13042例孕妇早期产前筛查的研究分析

目的:评价孕早期唐氏综合征血清学筛查在产前诊断中的作用,降低染色体异常胎儿出生率。方法:取孕11~13+6周孕妇13042例,时间分辨荧光免疫术检测13042例单胎孕妇外周血妊娠相关蛋白-A(PAPP-A)和游离人绒毛膜促性腺激素β亚基(β-HCG)含量,综合超声测量胎儿颈项透明膜厚度(NT)及孕妇年龄、体质量和孕周,Life-Cycle4.0软件计算胎儿患21三体和18三体的风险率。高风险者进一步行绒毛或羊水细胞染色体核型分析。结果:13042例病例中,唐筛阳性373例(3.00%)。早筛21三体阳性PAPPA平均MoM值为0.98,游离β-HCG平均MoM值为2.218,NT平均MoM值2.56;18三体阳性PAPPA平均MoM值为0.647,游离β-HCG平均MoM值1.847,NT平均MoM值3.07。早期唐筛阳性孕妇中,行绒毛活检或羊膜腔穿刺术染色体核型分析248例(占66.5%),发现染色体异常58例(占23.4%),其中21三体30例,18三体7例,13三体3例,性染色体异常8例,嵌合体7例,多倍体3例。≥35岁和35岁患者早期筛查的真阳性率分别为14.8%和34.9%。结论:孕早期血清学筛查能有效筛查出染色体异常胎儿,降低了出生缺陷发病率,对于年龄35岁的孕妇应作为常规筛查。     

血清高糖基化hCG检测在21-三体综合征产前筛查中的意义探讨

目的初步探讨孕母血清高糖基化hCG(HhCG)用于孕中期产前筛查21-三体的临床意义。方法采用Nichols全自动化学免疫发光分析仪测定115例孕15～20周的孕妇(包括17例21-三体妊娠和98例正常妊娠)的血清高糖基化hCG水平。结果 17例21-三体妊娠的孕妇HhCGMoM值中位数为10.11,约是正常妊娠中位数值(3.55)的3倍。将115例孕妇按AFP、F-β-hCG筛查结果分成21-三体妊娠者和高风险、低风险正常妊娠3组,3组数据呈对数正态分布,组间比较,21-三体妊娠孕妇HhCGMoM值高于高风险、低风险正常妊娠(P0.02、P0.001)。除此,17例21-三体妊娠者HhCGMoM值均大于2.9(文献提示的21三体高风险判断阈值);2例AFP、F-β-hCG产前筛查为假阴性患者其HhCGMoM值分别为7.5、10.11,均大于2.9。结论 21-三体妊娠者孕中期血清HhCG较正常妊娠升高,血清HhCG指标有产前筛查的应用价值。     

妊娠早期超声多指标筛查胎儿染色体异常的临床价值

目的 探讨妊娠早期超声多指标筛查胎儿染色体异常的临床价值.方法 对2008年9月至2010年9月在暨南大学附属第一医院产科就诊的2789例妊娠早期(11～13+6周)单胎初产孕妇超声测量胎儿颈项透明层(nuchal translucency,NT)厚度,记录胎心率(fetal heart rate,FHR)、面部角度(facial angle,FA)、静脉导管(ductus venosus,DV)、三尖瓣反流(tricuspid reverse,TR)、胎儿鼻骨(nasal bone,NB)等超声指标,观察胎儿结构.全部超声指标检查结果输入Astraia风险筛查软件计算染色体异常风险值(＞1/300为高风险截断值),根据知情同意原则对高风险者取绒毛或羊水进行染色体核型产前诊断.所有研究对象随访至分娩后6个月.率的比较用x2检验或Fisher精确概率法.结果 (1) 2789例孕妇筛查出21三体高风险107例,其中96例接受侵入性产前诊断,诊断染色体异常16例,染色体异常发生率为0.6％(16/2789),其中6例21-三体.2789例孕妇中,超声筛查21-三体高风险孕妇4例,最终确诊21-三体6例,假阳性率为3.6％ (101/2783).(2) NT≥2.5 mm者196例,21-三体高风险66例,均经绒毛穿刺诊断,发现染色体异常16例;有创性检查率2.3％(66/2789).(3)≥35岁孕妇占筛查总数的6.7％(186/2789),其中检出21三体高风险32例,占21-三体高风险总数的29.9％ (32/107);诊断21-三体2例,21-三体检出率为1.1％(2/186);年龄＜35岁者21-三体检出率为0.2％(4/2597);年龄≥35岁和年龄＜35岁人群中胎儿21-三体检出率差异无统计学意义(P=0.055).(4)筛查过程诊断胎儿结构异常13例,其中5例染色体核型异常.结论 妊娠早期超声多指标筛查将明显提高染色体异常胎儿检出率并降低假阳性和假阴性率,大大降低有创性检查率.尤其对高龄孕妇的染色体异常风险评估更有明显的指导意义.妊娠早期超声筛查不仅可以有效检出核型异常,同时可以诊断严重的胎儿结构异常.     

高通量测序胎儿染色体非整倍体筛查方法在双胎妊娠中的应用

目的探讨高通量测序用于胎儿染色体异常产前筛查在双胎妊娠胎儿非整倍体染色体异常产前检测中的应用价值。方法选择妊娠15~18周接受孕中期血清学筛查和核型分析的200例双胎孕妇,妊娠12~27周行非侵入产前诊断(NIPT),对于染色体异常风险度升高者行双胎妊娠羊膜腔穿刺染色体核型分析;未提示风险度升高者,分娩时留取脐血检查有无染色体异常;双胎妊娠出现流产等不良妊娠结局者,留取胎儿组织提取DNA等进行高通量测序及染色体核型分析。以胎儿/新生儿染色体核型分析结果为金标准,分析NIPT结果。结果200例双胎妊娠患者,行孕中期血清学筛查155例(77.5%,155/200),45例(22.5%,50/200)因年龄高风险未行血清学筛查。155例血清学筛查中,高风险孕妇13例(8.4%,13/155),核型分析和妊娠结局均未发现异常。200例NIPT显示,1例性染色体异常(0.5%,1/200),染色体核型分析证实双胎之一胎儿核型为45,XO;1例18-三体综合征高风险(0.5%,1/200),双胎核型未见明显异常;1例21-三体高风险(0.5%,1/200),双胎之一核型为47,+21,XN;余197例染色体核型分析未提示明显异常。结论高通量测序胎儿染色体异常产前筛查在双胎胎儿染色体非整倍体的检测有一定的应用价值。     

孕早、中期三倍体胎儿超声影像及母体血清标志物异常临床研究

目的探讨三倍体妊娠在孕早、中期的胎儿超声影像特征和产前筛查母体血清标志物的变化特点。方法回顾性分析云南省第一人民医院2012年1月至2019年12月及广西壮族自治区妇幼保健院2014年1月至2019年6月经细胞分子遗传学产前诊断和超声检查确诊为三倍体胎儿的超声影像发现、母体血清学产前筛查指标,以及文献报道的三倍体胎儿的临床资料,按三倍体分型归类后用卡方检验统计分析差异。结果 50例三倍体胎儿中染色体核型为69,XXX共34例,69,XXY共16例。2例Ⅰ型三倍体胎儿在孕中期不表现明显的胎儿生长受限(FGR)及结构异常,但合并有部分性葡萄胎、母体血清β-hCG和甲胎蛋白(AFP)浓度升高;38例Ⅱ型三倍体胎儿在孕早、中期表现为严重的非匀称型FGR(aFGR)合并结构异常,母体血清妊娠相关血浆蛋白A(PAPP-A)、β-hCG、AFP、游离雌三醇(uE3)浓度均明显降低,18-三体综合征高风险。结论胎儿超声检查能够明确分辨胎儿aFGR和部分性葡萄胎,联合应用超声影像学检查和孕妇血清标志物检测有助于在孕早、中期高效检出三倍体胎儿。     

筛查孕妇血清对非21三体染色体异常的遗传咨询价值

筛查孕妇血清以帮助诊断胎儿21三体,在很多地区已成为产前检查的一部分。对筛查结果阳性者采用羊膜腔穿刺术,取材做进一步染色体核型分析。羊膜腔穿刺术除检测21三体外,还可检测在胎儿中较常见的其它几种染色体数目和结构异常。 检测孕13～18周妇女血清β-hCG、雌三醇和甲胎蛋白,用三变量Gaussian分析法计算与母亲年龄相关的21三体发生危险。研究对象均为单活胎孕妇,仅为血清筛查后接受羊膜腔穿刺术者,不含因高龄妊娠或以往妊娠有染色体异常儿,或常规超声波检查发现胎儿畸形的孕妇。核型分析结果仅通过检     

孕早期性染色体缺陷胎儿母血清Fβ-hCG和PAPP-A水平的研究

胎儿性染色体畸形(47,XXX;47,XXY;47,XYY,45,X)是活婴中最常见一类染色体异常。在妊娠10～14周行产前筛查时其检出率为2‰～3‰。孕中期筛查显示:特纳氏综合征(45,X)母血清中游离绒毛膜促性腺激素β-亚单位(Fβ-hCG),抑制素-A及孕酮水平增高。通过对常染色体畸形孕妇血清Fβ-hCG和妊娠相关血浆蛋白-A(PAPP-A)以及超声波胎儿颈项部皮肤厚度(NT)的联合检测可筛查出90％唐氏     

PCR技术在产前诊断胎儿非整倍体的应用

大多数染色体异常为21,13,18号染色体及性染色体的非整倍体异常,血清筛查结果为高风险及年龄35岁以上的妊娠妇女均需进行产前诊断。而产前诊断染色体异常的传统方法是核型分析,染色体核型分析结果一般需要2～3周。随着分子生物学的飞速发展,聚合酶链反应技术不断应用于染色体非整倍体的产前诊断,这些新技术敏感性高、特异性强、操作简便、实验周期短,适合于非整倍体的产前诊断。     

PCR技术在产前诊断胎儿非整倍体的应用

大多数染色体异常为21,13,18号染色体及性染色体的非整倍体异常,血清筛查结果为高风险及年龄35岁以上的妊娠妇女均需进行产前诊断。而产前诊断染色体异常的传统方法是核型分析,染色体核型分析结果一般需要2～3周。随着分子生物学的飞速发展,聚合酶链反应技术不断应用于染色体非整倍体的产前诊断,这些新技术敏感性高、特异性强、操作简便、实验周期短,适合于非整倍体的产前诊断。     

9 508例妊娠中期孕妇血清学筛查结果分析

目的：回顾性分析妊娠中期孕妇产前血清学筛查结果,探讨血清学筛查的重要意义。方法：检测2010年9月—2014年3 月于北京军区总医院妇产科门诊产检的妊娠中期（15～20+6周）9 508例孕妇血清中的甲胎蛋白（AFP）、人绒毛膜促性腺激素β亚单位（β-hCG）和游离雌三醇（uE3）的浓度并结合孕周、年龄、体质量等因素进行风险评估。结果：9 508例接受妊娠中期唐氏筛查的孕妇中,有743例孕妇筛查结果为高风险,筛查阳性率为7.81%。其中唐氏综合征（DS）高风险检出率为5.92%（563/9 508）,18-三体高风险检出率为0.20%（19/9 508）,开放性神经管缺陷（NTD）高风险检出率为1.69%（161/9 508）。羊水细胞染色体核型分析确诊DS 5例,18-三体1例,其他染色体异常共12例。本研究结果显示： 20岁～组,25岁～组,30岁～组和≥35岁组间DS和NTD的高风险检出率差异均有统计学意义（P＜0.01）;年龄≥35岁高风险孕妇中DS阳性率明显高于年龄＜35岁高风险孕妇（P＜0.01）;对筛查低风险孕妇进行随访发现DS假阴性结果1例。结论：产前血清学筛查对降低出生缺陷、提高人口素质有一定的指导意义。     

Nuchal Translucency Thresholds in Prenatal Screening for Down Syndrome and Trisomy 18

ObjectiveTo determine if nuchal translucency (NT) can be used as a first trimester triage marker in prenatal screening for Down syndrome and trisomy 18.MethodsData from first trimester prenatal screening in 77 443 women were stratified by maternal and gestational ages. They were then analyzed to identify NT thresholds above or below which only positive (high-risk) or negative (low-risk) results were reported by a first trimester prenatal screening test combining PAPP-A, free β-hCG and NT.ResultsCombined prenatal screening was always positive for Down syndrome when NT thickness exceeded 4.0 mm. As women aged, this upper NT threshold value changed according to gestational age. In women aged 35 to 37 years, combined prenatal screening was always positive when NT exceeded 2.8 mm, 3.0 mm, and 3.4 mm at 11, 12, and 13 weeks of gestation, respectively. In women over 42 years of age, the upper threshold value for NT was 1.8 mm, 2.4 mm, and 2.7 mm at 11, 12, and 13 weeks of gestation, respectively. In women less than 35 years of age, we identified lower threshold values below which combined prenatal screening for Down syndrome was always negative.ConclusionIn prenatal screening for Down syndrome and trisomy 18, it is possible to identify NT threshold values above which biochemical screening provides no additional benefit. In pregnancies in which NT is above the established upper cut-offs, invasive prenatal screening can be offered without delay.     

Screening for trisomy 21 with maternal age, fetal nuchal translucency and maternal serum biochemistry at 11-14 weeks: a regional experience from Germany

OBJECTIVE: To examine the efficacy of first trimester screening for trisomy 21 using a combination of maternal age, fetal nuchal translucency (NT), maternal serum free beta-human chorionic gonadotropin (free beta-hCG) and pregnancy-associated plasma protein A (PAPP-A) in a regional setting [maternity unit of the Women's University Hospital, Hannover Medical School (study center); two regional private centers for prenatal diagnosis and human genetics; laboratory for prenatal diagnosis and human genetics]. METHODS: Fetal NT, crown-rump length, maternal serum free beta-hCG and PAPP-A were measured at 11-14 weeks of gestation. Risk calculation was carried out using the FMF computer algorithm. The patients were informed and counseled about possible invasive test options if the risk was 1 in 300 or greater. Fetal outcome was obtained by questionnaires given to the patients or sent to their gynecologists. The detection and false-positive rates for the different screening strategies were calculated. RESULTS: Pregnancy outcome was obtained in 2,497 cases, of which 2,196 cases had completed first trimester screening with NT and maternal serum biochemistry and 301 additional cases had NT measurement only. The median age was 32.5 years. In our population 11 affected fetuses were found. The estimated risk for trisomy 21 was 1 in 300 or greater in 64, 82, 88 and 88% of affected fetuses using maternal age alone, in combination with nuchal translucency, with maternal serum biochemical markers or with both NT and biochemical markers for a false-positive rate of 28.2, 5.1, 15.3 and 4.0%. CONCLUSIONS: First trimester screening using maternal age, NT, free beta-hCG and PAPP-A is highly effective for the detection of trisomy 21 and is associated with a sensitivity of about 90% for 5% false-positive patients.     

Examination of a first-trimester Down syndrome screening concept on a mix of 11,107 high- and low-risk patients at a private center for prenatal medicine in Germany

Objective

To assess the performance of a combined first-trimester screening concept for trisomies 21, 18 and 13 applied to a low- and high-risk patient sample in a specialized private center for prenatal medicine.

Study design

The quality of different first-trimester screening algorithms (risk calculation based on maternal age and nuchal translucency alone, maternal age and serum parameters (free β-hCG and PAPP-A) alone and a combination of both) was evaluated in a study population of low- and high-risk cases for fetal aneuploidies. All measurements were performed between the 11th + 0 and 13th + 6 weeks of gestation during the study period from November 2000 to December 2006, in accordance with the guidelines of the Fetal Medicine Foundation (FMF), London.

Results

Of 11,107 women included in the study, we had a complete follow-up on 10,668. The difference between the detection rate was insignificant for both the low-risk and the high-risk groups. In the overall study population, 52 of 59 cases of trisomy 21 were detected when a pre-defined cut-off of 1:300 was applied (detection rate (DR) 88.1%; 95% confidence interval (CI): 79.8–96.4 and false-positive rate (FPR) 4.9%; 95% CI: 4.5–5.3). For trisomies 13 and 18 with a pre-defined cut-off of 1:150, 26 of 32 cases were detected (DR 81.3%; 95% CI: 67.8–94.8 and FPR 0.7%; 95% CI: 0.5–0.9). The highest sensitivity was between 11 + 0 and 11 + 6 weeks of gestation with all cases of trisomy 21 detected with a FPR 5.1%; 95% CI: 3.7–6.5.

Conclusion

In our study population of different risk categories, the detection rate using the combined risk calculation based on maternal age, fetal NT, maternal PAPP-A and free β-hCG levels was superior to the application of either parameter alone.     

Integrated ultrasound and biochemical screening for trisomy 21 using fetal nuchal translucency,absent fetal nasal bone,free beta-hCG and PAPP-A at 11 to 14 weeks

BACKGROUND: Screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free beta-hCG and pregnancy-associated plasma protein-A (PAPP-A) at 11 to 14 weeks of gestation is associated with a detection rate of 90% for a false-positive rate of 5%. Recent evidence suggests that in about 70% of fetuses with trisomy 21, the nasal bone is not visible at the 11th- to 14th-week scan (Cicero et al., 2001). The aim of this study was to examine whether fetal NT thickness and the level of maternal serum biochemical markers is independent of the presence or absence of the nasal bone, and to estimate the performance of a screening test that integrates the two sonographic and the two biochemical markers. METHODS: This was a retrospective case-control study comprising 100 trisomy 21 and 400 chromosomally normal singleton pregnancies at 11 to 14 weeks of gestation. Ultrasound examination was carried out for measurement of fetal NT and assessment of the presence or absence of the fetal nasal bone. Maternal serum free beta-hCG and PAPP-A were measured using the Kryptor rapid random-access immunoassay analyser (Brahms Diagnostica GmbH, Berlin). The distribution of fetal NT, maternal serum free beta-hCG and PAPP-A in trisomy 21 fetuses with absent and present nasal bone was examined. RESULTS: The nasal bone was absent in 69 and present in 31 of the trisomy 21 fetuses. There were no significant differences in median maternal age, median gestational age, NT delta, free beta-hCG MoM and PAPP-A MoM in trisomy 21 fetuses with and without a visible nasal bone. For a false-positive rate of 5%, it was estimated that screening with the four markers in combination with maternal age would be associated with a detection rate of 97%. For a false-positive rate of 0.5%, the detection rate was 90.5%. CONCLUSIONS: An integrated sonographic and biochemical test at 11 to 14 weeks can potentially identify about 90% of trisomy 21 fetuses for a false-positive rate of 0.5%.     

Analysis of the impact of PAPP-A, free β-hCG and nuchal translucency thickness on the advanced first trimester screening

Objectives

The intention of this study is to analyze the impact of the single parameters NT, PAPP-A and free β-hCG used in combined first trimester screening and to determine their contribution in the risk assessment.

Methods

A retrospective risk assessment on the advanced first trimester screening (AFS) algorithm was made to determine the effect of a particular parameter while the remaining ones were fixed for calculation. Afterward data were recalculated by the AFS module. Test performance was measured by receiver operating characteristics (ROC) curves and their area under curve (AUC).

Results

Among the 14,862 cases are 14,748 healthy fetuses, 86 with trisomy 21, 22 with trisomy 18 and 6 with trisomy 13. Some settings obtain at default cut-off a very high sensitivity. However, a lack of specificity, as a high false-positive rate, too. The ROC analysis was best for NT, followed by PAPP-A. Free β-hCG showed the lowest AUC. Combining PAPP-A and free β-hCG offered a better AUC than each parameter alone. Best test performance was obtained by including all three parameters.

Discussion

A detection rate of 69 % for testing NT discretely is in order with present study data. PAPP-A is following and free β-hCG is not useful with a test positive rate of about a third. The detection rate of the biochemical parameters combined is higher than for NT alone, but results in a five times higher punctuation rate. All parameters together in the AFS provide the best test performance. The impact of each parameter NT, PAPP-A and free-β-hCG in a combined test strategy is nearly a third. Thus, every single parameter is needed to provide a high detection rate for all of the trisomies and minimize the number of unnecessary invasive diagnostics.     

A first trimester trisomy 13/trisomy 18 risk algorithm combining fetal nuchal translucency thickness,maternal serum free beta-hCG and PAPP-A

This study examines 45 cases of trisomy 13 and 59 cases of trisomy 18 and reports an algorithm to identify pregnancies with a fetus affected by trisomy 13 or 18 by a combination of maternal age fetal nuchal translucency (NT) thickness, and maternal serum free beta-hCG and PAPP-A at 11-14 weeks of gestation. In this mixed trisomy group the median MoM NT was increased at 2.819, whilst the median MoMs for free beta-hCG and PAPP-A were reduced at 0.375 and 0.201 respectively. We predict that with the use of the combined trisomy 13 and 18 algorithm and a risk cut-off of 1 in 150 will for a 0.3% false positive rate allow 95% of these chromosomal defects to be identified at 11-14 weeks. Such algorithms will enhance existing first trimester screening algorithms for trisomy 21.     

Evaluation of pregnancy-associated plasma protein A (PAPP-A) and free beta subunit of human chorionic gonadotropin (beta hCG) levels and sonographic assesement of fetal nuchal translucency (NT) in singleton pregnancies between 11 and 14 weeks of gestation--Polish multi-centre research

Evaluation of pregnancy-associated plasma protein A (PAPP-A) and free beta subunit of human chorionic gonadotropin (beta hCG) levels and sonographic assessment of fetal nuchal translucency (NT) in singleton pregnancies between 11 and 14 weeks of gestation--Poland's multi-centers research. OBJECTIVES: Pregnancy-associated plasma protein A has been reported to be low in Down syndrome affected pregnancies during the first trimester of pregnancy. Enlarged nuchal translucency (NT) is observed in about 80% of fetuses affected with chromosomal abnormalities and congenital heart defects (CHD). MATERIAL AND METHODS: The aim of this study were to determine value and the medians of free beta-human chorionic gonadotropin (beta-hCG) and pregnancy associated plasma protein-A (PAPP-A) and nuchal translucency thickness in the first trimester in a prospective study of a non-selected Polish population. RESULTS: All examinations have been performed according to the Fetal Medicine Foundation (FMF) rules. We have included 800 women between 11 weeks 0 days and 13 weeks 6 days gestation into a biochemical examination. Women booked into the clinic were offered screening, using a combination of maternal serum free beta-hCG and pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency thickness. The maternal serum were measured using the Kryptor analyzer (Brahms Diagnostica). All pregnant women have been divided into 2 groups younger than (first group) and older than (second group) 35 years of age. CONCLUSIONS: Nomogrames for free beta-hCG and PAPP-A levels in physiological pregnancy between 11(+0) and 13(6) weeks were determined in the examined population. A positive correlation between PAPP-A and CRL levels, as well as a weak negative correlation between free beta-hCG and CRL, were demonstrated.     

Maternal serum biochemistry at 11-13(+6) weeks in relation to the presence or absence of the fetal nasal bone on ultrasonography in chromosomally abnormal fetuses: an updated analysis of integrated ultrasound and biochemical screening

BACKGROUND: Screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free beta-hCG and pregnancy associated plasma protein-A (PAPP-A) at 11-13(+6) weeks of gestation is associated with a detection rate of 90%, for a false-positive rate of 5%. Recent evidence suggests that in about 70% of fetuses with trisomy 21 the nasal bone is not visible at the 11-13(+6) week scan and that the frequency of absence of nasal bone differs in different ethnic groups. In addition, there is a relationship between absent nasal bone and nuchal translucency thickness. In a preliminary study we showed that while PAPP-A levels were lower and free beta-hCG levels were higher in trisomy 21 fetuses with an absent nasal bone, this difference was not statistically different. In fetuses with trisomy 13 and trisomy 18, there is also a high (57 and 67%) incidence of an absent nasal bone. The aim of this present study was to extend our examination of whether the level of maternal serum biochemical markers is independent of the presence or absence of the nasal bone in cases with trisomy 21 and to ascertain if any differences exist in cases with trisomies 13 and 18. METHODS: This study data comprised 100 trisomy 21 singleton pregnancies at 11-13(+6) weeks of gestation from our previous study and an additional 42 cases analysed as part of routine OSCAR screening. A total of 34 cases with trisomy 18 and 12 cases with trisomy 13 were also available. Ultrasound examination was carried out for measurement of fetal NT and assessment of the presence or absence of the fetal nasal bone. Maternal serum free beta-hCG and PAPP-A were measured using the Kryptor rapid random access immunoassay analyser (Brahms Diagnostica AG, Berlin). The distribution of maternal serum free beta-hCG and PAPP-A in chromosomally abnormal fetuses with absent and present nasal bone was examined. RESULTS: The nasal bone was absent in 29 and present in 13 of the new trisomy 21 cases and in 98 (69%) and 44 respectively in the combined series. For the trisomy 18 cases, the nasal bone was absent in 19 (55.9%) cases and in 3 (25%) of cases of trisomy 13. There were no significant differences in median maternal age, median gestational age, NT delta, free beta-hCG MoM and PAPP-A MoM in trisomy 21 fetuses with and without a visible nasal bone, and similarly for those with trisomies 13 or 18. For a false-positive rate of 5%, it was estimated that screening with the four markers in combination with maternal age would be associated with a detection rate of 96% of cases with trisomy 21. For a false-positive rate of 0.5%, the detection rate was 88%. CONCLUSIONS: There is no relationship between an absent fetal nasal bone and the levels of maternal serum PAPP-A or free beta-hCG in cases with trisomies 13, 18 or 21. An integrated sonographic and biochemical test at 11-13(+6) weeks can potentially identify about 88% of trisomy 21 fetuses for a false-positive rate of 0.5%.     

First trimester fetal ultrasound parameters associated with PAPP-A and fβ-hCG

Objective: To study the association of fβ-hCG and PAPP-A measured at 11–14 weeks of gestation with delta crown-rump-length (dCRL), delta fetal heart rate (dFHR) and delta nuchal translucency (dNT). To calculate adjusted MoM taking into consideration these associations. Methods: Retrospective cross-sectional study on 5,536 singleton euploid pregnancies participating in a first trimester screening program for chromosomal abnormalities by nuchal translucency and maternal serum biochemistry. Adjusted MoM were calculated for fβ-hCG and PAPP-A and compared to the observed MoM (calculated by the Fetal Medicine Foundation screening algorithm). Results: fβ-hCG correlates positively with dCRL and negatively with dNT, whereas PAPP-A shows a positive correlation with dNT and a negative one with dCRL and dFHR. After adjustment for the ultrasound parameters, the median MoM values for fβ-hCG and PAPP-A changed from 1.02 and 0.92 observed MoM to 0.98 and 0.99 adjusted MoM respectively. The difference between the observed and adjusted MoM was statistically significant (p?<?0.001). Delta CRL increases with gestation and this effect manifests mainly after CRL of 62?mm. Conclusions: Adjustment for dCRL, dFHR and dNT improves the calculation of MoM for fβ-hCG and PAPP-A. CRL measurement overestimates fetal size at the end of the screening period 11–14 weeks.     

Relationship between maternal thyroid hormones and the biochemical markers of the first trimester aneuploidy screening

Purpose

The role of thyroid function in biochemical markers of first trimester screening has not been assessed. The aim of the present study was to investigate if there were any relation between maternal thyroid hormones and free-beta subunit of human chorionic gonadotropin (fβ-hCG) and pregnancy-associated plasma protein A (PAPP-A) levels as the biochemical markers of the combined first trimester aneuploidy screening.

Methods

375 pregnant women between 11 and 14 weeks of gestation who were offered routine first trimester prenatal aneuploidy screening and whose thyroid hormone levels (Thyroid stimulating hormone (TSH), free and total thyroxine, free and total triiodothyronine, anti thyroid peroxidase antibody) were measured were assessed. Correlation of free-β-hCG and PAPP-A with maternal thyroid hormones was analyzed.

Results

There was no statistically significant correlation between maternal TSH, free and total thyroxine, free and total triiodothyronine, anti-thyroid peroxidase antibodies and free-β-hCG and PAPP-A as biochemical markers of first trimester aneuploidy screening.

Conclusion

Maternal thyroid function does not seem to affect secretion of fβ-hCG and PAPP-A.