Community-based screening for Down's Syndrome in the first trimester using ultrasound and maternal serum biochemistry

Two years of community-based first trimester screening (FTS) were audited. All women with singleton pregnancy in a defined health region who completed FTS (ultrasound and biochemistry) were included (n= 10,436) and outcomes obtained for 98.4%. All scans were performed or supervised by experienced sonologists with Fetal Medicine Foundation (FMF) accreditation. FMF software generated all risk assessments based on nuchal translucency (NT), maternal serum-free beta human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein A (PAPP-A). The detection rate for Trisomy 21 was 90.6% with a screen-positive rate of 3.9%. These findings indicate that where FTS is accessible within routine antenatal care, a detection rate of 90% and low screen-positive rate can be achieved using the FMF programme.     

Estimation of ultrasonographic markers of chromosomal abnormalities in verification of second trimester maternal serum biochemistry

In the case of positive triple test results the presence or absence of sonographic markers is associated not only with fetal abnormalities, but also with a variety of adverse outcomes of pregnancy. OBJECTIVE: Evaluation of sonographic markers of chromosomal abnormalities in verification of positive results of triple tests. MATERIAL AND METHODS: In consecutive series of 780 pregnant women we performed triple tests at 14-19 weeks. We reviewed the presence or absence of sonographic markers for fetal abnormalities including nuchal thickening (NT), nasal bones (NB), extermities (HL, FL), umbilical cord diameter (UCD), bowel echogenity (BE), renal pyelectasis (DPR) and chorioid plexus cyst (CPC). RESULTS: There were 47 (6.02%) positive results of triple tests including 36 (4.6%) cases with false positive result. In the group of affected fetuses we observed at least two sonographic markers. In the group with false-positive results 15 (41.6%) fetuses had adverse pregnancy outcome with only one ultrasound marker. CONCLUSION: Positive result of the triple test and the presence of two or more markers of fetal abnormalities increase the risk of fetal abnormalities, whereas absence or presence of only one marker and normal karyotype should classify pregnancy to high risk of adverse perinatal outcome.     

Screening for fetal chromosomal abnormalities with nuchal translucency measurement in the first trimester

OBJECTIVE: To describe the detection rate of first-trimester chromosomal abnormality screening with nuchal translucency (NT) measurement and maternal age in our population. METHODS: We have screened the fetuses between 11 to 14 weeks' gestation according to the Fetal Medicine Foundation's (London) instructions and used the FMF's software to assess the risk based on maternal age, crown-rump length (CRL) and NT. Fetal karyotyping was offered when screening for Down syndrome identified a risk greater than 1 in 300. Sensitivity and false-positive rates were calculated for different cut-offs. RESULTS: Pregnancy outcome was obtained from 4,598 babies of 4,365 mothers. The median maternal age of the 4,365 women was 28.2+/-5.3 (range 15-47) years, and the median fetal CRL was 65.4+/-9.4 (range 45-81) mm. There was risk estimate of >or=1 in 300 in 214 fetuses (4.7%). Chromosomal abnormalities were identified in 32 fetuses, including 19 cases of trisomy 21, and 13 cases of other abnormalities. The sensitivity using NT and maternal age in detecting trisomy 21 with a cut-off 1 in 300 was 73.6% (14/19) with a false-positive rate of 4.7%. At a false-positive rate of 3%, with a cut-off level 1 in 210, the detection rate was 73.6%. The detection rate for all chromosomal abnormalities with a cut-off level 1 in 300 was 68.8% (22/32) at a false-positive rate of 4.7%. CONCLUSION: The first-trimester screening for chromosomal anomalies with NT measurement, when carried out according to the accepted standards of quality, is useful.     

Routinisation and constraints on informed choice in a one-stop clinic offering first trimester chromosomal antenatal screening for Down's syndrome

Objective

to explore routinisation and constraints on informed choice in a one-stop clinic offering first trimester antenatal chromosomal screening for Down’s syndrome.

Design

recordings of booking appointments and pre-screening consultations in both a community and a hospital clinic setting.

Setting

one antenatal clinic site in the UK offering first trimester nuchal translucency screening in combination with maternal serum screening.

Participants

57 taped clinical consultations involving pregnant women and midwives and health-care assistants (HCAs).

Findings

midwives and HCAs expected women to make informed decisions about screening for Down’s syndrome. However, midwives’ attempts to maintain the normality of pregnancy and avoid discussions about potential scenarios, as well as their emphasis on the high accuracy rate of first trimester screening have routinised first trimester antenatal screening for Down’s syndrome. Also, a general expectation in the clinic to take up screening and the constrained service context in which midwives and HCAs work had implications for women’s informed choices.

Key conclusions

directive information combined with lack of purposeful dialogue with pregnant women have constrained the process of information-giving about antenatal screening for Down’s syndrome.

Implications

the provision of information about antenatal screening for Down’s syndrome is a challenging role for midwives. Changes in midwifery practice resulting from continuing education as well as less constraining service contexts could improve the quality of information about antenatal screening for Down’s syndrome.     

Prospective evaluation of a first trimester screening program for Down syndrome and other chromosomal abnormalities using maternal age, nuchal translucency and biochemistry in an Australian population

BACKGROUND: A combination of maternal age and ultrasound assessment of the nuchal translucency (NT) has been used in the first trimester to screen for chromosomal abnormality. In the United Kingdom, the addition of NT screening was shown to be beneficial. AIMS: To report the sensitivity of combined first trimester biochemistry and ultrasound screening for Down syndrome in an Australian private practice specialising in obstetric ultrasound. METHODS: A prospective study in a private obstetric ultrasound practice. Over 22 months, 2121 patients were screened and data was analysed for sensitivity (detection) and false positive rates for all chromosome abnormalities. RESULTS: There were 17 chromosomal abnormalities, five of which were Down syndrome. Using maternal age alone or age and biochemistry, four of the Down syndrome cases were detected for a 29 and 19% false positive rate, respectively. Using age and NT or age, NT and biochemistry, all the Down syndrome cases were detected, for a false positive rate of 5.7 and 7.2%, respectively. The difference in detection rates for Down syndrome or other chromosomal abnormalities, using the four screening methods, did not reach statistical significance. However, the false positive rates in screening methods without ultrasound to assess the NT was significantly higher (P < 0.01). CONCLUSIONS: A combination of maternal age, NT and maternal serum biochemistry gives a high detection rate for both trisomy 21 and other chromosomal abnormalities. Down syndrome screening using either maternal age alone or age in combination with first trimester biochemistry conferred screen positive rates significantly higher than when combined with NT.     

The impact of correcting for smoking status when screening for chromosomal anomalies using maternal serum biochemistry and fetal nuchal translucency thickness in the first trimester of pregnancy

OBJECTIVES: To evaluate the influence of cigarette smoking status on maternal serum free beta-hCG, PAPP-A and fetal nuchal translucency (NT) thickness at 11 to 14 weeks of gestation in a large cohort of women screened prospectively for chromosomal anomalies. METHODS: Information on maternal cigarette smoking status, maternal age, maternal serum biochemical marker levels and fetal NT were collected from the prenatal screening computer records in two OSCAR screening centres. Data was available from 32,730 unaffected pregnancies and from 124 with Down syndrome. Statistical analysis of the marker levels in the smoking and non-smoking group were carried out. The impact on false-positive rate of correcting for smoking status was assessed from a modelling exercise. RESULTS: Prevalence of smoking was significantly affected by maternal age with an overall incidence of 11.5%, which varied from 35% in women under 20 to 7% in women over 35. In the unaffected population, the median free beta-hCG MoM was significantly lower in the smoking group (0.97 vs 1.00) as was that for PAPP-A (0.84 vs 1.02). The standard deviation of the log(10) MoM free beta-hCG was lower in the smoking group and that for PAPP-A was higher in the smoking group. The difference in median marker levels did not seem to be related to the number of cigarettes smoked per day. In the group with Down syndrome, the median MoM free beta-hCG was not significantly different in the smokers (1.69 vs 1.86) as was that for PAPP-A (0.53 vs 0.57). Fetal delta NT was not significantly different in the unaffected smokers (0.11 vs 0.0 mm) or in those with Down syndrome (1.96 vs 2.25 mm). In the smoking group, when screening using maternal serum biochemistry and age alone, the false-positive rate was 6.17%, compared to 4.67% in an age-matched group of non-smokers. Correcting for smoking status by dividing the measured MoM by the median found in the smoking group resulted in the false-positive rate falling to 4.40%. When screening using NT, maternal serum biochemistry and age, the false-positive rate in smokers was 4.48%, which reduced to 3.46% after correction-in line with the 3.76% in the non-smoking group. The impact on detection rate was too small to be accurately measured. CONCLUSIONS: The impact of smoking on first-trimester biochemical marker levels does not seem to be dose related. Whilst correcting first-trimester biochemical markers for maternal smoking status has little impact at the population level for detection rates, a considerable reduction in false-positive rate can be achieved, reducing the level to that seen in non-smokers. However, the effect on the individual patient-specific risk can be substantial and could certainly make a difference to the patient's decision on whether to have an invasive test.     

The joint vulval clinic: a review of the first three years.

This aim of this study was to undertake a retrospective analysis of the notes of all new patients who attended the joint vulval clinic between 1994 and 1997. One hundred and forty-five patients were seen, and data analysed for 133 (92%). The study identified the range of diagnoses seen; treatment modalities undertaken; and enabled comparisons to be made between our findings and those of other workers.     

Serum parameters and nuchal translucency in first trimester screening for fetal chromosomal abnormalities

Objective To assess the relation between serum parameters and nuchal translucency in pregnancies affected by fetal aneuploidy in the first trimester.
Design Retrospective study of different serum parameters collected prior to chorionic villus sampling and measurement of nuchal translucency in relation to fetal aneuploidy.
Setting Switzerland (German and Italian sector) and Bregenz, Austria.
Population One thousand one hundred and fifty-one women aged 25 to 44 years at 10 to 13 weeks of gestation undergoing chorionic villus sampling, mostly for advanced maternal age. Fetal aneuploidy was found in 23 pregnancies including four cases of trisomy 21, five of trisomy 18 and one case of trisomy 13.
Main outcome measure Fetal karyotype, serum levels of free β-hCG, pregnancy-associated plasma protein A (PAPP-A) and alpha-fetoprotein and the measurement of nuchal translucency.
Results Serum PAPP-A was decreased in all common chromosomal abnormalities. Free β-hCG levels were increased in trisomy 21 but decreased in trisomy 18, whereas alpha-fetoprotein was low in trisomy 21, 18 and other chromosomal abnormalities. Nine of twenty-three abnormal embryos had evidence of an increased nuchal translucency. Nuchal translucency, however, did not seem to be associated with any alteration in the levels of the biochemical parameters in either chromosomally normal or abnormal embryos. A low serum PAPP-A or an increased nuchal translucency was seen in two-thirds of all pregnancies with chromosomal abnormalities.
Conclusion A nuchal translucency 3 mm and depressed serum PAPP-A levels have a good predictive value in the detection of fetal aneuploidy at 10 to 13 weeks of pregnancy. Serum free 0-hCG and alpha-fetoprotein levels may give additional information. An increased nuchal translucency was not-associated with altered serum parameters. This would allow these different markers to be used in combination.     

妊娠中期母血清生化标志物筛查唐氏综合征的临床价值

目的评价妊娠中期母血清生化标志物筛查唐氏综合征(21-三体综合征)的临床价值。方法1996年7月至2003年6月,南京市妇幼保健院用时间分辨荧光分析法对13175例妊娠14~20周的孕妇进行血清甲胎蛋白(AFP)、游离绒毛膜促性腺激素(free-β-HCG)检测,切割值1∶300,对高风险者行羊水检查。结果21-三体综合征及18-三体综合征的检出率为5.3/万,假阳性率为10.69%。唐氏综合征高风险组胎儿异常的发生率高于唐氏综合征低风险组(P<0.01)。≥35岁孕妇组胎儿异常的发生率高于<35岁孕妇组(P<0.05)。结论AFP、free-β-HCG可用于筛查唐氏综合征及胎儿异常。     

The feasibility of a one-stop colposcopy clinic in the management of women with low grade smear abnormalities: a prospective study

OBJECTIVES: To assess the feasibility of a one-stop colposcopy clinic for the management of women with low-grade smear abnormalities. Secondly, to determine whether the approach of immediate information of biopsy results combined with treatment if indicated helps to reduce patient anxiety and improve overall patient satisfaction with the colposcopy process. DESIGN: Prospective study following the introduction of a "one-stop" process for the management of women with low grade smear abnormalities. SUBJECTS: First 118 women managed in a "one-stop" clinic during an 8-month period. METHODS: Assessment of patient anxiety via self-completed questionnaires and comparison of anxiety scores with a control group managed via a standard clinic. RESULTS: The median waiting time for results in the one-stop clinic was 120 min (range: 100-165). All women in both groups felt anxious at the time of the clinic visit. However, after 1 week the majority of patients managed via the one-stop process felt slight anxiety only (P=0.0001) as opposed to those patients in the control group who remained anxious (P=NS). In addition, all women said they would prefer the one-stop approach for further smear abnormalities if a further colposcopic examination was warranted. CONCLUSION: A one-stop colposcopy clinic is feasible for the management of women with low-grade smear abnormalities. In addition, it delivers a quality service, optimises patient management, reduces anxiety and is the patient's choice.     

Principles of first trimester screening in the age of non-invasive prenatal diagnosis: screening for chromosomal abnormalities

Purpose

First trimester risk assessment for chromosomal abnormalities plays a major role in the contemporary pregnancy care. It has evolved significantly since its introduction in the 1990s, when it essentially consisted of just the nuchal translucency measurement. Today, it involves the measurement of several biophysical and biochemical markers and it is often combined with a cell-free DNA (cfDNA) analysis as a secondary test.

Methods

A search of the Medline and Embase databases was done looking for articles about first trimester aneuploidy screening. We performed a detailed review of the literature to evaluate the screening tests currently available and their respective test performance.

Results

Combined screening for trisomy 21 based on maternal age, fetal NT, and the serum markers free beta-hCG and PAPP-A results in a detection rate of about 90% for a false positive of 3–5%. With the addition of further ultrasound markers, the false positive rate can be roughly halved. Screening based on cfDNA identifies about 99% of the affected fetuses for a false positive rate of 0.1%. However, there is a test failure rate of about 2%. The ideal combination between combined and cfDNA screening is still under discussion. Currently, a contingent screening policy seems most favorable where combined screening is offered for everyone and cfDNA analysis only for those with a borderline risk result after combined screening.

Conclusion

Significant advances in screening for trisomy 21 have been made over the past 2 decades. Contemporary screening policies can detect for more than 95% of affected fetuses for false positive rate of less than 3%.

     

Screening for trisomy 21 in Flanders: a 10 years review of 40.490 pregnancies screened by maternal serum

OBJECTIVE: To evaluate maternal serum screening for trisomy 21 (MSS) in Flanders between 1992 and 2002. STUDY DESIGN: Data of a large database on the results of MSS, nuchal translucency (NT) and pregnancy outcome were analysed retrospectively. RESULTS: Despite an excellent performance of second trimester MSS at a maternal age > or = 35 years (94.4% detection rate (DR) of trisomy 21 at a false positive rate (FPR) of 22.4%), the proportion of patients above 35 years of age in the study population was significantly lower than in the Flemish general pregnant population (5.5% versus 8.9%, P < 0.001). In the population screened by MSS and NT, the DR of second trimester MSS at a 5% FPR was 44.4%, which was lower than 66.6% in the population screened by MSS without NT. When nine trisomy 21-affected pregnancies were compared to 3265 normal pregnancies, the mean NT-MoM values were not significantly different (1.16 +/- 0.89 versus 1.00 +/- 0.46, P > 0.05). Both the findings comply to a sequential screening practice where second trimester MSS is only performed after a normal measurement of NT in the first trimester. CONCLUSION: In Flanders, the uptake of second trimester maternal serum screening is low in women aged 35 years or more. Its screening performance decreased after the introduction of sequential screening.