Fetal nuchal translucency and skinfold to screen for fetal aneuploidy

Nuchal translucency (NT) is defined as the accumulation of subcutaneous fluid in the nuchal region of the fetus at 11-14 weeks. Its measurement in order to modify the previous background risk has been proved to be able to detect around 70% of trisomy 21 pregnancies (for a 5% fixed positive rate). When affected fetuses dying before 20 weeks are excluded, detection rate may decrease to 60%. Given that appropriate training of sonographers and adherence to a standard technique for the measurement of NT is of paramount importance to reduce variability, the Fetal Medicine Foundation has established a certification process. Fetal nuchal edema displayed at 15-20 weeks was described as enlarged nuchal skinfold, and is a less sensitive but more specific marker than nuchal translucency. Webbing of the neck in infants with trisomy 21 may be envisaged as the remainder of nuchal distension.     

If nuchal translucency screening is combined with first-trimester serum screening the need for fetal karyotyping decreases

BACKGROUND: This case-control study was performed to evaluate whether adding first-trimester maternal serum testing to nuchal translucency measurement would improve the antenatal detection of Down's syndrome and decrease the number of women offered fetal karyotyping. METHODS: In the Swedish Nuchal Translucency Trial (the NUPP trial), 39,572 pregnant women were randomized to a routine scan at 12-14 gestational weeks including nuchal translucency screening for Down's syndrome, or a routine scan at 16-18 gestational weeks. From the early scan group 47 pregnancies with Down's syndrome were identified and for each case three controls were chosen. Of the 189 women asked to participate, 31 cases and 108 controls with a singleton pregnancy and frozen serum from 8-14 gestational weeks available for analysis accepted participation. Maternal sera were analyzed for free beta human chorionic gonadotrophin and pregnancy-associated plasma protein A. The risk for Down's syndrome was calculated using combinations of maternal age, crown-rump length, nuchal translucency, and biochemistry. A risk > or =1/250 was considered increased and an indication for fetal karyotyping. RESULTS: Risk calculated on the basis of maternal age alone would have identified 21 of the 31 Down's syndrome cases by karyotyping 61 of the 139 fetuses. Maternal age and nuchal translucency would have identified 29 cases by karyotyping 51 fetuses. Maternal age, nuchal translucency, and biochemistry would also have identified 29 cases by karyotyping 37 fetuses. CONCLUSIONS: By adding first trimester biochemistry to nuchal translucency measurement the detection rate of fetuses with Down's syndrome seems to remain unchanged whereas the antenatal risk group to be offered fetal karyotyping decreases.     

The influence of maternal insulin-dependent diabetes on fetal nuchal translucency thickness and first-trimester maternal serum biochemical markers of aneuploidy

OBJECTIVE: To evaluate the influence of maternal insulin dependent diabetes mellitus (IDDM) on maternal serum free beta-hCG, PAPP-A and fetal nuchal translucency (NT), thickness at 11 to 13(+6) weeks of gestation in a large cohort of women screened prospectively for chromosomal anomalies. METHODS: Information on maternal IDDM status, maternal serum biochemical marker levels and fetal NT were collected from the prenatal screening computer records in two first-trimester screening centres. In total the control group included 33 301 pregnancies of which 16 366 had NT and maternal serum biochemistry results and 16 305 with NT only. The IDDM group included 195 pregnancies of which 79 had NT and maternal serum biochemistry results and 127 with NT only. The median maternal weight corrected free beta-hCG and PAPP-A, expressed as multiple of the median (MoM), and fetal NT, expressed as delta values, in the IDDM and non-IDDM groups were compared. RESULTS: There were no significant differences between the IDDM and non-IDDM groups in median maternal weight corrected free beta-hCG (IDDM 0.87 MoM, 95% Confidence Interval 0.75 to 1.16 MoM, non-IDDM 1.00 MoM), median maternal weight corrected PAPP-A (IDDM 1.02 MoM, 95% Confidence Interval 0.83 to 1.05 MoM, non-IDDM 1.01 MoM), or mean delta NT (IDDM 0.0358 mm, non-IDDM 0.0002 mm). CONCLUSIONS: In pregnancies with maternal IDDM, first-trimester screening for chromosomal defects does not require adjustments for the measured fetal NT. However, more data are required before the possible reduction in maternal serum free beta-hCG and the reduction of PAPP-A suggested by the published world series can be considered sufficiently important to take into account in the calculation of risks for chromosomal defects.     

First-trimester screening for Down syndrome in France combining fetal nuchal translucency measurement and biochemical markers

BACKGROUND: In France, there is a strictly regulated National Screening Programme for Down syndrome, based on second-trimester maternal serum markers. A prospective study of nuchal translucency together with retrospective evaluation of maternal serum markers was carried out to inform decisions on whether to move the programme to the first trimester. METHODS: Between January 1998 and June 2001, all women who presented for their prenatal care at 12 participating maternity units were, regardless of age, invited to provide a blood sample and to attend for an NT scan at 11 to 13 weeks. The results were used to derive Gaussian distribution parameters. Detection and false-positive rates were computed in two ways: statistical modelling and directly. The cut-off risk was 1 in 250 at term. RESULTS: A total of 5694 women with singleton pregnancies were screened including 26 with Down syndrome and 24 with other aneuploidies. The model-predicted detection and false-positive rates for combined ultrasound and serum screening were 81 and 4.5% compared to 64 and 6.0% for ultrasound alone. The directly observed rates were 73 and 4.7%, compared to 62 and 5.0% respectively. CONCLUSION: In France, first-trimester screening with nuchal translucency and maternal serum markers is likely to achieve a high screening efficiency. This has important implications for the national screening policy.     

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.     

Comparison and integration of first trimester fetal nuchal translucency and second trimester maternal serum screening for fetal Down syndrome

BACKGROUND: It is uncertain whether first trimester nuchal translucency (NT) is more effective than the well-established second trimester serum screening for fetal Down syndrome or whether their combination works best. We report data from a large multicentre non-interventional trial in which all subjects underwent both first and second trimester screening. METHODS: All women who attended the obstetric clinic before 15 weeks' gestation were recruited. An ultrasound examination was performed at 10 to 14 weeks to measure the NT. The nuchal measurements were not acted upon unless the fetus showed gross features of hydrops fetalis. All women had serum alpha-fetoprotein (AFP) and human chorionic gonadotrophin (hCG) assay at 15 to 20 weeks. The Down syndrome risk assigned by serum screening was disclosed and amniocentesis was offered if this assigned risk was >or=1:250 or if the women were 35 years and older. The efficacy of different combinations of screening markers was compared. RESULTS: Between January 1997 and August 2000, 17 590 women were recruited (19% >or=35 years old). After excluding subjects who miscarried, defaulted the serum test and other reasons, 16 237 pregnancies were analysed. Of these, 35 pregnancies were affected by Down syndrome (2.2 cases per 1000 pregnancies). At a false-positive rate of 5%, the detection rate of Down syndrome by NT alone, NT and age, serum hCG, AFP and age, and NT, hCG, AFP and age were 61%, 69%, 73% and 86%, respectively. CONCLUSION: Integration of NT and second trimester serum AFP and hCG assay yielded the best screening efficacy for Down syndrome.     

The role of fetal nuchal translucency in prenatal screening

PURPOSE OF REVIEW: An update of findings from studies on first trimester nuchal translucency screening. RECENT FINDINGS: New first trimester markers can substantially improve efficacy of screening. When fully informed, preliminary data indicate that women prefer first trimester above second trimester testing. SUMMARY: Recent reports on nuchal translucency screening reiterate the importance of standardization of technique and quality control as proposed by the Fetal Medicine Foundation in London. Effective quality control can be achieved through quantitative analysis of operator specific data. Three-dimensional ultrasound does not provide substantially higher success rates in obtaining reliable nuchal translucency measurements than two-dimensional ultrasound. New data confirm the previously reported association between increased nuchal translucency and increased rate of spontaneous fetal loss, genetic syndromes and a high prevalence (15%) of anomalies, among which cardiac defects are the commonest. Researchers agree that increased nuchal translucency ought to be an indication for specialized echocardiography. Promising data have become available on new markers that can enhance first trimester screening. It is estimated that when assessment of nasal bone and maternal serum analytes are taken into account, first trimester screening can identify 97.5% of trisomy 21 pregnancies for a 5% false-positive rate. It is stressed that parents need to be informed about the possible implications of screening before testing. Preliminary data indicate that when appropriately informed, women prefer first trimester above second trimester testing. Furthermore, the uptake of screening is likely to be relatively low among younger women.     

Quality assurance of nuchal translucency for prenatal fetal Down syndrome screening

Objective: To assess the quality of nuchal translucency, (NT) measurements were performed at four public institutions performing routine first trimester combined prenatal screening for Down syndrome. Methods: The median of the NT-MoM distribution and standard deviation (SD) of the log₁₀ NT-MoM were determined. Sonographers and screening centres distributions were assessed for measures of central tendency (median) and dispersion (log₁₀ SD). Cumulative Sum (CUSUM) charts were created to assess whether screening centres and individual sonographers who had performed at least 30 NT measurements exhibited any systematic bias by checking whether their CUSUM scores exceeded predefined upper and lower control limits. Results: Of the 36 sonographers, only 67% (n?=?24) had performed 30 or more scans. The median NT-MOM at each screening centre ranged from 1.02 to 1.09. Screening centre standard deviations ranged from 0.073 to 0.099. CUSUM charts indicated that only one screening centre remained within the predefined control limits throughout the assessment period. Analysis of variance indicated that a statistically significant difference existed between the log NT-MoM distributions of the individual sonographers (F?=?10.7; p <0.0001). Inspection of the individual sonographer CUSUM charts indicated that 11 (45%) of the 24, with more than 30 NT measurements were either under or over measuring the NT. Conclusion: Prospective monitoring and feedback of quality assurance assessment results of sonographers and screening centres should be routinely reported as both are responsible, if equity of screening performance is to be maintained.     

First-trimester screening for Down syndrome with ductus venosus Doppler studies in addition to nuchal translucency and serum markers

OBJECTIVE: To estimate the improvement in screening efficiency when fetal ductus venosus Doppler studies are added to existing first-trimester Down syndrome screening protocols. METHODS: Statistical modelling was used with parameters derived from prospective ductus venosus studies and from the published literature. The pulsatility index for veins (PIV), was determined in the fetal ductus venosus for 3706 unaffected and 25 Down syndrome pregnancies at 10-14 weeks' gestation. Concurrent nuchal translucency measurement and maternal serum pregnancy associated plasma protein A and free-beta human chorionic gonadotrophin were also measured. RESULTS: The median PIV in Down syndrome was 1.70 times higher than in unaffected pregnancies (95% confidence interval 1.36-2.12). PIV levels followed an approximately log Gaussian distribution with log(10) standard deviations of 0.193 and 0.076 in Down syndrome and unaffected pregnancies. There were no statistically significant correlations between PIV and the other markers. Modelling predicts that for a fixed 5% false-positive rate, the addition of PIV to nuchal translucency alone will increase the detection rate from 76 to 85%, and combined with serum markers, from 88 to 92%. For a fixed 85% detection rate, the false-positive rate reduced from 15 to 4.8% and from 3.2 to 1.2% respectively. CONCLUSION: Ductus venosus Doppler studies can substantially improve Down syndrome screening efficiency.     

Presenting and discussing nuchal translucency screening for fetal abnormality in the UK

OBJECTIVE: to investigate the relationship between information giving by midwives and decision-making by women offered nuchal translucency (NT) screening. To establish how risk figures are discussed in practice, with the intention of relating this to the existing, and often critical, literature on women's accounts of antenatal screening. DESIGN: a qualitative study following women through the process of being offered and deciding to undergo NT screening. Tape recording of consultations, analysed in their entirety, was combined with post-screening interviews. SETTING: a large teaching hospital in the UK. PARTICIPANTS: fourteen pregnant women eligible for NT screening at the time of recruitment. DATA COLLECTION: (i) tape recordings of consultations between community midwives and pregnant women where nuchal translucency screening was offered; (ii) tape recordings of consultations between hospital midwives and pregnant women immediately post-screening; (iii) individual face-to-face interviews with pregnant women between two and six weeks after the screening, carried out by the first author. FINDINGS: NT screening was in general well received, particularly by those women who had undergone serum screening with previous pregnancies. However, communicating the nature of a risk figure is an interactionally complex process. A large amount of interactional work is required by midwives both before and after screening to ensure that women comprehend this information. Despite the emphasis placed in these consultations on understanding the purpose of NT screening and the status of the results, women often framed their decision to undergo NT screening in terms of it being a formality, or of presuming that all was well. This sometimes created practical and personal difficulties in terms of decision-making. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: previous sociological and psychological research has tended to be critical of midwives in terms of ensuring informed choice in screening, but this research is often based on post hoc accounts. Examining actual consultations with these accounts helps to illustrate the other factors that affect women's perceptions of testing, and the way in which risk, choice and decision-making are introduced and discussed in practice. Encouraging women to consider what action they might take on the basis of a personally unfavourable NT result in advance of undergoing the scan may help them to decide whether the information gained will be useful to them. Recognising the complex interactional work required in making sure that women understand the nature of the results that will be obtained is an important issue for the education and training of midwives.     

First-trimester Down's syndrome screening by fetal nuchal translucency measurement in Taiwan.

BACKGROUND: Fetal nuchal translucency (NT) measurement is now widely used in many Western countries as a screening tool for Down's syndrome during the first trimester. However, at present there is no data on its use in Taiwan. The purpose of the present study was to evaluate the efficacy of NT measurement in first-trimester Down's syndrome screening in Taiwan. METHODS: We conducted a prospective study from October 1997 to May 1999. Sonographic measurement of fetal NT was performed in 1,249 fetuses at 9-14 weeks of gestation. Transabdominal ultrasound scanning was performed to obtain a sagittal section of the fetus for measuring the crown-rump length (CRL) and the maximum thickness of the subcutaneous translucency between the skin and the soft tissue overlying the cervical spine. Two different cut-off points were used for screening: a fixed cut-off point of at least 2.5 mm and a CRL-related cut-off point. In the latter method, fetuses with an NT measurement in the 95th percentile were considered at high risk for Down's syndrome. RESULTS: Three fetuses had Down's syndrome, with NT measurements of 2.1 mm, 2.7 mm, and 4.0 mm. The false positive rates for the fixed cut-off point and CRL-related cut-off point were 6.3% and 4.6%, respectively. Both methods had a sensitivity of 66.7%. However, the screening program using the CRL-related cut-off point had two advantages: a higher specificity (95.5% vs 93.8%) and a more reasonable distribution pattern for screening. CONCLUSION: This study showed that NT measurement is a potential screening tool for Down's syndrome during the first trimester in Taiwan. Using CRL-related cut-off points for screening is more reasonable than using a fixed cut-off point.