to 47.7% for front axle tire inflation pressures at 70% of nominal values, whereas the vehicle slip angle was up to 77.8% larger when all tires were inflated to 70% of the recommended pressure. These results suggest that under-inflated front axle tires result in understeer tendencies while rear axle under-inflation creates oversteer behavior.

The triple test as a screening technique for Down syndrome: reliability and relevance

The triple test is a second trimester screening test used to identify those pregnant women who should be offered a diagnostic test to identify whether their fetus has an aneuploidy. It was first described in 1988, but has largely been superseded by newer tests either conducted earlier in the first trimester (ie, the combined test, using ultrasound measurement of nuchal translucency, pregnancy-associated plasma protein A, and human chorionic gonadotrophin [hCG]) or in the second trimester (ie, the quadruple test, using α-fetoprotein, hCG, uE3, and inhibin). These newer tests have been introduced because they offer greater detection and lower screen positive results thereby enhancing diagnosis rates, while decreasing the risk of iatrogenic harm caused by the invasive testing required when collecting suitable sample tissue. Noninvasive alternatives to the triple test have been identified, but these have not been adopted despite 13 years of development. It is likely, therefore, that the triple test (or variants thereof) will continue to be used in routine antenatal care for the foreseeable future.

Chromosome abnormalities investigated by non‐invasive prenatal testing account for approximately 50% of fetal unbalances associated with relevant clinical phenotypes

During the past 20 years non-invasive screening tests have been increasingly utilized in prenatal diagnosis (PD) practice. Considerable effort has been exerted by multicenter consortia to evaluate the reliability of non-invasive screening tests in detecting those women with an increased risk of having a pregnancy affected by trisomies 21, 18, and 13, monosomy X, and triploidies. To what extent this group of abnormal karyotypes accounts for the total number of phenotypically relevant fetal chromosome abnormalities has, however, never been investigated. The present report is an attempt aimed to quantify this proportion. A retrospective analysis of a homogeneous survey of 115,128 consecutive invasive prenatal tests was undertaken. All cases were classified in accordance with the indication given for the invasive testing. Cytogenetic results regarding 96,416 karyotype analyses performed because of advanced maternal age (>or=35 years) or gestational anxiety (<35 years) were considered since these are the patients who usually undergo non-invasive screening tests. We calculated the number of cases (T21, T18, T13, 45,X, and triploidy) that would have been detected by prenatal screening on the basis of the published detection rate of the combined-2 test or the quadruple test. Our findings indicate that the chromosomal abnormalities investigated by screening tests represent <50% of the fetal chromosomal abnormalities associated with an abnormal outcome ranging from intermediate-to-severe in women <35 years (45.8% and 39.6% in the first and second trimesters, respectively), and sensitivity >50% in women >or=35 years (65.1% and 61.8%, respectively). To conclude, approximately 50% of the phenotypically relevant abnormal karyotypes cannot be detected by non-invasive prenatal screening tests.

Performance Characteristics of the UniCel DxI 800 Immunoassay for the Maternal Serum Quadruple Test, Including Median Values for Each Week of Gestation, in Korean Women

Maternal serum prenatal quadruple screening includes testing for alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), unconjugated estriol (uE3), and dimeric inhibin A (DIA). We evaluated quadruple screening using an automated platform and looked for any ethnic differences in the median values of each marker. We measured the concentrations of each quadruple test analyte using the UniCel DxI 800 system (Beckman Coulter, USA) in 788 Korean mid-trimester maternal serum samples and calculated their median values using Benetech software (Benetech, Canada). We also compared the results with those obtained using the Immulite 2000 assay (Siemens Healthcare Diagnostics, USA) or ELISA (DSL, USA) in 442 samples. We obtained mid-trimester median values for each marker. The following are the comparative results for each test using the Immulite 2000 assay or ELISA (x) and the UniCel DxI 800 immunoassay (y): AFP, y=1.10x+0.01, r=0.925; uE3, y=0.28x+0.24, r=0.885; hCG, y=1.22x-3047.8, r=0.944; and DIA, y=0.86x+15.31, r=0.833. Assay results for each of the four markers showed good correlations. However, significant biases necessitated new median calculations of prenatal risk estimates in all four tests. We established gestational age-specific second-trimester median values for four markers in Korean samples using the UniCel DxI 800 immunoassay system. Despite significant bias, there were good correlations between the results obtained using the UniCel DxI 800 immunoassay and those obtained using the Immulite 2000 assay.

Second-trimester Maternal Serum Quadruple Test for Down Syndrome Screening: A Taiwanese Population-based Study

To assess the usefulness of quadruple test screening for Down syndrome in Taiwan. Maternal serum concentrations of alpha-fetoprotein, human chorionic gonadotropin, unconjugated estriol, and inhibin A were measured in 21,481 pregnant women from 15 to 20 weeks of gestation. Of the 21,481 women, 977 returned values greater than the high-risk cut-off value (1 in 270). Most of these women (86.2%) decided to have an invasive procedure for genetic diagnosis. Nine cases of Down syndrome and 19 cases of other chromosomal anomalies were detected prenatally. Two children with Down syndrome were diagnosed after delivery even though a low estimated risk was determined following the quadruple test. The detection rate was 81.8% (nine out of 11 cases), with a 4.4% false-positive rate. The median multiple of the median value for a-fetoprotein, human chorionic gonadotropin, unconjugated estriol and inhibin A were 0.87, 2.34, 0.77 and 2.16, respectively, in affected cases. This is the first study of the quadruple test for Down syndrome in a Chinese population. Our findings suggested that the second-trimester quadruple test provides an effective screening tool for Down syndrome in Taiwan.

Andrology Laboratory Manual

ABSTRACTA 25 years old woman with Down syndrome (DS) presented at 9 weeks gestational age. She belonged to a very supportive family. She was married to a person with normal karyotype and conceived within 3 months of marriage. Her antenatal period was uneventful, except for mild IUGR and oligohydroamnios 32 weeks onwards. At 38 weeks, she underwent induction of labor. She tolerated labor pains well but because of failure to progress, cesarean section was performed. She delivered a 2 kg male baby, who was phenotypically and genotypically normal. Screening for trisomy 21 should be offered to all women as part of routine antenatal care. This offer should include detailed counseling about the implications and limitations of the test used in the screening program. The available second trimester screening tests are the double, triple and quadruple tests. Children with Down syndrome may benefit from speech therapy, physical therapy and occupational therapy. They may receive special education and assistance in school. Full potential of Down patients can be utilized only with complete support of family and society.

Role of Second-Trimester Genetic Sonography After Down Syndrome Screening

To estimate the effectiveness of second-trimester genetic sonography in modifying Down syndrome screening test results. The First and Second Trimester Evaluation of Risk (FASTER) aneuploidy screening trial participants were studied from 13 centers where a 15- to 23-week genetic sonogram was performed in the same center. Midtrimester Down syndrome risks were estimated for five screening test policies: first-trimester combined, second-trimester quadruple, and testing sequentially by integrated, stepwise, or contingent protocols. The maternal age-specific risk and the screening test risk were modified using likelihood ratios derived from the ultrasound findings. Separate likelihood ratios were obtained for the presence or absence of at least one major fetal structural malformation and for each "soft" sonographic marker statistically significant at the P<.005 level. Detection and false-positive rate were calculated for the genetic sonogram alone and for each test before and after risk modification. A total of 7,842 pregnancies were studied, including 59 with Down syndrome. Major malformations and 8 of the 18 soft markers evaluated were highly significant. The detection rate for a 5% false-positive rate for the genetic sonogram alone was 69%; the detection rate increased from 81% to 90% with the combined test, from 81% to 90% with the quadruple test, from 93% to 98% with the integrated test, from 97% to 98% with the stepwise test, and from 95% to 97% with the contingent test. The stepwise and contingent use of the genetic sonogram after first-trimester screening both yielded a 90% detection rate. Genetic sonography can increase detection rates substantially for combined and quadruple tests and more modestly for sequential protocols. Substituting sonography for quadruple markers in sequential screening was not useful. II.

The Ability of the Quadruple Test to Predict Adverse Perinatal Outcomes in a High-risk Obstetric Population

To determine the ability of the quadruple Down's syndrome screening test (quad screen) to predict other adverse perinatal outcomes (APO) in a high-risk obstetric population. A tertiary medical centre in West Virginia. We retrospectively reviewed 342 obstetric patients with quad screen data from a single clinic. The quad screen included maternal serum levels of alphafetoprotein (AFP), human chorionic gonadotrophin (hCG), uncongjugated oestriol (uE(3)), and inhibin A. The risk of APO was compared between patients with at least one abnormal marker versus no abnormal markers and >or=2 abnormal markers versus <2 abnormal markers. Abnormal markers were determined by cut-off values produced by Receiver Operator Characteristic (ROC) curves and the FASTER trial. Unadjusted and adjusted effects were estimated using logistic regression analysis. The risk of having an APO increased significantly for patients with abnormal markers by about three-fold using ROC and two-fold using FASTER trial thresholds. The quad screen shows value in predicting risk of APO in high-risk patients.

Protection of Chocolate Products from Indian Meal Moth by Adding Cinnamon Extract to the Adhesive on the Wrapping

초콜렛 포장에 스티커를 붙이기 위해 사용되는 접착물에 계피(Cinnamonum cassia Blume) 추출물을 혼합하는 것은 화랑곡나방(Plodia interpunctella Hubner)에 의한 침입으로부터 초콜렛 제품을 보호하기 위한 효과적인 한 방법이다. 처리농도별 제품을 개별적으로 투입한 비선택 실험에서 0.02와 0.025%의 계피 추출물을 처리한 포장지로 포장된 초콜렛 제품은 <TEX>$28.1^{\circ}C$</TEX>와 70-75%의 실험 조건에서 30일까지 화랑곡나방이 침입하지 않았으나, 계피 추출물이 첨가되지 않은 포장은 화랑곡나방에 의해 침입되었다. 처리농도별 제품을 혼합 투입한 선택 실험에서 0.02와 0.025%의 계피 추출물을 처리한 포장지로 포장된 초콜렛 제품은 <TEX>$28.1^{\circ}C$</TEX>와 70-75%의 실험 조건에서 60일까지 화랑곡나방에 의해 침입받지 않았는데 반해, 계피 추출물이 첨가되지 않은 제품은 화랑곡나방에 의해 침입을 받았다. 제품의 계피향 흡착 유무를 알아보기 위해 실시한 패널 테스트 결과 포장지에 계피 추출물을 처리하여도 제품에 향이 흡착되지 않아 소비자의 선택에 영향을 미치지 않을 것이라 판단되었다. Adding cinnamon (Cinnamonum cassia Blume) extract into the adhesive used to affix stickers to a chocolate package is an effective method for protecting chocolate products from infestation by the Indian meal moth (Plodia interpunctella Hubner). Chocolate packages treated with adhesive including 0.02% and 0.025% of cinnamon extract were not infested with the Indian meal moth for up to 30 days at <TEX>$28.1^{\circ}C$</TEX> and 70-75% RH, whereas 100% of the packages without the extract were infested in the no-choice test. Chocolate packages treated with adhesive including 0.02% and 0.025% of cinnamon extract in the quadruple choice test were not infested with the Indian meal moth for up to 60 days at <TEX>$28.1^{\circ}C$</TEX> and 70-75% RH, whereas 100% of the packages without the extract were infested. A panel test showed that the cinnamon extract treatment would not affect consumers' choices.