Optimising the timing for nuchal translucency measurement

It appears from current evidence that the most effective screening strategy for Down syndrome will involve a combination of first trimester nuchal translucency and serum biochemistry, whether performed in the first or second trimester. The aim of this study was to determine the optimum gestation based upon menstrual dates at which to schedule nuchal translucency (NT) measurement for the evaluation of fetal Down syndrome risk. Five thousand eight hundred and thirty-five pregnancies had an ultrasound scan scheduled between 11 and 14 completed weeks of gestation based upon either the last menstrual period (n = 3199) or a prior ultrasound scan (n = 2636). For last menstrual period-based ultrasound scans, with advancing gestation the frequency of missed miscarriage significantly decreased (p = 0.009, chi squared test), as did the need to reschedule a further scan because the gestation of the scheduled scan was too early to measure NT (p < 0.0001, Chi-squared test). In contrast, with advancing gestation the rate of unsuccessful NT measurement because the crown–rump length (CRL) was greater than 84 mm significantly increased (p < 0.0001, Chi-squared test). Of the women who had had an earlier ultrasound, 42 (1.6%) had a missed miscarriage and 9 (0.3%) were over gestation at the time of the NT scan. These data suggest that when only the last menstrual period is known the optimum time to schedule a nuchal translucency measurement is at 12 to 13 weeks' gestation. Copyright © 2002 John Wiley & Sons, Ltd.     

The effect of fetal gender on nuchal translucency at 10–14 weeks of gestation

Recent data have suggested that fetal nuchal translucency (NT) is affected by fetal gender. We investigated the size of this effect in 12 189 unselected pregnancies with known normal outcomes that had undergone NT measurements between 10 and 14 weeks of gestation. NT increased with gestation and was converted to multiples of the median (MoM) for the gestational day. The median NT MoM (95% CI) for female fetuses was 0.98 (0.97–0.99). This was significantly lower than that of the male fetuses (1.03; range1.02–1.04) (p<0.0005; Wilcoxon rank-sum test). The gender difference was not observed at 10 weeks but was observed from 11 weeks onwards. There is no obvious explanation for the above findings. Copyright © 2001 John Wiley & Sons, Ltd.     

Association between fetal nuchal translucency thickness in first trimester and subsequent gestational hypertension and preeclampsia

Increased fetal nuchal translucency (NT) in the first trimester is associated with adverse pregnancy outcomes. Whether the increased NT is also associated with an increased frequency of pregnancy-associated hypertension (PAH) is not known. Seven hundred and seventy-nine pregnant women who received NT-based Down syndrome screening and delivered their babies at our hospital by September 2000 were enrolled into this study. Among these women, there are 46 cases of preeclampsia, 68 cases of gestational hypertension (GH); 665 women without any adverse pregnancy outcomes served as controls. Correlation analysis demonstrated that NT MoM (multiples of median) level had a positive association with maternal diastolic blood pressure at the time of admission for delivery (r = 0.104; p < 0.01). The severity of PAH was concordant with the stepwise increase of mean NT MoM level, which was 0.88 in control, 1.07 in gestational hypertension, and 1.13 in preeclampsia (p < 0.001). Using the 95th (1.52 MoM) and 90th (1.31 MoM) percentiles of NT thickness as cut-offs, the sensitivities and odds ratios of the women at risk for developing GH after 20 weeks of gestation were 8.8%, 19.1% and 1.98, 2.15 respectively, while for preeclampsia were 10.9%, 28.3% and 2.49, 3.58 respectively. It is concluded that the pathological changes in the placenta responsible for the development of PAH may also influence the physiological decrease of NT thickness in late first trimester. However, the sensitivity of fetal NT measurement in first trimester is not sufficient as a single marker for predicting the pregnant women at risk for subsequent PAH. Copyright © 2002 John Wiley & Sons, Ltd.     

The nuchal translucency and the fetal heart: a literature review

In this overview the current knowledge of the relationship between an increased nuchal translucency (NT) measurement and fetal heart structure and function in chromosomally normal fetuses is reviewed. Relevant pathophysiological theories behind the increased NT are discussed. Fetuses with an increased NT have an increased risk for congenital heart disease (CHD) with no particular bias for one form of CHD over another. This risk increases with increasing NT measurement. Although the NT measurement is only a modestly effective screening tool for all CHD when used alone, it may indeed be effective in identifying specific CHD “likely to benefit” from prenatal diagnosis. The combination of an increased NT, tricuspid regurgitation and an abnormal ductus venosus (DV) Doppler flow profile, is a strong marker for CHD. A fetal echocardiogram should be performed at 20 weeks' gestation in fetuses with an NT ≥ 95th percentile but < 99th percentile. When the NT measurement is ≥ 99th percentile, or when tricuspid regurgitation and/or an abnormal DV flow pattern is found along with the increased NT, an earlier echocardiogram is indicated, followed by a repeat scan at around 20 weeks' gestation. The resultant increased demand for early fetal echocardiography and sonographers with this special expertise needs to be planned and provided for. Copyright © 2009 John Wiley & Sons, Ltd.     

First trimester screening for Down syndrome and assisted reproduction: no basis for concern

In pregnancies obtained after assisted reproduction the false-positive rate of second trimester Down syndrome (DS) screening is increased by 1.5–3-fold. This may cause an increase in the number of amniocenteses and the fetal loss rate. The present study for the first time examined whether assisted reproductive technologies affect the results of first trimester screening. The markers PAPP-A, free β-hCG and the nuchal translucency (NT) thickness were examined at 12–14 weeks' gestation. Screening markers in 47 in vitro fertilisation (IVF), 63 ovulation induction (OI) and 3026 spontaneously conceived singleton pregnancies were compared. The MoM (multiples of the median) value in the IVF pregnancies was 1.02 (95% CI: 0.85–1.22) for PAPP-A, 1.14 (95% CI: 0.95–1.37) for β-hCG and 0.97 (95% CI: 0.89–1.05) for NT; the MoM value in the OI pregnancies was 0.89 (95% CI: 0.76–1.05) for PAPP-A, 1.08 (95% CI: 0.93–1.25) for β-hCG and 1.02 (95% CI: 0.95–1.11) for NT. The first trimester marker values in assisted reproductive pregnancies and spontaneously conceived pregnancies were not significantly different. Estimated false-positive rates for a risk cut-off of 1:400 varied from 4.7% in IVF pregnancies to 5.1% in OI pregnancies. Therefore the false-positive rate in Down syndrome screening should be independent of the method of conception. Copyright © 2001 John Wiley & Sons, Ltd.     

Does a ‘notched’ nuchal translucency indicate Down syndrome fetuses or other adverse pregnancy outcome?

The aim of the present study was to assess the sonographic contour of the increased nuchal translucency (NT) and to correlate this with pregnancy outcome. Fifty sonographic images of fetuses with increased NT [>95th centile thickness of the normal range for crown–rump length (CRL) between 38 and 84 mm] were retrospectively assessed. In all the cases a complete pregnancy and even infancy follow-up (<36 months) was available. The NT appearances were subdivided into two forms: a ‘notched’ or ‘uniform’ appearance. The images were correlated with karyotype results [trisomy 21 (DS) vs euploid cases] and pregnancy outcome. Complicated outcomes were classified as being either DS fetuses, miscarriage or termination of pregnancy because of structural anomaly. Thus 30/35 (86%) of the euploid fetuses had a ‘uniformly’ increased NT, whereas 8/13 DS cases (62%) had a ‘notched’ appearance (Fisher's exact test, p=0.004). Additionally, 27/29 fetuses (93%) which had an uneventful pregnancy outcome had a ‘uniform’ increased NT, whereas 12/26 (57%) of the fetuses which had adverse pregnancy outcome had a ‘notched’ appearance of their NT (Fisher's exact test, p<0.001). Although it was not possible to correlate the sonographic data with post-evacuation microdissection findings, it is possible that a uniformly shaped, increased NT may be more representative of a developmental delay in a normal fetus. Conversely, a ‘notched’ nuchal surface may represent abnormal lymphatic or cardiovascular development more commonly seen in DS fetuses. Copyright © 2001 John Wiley & Sons, Ltd.     

Increased nuchal translucency in euploid fetuses—what should we be telling the parents?

Nuchal translucency (NT) measurement between 11 and 14 weeks' gestation is an undisputed marker for aneuploidies. When conventional karyotyping is normal, enlarged NT is a strong marker for adverse pregnancy outcome, associated with miscarriage, intrauterine death, congenital heart defects, and numerous other structural defects and genetic syndromes. The risk of adverse outcome is proportional to the degree of NT enlargement. Although the majority of structural anomalies are amenable to ultrasound detection, unspecified genetic syndromes involving developmental delay may only emerge after birth. Concern over these prenatally undetectable conditions is a heavy burden for parents. However, following detection of enlarged NT the majority of babies with normal detailed ultrasound examination and echocardiography will have an uneventful outcome with no increased risk for developmental delay when compared to the general population. Counseling should emphasize this to help parents restore hope in normal pregnancy outcome and infant development. Copyright © 2010 John Wiley & Sons, Ltd.     

Three- versus two-dimensional ultrasound for nuchal translucency thickness measurements: comparison of feasibility and levels of agreement

We have determined feasibility and levels of agreement for visualizing the nuchal translucency within a time limit with three-dimensional (3D) and two-dimensional (2D) transvaginal ultrasound. A total of 213 women of median gestational age 13 weeks (range 11–14 weeks) undergoing first-trimester nuchal translucency (NT) thickness measurements with 2D transabdominal ultrasound were included in the study. Additionally all women underwent 2D and 3D transvaginal NT examination within a time limit of 90 s. These two methods were compared with each other and with our standard method (2D transabdominal ultrasound) with respect to visualization of fetal nuchal fold and to the levels of agreement. The nuchal fold was visualized by 3D and 2D transvaginal ultrasound in 85.9% (95% CI: 80.5%, 90.3%) and 25.8% (95% CI: 20.1%, 32.2%), respectively (p<0.001). There was a statistically significant underestimation of the NT by 2D transabdominal as compared with 3D transvaginal ultrasound of 0.1 mm (p<0.001), and by 3D transvaginal as compared with 2D transvaginal ultrasound of even 0.1 mm (p<0.001). 3D transvaginal ultrasound of the nuchal fold has increased feasibility to 2D transvaginal ultrasound within a short examination time and with minimal, but significant, measurement differences. Copyright © 2001 John Wiley & Sons, Ltd.     

Maternal serum hyperglycosylated human chorionic gonadotrophin (HhCG) in the first trimester of pregnancies affected by Down syndrome,using a sialic acid-specific lectin immunoassay

In a series of 54 cases of pregnancies complicated by Down syndrome and 224 unaffected pregnancies we examined maternal serum levels of hyperglycosylated human chorionic gonadotrophin (HhCG) in samples collected in the first trimester (11–13 weeks) using a sialic acid-specific lectin immunoassay. We compared these levels with those of other potential first trimester serum markers [free β-hCG, pregnancy-associated plasma protein A (PAPP-A) and total hCG (ThCG)] and modeled detection rates and false-positive rates of various biochemical markers in conjunction with fetal nuchal translucency (NT) and maternal age using an maternal age standardized population. Maternal serum HhCG in cases of Down syndrome were significantly elevated (median MoM 1.97) with 24/54 (44%) of cases above the 95th centile for unaffected pregnancies. Free β-hCG was also elevated (median MoM 2.09) with 33% of cases above the 95th centile. PAPP-A levels were reduced (median MoM 0.47) with 38% below the 5th centile. ThCG levels, whilst elevated (median MoM 1.34), had only 20% of cases above the 95th centile. Maternal serum HhCG levels were not correlated with fetal NT but showed significant correlation with ThCG and free β-hCG and with PAPP-A in the Down syndrome group (r=0.536). Maternal serum HhCG levels in cases with Down syndrome had a significant correlation with gestational age, increasing as the gestation increased. When HhCG was combined together with fetal NT, PAPP-A and maternal age, at a 5% false-positive rate the modeled detection rate was 83%, some 6% lower than when free β-hCG was used and some 4% better than when ThCG was used. Maternal serum HhCG is unlikely to be of additional value when screening for Down syndrome in the first trimester. Copyright © 2002 John Wiley & Sons, Ltd.     

A first trimester trisomy 13/trisomy 18 risk algorithm combining fetal nuchal translucency thickness,maternal serum free β-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 β-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 β-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. Copyright © 2002 John Wiley & Sons, Ltd.     

Quantitative evaluation of collagen type VI and SOD gene expression in the nuchal skin of human fetuses with trisomy 21

Objective To investigate the involvement of the genes encoding for COL6A1, COLA2 and super-oxide dismutase (SOD) in the mechanism for the retention of subcutaneous fluid in fetuses with trisomy 21. Methods During a 7-month period (November 2004–May 2005), human fetal skin from the nuchal region was obtained from euploid fetuses and from fetuses with trisomy 21 following abortions and terminations of pregnancy. Cell cultures were performed from nuchal skin. Quantification of COL6A1, COL6A2, COL6A3 and SOD mRNAs were performed using real-time quantitative RT-PCR. Results Twelve fetuses were studied between 13–15 and 19–20 weeks of gestation including 7 cases of trisomy 21. A significant overexpression of genes of interest was demonstrated in trisomy 21 fetuses when compared with euploid fetuses, in the first and in the second trimester of pregnancy (p < 0.0001). Conclusion This study demonstrates a homogeneous overexpression of the genes encoding for α1 and α2 chains of Collagen type VI, and SOD in nuchal skin of human trisomy 21 fetuses. Persistence of this overexpression in the second trimester of pregnancy, despite the absence of an enlarged nuchal translucency (NT), may characterize some compensatory mechanisms. Copyright © 2007 John Wiley & Sons, Ltd.     

Increased nuchal translucency after low-risk noninvasive prenatal testing: What should we tell prospective parents?

Three decades ago, the observation that first trimester fetuses with excess fluid accumulation at the back of the neck were more likely to be aneuploid, gave rise to a new era of prenatal screening. The nuchal translucency (NT) measurement in combination with serum biomarkers and maternal age, resulted in the first trimester combined screening (FTCS) program. The introduction of noninvasive prenatal testing (NIPT) over the past decade has introduced the option for parents to receive highly sensitive and specific screening information for common trisomy from as early as 10 weeks gestation, altering the traditional pathway FTCS pathway. The retention of the 11–13-week NT ultrasound remains important in the detection of structural anomalies; however, the optimal management of pregnancies with a low-risk NIPT result and an isolated increased NT measurement in an era of advanced genomic testing options is a new dilemma for clinicians. For parents, the prolonged period between the initial diagnosis in first trimester, and prognostic information at each successive stage of investigations up to 22–24 weeks, can be emotionally challenging. This article addresses the common questions from parents and clinicians as they navigate the uncertainty of having a fetus diagnosed with an increased NT after a low-risk NIPT result and presents suggested approaches to management.     

Between pregnancy biological variability of first trimester markers of Down syndrome: implications for screening in subsequent pregnancies

In a group of 149 women who had undergone routine first trimester screening using fetal nuchal translucency thickness (NT) and maternal serum free β-hCG and pregnancy associated plasma protein-A (PAPP-A) in two consecutive pregnancies the within person between pregnancy biological variability of these markers has been assessed. For fetal NT there was no correlation between NT MoM in the first and second pregnancy (r=0.0800). For maternal serum free β-hCG MoM a significant correlation was observed (r=0.4174) as was also found for PAPP-A MoM (r=0.3270). The implications for such between pregnancy marker association is that women who have an increased risk of Down syndrome in their first pregnancy are 1.5–2 times more likely to repeat this event in their next pregnancy. This observation may be useful in counselling women in the first trimester screening of a subsequent pregnancy. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal diagnosis of a fetus with androgen insensitivity syndrome (AIS)

Objective The aim of this study is to describe a fetus with androgen insensitivity syndrome diagnosed at mid-second trimester. Case and Methods Nuchal translucency was measured thick and double test was found higher. The patient referred to our center at 16^th weeks of gestation. Fetal ultrasound examination and amniocentesis was performed. Results The nuchal translucency (NT) of fetus in present pregnancy was measured approximately 10 mm at 13 weeks and Down syndrome risk was calculated 1 in 10 by double test. On ultrasound examination; thick nuchal fold (NF) and short fetal limbs were found, and the fetus was seen a female and amniocentesis was performed. Three weeks later the fetal karyotype was reported normal as 46,XY. Thereupon the fetus reexamined for 2D and 4D ultrasound, and confirmed previous findings. The fetus was terminated at 19^th weeks and seen a female phenotype. The fetal gonads removed in abdomen and testicles confirmed histopatologically. Conclusion In generally, diagnosis of AIS is most made postnatally. This is the second case in English literature, which diagnosed mid-second trimester. In this situation, the fetus with thick NT/NF and short limbs may be AIS, therefore appearance of fetal sex on ultrasound should be compared with genetic sex Copyright © 2007 John Wiley & Sons, Ltd.     

Screening for trisomy 21 in twin pregnancies in the first trimester: does chorionicity impact on maternal serum free β-hCG or PAPP-A levels?

In a study of 180 twin pregnancies I have examined the distribution of maternal serum free β-human chorionic gonadotrophin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A), in addition to fetal nuchal translucency thickness (NT), in twins classified as monochorionic or dichorionic, based on ultrasound appearance at 10–14 weeks of gestation. In 45 monochorionic and 135 dichorionic twin pregnancies the median MoM free β-hCG was not significantly different (1.00 vs 1.01), whilst that for PAPP-A was lower (0.89 vs 1.01) but again with no statistical significance. Previous reports of an increased fetal NT in monochorionic twins pregnancies could not be confirmed (1.03 vs 1.00). It is concluded that the existing pseudo risk twin correction algorithm is appropriate for both monochorionic and dichorionic twins in providing accurate first trimester risks for trisomy 21. Copyright © 2001 John Wiley & Sons, Ltd.     

短期保护性耕作措施对大豆-冬小麦轮作系统温室气体排放的影响

通过田间试验,在大豆和冬小麦生长季,进行常规翻耕(conventional tillage,T)、免耕(no-tillage with no straw cover,NT)、常规翻耕+秸秆(conventional tillage with straw cover,TS)、免耕+秸秆(no-till with straw cover,NTS)4种耕作措施处理,采用静态箱-气相色谱法测定土壤-作物系统CO_2和N_2O排放通量.结果表明:在大豆生长季,与T相比,NTS在开花-结荚期显著增加了CO_2累积排放量(P=0.045),增幅达27.9%;NT在鼓粒-成熟期显著降低了CO_2累积排放量(P=0.043),降幅达28.9%.与T相比,NT在鼓粒-成熟期的N_2O累积排放量降低了28.3%(P=0.042).在冬小麦生长季,与T相比,TS、NT在拔节-孕穗期使CO_2累积排放量降低了24.3%(P=0.032)和36.0%(P=0.041),在成熟期降低了26.8%(P=0.027)和33.1%(P=0.038).在返青期,NT、NTS、TS的N_2O累积排放量与T比较均没有明显差异,NTS比NT的N_2O累积排放量降低了42.0%(P=0.035).可见,保护性耕作措施对土壤-作物系统CO2排放的影响较大,对N2O排放的影响不明显.     

Combining nuchal translucency and serum markers in prenatal screening for Down syndrome in twin pregnancies

A method is described to combine the ultrasound marker nuchal translucency (NT) with serum markers so that they can be used together in prenatal screening for Down syndrome in twin pregnancies. For monochorionic twin pregnancies (taken as monozygous), the two fetus-specific NT measurements are averaged before risk is calculated and before the contribution of the serum markers is incorporated. For dichorionic twin pregnancies (taken as dizygous), the risk for each fetus based on the individual NT measurements is calculated, the two fetus-specific risks are added together, and then the contribution of the serum markers is incorporated. In this way, all the screening markers can be used in combination to produce a pregnancy-specific ‘pseudo-risk’, rather than a fetus-specific pseudo-risk. We refer to pseudo-risk because in the absence of sufficient data on the screening markers in affected twin pregnancies, a true risk estimate cannot be calculated. Tentative estimates are given of screening performance in twins using NT, the combined test (NT with first-trimester serum markers), and the integrated test (NT with first- and second-trimester serum markers), all interpreted with maternal age. Copyright © 2003 John Wiley & Sons, Ltd.     

成晶节杆菌NT16和共生芽孢杆菌NG16联合代谢1-萘酚的特性

1-萘酚是多环芳烃降解过程中极易积累的典型含氧多环芳烃,其难降解、毒性大,直接影响多环芳烃污染环境的修复效果.为探究微生物联合代谢1-萘酚的特性,以前期从含氧多环芳烃污染土壤中分离出的两种共生菌株——成晶节杆菌NT16和芽孢杆菌NG16为受试菌株,结合HPLC、TOC、GC-MS等测定方法进行降解特性的测定.结果表明,NT16菌和NG16菌均能以1-萘酚为唯一碳源和能源生长,两种菌株联合代谢比NT16菌、NG16菌单独降解1-萘酚的生长量分别高2.758×10~9 cfu·mL~(-1)和1.4×10~9 cfu·mL~(-1),对1-萘酚的降解率可提高20%,使体系中TOC值加速降低.NT16菌和NG16菌联合代谢1-萘酚可按照两个途径进行,其一,1-萘酚羟化后开环,进入邻苯二甲酸代谢途径.NT16菌更易进入该途径,而NG16菌则不易通过该途径降解1-萘酚;其二,1-萘酚羟化后开环,进入苯丙酸代谢途径.NG16菌迅速将1-萘酚降解为对羟基苯乙酸,其在降解体系中积累,NT16菌无法高效降解1-萘酚却能够降解对羟基苯乙酸至较短烷基链的小分子化合物.该研究结果将为含氧多环芳烃污染环境实际修复中微生物群落协同作用降解污染物奠定基础.     

Transverse limb reduction defects after chorion villus sampling: A retrospective Cohort study

A retrospective cohort study was performed in five Italian obstetrical centres from 1984 to 1991 in order to verify the association between chorionic villus sampling (CVS) and transverse limb reduction defects (TLRDs). TLRD rates by period of gestation at CVS were calculated, and the study's results were compared with data from the general population. Of the 3430 pregnancies for which CVS was performed, 2759 had a known outcome. The overall rate for TLRDs was 1 in 1143 CVS pregnancies, four times higher than that of the general population in Italy (1 in 4458). The rate of TLRDs was 2·9/1000 for CVS performed at 9 weeks' gestation and 1·0/1000 for CVS at 10 weeks' gestation. A scalp defect was detected in a pregnancy in which CVS was performed at 10 weeks. A high proportion of pregnancies lost to follow-up and the poor quality of the data may have affected the results. Nevertheless, our results suggest an association between CVS carried out at less than 10 weeks' gestation and TLRDs which is consistent with the findings of other studies. CVS should not be prepared at less than 10 weeks' gestation until additional evidence is obtained.